1
GOVERNMENT OF INDIA
MINISTRY OF HEALTH AND FAMILY
WELFARE
(Department of Health)
THE DRUGS AND COSMETICS ACT
AND RULES
THE DRUGS AND COSMETICS ACT,
1940
(23 OF
1940)
(As amended up to the 31
st
December,
2016)
and
THE DRUGS AND COSMETICS RULES,
1945
(As amended up to the 31
st
December,
2016
)
2
LIST OF ABBREVIATIONS USED
A.O. 1950 ………………………………
For
Adaptation of Laws Order, 1950
Cl. …………………………………. . …
‖
Clause
Ins. ……………………………………..
‖
Inserted
P. ………………………………………
‖
Page
Pt. ………………………………………
‖
Part
Reg. ………………………………........
‖
Regulation
Rep. ……………………………………
‖
Repealed
S. ………………………………………
‖
Section
Sch. …………………………………….
‖
Schedule
Sec. ……………………………….........
‖
Section
Subs. ……………………………………
‖
Substituted
w.e.f. ……………………………………
‖
With effect from
CONTENTS
Pages
The Drugs and Cosmetics Act, 1940 (23 of 1940) …………. 1−30
The Drugs and Cosmetics Rules, 1945 ……. . . ……………... 31−546
3
iii
THE DRUGS AND COSMETICE ACT, 1940
CHAPTER I
INTRODUCTORY
Sections
1. Short title, extent and commencement.
2. Application of other laws not barred.
3. Definitions.
3A. Construction of references to any law not in force or any
functionary not in existence in the State of Jammu and Kashmir.
4. Presumption as to poisonous substances.
CHAPTER II
THE DRUGS TECHNICAL ADVISORY BOARD, THE CENTRAL DRUGS LABORATORY
AND THE DRUGS CONSULTATIVE COMMITTEE
5. The Drugs Technical Advisory Board.
6. The Central Drugs Laboratory.
7. The Drugs Consultative Committee.
7A. Sections 5 and 7 not to apply to Ayurvedic, Siddha or Unani
drugs.
CHAPTER III
IMPORT OF DRUGS AND COSMETICS
8. Standards of quality.
9. Misbranded drugs.
9A. Adulterated drugs.
9B. Spurious drugs.
9C. Misbranded cosmetics.
9D. Spurious cosmetics.
10. Prohibition of import of certain drugs or cosmetics.
10A. Power of Central Government to prohibit import of drugs and
cosmetics in public interest.
11. Application of law relating to sea customs and powers of
Customs officers.
12. Power of Central Government to make rules.
13. Offences.
14. Confiscation.
15. Jurisdiction.
Drugs and Cosmetics Act, 1940
4
CHAPTER IV
MANUFACTURE, SALE AND DISTRIBUTION OF DRUGS AND
COSMETICS
Sections
16. Standards of quality.
17. Misbranded drugs.
17A. Adulterated drugs.
17B. Spurious drugs.
17C. Misbranded cosmetics.
17D. Spurious cosmetics.
18. Prohibition of manufacture and sale of certain drugs
and cosmetics.
18A. Disclosure of the name of the manufacturer, etc.
18B. Maintenance of records and furnishing of information.
19. Pleas.
20. Government Analysts.
21. Inspectors.
22. Powers of Inspectors.
23. Procedure of Inspectors.
24. Persons bound to disclose place where drugs or cosmetics
are manufactured or kept.
25. Reports of Government Analysts.
26. Purchaser of drug or cosmetic enabled to obtain test or analysis.
26A. Power of Central Government to prohibit manufacture, etc.,
of drug and cosmetic in public interest.
27. Penalty for manufacture, sale, etc., of drugs in contravention
of this Chapter.
27A. Penalty for manufacture, sale, etc., of cosmetics in
contravention of this Chapter.
28. Penalty for non-disclosure of the name of the manufacturer, etc.
28A. Penalty for not keeping documents, etc., and for non-disclosure
of information.
28B. Penalty for manufacture, etc. of drugs or cosmetics
in contravention of section 26A.
29. Penalty for use of Government Analyst‘s report for advertising.
30. Penalty for subsequent offences.
31. Confiscation.
31A. Application of provisions to Government departments.
32. Cognizance of offences.
32A. Power of Court to implead the manufacturer, etc.
33. Power of Central Government to make rules.
33A. Chapter not to apply to Ayurvedic, Siddha or Unani drugs.
CHAPTER IV A
PROVISIONS RELATING TO AYURVEDIC SIDDHA AND UNANI DRUGS
33B. Application of Chapter IV A.
Drugs and Cosmetics Act, 1940
5
Sections
33C. Ayurvedic, Siddha and Unani Drugs Technical
Advisory Board.
33D. The Ayurvedic, Siddha and Unani Drugs Consultative
Committee.
33E. Misbranded drugs.
33EE. Adulterated drugs.
33EEA. Spurious drugs.
33EEB. Regulation of manufacture for sale of Ayurvedic,
Siddha and Unani drugs.
33EEC. Prohibition of manufacture and sale of certain
Ayurvedic, Siddha and Unani drugs.
33EED. Power of Central Government to prohibit manufacture,
etc., of Ayurvedic, Siddha or Unani drugs in public
interest.
33F. Government Analysts.
33G. Inspectors.
33H. Application of provisions of sections 22, 23, 24 and
25.
33-I. Penalty for manufacture, sale, etc., of Ayurvedic,
Siddha or Unani drugs in contravention of this
Chapter.
33J. Penalty for subsequent offences.
33K. Confiscation.
33L. Application of provisions to Government departments.
33M. Cognizance of offences.
33N. Power of Central Government to make rules.
33O. Power to amend First Schedule.
CHAPTER V
MISCELLANEOUS
33P. Power to give directions.
34. Offences by companies.
34A. Offences by Government departments.
34AA. Penalty vexatious search or seizure.
35. Publication of sentences passed under this Act.
36. Magistrate‘s power to impose enhanced penalties.
36A. Certain offences to be tried summarily.
37. Protection of action taken in good faith.
38. Rules to be laid before Parliament.
THE FIRST SCHEDULE.
THE SECOND SCHEDULE.
6
1 Drugs and Cosmetics Act, 1940
THE DRUGS AND COSMETICS ACT, 1940
(23 OF 1940)
1
[10th April, 1940.]
An Act to regulate the import, manufacture, distribution and sale of drugs
2
[and cosmetics];
WHEREAS it is expedient to regulate the
3
[import, manufacture, distribution and sale] of drugs
2
[and
cosmetics];
AND WHEREAS the Legislature of all the Provinces have passed resolutions in terms of section 103
of the
Government of India Act, 1935 (26 Geo. 5, c.2), in relation to such of the above-mentioned
matters and matters
ancillary thereto as are enumerated in List II of the Seventh Schedule to the said Act;
It is hereby enacted as follows:-
CHAPTER I
INTRODUCTORY
1. Short title, extent and commencement.
⎯
(1) This Act may be called the Drugs
2
[and Cosmetics]
Act, 1940.
(2) It extends to the whole of India
4
[
* * *].
(3) It shall come into force at once; but Chapter III shall take effect only from such date
5
as the
Central Government may, by notification in the Official Gazette, appoint in this behalf, and Chapter IV shall
take effect in a particular State only from such date
5
as the State Government may, by like notification,
appoint in this behalf:
6
[Provided that in relation to the State of Jammu and Kashmir, Chapter III shall take effect only from
such date
10
after the commencement of the Drugs and Cosmetics (Amendment) Act, 1972 (19 of 1972), as
the Central Government may, by notification in the Official Gazette, appoint in this behalf.]
2. Application of other laws not barred.- The provisions of this Act shall be in addition to and not in
derogation of, the Dangerous Drugs Act, 1930 (2 of 1930), and any other law for the time being in force.
3. Definitions.—In this Act, unless there is anything repugnant in the subject or context,
7
[(a) ―
8
[Ayurvedic, Siddha or Unani] drug‖ includes all medicines intended for internal or external use
for or in the diagnosis, treatment, mitigation or prevention of
8
[disease or disorder in human beings or
animals, and manufactured] exclusively in accordance with the formulae described in, the authoritative
books of
9
[Ayurvedic, Siddha and Unani Tibb systems of medicine], specified in the First Schedule;]
9
[(aa) ―the Board‖ means—
(i) in relation to
9
[Ayurvedic, Siddha or Unani] drug, the
9
[Ayurvedic, Siddha and Unani
Drugs Technical Advisory Board] constituted under section 33C; and
(ii) in relation to any other drug or cosmetic, the Drugs Technical Advisory Board
constituted under section 5;]
1. For Statement of Object and Reasons, see Gazette of India, 1940, Pt. V, p. 34; for the Report of the Select Committee, see ibid., p. 143.
The Act has been applied to all the partially excluded areas in the State of Orissa, see Orissa Government Notification No. 3358-LSG., dated the
25
th
August, 1941.
2. Ins. by Act 21 of 1962, s. 2 (w.e.f. 27-7-1964).
3. Subs. by the A.O. 1950, for certain words.
4. The words ―except the State of Jammu and Kashmir‖ omitted by Act 19 of 1972, s .2. (w.e.f. 31-5-1972).
5 1
st
April, 1947; see Notifn. No. F. 28 (10) (3) 45-H (1), dated the 2
nd
September 1946, Gazette of India, 1946, Pt. I, p.1349.
Chapter IV came into force in the States of Delhi, Ajmer and Coorg on the 1
st
April, 1947, see ibid., Chapters III and IV came into force in the
States of Himachal Pradesh, Bilaspur, Kutch, Bhopal, Tripura, Vindhya Pradesh and Manipur on the 1
st
April, 1953, vide Notification No. S.R.O.
663, dated the 30
th
March, 1953, Gazette of India, Pt. II, Sec. 3, p. 451.
Chapter IV came into force in the Union territory of Dadra and Nagar Haveli w.e.f. 1
st
August, 1968, see Notification No. ADM/Law/117(74),
dated the 20
th
July, 1968, Gazette of India, Pt. III, Sec. 3, p.128. The Act is extended to Dadra and Nagar Haveli by Reg. 6 of 1963, s. 2 and Sch.
I; to Pondicherry by Reg. 7 of 1963. s. 3 and Sch. I; to Goa, Daman and Diu by Reg. 11 of 1963, s. 3 and Sch. and to Laccadive, Minicoy and
Amindivi Islands by Reg. 8 of 1965. s.3 and Sch.
6. Added by Act 19 of 1972, s. 2.
7 Ins. by Act 13 of 1964, s. 2 (w.e.f. 15-9-1964).
8. Subs. by Act 68 of 1982, s. 2, for certain words (w.e.f. 1-2-1983).
9. Clause. (a) was relettered as cl. (aa) by Act 13 of 1964 s. 2, (w.e.f. 15-9-1964).
10. 24
th
August, 1974, vide notifin no. S.O. 2185, dt. 9
th
August, 1974.
Drugs and Cosmetics Act, 1940
7
1
[
2
[(aaa)] ―cosmetic‖ means any article intended to be rubbed, poured, sprinkled or sprayed on, or
introduced into, or otherwise applied to, the human body or any part thereof for cleansing, beautifying,
promoting attractiveness, or altering the appearance, and includes any article intended for use as a component
of cosmetic
3
[* * *] ;]
4
[(b) ―drug‖ includes—
5
[(i) all medicines for internal or external use of human beings or animals and all substances
intended to be used for or in the diagnosis, treatment, mitigation or prevention of any disease or disorder
in human beings or animals, including preparations applied on human body for the purpose of repelling
insects like mosquitoes;]
(ii) such substances (other than food) intended to affect the structure or any function of the human
body or intended to be used for the destruction of
6
[vermin] or insects which cause disease in human
beings or animals, as may be specified from time to time by the Central Government by notification in
the Official Gazette;]
7
[(iii) all substances intended for use as components of a drug including empty gelatin capsules; and
(iv) such devices* intended for internal or external use in the diagnosis, treatment, mitigation or
prevention of disease or disorder in human beings or animals, as may be specified from time to time by
the Central Government by notification in the Official Gazette, after consultation with the Board;]
8
[(c) ―Government Analyst‖ means—
(i) in relation to
9
[Ayurvedic, Siddha or Unani] drug, a Government Analyst appointed by the
Central Government or a State Government under section 33F; and
(ii) in relation to any other drug or cosmetic, a Government Analyst appointed by the Central
Government or a State Government under section 20;]
10
[* * * * *]
11
[(e) ―Inspector‖ means—
(i) in relation to
9
[Ayurvedic, Siddha or Unani] drug, an Inspector appointed by the Central
Government or a State Government under section 33G; and
(ii) in relation to any other drug or cosmetic, an Inspector appointed by the Central Government
or a State Government under section 21;]
12
[
13
[(f)] ―manufacture‖ in relation to any drug
14
[or cosmetic] includes any process or part of a
process for making, altering, ornamenting, finishing, packing, labelling, breaking up or otherwise
treating or adopting any drug
14
[or cosmetic] with a view to its
15
[sale or distribution] but does not
include the compounding or dispensing
16
[of any drug, or the packing of any drug or cosmetic,] in
the ordinary course of retail business; and ―to manufacture‖ shall be construed accordingly;]
17
[(g)] ―to import‖, with its grammatical variations and cognate expressions means to bring into
18
[India];
1. Ins. by Act 21 of 1962, s. 4 (w.e.f. 27-7-1964).
2. Clause. (aa) relettered by Act 13 of 1964, s. 2 (w.e.f. 15-9-1964).
3. omitted by Act 68 of 1982, s.3, certain words.
4. Subs. by Act 11 of 1955, s. 2, for cl. (b).
5. Subs. by Act 68 of 1982, s. 3 (w.e.f. 1-2-1983).
6. Subs. by Act 13 of 1964, s. 2, for ―vermins‖ (w.e.f. 15-9-1964).
7. Ins. by Act 68 of 1982, s.3 (w.e.f. 1-2-1983).
The Central Government has specified (vide S.O. 1468 (E), dated 6-10-2005) the following devices intended for external or internal use in human
beings or drugs with immediate effect, namely:-
(i) Cardiac Stents (ii) Drug Eluding Stents (iii) Catheters (iv) Intra Ocular Lenses (v) I.V. Cannulac (vi) Bone Cements
(vii) Heart Valves (viii) Scalp Vein Set (ix) Orthopaedic Implants (x) Internal Prosthetic Replacements
8. Subs. by Act 13 of 1964, s. 2, for cl. (c) (w.e.f.15-9-1964).
9. Subs. by Act 68 of 1982 s.2, for ―Ayurvedic (including sidda) or Unani‖ (w.e.f. 1-2-1983).
10. Cl. (d) omitted by Act 19 of 1972, s. 3. 15. Subs. by Act 68 of 1982, s.3, for ―sale and distribution‖(w.e.f. 1-2-1983).
11. Subs. by Act 13 of 1964, s. 2, for cl. (e) (w.e.f. 15-9-1964). 16. Subs. by Act 21 of 1962 s. 4, for ―or the packing of any drug‖.
12. Ins. by Act 11 of 1955, s. 2. 17. Cls.(c), (d) and (e) relettered as cls. (g), (h) and (i) respectively by Act 35 of 1960, s. 2 (w.e.f. 16-3-1961).
13. Clause. (bbb) relettered as cl. (f) by Act 35 of 1960, s. 2 (w.e.f. 16-3-1961).
14. Ins. by Act 21 of 1962, s. 4 (w.e.f. 27-7-1964). 18. Subs. by Act 3 of 1951, s. 3 and Sch., for ―the States‖.
Drugs and Cosmetics Act, 1940
8
1
[
2
[(h)] ―patent or proprietary medicine‖ means,—
(i) in relation to Ayurvedic, Siddha or Unani Tibb systems of medicine all formulations containing only
such ingredients mentioned in the formulae described in the authoritative books of Ayurveda, Siddha or Unani
Tibb systems of medicine specified in the First Schedule, but does not include a medicine which is
administered by parenteral route and also a formulation included in the authoritative books as specified in
clause (a);
(ii) in relation to any other systems of medicine, a drug which is a remedy or prescription presented in
a form ready for internal or external administration of human beings or animals and which is not included in
the edition of the Indian Pharmacopoeia for the time being or any other Pharmacopoeia authorised in this
behalf by the Central Government after consultation with the Drugs Technical Advisory Board constituted
under section 5;]
3
[
2
[(i)] ―prescribed‖ means prescribed by rules made under this Act.]
4
[* * * * *]
5
[3A. Construction of references to any law not in force or any functionary not in existence in the
State of Jammu and Kashmir.—Any reference in this Act to any law which is not in force, or any
functionary not in existence, in the State of Jammu and Kashmir, shall, in relation to that State, be construed
as a reference to the corresponding law in force, or to the corresponding functionary in existence, in that
State.]
4. Presumption as to poisonous substances.—Any substance specified as poisonous by rule made under
Chapter III or Chapter IV
6
[or Chapter IVA] shall be deemed to be a poisonous substance for the purposes of
Chapter III or Chapter IV
6
[or Chapter IVA], as the case may be.
CHAPTER II
THE DRUGS TECHNICAL ADVISORY BOARD, THE CENTRAL DRUGS LABOURATORY
AND THE DRUGS CONSULTATIVE COMMITTEE
5. The Drugs Technical Advisory Board.—(1) The Central Government shall, as soon as may be,
constitute a Board (to be called the Drugs Technical Advisory Board) to advise the Central Government and
the State Governments on technical matters arising out of the administration of this Act and to carry out the
other functions assigned to it by this Act.
7
[(2) The Board shall consist of the following members, namely:—
(i) the Director General of Health Services, ex officio, who shall be Chairman; (ii) the Drugs
Controller, India, ex officio;
(iii) the Director of the Central Drugs Laboratory, Calcutta, ex officio;
(iv) the Director of the Central Research Institute, Kasauli, ex officio;
(v) the Director of Indian Veterinary Research Institute, Izatnagar, ex officio;
(vi) the President of Medical Council of India, ex officio;
(vii) the President of the Pharmacy Council of India, ex officio;
(viii) the Director of Central Drug Research Institute, Lucknow, ex officio;
(ix) two persons to be nominated by the Central Government from among persons who are in
charge of drugs control in the States;
1. Subs. by Act 68 of 1982, s. 3, for cl. (h) (w.e.f. 1-2-1983).
2. Cls. (c), (d) and (e) relettered as cls. (g), (h) and (i) respectively by Act 35 of 1960, s. 2 (w.e.f. 16-3-1961).
3. Subs. by Act 11 of 1955, s. 2, for cl. (e).
4. Clause. (f) ins. by the A.O. 1950 and omitted by Act 3 of 1951, s. 3 and Sch.
5. Ins. by Act 19 of 1972, s. 4 (w.e.f. 31-5-1972).
6. Ins. by Act 13 of 1964, s. 3 (w.e.f. 15-9-1964).
7. Subs. by Act 13 of 1964, s. 4, for sub-section (2) (w.e.f. 15-9-1964).
Drugs and Cosmetics Act, 1940
9
(x) one person, to be elected by the Executive Committee of the Pharmacy Council of India, from
among teachers in pharmacy or pharmaceutical chemistry or pharmacognosy on the staff of an
Indian university or a college affiliated thereto;
(xi) one person, to be elected by the Executive Committee of the Medical Council of India, from
among teachers in medicine or therapeutics on the staff of an Indian university or a college affiliated
thereto;
(xii) one person to be nominated by the Central Government from the pharmaceutical industry;
(xiii) one pharmacologist to be elected by the Governing Body of the Indian Council of Medical
Research;
(xiv) one person to be elected by the Central Council of the Indian Medical Association;
(xv) one person to be elected by the Council of the Indian Pharmaceutical Association;
(xvi) two persons holding the appointment of Government Analyst under this Act, to be
nominated by the Central Government.]
(3) The nominated and elected members of the Board shall hold office for three years, but shall be
eligible for re- nomination and re-election:
1
[Provided that the person nominated or elected, as the case may be, under clause (ix) or clause (x) or
clause (xi) or clause (xvi) of sub-section (2) shall hold office for so long as he holds the appointment of the
office by virtue of which he was nominated or elected to the Board.]
(4) The Board may, subject to the previous approval of the Central Government, make bye-laws fixing a
quorum and regulating its own procedure and the conduct of all business to be transacted by it.
(5) The Board may constitute sub-committees and may appoint to such sub-committees for such periods,
not exceeding three years, as it may decide, or temporarily for the consideration of particular matters,
persons who are not members of the Board.
(6) The functions of the Board may be exercised notwithstanding any vacancy therein.
(7) The Central Government shall appoint a person to be Secretary of the Board and shall provide the
Board with such clerical and other staff as the Central Government considers necessary.
6. The Central Drugs Laboratory.—(1) The Central Government shall, as soon as may be, established
a Central Drugs Laboratory under the control of a Director to be appointed by the Central Government, to
carry out the functions entrusted to it by this Act or any rules made under this Chapter:
Provided that, if the Central Government so prescribes, the functions of the Central Drugs Laboratory in
respect of any drug or class of drugs
2
[or cosmetic or class of cosmetics] shall be carried out at the Central
Research Institute, Kasauli, or at any other prescribed Laboratory and the functions of the Director of the
Central Drugs Laboratory in respect of such drug or class of drugs
2
[or such cosmetic or class of
cosmetics] shall be exercised by the Director of that Institute or of that other Laboratory, as the case may
be.
(2) the Central Government may, after consultation with the Board, make rules prescribing—
(a) the functions of the Central Drugs Laboratory;
3
[* * * * *]
(d) the procedure for the submission to the said Laboratory
4
[under Chapter IV or Chapter IVA] of
samples of drugs
2
[or cosmetics] for analysis or test, the forms of Laboratory‘s reports thereon and the
fees payable in respect of such reports;
1. Subs. by Act 13 of 1964, s. 4, for the proviso (w.e.f. 15-9-1964).
2. Ins. by Act 21 of 1962, s. 5 (w.e.f. 27-7-1964).
3. Cls. (b) and (c) omitted by Act 11 of 1955, s. 4.
4. Subs. by Act 13 of 1964, s. 5, for ―under Chapter IV‖ (w.e.f. 15-9-1964).
Drugs and Cosmetics Act, 1940
10
(e) such other matters as may be necessary or expedient to enable the said Laboratory to
carry out its functions;
(f) the matters necessary to be prescribed for the purposes of the proviso to sub-section (1).
7. The Drugs Consultative Committee.—(1) The Central Government may constitute an advisory
committee to be called ―the Drugs Consultative Committee‖ to advise the Central Government, the State
Governments and the Drugs Technical Advisory Board on any other matter tending to secure uniformity
throughout
1
[India] in the administration of this Act.
(2) The Drugs Consultative Committee shall consist of two representatives of the Central
Government to be nominated by that Government and one representative of each State Government to
be nominated by the State Government concerned.
(3) The Drugs Consultative Committee shall meet when required to do so by the Central Government and
shall have power to regulate its own procedure.
2
[7A. Sections 5 and 7 not to apply to Ayurvedic, Siddha or Unani drugs.—Nothing contained in
sections 5 and 7 shall apply to
3
[Ayurvedic, Siddha or Unani] drugs.]
CHAPTER III
4
[IMPORT OF DRUGS AND
COSMETICS
]
8. Standards of quality.—
5
[(1) For the purposes of this Chapter, the expression ―standard quality‖
means—
(a) in relation to a drug, that the drug complies with the standard set out in
6
[the Second Schedule],
and
(b) in relation to a cosmetic, that the cosmetic compiles with such standard as may be
prescribed].
(2) The Central Government, after consultation with the Board and after giving by notification in the
Official Gazette not less than three months‘ notice of its intention so to do, may by a like notification add to or
otherwise amend
6
[the Second Schedule], for the purposes of this Chapter, and thereupon
6
[the Second
Schedule] shall be deemed to be amended accordingly.
7
[9. Misbranded drugs.—For the purposes of this Chapter a drug shall be deemed to be misbranded—
(a) if it is so coloured, coated, powdered or polished that damage is concealed or if it is made to
appear of better or greater therapeutic value than it really is; or
(b) if it is not labelled in the prescribed manner; or
(c) if its label or container or anything accompanying the drug bears any statement, design or
device which makes any false claim for the drug or which is false or misleading in any particular.]
8
[9A. Adulterated drugs.— For the purposes of this Chapter, a drug shall be deemed to be adulterated.—
(a) if it consists, in whole or in part, of any filthy, putrid or decomposed substance; or
(b) if it has been prepared, packed or stored under insanitary conditions whereby it may
have been contaminated with filth or whereby it may have been rendered injurious to health; or
1. Subs. by Act 3 of 1951, s. 3 and Sch., for ―the States‖.
2. Ins. by Act 13 of 1964, s. 6 (w.e.f. 15-9-1964).
3. Subs. by Act 68 of 1982, s. 2 for certain words (w.e.f. 1-2-1983).
4. Subs. by Act 68 of 1982, s. 4, for ―IMPORT OF DRUGS‖ (w.e.f. 1-2-1983).
5. Subs. by Act 21 of 1962, s. 6, for sub-section (1) (w.e.f. 27-7-1964).
6. Subs. by Act 13 of 1964, s. 7, for ―the Schedule‖ (w..e.f. 15-9-1964).
7. Subs. by Act 68 of 1982, s. 5, for s. 9 (w.e.f. 1-2-1983).
8. Subs. by Act 68 of 1982, s. 6, (w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
11
(c) if its container is composed in whole or in part, of any poisonous or deleterious substance
which may render the contents injurious to health; or
(d) if it bears or contains, for purposes of colouring only, a colour other than one which is
prescribed; or
(e) if it contains any harmful or toxic substance which may render it injurious to health; or
(f) if any substance has been mixed therewith so as to reduce its quality or strength.
9B. Spurious drugs.— For the purposes of this Chapter, a drug shall be deemed to be spurious—
(a) if it is imported under a name which belongs to another drug; or
(b) if it is an imitation of, or a substitute for, another drug or resembles another drug in a manner
likely to deceive or bears upon it or upon its label or container the name of another
drug unless it is plainly and conspicuously marked so as to reveal its true character and its
lack of identity with such other drug; or
(c) if the label or the container bears the name of an individual or company purporting to be the
manufacturer of the drug, which individual or company is fictitious or does not exist; or
(d) if it has been substituted wholly or in part by another drug or substance; or
(e) if it purports to be the product of a manufacturer of whom it is not truly a product.
9C. Misbranded cosmetics.—For the purposes of this chapter, a cosmetic shall be deemed to be
misbranded—
(a) if it contains a colour which is not prescribed; or
(b) if it is not labelled in a prescribed manner; or
(c) if the label or container or anything accompanying the cosmetic bears any statement which is
false or misleading in any particular.
9D. Spurious cosmetics.—For the purposes of this Chapter, a drug shall be deemed to be spurious,—
(a) if it is imported under the name which belongs to another cosmetic; or
(b) if it is an imitation of, or is a substitute for, another cosmetic or resembles another cosmetic in a
manner likely to deceive or bears upon it or upon its label or container the name of another cosmetic,
unless it is plainly or conspicuously marked so as to reveal its true character and its lack of identity with
such other cosmetic; or
(c) if the label or the container bears the name of an individual or company purporting to be the
manufacturer of the cosmetic, which individual or company is fictitious or does not exist; or
(d) if it purports to be the product of a manufacturer of whom it is not truly a product.]
10. Prohibition of import of certain drugs or cosmetics.— From such date
1
as may be fixed by the
Central Government by notification in the Official Gazette in this behalf, no person shall import—
(a) any drug
2
[or cosmetic] which is not of standard quality;
3
[(b) any misbranded drug
4
[or misbranded or spurious cosmetic;]
1. 1st April, 1947 for cls. (a), (b), (c), (e) and (f) and 1st April 1949 for cl. (d) see Notifn. No.18- 12/46-D (I), dated the 11th February 1947, Gazette of
India, 1947, Pt. 1, P. 189 as amended by Notifn. No.F.1-2/48-D (1), dated the 29th September,1948.
1st April, 1953 for the States of Himachal Pradesh, Bilaspur, Kutch, Bhopal,Tripura, Vindhya Pradesh and Manipur; vide Notifn. No. S.R.O. 666,
dated the 30th March, 1953, Gazette of India, 1953, Pt. II, Sec. 3, p.451.
2. Ins. by Act 21 of 1962, s. 8 (w.e.f. 27-7-1964).
3. Subs. by Act 21 of 1962, s. 8, for cl. (b) (w.e.f. 27-7-1964).
4. Subs. by Act 68 of 1982, s.7, for ―or misbranded cosmetic‖ (w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
12
1
[(bb) any
2
[adulterated or spurious] drug;]
(c) any drug
3
[or cosmetic] for the import of which a licence is prescribed, otherwise than under, and
in accordance with, such licence;
4
[(d) any patent or proprietary medicine, unless there is displayed in the prescribed manner on the
label or container thereof
5
[the true formula or list of active ingredients contained in it, together with the
quantities thereof;]
(e) any drug which by means of any statement, design or device accompanying it or by any
other means, purports or claims to cure or mitigate any such disease or ailment, or to have any such other
effect, as may be prescribed;
3
[(ee) any cosmetic containing any ingredient which may render it unsafe or harmful for use
under the directions indicated or recommended;]
(f) any drug
3
[or cosmetic] the import of which is prohibited by rule made under this Chapter:
Provided that nothing in this section shall apply to the import, subject to prescribed conditions, of small
quantities of any drug for the purpose of examination, test or analysis or for personal use:
Provided further that the Central Government may, after consultation with the Board, by notification in the
Official Gazette, permit, subject to any conditions specified in the notification, the import of any drug or class
of drugs not being of standard quality.
6
[* * * * *]
7
[10A. Power of Central Government to prohibit import of drugs and cosmetics in public interest.—
Without prejudice to any other provision contained in this Chapter, if the Central Government is satisfied that
the use of any drug or cosmetic is likely to involve any risk to human beings or animals or that any drug does
not have the therapeutic value claimed for it or contains ingredients and in such quantity for which there is no
therapeutic justification and that in the public interest it is necessary or expedient so to do then, that
Government may, by notification in the Official Gazette, prohibit the import of such drug or cosmetic.]
11. Application of law relating to sea customs and powers of Customs Officers.— (1) The law for the
time being in force relating to sea customs and to goods, the import of which is prohibited by section 18 of
the Sea Customs Act, 1878 (8 of 1878)
8
shall, subject to the provisions of section 13 of this Act, apply in
respect of drugs
9
[and cosmetics] the import of which is prohibited under this Chapter, and officers of Customs
and officers empowered under that Act to perform the duties imposed thereby on a
10
[Commissioners of
Customs] and other officers of Customs, shall have the same powers in respect of such drugs
9
[and
cosmetics] as they have for the time being in respect of such goods as aforesaid.
11
[(2) Without prejudice to the provisions of sub-sections (1), the
10
[Commissioners of Customs] any
officer of the Government authorized by the Central Government in this behalf, may detain any imported
package which he suspects to contain any drug
9
[or cosmetic] the import of which is prohibited under this
Chapter and shall forthwith report such detention to the Drugs Controller, India, and, if necessary, forward the
package or sample of any suspected drug
9
[or cosmetic] found therein to the Central Drugs Laboratory.]
12. Power of Central Government to make rules.—(1) The Central Government may,
12
[after
consultation with or on the recommendation of the Board] and after previous publication by notification in
the Official Gazette, make rules for the purpose of giving effect to the provisions of this Chapter:
1. Ins. by Act 13 of 1964, s. 9 (w.e.f. 15-9-1964).
2. Subs. by Act 68 of 1982, s.7, for ―adulterated‖ (w.e.f. 1-2-1983).
3. Ins. by Act 21 of 1962, s. 8 (w.e.f. 27-7-1964).
4. Subs. by Act 11 of 1955, s. 5, for cl. (d).
5. Subs. by Act 68 of 1982, s.7, for certain words (w.e.f. 1-2-1983).
6. Explanation omitted by s.7, ibid. (w.e.f. 1-2-1983).
7. Ins. by s. 8, Act 68 of 1982. (w.e.f. 1-2-1983).
8. Now see the Customs Act, 1962.
9. Ins. by Act 21of 1962, s. 9 (w.e.f. 27-7-1964).
10. Subs. by Act 22 of 1995, s. 83, for ―Customs Collector‖.
11. Subs. by Act 11 of 1955, s. 6, for sub-section (2).
12. Subs. by Act 68 of 1982, s.9, for certain words (w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
13
1
[Provided that consultation with the Board may be dispensed with if the Central Government is of
opinion that circumstances have arisen which render it necessary to make rules without such consultation,
but in such a case the Board shall be consulted within six months of the making of the rules and the Central
Government shall take into consideration any suggestions which the Board may make in relation to the
amendment of the said rules.]
(2) Without prejudice to the generality of the forgoing power, such rules may—
(a) specify the drugs or classes of drugs
2
[or cosmetics or classes of cosmetics] for the import of
which a licence is required,
3
[and prescribe the form and conditions of such licences, the authority
empowered to issue the same, the fees payable therefor and provide for the cancellation, or suspension of
such licence in any case where any provision of this Chapter or the rules made thereunder is contravened
or any of the conditions subject to which the licence is issued is not complied with];
(b) prescribe the methods of test or analysis to be employed in determining whether a drug
2
[or
cosmetic] is of standard quality;
(c) prescribe, in respect of biological and organometallic compounds, the units or
methods of standardization;
4
[(cc) prescribe under clause (d) of
5
[section 9A] the colour or colours which a drug may bear or
contain for purposes or colouring;]
(d) specify the diseases or ailments which an imported drug may not purport or claim
6
[to prevent,
cure or mitigate] and such other effects which such drug may not purport or claim to have;
(e) prescribe the conditions subject to which small quantities of drugs, the import of which is
otherwise prohibited under this Chapter, may be imported for the purpose of examination, test or
analysis or for personal use;
(f) prescribe the places at which drugs
2
[or cosmetics] may be imported, and prohibit their
import at any other place;
(g) require the date of manufacture and the date of expiry of potency to be clearly and truly
stated on the label or container of any specified imported drug or class of such drug, and prohibit the
import of the said drug or class of drug after the expiry of a specified period from the date of
manufacture;
(h) regulate the submission by importers, and the securing, of samples of drugs
2
[or
cosmetics] for examination, test or analysis by the Central Drugs Laboratory, and prescribe the fees, if
any, payable for such examination, test or analysis;
(i) prescribe the evidence to be supplied, whether by accompanying documents or otherwise, of
the quality of drugs
2
[or cosmetics] sought to be imported, the procedure of officers of Customs
in dealing with such evidence, and the manner of storage at places of import of drugs
2
[or cosmetics]
detained pending admission;
(j) provide for the exemption, conditionally or otherwise, from all or any of the provisions of
this Chapter and the rules made thereunder of drugs
2
[or cosmetics] imported for the purpose only of
transport through, an export from,
7
[India];
(k) prescribe the conditions to be observed in the packing in bottles, packages or other containers,
of imported drugs
2
[or cosmetics]
8
[including the use of packing material which comes into direct
contact with the drugs];
(l) regulate the mode of labeling drugs
2
[or cosmetics] imported for sale in packages, and
prescribe the matters which shall or shall not be included in such labels;
(m) prescribe the maximum proportion of any poisonous substance which may be added to or
contained in any imported drug, prohibit the import of any drug in which that proportion is exceeded,
and specify substances which shall be deemed to be poisonous for the purposes of this Chapter and the
rules made thereunder;
1. Ins. by Act 11 of 1955, s. 7.
2. Ins. by Act 21of 1962, s. 10 (w.e.f. 27-7-1964).
3. Subs. by Act 68 of 1982, s. 9, for certain words (w.e.f. 1-2-1983).
4. Ins. by Act 13 of 1964, s. 10 (w.e.f. 15-9-1964).
5. Subs. by Act 68 of 1982, s. 9, for ―section 9B‖ (w.e.f. 1-2-1983).
6. Subs. by Act 11 of 1955, s. 7, for ―to cure or mitigate‖.
7. Subs. by Act 3 of 1951, s. 3 and Sch., for ―the States‖.
8. Ins. by Act 68 of 1982, s. 9 (w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
14
(n) require that the accepted scientific name of any specified drug shall be displayed in the
prescribed manner on the label or wrapper of any imported, patent or proprietary medicine containing
such drug;
(o) provide for the exemption, conditionally or otherwise, from all or any of the provisions of this
Chapter or the rules made thereunder, of any specified drug or class of drugs
1
[or cosmetic or class of
cosmetics].
2
[13. Offences.—(1) Whoever himself or by any other person on his behalf imports, —
(a) any drug deemed to be adulterated under section 9A or deemed to be a spurious drug under section
9B or any spurious cosmetic referred to in section 9D or any cosmetic of the nature referred to in clause (ee)
of section 10 shall be punishable with imprisonment for a term which may extend to three years and a fine
which may extend to five thousand rupees;
(b) any drug or cosmetic other than a drug or cosmetic referred to in clause (a), the import of which is
prohibited under section 10, or any rule made under this Chapter, shall be punishable with imprisonment for a
term which may extend to six months, or with fine which may extend to five hundred rupees, or with both;
(c) any drug or cosmetic in contravention of the provisions of any notification issued under section 10A,
shall be punishable with imprisonment for a term which may extend to three years, or with fine which may
extend to five thousand rupees, or with both;
(2) Whoever having been convicted of an offence—
(a) under clause (a) or clause (c) of sub-section (1), is again convicted of an offence under that clause,
shall be punishable with imprisonment for a term which may extend to five years, or with fine which may
extend to ten thousand rupees, or with both;
(b) under clause (b) of sub-section (1), is again convicted of an offence under that clause, shall be
punishable with imprisonment for a term which may extend to one year, or with fine which may extend to
one thousand rupees, or with both.
(3) The punishment provided by this section shall be in addition to any penalty to which the offender
may be liable under the provisions of section 11.]
14. Confiscation.—Where any offence punishable under section 13 has been committed, the consignment
of the drugs
3
[or cosmetics] in respect of which the offence has been committed shall be liable to confiscation.
15. Jurisdiction.—No Court inferior to that
4
[of a Metropolitan Magistrate or of a Judicial Magistrate
of the first class] shall try an offence punishable under section 13.
CHAPTER IV
MANUFACTURE, SALE AND DISTRIBUTION OF
5
[DRUGS AND
COSMETICS
]
16. Standards of quality.—
6
[(1) For the purposes of this Chapter, the expression ―standard quality‖
means—
(a) in relation to a drug, that the drug complies with the standard set out in
7
[the Second
Schedule], and
(b) in relation to a cosmetic, that the cosmetic complies with such standard as may be
prescribed.]
(2) The
8
[Central Government], after consultation with the Board and after giving by notification in
the Official
Gazette not less than three months‘ notice of its intention so to do, may by a like notification
add to or otherwise amend
7
[the Second Schedule] for the purposes of this Chapter, and thereupon
7
[the
Second Schedule] shall be deemed to be amended accordingly.
1. Ins. by Act 21 of 1962, s. 10 (w.e.f. 27-7-1964).
2. Subs. by Act 68 of 1982, s.10, for s.13 (w.e.f. 1-2-1983).
3. Ins. by Act 21 of 1962, s. 11 (w.e.f. 27-7-1964).
4. Subs. by Act 68 of 1982, s. 11, for certain words (w.e.f. 1-2-1983).
5. Subs. by Act 68 of 1982 for ―DRUGS‖ (w.e.f. 1-2-1983).
6. Subs. by Act 21 of 1962, s. 12, for sub-section (1) (w.e.f. 27-7-1964).
7. Subs. by Act 13 of 1964, s. 11, for ―the Schedule‖ (w.e.f 15-9-1964).
8. Subs. by Act 11 of 1955, s. 8, for ―State Government‖.
Drugs and Cosmetics Act, 1940
15
1
[17. Misbranded drugs.—For the purposes of this Chapter, a drug shall be deemed to be misbranded,—
(a) if it is so coloured, coated, powdered or polished that damage is concealed or if it is made to
appear of betapeutic value than it really is; or
(b) if it is not labelled in the prescribed manner; or
(c) if its label or container or anything accompanying the drug bears any statement, design or
device which makes any false claim for the drug or which is false or misleading in any particular.
17A. Adulterated drugs.—For the purposes of this Chapter, a drug shall be deemed to be adulterated,—
(a) if it consists in whole or in part, of any filthy, putrid or decomposed substance; or
(b) if it has been prepared, packed or stored under insanitary conditions whereby it may have been
contaminated with filth or whereby it may have been rendered injurious to health; or
(c) if its container is composed, in whole or in part, of any poisonous or deleterious substance which
may render the contents injurious to health; or
(d) if it bears or contains, for the purposes of colouring only, a colour other than one which is
prescribed; or
(e) if it contains any harmful or toxic substance which may render it injurious to health; or
(f) if any substance has been mixed therewith so as to reduce its quality or strength.
17B. Spurious drugs.—For the purposes of this Chapter, a drug shall be deemed to be spurious,—
(a) if it is manufactured under a name which belongs to another drug; or
(b) if it is an imitation of, or is a substitute for, another drug or resembles another drug in a manner
likely to deceive or bears upon it or upon its label or container the name of another drug unless
it is plainly and conspicuously marked so as to reveal its true character and its lack of identity with such
other drug; or
(c) if the label or container bears the name of an individual or company purporting to be the
manufacturer of the drug , which individual or company is fictitious or does not exist; or
(d) if it has been substituted wholly or in part by another drug or substance; or
(e) if it purports to be the product of a manufacturer of whom it is not truly a product.
17C. Misbranded cosmetics.— For the purposes of this Chapter, a cosmetic shall be deemed to be
misbranded, --
(a) if it contains a colour which is not prescribed; or
(b) if it is not labelled in the prescribed manner; or
(c) if the label or container or anything accompanying the cosmetic bears any statement which is
false or misleading in any particular.
17D. Spurious cosmetics.—For the purposes of this Chapter, a cosmetic shall be deemed to be spurious,--
(a) if it is manufactured under a name which belongs to another cosmetic; or
(b) if it is an imitation of, or a substitute for, another cosmetic or resembles another cosmetic in
a manner likely to deceive or bears upon it or upon its label or container the name of another cosmetic
unless it is plainly and conspicuously marked so as to reveal its true character and its lack of identity with
such other cosmetic; or
(c) if the label or container bears the name of an individual or a company purporting to be the
manufacturer of the cosmetic which individual or company is fictitious or does not exist; or
(d) if it purports to be the product of a manufacturer of whom it is not truly a product.]
2
[17E Adulterated cosmetics.- For the purposes of this Chapter, a cosmetic shall be deemed to be
adulterated,-
(a) if it consists in whole or in part, of any filthy, putrid or decomposed substance; or
(b) if it has been prepared, packed or stored under insanitary conditions whereby it may have been
contaminated with filth or whereby it may have been rendered injurious to health; or
(c) if its container is composed, in whole or in part, of any poisonous or deleterious substance which may
render the contents injurious to health; or
(d) if it bears or contains, for purposes of colouring only, a colour other than one which is prescribed; or
(e) if it contains any harmful or toxic substance which may render it injurious to health; or
(f) if any substance has been mixed therewith so as to reduce its quality or strength.]
1. Subs. by Act 68 of 1982, s.13, for s.17, 17A and 17B (w.e.f. 1-2-1983).
2. Ins. by Act 26 of 2008, s 2 (w.e.f 10-8-2009)
Drugs and Cosmetics Act, 1940
16
18. Prohibition of manufacture and sale of certain drugs and cosmetics.—From such date
1
as may
be fixed by the State Government by notification in the Official Gazette in this behalf, no person shall himself
or by any other person on his behalf—
(a)
2
[manufacture for sale or for distribution, or sell, or stock or exhibit or offer for sale] or
distribute—
2
[(i) any drug which is not of a standard quality, or is misbranded, adulterated or spurious;
12
[(ii) any cosmetic which is not of a standard quality or is misbranded or spurious;]
3
[(iii) any patent or proprietary medicine, unless there is displayed in the prescribed manner on the
label or container thereof
2
[the true formula or list of active ingredients contained in it together with
the quantities thereof];]
(iv) any drug which by means of any statement, design or device accompanying it or by any other
means, purports or claims
4
[to prevent, cure or mitigate] any such disease or ailment, or to have any
such other effect as may be prescribed;
5
[(v) any cosmetic containing any ingredient which may render it unsafe or harmful for use under
the directions indicated or recommended;
(vi) any drug or cosmetic in contravention of any of the provisions of this Chapter or any
rule made thereunder;]
(b)
6
[sell, or stock or exhibit or offer for sale,] or distribute any drug
7
[or cosmetic] which has been
imported or manufactured in contravention of any of the provisions of this Act or any rule made
thereunder;
(c)
6
[manufacture for sale or for distribution, or sell, or stock or exhibit or offer for sale,] or
distribute any drug
7
[or cosmetic], except under, and in accordance with the conditions of, a licence
issued for such purpose under this Chapter:
Provided that nothing in this section shall apply to the manufacture, subject to prescribed
conditions, of small quantities of any drug for the purpose of examination, test or analysis:
Provided further that the
8
[Central Government] may, after consultation with the Board, by notification in
the Official Gazette, permit, subject to any conditions specified in the notification, the
6
[manufacture for sale,
or for distribution, sale, stocking or exhibiting or offering for sale] or distribution of any drug or class of drugs
not being of standard quality.
9
[* * * * *]
10
[18A. Disclosure of the name of the manufacturer, etc.—Every person, not being the manufacturer
of a drug or cosmetic or his agent for the distribution thereof, shall, if so required, disclose to the Inspector the
name, address and other particulars of the person from whom he acquired the drug or cosmetic.]
11
[18B. Maintenance of records and furnishing of information.—Every person holding a licence under
clause (c) of section 18 shall keep and maintain such records, registers and other documents as may be
prescribed and shall furnish to any officer or authority exercising any power or discharging any function
under this Act such information as is required by such officer or authority for carrying out the purposes of
this Act.]
1. 1st April,1947 for sub-clauses (i), (ii), (iv) and (v) of clause (a) and clauses (b) and (c) ; 1st April, 1949 for sub-clause (iii) of clause (a) in so far as it
takes effect in Delhi, Ajmer and Coorg, see Notifn. No. 18-12/46-D. II, dated the 11th February, 1947. Gazette of India, 1947, Pt. I, p.189; as
amended by Notifn. No. F. 1-2/48-D(II), dated the 29th September, 1948; 1st April, 1953 for the States of Himachal Pradesh, Bilaspur, Kutch,
Bhopal, Tripura, Vindhya Pradesh and Manipur, vide Notifn. No. S.R.O. 664, dated the 30th March,1953, Gazette of India, 1953, Pt. II, Sec. 3, p.
451.
2. Subs. by Act 68 of 1982, s.14, for certain words (w.e.f. 1-2-1983).
3. Subs. by Act 11 of 1955, s. 9, for sub-clause (iii).
4. Subs. by Act 11 of 1955, s. 9, for ―to cure or mitigate‖.
5. Subs. by Act 21 of 1962, s. 14, for sub-clause (v) (w.e.f. 27-7-1964).
6. Subs. by Act 68 of 1982, s. 14, for certain words (w.e.f.1-2-1983).
7. Ins. by Act. 21 of 1962, s. 14 (w.e.f. 27-7-1964).
8. Subs. by Act 11 of 1955, s. 9, for ―State Government‖.
9. Explanation omitted by Act 68 of 1982, s.14 (w.e.f. 1-2-1983).
10. Ins. by Act 13 of 1964, s. 14 (w.e.f. 15-9-1964).
11. Ins. by Act 68 of 1982, s. 15 (w.e.f. 1-2-1983).
12. Sub. by Act 26 of 2008, s 3, for sub-clause (ii) (w.e.f 10-8-2009), before substitution, stood as under :
―any cosmetic which is not of a standard quality or is misbranded or spurious‖
Drugs and Cosmetics Act, 1940
17
19. Pleas.—(1) Save as hereinafter provided in this section, it shall be no defence in a prosecution under
this Chapter to prove merely that the accused was ignorant of the nature, substance or quality of the drug
1
[or cosmetic] in respect of which the offence has been committed or of the circumstances of its
manufacture or import, or that a purchaser, having bought only for the purpose of test or analysis, has not
been prejudiced by the sale.
(2)
2
[For the purposes of section 18 a drug shall not be deemed to be misbranded or
2
[adulterated or
spurious] or to be below standard quality nor shall a cosmetic be deemed to be misbranded or to be below
standard quality] only by reason of the fact that—
(a) there has been added thereto some innocuous substance or ingredient because the same is required
for manufacture or preparation of the drug
1
[or cosmetic] as an article of commerce in a state fit for
carriage or consumption, and not to increase the bulk, weight or measure of the drug
1
[or cosmetic] or to
conceal its inferior quality or other defects; or
4
[* * * * *]
(b) in the process of manufacture, preparation or conveyance some extraneous substance has
unavoidably become intermixed with it: Provided that this clause shall not apply in relation to any sale or
distribution of the drug
1
[or cosmetic] occurring after the vendor or distributor became aware of such
intermixture.
5
[(3) A person, not being the manufacturer of a drug or cosmetic or his agent for the distribution thereof,
shall not be liable for a contravention of section 18 if he proves—
(a) that he acquired the drug or cosmetic from a duly licensed manufacturer, distributor or
dealer thereof;
(b) that he did not know and could not, with reasonable diligence, have ascertained that the drug
or cosmetic in any way contravened the provisions of that section; and
(c) that the drug or cosmetic, while in his possession, was properly stored and remained in the
same state as when he acquired it.]
6
[20.Government Analysts.— (1) The State Government may, by notification in the Official Gazette,
appoint such persons as it thinks fit, having the prescribed qualifications, to be Government Analysts for such
areas in the state and in respect of such drugs or
7
[classes of drugs or such cosmetics or classes of cosmetics]
as may be specified in the notification.
(2) The Central Government may also, by notification in the Official Gazette, appoint such persons as it
thinks fit, having the prescribed qualifications, to be Government Analysts in respect of such drugs or
7
[classes
of drugs or such cosmetics or classes of cosmetics] as may be specified in the notification.
(3) Notwithstanding anything contained in sub-section (1) or sub-section (2), neither the Central
Government nor a State Government shall appoint as a Government Analyst any official not serving under it
without the previous consent of the Government under which he is serving.
8
[(4) No person who has any financial interest in the import, manufacture or sale of drugs or cosmetics
shall be appointed to be a Government Analyst under sub-section (1) or sub-section (2) of this section.]
21. Inspectors.—(1) The Central Government or a State Government may, by notification in the Official
Gazette, appoint such persons as it thinks fit, having the prescribed qualifications, to be Inspectors for such
areas as may be assigned to them by the Central Government or State Government, as the case may be.
(2) The powers which may be exercised by an Inspector and the duties which may be performed by him,
the drugs or
9
[classes of drugs or cosmetics or classes of cosmetics] in relation to which and the
conditions, limitations or restrictions subject to which, such powers and duties may be exercised or
performed shall be such as may be prescribed.
1. Ins. by Act 21 of 1962, s.15 (w.e.f. 27-7-1964).
2. Subs. by Act 13 of 1964, s. 15, for certain words (w.e.f. 15-9-1964).
3. Subs. by Act 68 of 1982, s.16, for ―adulterated‖ (w.e.f. 1-2-1983).
4. Cl.(aa) ins. by Act 11 of 1955, s. 10 and omitted by Act 13 of 1964, s. 15 (w.e.f. 15-9-1964).
5. Subs.by Act 13 of 1964, s. 15, for sub-section (3) (w.e.f. 15-9-1964).
6. Subs. by Act 35 of 1960, s. 4, for ss. 20 and 21 (w.e.f. 16-3-1961).
7. Subs. by Act 21 of 1962, s. 16, for ―class of drugs‖ (w.e.f. 27-7-1964).
8. Ins. by Act 68 of 1982, s.17 (w.e.f.1-2-1983).
9. Subs. by Act 21 of 1962, s.17, for ―class of drugs‖ (w.e.f. 27-7-1964).
Drugs and Cosmetics Act, 1940
18
(3) No person who has any financial interest
1
[in the import, manufacture or sale of drugs or cosmetics]
shall be appointed to be an Inspector under this section.
(4) Every Inspector shall be deemed to be public servant within the meaning of section 21 of the Indian
Penal Code (45 of 1860), and shall be officially subordinate to such authority
2
[having the prescribed
qualifications,] as the Government appointing him may specify in this behalf.]
3
[22. Powers of Inspectors.—(1) Subject to the provisions of section 23 and of any rules made by
the Central Government in this behalf, an Inspector may, within the local limits of the area for which he is
appointed,—
4
[(a) inspect,—
(i) any premises wherein any drug or cosmetic is being manufactured and the means employed for
standardising and testing the drug or cosmetic;
(ii) any premises wherein any drug or cosmetic is being sold, or stocked or exhibited or offered for
sale, or distributed;
(b) take samples of any drug or cosmetic,—
(i) which is being manufactured or being sold or is stocked or exhibited or offered for sale, or is
being distributed;
(ii) from any person who is in the course of conveying, delivering or preparing to deliver such
drug or cosmetic to a purchaser or a consignee;
(c) at all reasonable times, with such assistance, if any, as he considers necessary,--
(i) search any person, who, he has reason to believe, has secreted about his person, any drug or
cosmetic in respect of which an offence under this Chapter has been, or is being, committed; or
(ii) enter and search any place in which he has reason to believe that an offence under this Chapter
has been, or is being, committed; or
(iii) stop and search any vehicle, vessel or other conveyance which, he has reason to believe, is
being used for carrying any drug or cosmetic in respect of which an offence under this Chapter has
been, or is being, committed,
and order in writing the person in possession of the drug or cosmetic in respect of which the offence has
been, or is being, committed, not to dispose of any stock of such drug or cosmetic for a specified period
not exceeding twenty days, or, unless the alleged offence is such that the defect may be removed by the
possessor of the drug or cosmetic, seize the stock of such drug or cosmetic and any substance or article by
means of which the offence has been, or is being, committed or which may be employed for the
commission of such offence;]
5
[(cc) examine any record, register, document or any other material object found
4
[with any person, or
in any place, vehicle, vessel or other conveyance referred to in clause (c)], and seize the same if he has
reason to believe that it may furnish evidence of the commission of an offence punishable under
this Act or the rules made thereunder;]
4
[(cca) require any person to produce any record, register, or other document relating to the
manufacture for sale or for distribution, stocking, exhibition for sale, offer for sale or distribution of any
drug or cosmetic in respect of which he has reason to believe that an offence under this Chapter has been,
or is being, committed;]
(d) exercise such other powers as may be necessary for carrying out the purposes of this Chapter or
any rules made thereunder.
1. Subs. by Act 21 of 1962, s.17, for ―in the manufacture, import or sale of drugs‖ (w.e.f 27-7-1964).
2. Ins. by Act 68 of 1982, s.18 (w.e.f. 1-2-1983).
3. Subs. by Act 11of 1955, s. 11, for s. 22.
4. Subs. by Act 68 of 1982, s.19, for certain words (w.e.f. 1-2-1983).
5. Ins. by Act 35 of 1960, s. 5 (w.e.f. 16-3-1961).
Drugs and Cosmetics Act, 1940
19
(2) The provisions of
1
[the Code of Criminal Procedure, 1973 (2 of 1974)] shall, so far as may be,
apply to any search or seizure under this Chapter as they apply to any search or seizure made under the
authority of a warrant issued under
1
[section 94] of the said Code.
2
[(2A) Every record, register or other document seized under clause (cc) or produced under clause (cca)
shall be returned to the person, from whom they were seized or who produce the same, within a period of
twenty days of the date of such seizure or production, as the case may be, after copies thereof or extracts
therefrom certified by that person, in such manner as may be prescribed, have been taken.]
(3) If any person wilfully obstructs an Inspector in the exercise of the powers conferred upon him by or
under this Chapter,
2
[or refuses to produce any record, register or other document when so required under
clause (cca) of sub- section (1),] he shall be punishable with imprisonment which may extend to three years,
or with fine, or with both.]
23. Procedure of Inspectors.—(1) Where an Inspector takes any sample of a drug
3
[or cosmetic] under
this Chapter, he shall tender the fair price thereof and may require a written acknowledgment therefor.
(2) Where the price tendered under sub-section (1) is refused, or where the Inspector seizes the stock of
any drug
3
[or cosmetic] under clause (c) of section 22, he shall tender a receipt therefor in the prescribed form.
(3) Where an Inspector takes a sample of a drug
3
[or cosmetic] for the purpose of test or analysis, he shall
intimate such purpose in writing in the prescribed form to the person from whom he takes it and, in the
presence of such person unless he wilfully absents himself, shall divide the sample into four portions and
effectively seal and suitably mark the same and permit such person to add his own seal and mark to all or any
of the portions so sealed and marked:
Provided that where the sample is taken from premises whereon the drug
3
[or cosmetic] is being
manufactured, it shall be necessary to divide the sample into three portions only:
Provided further that where the drug
3
[or cosmetic] is made up in containers of small volume, instead of
dividing a sample as aforesaid, the Inspector may, and if the drug
3
[or cosmetic] be such that it is likely
to deteriorate or be otherwise damaged by exposure shall, take three or four, as the case may be, of the said
containers after suitably marking the same and, where necessary, sealing them.
(4) The Inspector shall restore one portion of a sample so divided or one container, as the case may be, to
the person from whom he takes it, and shall retain the remainder and dispose of the same as follows:—
(i) one portion or container he shall forthwith send to the Government Analyst for test or analysis;
(ii) the second he shall produce to the Court before which proceedings, if any, are instituted in
respect of the drug
3
[or cosmetic];
4
[(iii) the third, where taken, he shall send to the person, if any, whose name, address and other
particulars have been disclosed under section 18A.]
(5) Where an Inspector takes any action under clause (c) of section 22,—
(a) he shall use all despatch in ascertaining whether or not the drug
3
[or cosmetic] contravenes any of
the provisions of the section 18 and, if it is ascertained that the drug
3
[or cosmetic] does not so contravene,
forthwith revoke the order passed under the said clause or, as the case may be, take such action as may be
necessary for the return of the stock seized;
(b) if he seizes the stock of the drug
3
[or cosmetic], he shall as soon as may be inform
5
[a Judicial
Magistrate] and take his orders as to the custody thereof;
(c) without prejudice to the institution of any prosecution, if the alleged contravention be such that
the defect may be remedied by the possessor of the drug
3
[or cosmetic], he shall, on being satisfied that
the defect has been so remedied, forthwith revoke his order under the said clause.
1. Subs. by Act 68 of 1982, s.19, for ―the Code of Criminal Procedure, 1898‖ (w.e.f. 1-2-1983).
2. Ins. by Act 68 of 1982, s. 19. (w.e.f. 1-2-1983).
3. Ins.by Act 21 of 1962, s.15 (w.e.f. 27-7-1964).
4. Subs. by Act 13 of 1964, s.16, for cl. (iii) (w.e.f.15-9-1964).
5. Subs. by Act 68 of 1982, s. 20, for ―a Magistrate‖ (w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
20
1
[(6) Where an Inspector seizes any record, register, document or any other material object under clause
(cc) of sub- section (1) of section 22, he shall, as soon as may be, inform
2
[a Judicial Magistrate] and take his
orders as to the custody thereof.]
24. Persons bound to disclose place where drugs or cosmetics are manufactured or kept. —Every
person for the time being in charge of any premises whereon any drug
3
[or cosmetic] is being manufactured or
is kept for sale or distribution shall, on being required by an Inspector so to do, be legally bound to disclose to
the Inspector the place where the drug
3
[or cosmetic] is being manufactured or is kept, as the case may be.
25. Reports of Government Analysts.—(1) The Government Analyst to whom a sample of any drug
3
[or
cosmetic] has been submitted for test or analysis under sub-section (4) of section 23, shall deliver to the
Inspector submitting it a signed report in triplicate in the prescribed form.
(2) The Inspector on receipt thereof shall deliver one copy of the report to the person from whom the
sample was taken
4
[and another copy to the person, if any, whose name, address and other particulars have
been disclosed under section 18A], and shall retain the third copy for use in any prosecution in respect of the
sample.
(3) Any document purporting to be a report signed by a Government Analyst under this Chapter shall be
evidence to the facts stated therein, and such evidence shall be conclusive unless the person from whom the
sample was taken
5
[or the person whose name, address and other particulars have been disclosed under
section 18A] has, within twenty-eight days of the receipt of a copy of the report, notified in writing the
Inspector or the Court before which any proceedings in respect of the sample are pending that he intends to
adduce evidence in controversion of the report.
(4) Unless the sample has already been tested or analysed in the Central Drugs Laboratory, where a
person has under sub-section (3) notified his intention of adducing evidence in controversion of a Government
Analyst‘s report, the Court may, of its own motion or in its discretion at the request either of the complainant
or the accused, cause the sample of the drug
3
[or cosmetic] produced before the Magistrate under sub-
section (4) of section 23 to be sent for test or analysis to the said Laboratory, which shall make the test or
analysis and report in writing signed by, or under the authority of, the Director of the Central Drugs
Laboratory the result thereof, and such report shall be conclusive evidence of the facts stated therein.
(5) The cost of a test or analysis made by the Central Drugs Laboratory under sub-section (4) shall be
paid by the complainant or accused as the Court shall direct.
26. Purchaser of drug
3
[or cosmetic] enabled to obtain test or analysis.—Any person
6
[or any
recognised consumer association, whether such person is a member of that association or not,] shall, on
application in the prescribed manner and on payment of the prescribed fee, be entitled to submit for test or
analysis to a Government Analyst any drug
3
[or cosmetic]
7
[purchased by him or it] and to receive a report of
such test or analysis signed by the Government Analyst.
8
[Explanation.—For the purposes of this section and section 32, ―recognised consumer association‖
means a voluntary consumer association registered under the Companies Act, 1956 (1 of 1956) or any other
law for the time being in force.]
9
[26A. Power of Central Government to prohibit manufacture, etc., of drug and cosmetic in public
interest.— Without prejudice to any other provision contained in this Chapter, if the Central Government is
satisfied, that the use of any drug or cosmetic is likely to involve any risk to human beings or animals or that
any drug does not have the therapeutic value claimed or purported to be claimed for it or contains ingredients
and in such quantity for which there is no therapeutic justification and that in the public interest it is
necessary or expedient so to do, then, that Government may, by notification in the Official Gazette,
11
[regulate, restrict or prohibit] the manufacture, sale or distribution of such drug or cosmetic.]
12
[26B. Powers of Central Government to regulate or restrict, manufacture, etc., of drug in public
interest. – Without prejudice to any other provision contained in this Chapter, if the Central Government is
satisfied that a drug is essential to meet the requirements of an emergency arising due to epidemic or natural
calamities and that in the public interest it is necessary or expedient so to do, then, that Government may, by
notification in the Official Gazette, regulate or restrict the manufacture, sale or distribution of such drug.]
10
[27. Penalty for manufacture, sale, etc., of drugs in contravention of this Chapter.—Whoever,
himself or by any other person on his behalf, manufactures for sale or for distribution, or sells, or stocks or
exhibits or offers for sale or distributes, —
1. Ins. by Act 35 of 1960, s. 6 (w.e.f. 16-3-1961). 9. Ins. by Act 68 of 1982, s. 21 (w.e.f. 1-2-1983).
2. Subs. by Act 68 of 1982, s. 20, for ―a Magistrate‖ (w.e.f. 1-2-1983). 10. Subs. by Act 68 of 1982 s. 22, for s. 27 (w.e.f. 1-2-1983).
3. Ins. by Act 21 of 1962, s. 15 (w.e.f. 27-7-1964). 11. Sub. by Act 26 of 2008, s 4, for ―prohibit‖ (w.e.f 10-8-2009).
4. Subs. by Act 13 of 1964, s. 17, for certain words (w.e.f. 15-9-1964). 12. Ins. by Act 26 of 2008, sec 5(w.e.f. 10-8-2009).
5. Subs. by Act 13 of 1964 s.17, for ―or the said warrantor‖(w.e.f. 15-9-1964).
6. Ins. by Act 71 of 1986, s. 2 (w.e.f. 15-9-1987).
7. Subs. by Act 71 of 1986 s. 2, for ―purchased by him‖ (w.e.f. 15-9-1987).
8. Added by Act 71 of 1986 s. 2, (w.e.f. 15-9-1987).
Drugs and Cosmetics Act, 1940
21
(a) any drug deemed to be adulterated under section 17A or spurious under section
1
[17B and
which] when used by any person for or in the diagnosis, treatment, mitigation, or prevention of any
disease or disorder is likely to cause his death or is likely to cause such harm on his body as would
amount to grievous hurt within the meaning of section 320 of the Indian Penal Code (45 of 1860), solely
on account of such drug being adulterated or spurious or not of standard quality, as the case may be, shall
be
2
[punishable with imprisonment for a term which shall not be less than ten years but which may extend
to a term of life and with fine which shall not be less than ten lakh rupees or three times value of the drugs
confiscated, whichever is more;]
3
[Provided that the fine imposed on and released from, the person convicted under this clause shall be
paid, by way of compensation, to the person who had used the adulterated or spurious drugs referred to in
this clause.
Provided further that where the use of the adulterated or spurious drugs referred to in this clause has
caused the death of a person who used such drugs, the fine imposed on and realised from, the person
convicted under this clause, shall be paid to the relative of the person who had died due to the use of the
adulterated or spurious drugs referred to in this clause.
Explanation.—For the purposes of the second proviso, the expression "relative" means—
(i) spouse of the deceased person; or
(ii) a minor legitimate son, and unmarried legitimate daughter and a widowed mother; or
(iii) parent of the minor victim; or
(iv) if wholly dependent on the earnings of the deceased person at the time of his death, a son or a daughter
who has attained the age of eighteen years; or
(v) any person, if wholly or in part, dependent on the earnings of the deceased person at the time of this
death,—
(a) the parent; or
(b) a minor brother or an unmarried sister; or
(c) a widowed daughter-in-law; or
(d) a widowed sister; or
(e) a minor child of a pre-deceased son; or
(f) a minor child of a pre-deceased daughter where no parent of the child is alive; or
(g) the paternal grandparent if no parent of the member is alive.]
(b) any drug—
(i) deemed to be adulterated under section 17A, but not being a drug referred to in clause (a), or
(ii) without a valid licence as required under clause (c) of section 18,
shall be punishable with imprisonment for a term which shall
4
[not be less than three year but which may
extend to five years and with fine which shall not be less than one lakh rupees or three times the value of
the drugs confiscated, whichever is more]:
Provided that the Court may, for any adequate and special reasons to be recorded in the judgment,
impose a sentence of imprisonment for a term of
5
[less than three years and of fine of less than one lakh
rupees];
(c) any drug deemed to be spurious under section 17B, but not being a drug referred to in clause (a)
shall be punishable with imprisonment for a term which shall
6
[not be less than seven years but which
may extend to imprisonment for life and with fine which shall not be less than three lakh rupees or
three times the value of the drugs confiscated, whichever is more]:
Provided that the Court may, for any adequate and special reasons, to be recorded in the
judgment, impose a sentence of imprisonment for a term of
7
[less than seven years but not less than three
years and of fine of less than one lakh rupees];
(d) any drug, other than a drug referred to in clause (a) or clause (b) or clause (c), in contravention
of any other provision of this Chapter or any rule made thereunder, shall be punishable with
imprisonment for a term which shall not be less than one year but which may extend to two years
8
[and
with fine which shall not be less than twenty thousand rupees]:
Provided that the Court may, for any adequate and special reasons, to be recorded in the judgment
impose a sentence of imprisonment for a term of less than one year.
1. Sub. by Act 26 of 2008, s 6(i)(A), for ―17B or which‖ (w.e.f 10-8-2009).
2. Sub. by Act 26 of 2008, s 6(i)(B), for ―punishable with imprisonment for a term which shall not be less than five years but which may extend to a term
of life and with fine which shall not be less than ten thousand rupees;‖ (w.e.f 10-8-2009).
3. Ins. by Act 26 of 2008, s. 6(i)(C) (w.e.f.10-8-2009).
4. Sub. by Act 26 of 2008, s 6(ii)(A), for ―not be less than one year but which may extend to three years and with fine which shall not be less than five
thousand rupees;‖ (w.e.f 10-8-2009).
5. Sub. by Act 26 of 2008, s 6(ii)(B),for ―less than one year and of fine of less than five thousand rupees;‖ (w.e.f 10-8-2009).
6. Sub. by Act 26 of 2008, s 6(iii)(A),(w.e.f 10-8-2009).
7. Sub. by Act 26 of 2008, s 6(iii)(B),(w.e.f 10-8-2009). 8. Sub. by Act 26 of 2008, s 6(iv), for ―and with fine‖ (w.e.f 10-8-2009).
Drugs and Cosmetics Act, 1940
22
8
[27A. Penalty for manufacture, sale, etc., of cosmetics in contravention of this Chapter.—Whoever
himself or by any other person on his behalf manufactures for sale or for distribution, or sells, or stocks or
exhibits or offers for sale—
9
[(i) any cosmetic deemed to be spurious under section 17D or adulterated under section 17E shall be
punishable with imprisonment for a term which may extend to three years and with fine which shall not be
less than fifty thousand rupees or three times to value of the cosmetics confiscated, whichever is more;
(ii) any cosmetic other than a cosmetic referred to in clause (i) in contravention of any provisions of this
Chapter or any rule made thereunder shall be punishable with imprisonment for a term which may extend
to one year or with fine which may extend to twenty thousand rupees, or with both.]
1
[28. Penalty for non-disclosure of the name of the manufacturer, etc.—Whoever contravenes the
provisions of section 18A
2
[or section 24] shall be punishable with imprisonment for a term which may
extend to one year, or
3
[with fine which shall not be less than twenty
thousand rupees or with both.]
4
[28A. Penalty for not keeping documents, etc., and for non-disclosure of information.—Whoever
without reasonable cause or excuse, contravenes the provisions of section 18B shall be punishable with
imprisonment for a term which may extend to one year or
12
[with fine which shall not be less than twenty
thousand rupees or with both].
28B. Penalty for manufacture, etc., of drugs or cosmetics in contravention of section 26A.—Whoever
himself or by any other person on his behalf manufactures or sells or distributes any drug or cosmetic in
contravention of the provisions of any notification issued under section 26A, shall be punishable with
imprisonment for a term which may extend to three years and shall also be liable to fine which may extend to
five thousand rupees.]
29. Penalty for use of Government Analyst‘s report for advertising.—Whoever uses any report of a
test or analysis made by the Central Drugs Laboratory or by a Government Analyst, or any extract from
such report, for the purpose of advertising any drug
5
[or cosmetic], shall be punishable with fine, which may
extend to five hundred rupees.
6
[30. Penalty for subsequent offences.—
7
[(1) Whoever having been convicted of an offence—
(a) Under clause (b) of section 27, is again convicted of an offence under that clause, shall be
punishable with imprisonment for a term which shall not be
10
[less than seven years but which may
extend to ten years and with fine which shall not be less than two lakh rupees];
Provided that the Court may, for any adequate and special reasons to be mentioned in the judgment,
impose a sentence of imprisonment for a term of
11
[less than seven years and of fine of less than one lakh
rupees];
1. Subs. by Act 13 of 1964, s.19, for s. 28 (w.e.f.15-9-1964).
2. Ins. by Act 68 of 1982, s. 23 (w.e.f. 1-2-1983).
3. Subs. by Act 26 of 2008 s. 7. Earlier Subs. by Act 68 of 1982, s.23.
4. Ins. by Act 68 of 1982, s. 24, (w.e.f. 1-2-1983).
5. Ins. by Act 21 of 1962, s. 15 (w.e.f.27-7-1964).
6. Subs. by Act 11 of 1955, s. 14, for s. 30.
7. Subs. by Act 68 of 1982, s. 25, for sub-section (1) (w.e.f. 1-2-1983).
8. Subs. by Act 68 of 1982 s. 22, for s. 27A (w.e.f. 1-2-1983), Earlier s. 27A was inserted by Act 21 of 1962, s 19 (w.e.f. 27-7-1964).
9. Subs. by Act 26 of 2008 s. 7, for clause (i) and (ii) (w.e.f. 10-8-2009).
10. Subs. by Act 26 of 2008 sec. 11(a)(i)(A), for ―less than two years but which may extend to six years and with fine which shall not be less than ten
thousand rupees‖;( w.e.f. 10-8-2009)
11. Subs. by Act 26 of 2008 sec. 11(a)(i)(B), for ―less than two years and of fine of less than ten thousand rupees‖; (w.e.f. 10-8-2009).
12. Subs. by Act 26 of 2008 s. 7, for ―with fine which may extend to one thousand rupees or with both‖ (w.e.f. 10-8-2009).
Drugs and Cosmetics Act, 1940
23
(b) under clause (c) of section 27 is again convicted of an offence under that clause, shall be
punishable with imprisonment for a term which shall
1 2
[less than ten years but which may extend to
imprisonment for life and with fine which shall not be less than three lakh rupees];
(c) under clause (d) of section 27, is again convicted of an offence under that clause shall be
punishable with imprisonment for a term which shall not be less than two years but which may extend
to four years or with fine which shall not be less than
13
[fifty thousand rupees], or with both.]
1
[(1A) Whoever, having been convicted of an offence under section 27A is again convicted under that
section, shall be punishable with imprisonment for a term which may extend to two years, or with fine which
may extend to
2
[two thousand rupees], or with both.]
(2) Whoever, having been convicted of an offence under
3
[* * *] section 29 is again convicted of an
offence under the same section shall be punishable with imprisonment which may extend to
4
[two tears, or
with fine which shall not be less than ten thousand rupees], or with both.]
31. Confiscation.—
5
[(1)] Where any person has been convicted under this Chapter for contravening any
such provision of this Chapter or any rule made thereunder as may be specified by rule made in this behalf, the
stock of the drug
6
[or cosmetic] in respect of which the contravention has been made shall be liable to
confiscation
7
[and if such contravention is in respect of—
8
[(i) manufacture of any drug deemed to be misbranded under section 17, adulterated under section
17A or spurious under section 17B; or
(ii)
9
[manufacture for sale, or for distribution, sale, or stocking or exhibiting or offering for sale,] or
distribution of any drug without a valid licence as required under clause (c) of section 18;
any implements or machinery used in such manufacture, sale or distribution and any receptacles, packages or
coverings in which such drug is contained and the animals, vehicles, vessels or other conveyances used in
carrying such drug shall also be liable to confiscation.]
10
[(2) Without prejudice to the provisions contained in sub-section (1) where the Court is satisfied, on the
application of an Inspector or otherwise and after such inquiry as may be necessary that the drug or
cosmetic is not of standard quality or is a
9
[misbranded, adulterated or spurious drug or misbranded or
spurious cosmetic,] such drug or, as the case may be, such cosmetic shall be liable to confiscation.]
11
[31A. Application of provisions to Government departments.—The provisions of this Chapter except
those contained in section 31 shall apply in relation to the manufacture, sale or distribution of drugs of any
department of Government as they apply in relation to the manufacture, sale or distribution of drugs by any
other person.]
32. Cognizance of offence.—
14
[(1) No prosecution under this Chapter shall be instituted except by-
1. Ins. by Act 21 of 1962, s. 20 (w.e.f. 27-7-1964).
2. Subs. by Act 68 of 1982, s. 25, for ―one thousand rupees‖ (w.e.f. 1-2-1983).
3. The words and figures ―section 28 or‖ omitted by Act 13 of 1964, s. 26 (w.e.f. 15-9-1964).
4. Subs. by Act 26 of 2008 sec. 11(b), for ―ten years, or with fine, or with both‖.
5. S. 31 re-numbered as sub-section (1) by Act 35 of 1960, s. 9 (w.e.f. 16-3-1961).
6. Ins. by Act 21 of 1962, s. 21 (w.e.f. 27-7-1964).
7. Ins. by Act 13 of 1964, s. 21 (w.e.f. 15-9-1964).
8. Subs. by Act 68 of 1982, s. 26, for cl. (i) (w.e.f. 1-2-1983).
9. Subs. by s. 26, ibid., for certain words (w.e.f. 1-2-1983).
10. Sub-section (2) ins. by Act 35 of 1960, s. 9 and subs. by Act 21 of 1962, s. 21 (w.e.f. 27-7-1964).
11. Ins. by Act 13 of 1964, s. 22 (w.e.f.15-9-1964).
12. Subs. by Act 26 of 2008 sec. 11(a)(ii), for ―less than six years but which may extend to ten years and with fine which shall not be less than ten
thousand rupees ‖;( w.e.f. 10-8-2009)
13. Subs. by Act 26 of 2008 sec. 11(a)(iii), for ―five thousand rupees ‖; (w.e.f. 10-8-2009)
14. Subs. by Act 26 of 2008, sec 12, for sub-section (1) and (2) (w.e.f. 10-8-2009)
Drugs and Cosmetics Act, 1940
24
(a) an Inspector, or
(b) any gazetted Officer of the Central Government or a State Government authorized in writing in this
behalf by the Central Government or a State Government by a general or special order made in this
behalf by that Government; or
(c) the person aggrieved; or
(d) a recognised consumer association whether such person is a member of that association or not.
(2) Save as otherwise provided in this Act, no court inferior to that of a Court of Sessions shall try an
offence punishable under this Chapter.]
(3) Nothing contained in this Chapter shall be deemed to prevent any person from being prosecuted under
any other law for any act or omission which constitutes an offence against this Chapter.
1
[32A. Power of Court to implead the manufacturer, etc.—Where, at any time during the trial of any
offence under this Chapter alleged to have been committed by any person, not being the manufacturer of a
drug or cosmetic or his agent for the distribution thereof, the Court is satisfied, on the evidence adduced
before it, that such manufacturer or agent is also concerned in that offence, then, the Court may,
notwithstanding anything contained
2
[in sub-sections (1), (2) and (3) of section 319 of the Code of Criminal
Procedure,1973 (2 of 1974)] proceed against him as though a prosecution had been instituted against him
under section 32.]
3
[32B. Compounding of certain offences.- (1) Notwithstanding anything contained in the Code of
Criminal Procedure, 1973 (2 of 1974), any offence punishable under clause (b) of sub-section (1) of Section
13, Section 28 and Section 28A of this Act(whether committed by a company or any officer thereof), not being
an offence punishable with imprisonment only, or with imprisonment and also with fine, may, either before or
after the instructions of any prosecution, be compounded by the Central Government or by any State
Government or any officer authorized in this behalf Central Government or a State Government, on payment
for credit to that Government of such sum as that Government may, by rules made in this behalf, specify:
Provided that such sum shall not, in any case, exceed the maximum amount of the fine which may be
imposed under this Act for the offences so compounded:
Provided further that in cases of subsequent offences, the same shall not be compoundable.
(2) When the accused has been committed for trial or when he has been convicted and an appeal is
pending, no composition for the offences shall be allowed without the leave of the court to which he is
committed or, as the case may be, before which the appeal is to be heard.
(3) Where an offence is compounded under sub-section (1), no proccding or further proceeding, as the
case may be , shall be taken against the offender in respect of the offences so compounded and the offender, if
in custody, shall be released forthwith.]
33. Power of Central Government to make rules.—
4
[(1) The Central Government may
5
[after
consultation with, or on the recommendation of, the Board] and after previous publication by notification in
the Official Gazette, make rules for the purpose of giving effect to the provisions of this Chapter:
Provided that consultation with the Board may be dispensed with if the Central Government is of opinion
that circumstances have arisen which render it necessary to make rules without such consultation, but in
such a case the Board shall be consulted within six months of the making of the rules and the Central
Government shall take into consideration any suggestions which the Board may make in relation to the
amendment of the said rules.]
1. Ins. by Act 13 of 1964, s. 23 (w.e.f.15-9-1964).
2. Subs. by Act 68 of 1982, s. 28, for certain words (w.e.f. 1-2-1983).
3. Ins. by Act 26 of 2008, s. 13; (w.e.f. 10-8-2009)
4. Subs. by Act 11 of 1955, s. 15, for sub-section (1).
5. Subs. by Act 68 of 1982, s. 29, for certain words (w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
25
(2) Without prejudice to the generality of the foregoing power, such rules may—
(a) provide for the establishment of laboratories for testing and analysing drugs
1
[or cosmetics];
(b) prescribed the qualifications and duties of Government Analysts and the qualifications of
Inspectors;
(c) prescribe the methods of test or analysis to be employed in determining whether a drug
1
[or
cosmetic] is of standard quality;
(d) prescribe, in respect of biological and organometallic compounds, the units or methods of
standardisation;
2
[(dd) prescribe under clause (d) of
3
[section 17A] the colour or colours which a drug may bear or
contain for purposes of colouring;]
4
[(dda) prescribe under clause (d) of section 17E the colour or colours which a cosmetic may bear or
contain for purposes of colouring];
(e) prescribe the forms of licences
6
[for the manufacture for sale or for distribution], for the sale
and for the distribution of drugs or any specified drug or class of drugs
1
[or of cosmetics or any
specified cosmetic or class of cosmetics], the form of application for such licences, the conditions
subject to which such licences may be issued, the authority empowered to issue the same
3
[, the
qualification of such authority] and the fees payable therefor
3
[and provide for the cancellation or
suspension of such licences in any case where any provision of this Chapter or the rules made
thereunder is contravened or any of the conditions subject to which they are issued is not complied
with;]
3
[(ee) prescribe the records, registers or other documents to be kept and maintained under
section 18B;
(eea) prescribe the fees for the inspection (for the purposes of grant or renewal of licence) of
premises, wherein any drug or cosmetic is being or is proposed to be manufactured;
(eeb) prescribe the manner in which copies are to be certified under sub-section (2A) of
section 22;]
(f) specify the diseases or ailments which a drug may not purport or claim
5
[to prevent, cure or
mitigate]
and such other effects which a drug may not purport or claim to have;
(g) prescribe the conditions subject to which small quantities of drugs may be
manufactured for the purpose of examination, test or analysis;
1. Ins. by Act 21 of 1962, s. 22 (w.e.f. 27-7-1964).
2. Ins. by Act 13 of 1964, s. 24 (w.e.f. 15-9-1964).
3. Ins. by Act 68 of 1982, s. 29 ( w.e.f. 1-2-1983).
4. Ins. by Act 26 of 2008, s. 14(i) (w.e.f. 10-8-2009)
5. Subs. by Act 11 of 1955, s. 15, for ―to cure or mitigate‖.
6. Subs. By Act 68 of 1982, s. 29 ( w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
26
(h) require the date of manufacture and the date of expiry of potency to be clearly or truly stated
on the label or container of any specified drug or class of drugs, and prohibit the sale, stocking or
exhibition for sale, or distribution of the said drug or class of drugs after the expiry of a specified
period from the date of manufacture or after the expiry of the date of potency;
(i) prescribe the conditions to be observed in the packing in bottles, packages, and other
containers of drugs
1
[or cosmetics],
2
[including the use of packing material which comes into direct
contact with the drugs] and prohibit the sale, stocking or exhibition for sale, or distribution of drugs
1
[or cosmetics] packed in contravention of such conditions;
(j) regulate the mode of labelling packed drugs
1
[or cosmetics], and prescribe the matter which
shall or shall not be included in such labels;
(k) prescribe the maximum proportion of any poisonous substance which may be added or
contained in any drug, prohibit the manufacture, sale or stocking or exhibition for sale, or
distribution of any drug in which that proportion is exceeded, and specify substances which shall be
deemed to be poisonous for the purposes of this Chapter and the rules made thereunder;
(l) require that the accepted scientific name of any specified drug shall be displayed in the
prescribed manner on the label or wrapper of any patent or proprietary medicine containing such
drug;
3
[****]
4
[(n) prescribe the powers and duties of Inspectors
5
[and the qualifications of the authority to
which such Inspectors shall be subordinate] and
6
[specify the drugs or classes of drugs or cosmetics
or classes of cosmetics] in relation to which and the conditions, limitations or restrictions subject to
which, such powers and duties may be exercised or performed;]
(o) prescribe the forms of report to be given by Government Analysts, and the manner of
application for test or analysis under section 26 and the fees payable therefor;
7
[(p) specify the offences against this Chapter or any rule made thereunder in relation to
which an order of confiscation may be made under section 31;
8
[****]]
(q) provide for the exemption, conditionally or otherwise, from all or any of the provisions of
this Chapter or the rules made thereunder, of any specified drug or class of drugs
1
[or cosmetic or
class of cosmetics];
9
[and]
10
[(r) sum which may be specified by the Central Government under section 32-B.]
11
[****]
12
[33A. Chapter not to apply to
13
[Ayurvedic, Siddha or Unani] drugs.—Save as otherwise
provided in this Act, nothing contained in this Chapter shall apply to
13
[Ayurvedic, Siddha or Unani] drugs.]
14
[CHAPTER IVA
PROVISIONS RELATING TO
13
[AYURVEDIC, SIDDHA AND UNANI]
DRUGS
33B. Application of Chapter IVA.—This Chapter shall apply only to
13
[Ayurvedic, Siddha and Unani]
drugs.
33C.
15
[Ayurvedic, Siddha and Unani Drugs Technical Advisory Board].—(1) The Central
Government shall, by notification in the Official Gazette and with effect from such date as may be specified
therein, constitute a Board (to be called the
15
[Ayurvedic, Siddha and Unani Drugs Technical Advisory
Board]) to advise the Central Government and the State Governments on technical matters arising out of
this Chapter and to carry out the other functions assigned to it by this Chapter.
(2) The Board shall consist of the following members, namely:—
1. Ins. by Act 21 of 1962, s. 22 (w.e.f. 27-7-1964).
2. Ins. by Act 68 of 1982, s. 29 (w.e.f. 1-2-1983).
3. Cl. (m) omitted by Act 13 of 1964, s. 24 (w.e.f. 15-9-1965).
4. Subs. by Act 35 of 1960, s. 10, for cl. (n) (w.e.f. 16-3-1961).
5. Ins. by Act 68 of 1982, s. 29 (w.e.f. 15-9-1965).
6. Subs. by Act 21 of 1962, s. 22, for ―the drugs or class of drugs‖ (w.e.f. 27-7-1964).
7. Subs. by Act 13 of 1964, s. 24, for cl. (p) (w.e.f. 15-9-1964).
8. The word ―and‖omitted by Act 26 of 2008, sec. 14(ii) (w.e.f. 10-8-2009)
9. Ins. by Act 26 of 2008, Sec. 14 (iii) (w.e.f. 10-8-2009)
10. Ins. by Act 26 of 2008, Sec. 14 (iv) (w.e.f. 10-8-2009)
11. Sub-section (3) ins. by Act 35 of 1960 and omitted by Act 13 of 1964, s. 24 (w.e.f. 15-9-1964).
12. Ins. by Act 13 of 1964, s. 25 (w.e.f. 1-2-1969).
13. Subs. by Act 68 of 1982, s. 2, for ―AYURVEDIC (INCLUDING SIDDHA) OR UNANI‖ (w.e.f. 1-2-1983).
14. Ins. by Act 13 of 1964, s. 26 (w.e.f. 1-2-1969).
15. Subs. by Act 68 of 1982, s. 30, for certain words (w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
27
(i) the Director General of Health Services, ex officio;
(ii) the Drugs Controller, India, ex officio;
1
[(iii) the principal officer dealing with Indian systems of medicine in the Ministry of Health, ex officio;]
(iv) the Director of the Central Drugs Laboratory, Calcutta, ex officio;
(v) one person holding the appointment of Government Analyst under section 33F, to be nominated by the
Central Government;
(vi) one Pharmacognocist to be nominated by the Central Government;
(vii) one Phyto-chemist to be nominated by the Central Government;
2
[(viii) four persons to be nominated by the Central Government, two from amongst the members of the
Ayurvedic Pharmacopoeia Committee, one from amongst the members of the Unani Pharmacopoeia Committee and
one from amongst the members of the Siddha Pharmacopoeia Committee;]
(ix) one teacher in Dravyaguna and Bhaishajya Kalpana, to be nominated by the Central Government;
(x) one teacher in ILM-UL-ADVIA and TAKLIS-WA-DAWA-SAZI, to be nominated by the Central
Government;
3
[(xi) one teacher in Gunapadam, to be nominated by the Central Government;
(xii) three persons, one each to represent the Ayurvedic, Siddha and Unani drug industry, to be nominated by the
Central Government;
(xiii) three persons, one each from among the practitioners of Ayurvedic, Siddha and Unani Tibb system of
medicine, to be nominated by the Central Government.]
(3) The Central Government shall appoint a member of the Board as its Chairman.
(4) The nominated members of the Board shall hold office for three years but shall be eligible for renomination.
(5) The Board may, subject to the previous approval of the Central Government, make bye-laws fixing a quorum and
regulating its own procedure and conduct of all business to be transacted by it.
(6) The functions of the Board may be exercised notwithstanding any vacancy therein.
(7) The Central Government shall appoint a person to be Secretary of the Board and shall provide the Board with
such clerical and other staff as the Central Government considers necessary.
4
[33D. The Ayurvedic, Siddha and Unani Drugs Consultative Committee.—(1) The Central Government may
constitute an Advisory Committee to be called the Ayurvedic, Siddha and Unani Drugs Consultative Committee to advise
the Central Government, the State Governments and the Ayurvedic, Siddha and Unani Drugs Technical Advisory Board
on any matter for the purpose of securing uniformity throughout India in the administration of this Act in so far as it
relates to Ayurvedic, Siddha or Unani drugs.
(2) The Ayurvedic, Siddha and Unani Drugs Consultative Committee shall consist of two persons to be nominated
by the Central Government as representatives of that Government and not more than one representative of each State to
be nominated by the State Government concerned.
(3) The Ayurvedic, Siddha and Unani Drugs Consultative Committee shall meet when required to do so by the
Central Government and shall regulate its own procedure.
33E. Misbranded drugs.—For the purposes of this Chapter, an Ayurvedic, Siddha or Unani drugs shall be deemed
to be misbranded—
1. Subs. by Act 68 of 1982, s. 30, for cl. (iii) (w.e.f. 1-2-1983).
2. Subs. by Act 68 of 1982, s. 30, for cl. (viii) (w.e.f. 1-2-1983).
3. Subs. by Act 68 of 1982, s. 30, for cls. (xi) and (xii) (w.e.f. 1-2-1983).
4. Subs. by Act 68 of 1982, s. 31, for ss. 33D and 33E (w.e.f. 1-2-1983).
Drugs and Cosmetics Act, 1940
28
(a) if it is so coloured, coated, powered or polished that damage is concealed, or if it is made to appear of better
or greater therapeutic value than it really is; or
(b) if it is not labelled in the prescribed manner; or
(c) if its label or container or anything accompanying the drug bears any statement, design or device which
makes any false claim for the drug or which is false or misleading in any particular.
33EE. Adulterated drugs.—For the purposes of this Chapter, an Ayurvedic, Siddha or Unani drug shall be deemed
to be adulterated,—
(a) if it consists, in whole or in part, of any filthy, putrid or decomposed substance; or
(b) if it has been prepared, packed or stored under insanitary conditions whereby it may have been contaminated
with filth or whereby it may have been rendered injurious to health; or
(c) if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render
the contents injurious to health; or
(d) if it bears or contains, for purposes of coloring only, a colour other than one which is prescribed; or
(e) if it contains any harmful or toxic substance which may render it injurious to health; or
(f) if any substance has been mixed therewith so as to reduce its quality or strength.
Explanation.—For the purpose of clause (a), a drug shall not be deemed to consist, in whole or in part, of any
decomposed substance only by reason of the fact that such decomposed substance is the result of any natural
decomposition of the drug:
Provided that such decomposition is not due to any negligence on the part of the manufacturer of the drug or the
dealer thereof and that it does not render the drug injurious to health.
33EEA. Spurious drugs.—For the purposes of this Chapter, an Ayurvedic, Siddha or Unani drug shall be deemed
to be spurious—
(a) if it is sold, or offered or exhibited for sale, under a name which belongs to another drug; or
(b) if it is an imitation of, or is a substitute for, another drug or resembles another drug in a manner likely to
deceive, or bears upon it or upon its label or container the name of another drug, unless it is plainly and
conspicuously marked so as to reveal its true character and its lack of identity with such other drug; or
(c) if the label or container bears the name of an individual or company purporting to be the manufacturer of the
drug, which individual or company is fictitious or does not exist; or
(d) if it has been substituted wholly or in part by any other drug or substance; or
(e) if it purports to be the product of a manufacturer of whom it is not truly a product.
33EEB. Regulation of manufacture for sale of Ayurvedic, Siddha and Unani drugs.—No person shall
manufacture for sale or for distribution any Ayurvedic, Siddha or Unani drug except in accordance with such standards,
if any, as may be prescribed in relation to that drug.
33EEC. Prohibition of manufacture and sale of certain Ayurvedic, Siddha and Unani drug.—From such date
as the State Government may, by notification in the Official Gazette, specify in this behalf, no person, either by himself
or by any other person on his behalf, shall—
(a) manufacture for sale or for distribution—
(i) any misbranded, adulterated or spurious Ayurvedic, Siddha or Unani drugs;
(ii) any patent or proprietary medicine, unless there is displayed in the prescribed manner on the label or
container thereof the true list of all the ingredients contained in it; and
Drugs and Cosmetics Act, 1940
29
(iii) any Ayurvedic, Siddha or Unani drug in contravention of any of the provisions of this Chapter or any
rule made thereunder;
(b) sell, stock or exhibit or offer for sale or distribute, any Ayurvedic, Siddha or Unani drug which has been
manufactured in contravention of any of the provisions of this Act, or any rule made thereunder;
(c) manufacture for sale or for distribution, any Ayurvedic, Siddha or Unani drug, except under, and in
accordance with the conditions of, a licence issued for such purpose under this Chapter by the prescribed authority:
Provided that nothing in this section apply to Vaidyas and Hakims who manufacture Ayurvedic, Siddha or Unani
drug for the use of their own patients:
Provided further that nothing in this section shall apply to the manufacture, subject to the prescribed conditions, of
small quantities of any Ayurvedic, Siddha or Unani drug for the purpose of examination, test or analysis.
33EED. Power of Central Government to prohibit manufacture, etc., of Ayurvedic, Siddha or Unani drugs in
public interest.—Without prejudice to any other provision contained in this Chapter, if the Central Government is
satisfied on the basis of any evidence or other material available before it that the use of any Ayruvedic, Siddha or Unani
drug is likely to involve any risk to human beings or animals or that any such drug does not have the therapeutic value
claimed or purported to be claimed for it and that in the public interest it is necessary or expedient so to do then, that
Government may, by notification in the Official Gazette, prohibit the manufacture, sale or distribution of such drug.]
33F. Government Analysts.—(1) The Central Government or a State Government may, by notification in the
Official Gazette, appoint such persons as it thinks fit, having the prescribed qualifications, to be Government Analysts for
such areas as may be assigned to them by the Central Government or the State Government, as the case may be.
(2) Notwithstanding anything contained in sub-section (1), neither the Central Government nor a State Government
shall appoint as a Government Analyst any official not serving under it without the previous consent of the Government
under which he is serving.
1
[(3) No person who has any financial interest in the manufacture or sale of any drug shall be appointed to be a
Government Analyst under this section.]
33G. Inspectors.—(1) The Central Government or a State Government may, by notification in the Official Gazette,
appoint such persons as it thinks fit, having the prescribed qualifications, to be Inspectors for such areas as may be
assigned to them by the Central Government or the State Government, as the case may be.
(2) The powers which may be exercised by an Inspector and the duties which may be performed by him and the
conditions, limitations or restrictions subject to which such powers and duties may be exercised or performed shall be
such as may be prescribed.
(3) No person who has any financial interest in the manufacture or sale of any drug shall be appointed to be an
Inspector under this section.
(4) Every Inspector shall be deemed to be a public servant within the meaning of section 21 of the Indian Penal Code
(45 of 1860) and shall be officially subordinate to such authority as the Government appointing him may specify in this
behalf.
33H. Application of provisions of sections 22, 23, 24 and 25.—The provisions of sections 22, 23, 24 and 25 and
the rules, if any, made thereunder shall, so far as may be, apply in relation to an Inspector and a Government Analyst
appointed under this Chapter as they apply in relation to an Inspector and a Government Analyst appointed under
Chapter IV, subject to the modification that the references to ―drug‖ in the said section, shall be construed as references
to
2
[―Ayurvedic, Siddha or Unani] drugs‖.
3
[33-I. Penalty for manufacture, sale, etc., of Ayurvedic, Siddha or Unani drug in contravention of this
Chapter —Whoever himself or by any other person on his behalf—
(1) manufactures for sale or for distribution,—
1. Ins. by Act 68 of 1982, s. 32 (w.e.f.1-2-1983).
2. Subs. by Act 68 of 1982, s. 2, for certain words (w.e.f. 1-2-1983).
3. Subs. by Act 68 of 1982, s. 33, for ss. 33-I and 33J (w.e.f.1-2-1983).
Drugs and Cosmetics Act, 1940
30
1
[(a) Any Ayurvedic, Siddha or Unani drug –
(i) deemed to be misbranded under section 33E,
(ii) deemed to be adulterated under section 33EE, or
(ii) without a valid licence as required under clause (c) of section 33EEC,
shall be punishable with imprisonment for a term which may extend to one year and with fine which shall not be less
than twenty thousand rupees or three times the value of the drugs confiscated, whichever is more;]
(b) any Ayurvedic, Siddha or Unani drug deemed to be spurious under section 33EEA, shall be punishable
with imprisonment for a term which shall not be less than one year but which may extend to three years and with
fine which shall not be less than
2
[fifty thousand rupees or three times the value of the drugs confiscated, whichever
is more]:
Provided that the Court may, for any adequate and special reasons to be mentioned in the judgment, impose a
sentence of imprisonment for a term of less than one year and of fine of less than
2
[fifty thousand rupees or three
times the value of the drugs confiscated, whichever is more]; or
3
[(c) any Ayurvedic, Siddha or Unani drug in contravention of the provisions of any notifications issuedunder
Section 33-EED shall be punishable with imprisonment for a term which may extend to three years and with fine
which may extend to fifty thousand rupees or three times the value of the drugs confiscated, whichever is more.]
(2) contravenes any other provisions of this Chapter or of section 24 as applied by section 33H or any rule made
under this Chapter, shall be punishable with imprisonment for a term which may extend to
4
[six months and with
fine which shall not be less than ten thousand rupees.]
5
[33J. Penalty for subsequent offences.—Whoever having being convicted of an offence,—
(a) under clause (a) of sub-section (1) of section 33-I is again convicted of an offence under that clause, shall
be punishable with imprisonment for a term which may extend to two years and with fine which shall not be less
than
6
[fifty thousand rupees or three times the value of the drugs confiscated, whichever is more];
(b) under clause (b) of sub-section (1) of section 33-I is again convicted of an offence under that clause, shall
be punishable with imprisonment for a term which shall not be less than two years but which may extend to six years
and with fine which shall not be less than
7
[one lakh rupees or three times the value of the drugs confiscated,
whichever is more:]
Provided that the Court may, for any adequate and special reasons to be mentioned in the judgment, impose a
sentence of imprisonment for a term of less than two years and of fine of less than
7
[one lakh rupees or three times
the value of the drugs confiscated, whichever is more;]
1. Sub. by s. 15(a)(i), for clause (a) (w.e.f. 10.08.2008). Clause (a), before substitution, stood as:―(a) Any Ayurvedic, Siddha or Unani drug – (i) deemed
to be adulterated under section 33EE, or (ii) without a valid licence as required under clause (c) of section 33EEC, shall be punishable with imprisonment
for a term which may extend to one year and with fine which shall not be less than two thousand rupees;‖
2. Sub. by Act 26 of 2008, s. 15(a)(ii), for ―five thousand rupees‖ (w.e.f. 10.08.2008)
3. Ins. by Act 26 of 2008, s. 15(a)(iii) (w.e.f. 10.08.2008)
4. Sub. by Act 26 of 2008, s. 15(b) for ―three months and with fine which shall not be less than five hundred rupees.‖ (w.e.f. 10.08.2008)
5. Sub by Act 68 of 1982,s.33 for section 33J(w.e.f. 01.02.1983)
6. Sub. by Act 26 of 2008, s. 16(a), for ―two thousand rupees‖ (w.e.f. 10.08.2008)
7. Sub. by Act 26 of 2008, s. 16(b), for ―five thousand rupees‖ (w.e.f. 10.08.2008)
Drugs and Cosmetics Act, 1940
31
(c) under sub-section (2) of section 33-I is again convicted of an offence under that sub-section,
shall be punishable with imprisonment for a term which may extend to
5
[one year and with fine which
shall not be less than twenty thousand rupees or three times the value of the drugs confiscated, whichever
is more;]
33K. Confiscation.—Where any person has been convicted under this Chapter, the stock of the
1
[Ayurvedic, Siddha or Unani] drug, in respect of which the contravention has been made, shall be liable to
confiscation.
6
[33-KA. Disclosure of name of manufacturer etc., –Every person, not being the manufacturer of any
Ayurvedic, Siddha or Unani drug or his agent for the distribution thereof, shall, if so required, disclose to the
Inspector the name, address and other particulars of the person from whom he acquired the Ayurvedic, Siddha
or Unani drug.]
6
[33-KB. Maintenance of records and furnishing of information.— Every person holding a licence under
clause (c) of section 33-EEC shall keep and maintain such records, registers and other documents as may be
prescribed and shall furnish to any officer or authority exercising any power or discharging any function under
this Act such information as is required by such officer or authority for carrying out the purposes of this Act. ]
33L. Application of provisions to Government departments.—The provisions of this Chapter except
those contained in section 33K shall apply in relation to the manufacture for sale, sale or distribution of
any
1
[Ayurvedic, Siddha or Unani] drug by any department of Government as they apply in relation to the
manufacture for sale, sale or distribution of such drug by any other person.
33M. Cognizance of offences.—(1) No prosecution under this Chapter shall be instituted except by an
Inspector
2
[with the previous sanction of the authority specified under sub-section (4) of section 33G].
(2) No Court inferior to that
3
[of a Metropolitan Magistrate or of a Judicial Magistrate of the first class]
shall try an offence punishable under this Chapter.
33N. Power of Central Government to make rules.—(1) The Central Government may,
4
[after
consultation with, or on the recommendation of, the Board] and after previous publication by notification in
the Official Gazette, make rules for the purpose of giving effect to the provisions of this Chapter:
Provided that consultation with the Board may be dispensed with if the Central Government is of
opinion that circumstances have arisen which render it necessary to make rules without such consultation, but
in such a case, the Board shall be consulted within six months of the making of the rules and the Central
Government shall take into consideration any suggestions which the Board may make in relation to the
amendment of the said rules.
(2) Without prejudice to the generality of the foregoing power, such rules may—
(a) provide for the establishment of laboratories for testing and analysing
1
[Ayurvedic, Siddha or
Unani] drugs;
1. Subs. by Act 68 of 1982, s. 2, for ―Ayurvedic (including Siddha) and Unani‖ (w.e.f. 1-2-1983).
2. Ins. by Act 68 of 1982, s. 34, (w.e.f. 1-2-1983).
3. Subs. by Act 68 of 1982, s. 34, for certain words (w.e.f. 1-2-1983).
4. Subs. by Act 68 of 1982 , s. 35, for certain words (w.e.f. 1-2-1983).
5. Sub. by Act 26 of 2008, s. 16(c), for ―six months and with fine which shall not be less than one thousand rupees.‖ (w.e.f. 10.08.2008)
6. Ins. by Act 26 of 2008, s. 17, (w.e.f. 10.08.2008).
Drugs and Cosmetics Act, 1940
32
(b) prescribe the qualification and duties of Government Analysts and the qualifications of Inspectors;
(c) prescribe the methods of test or analysis to be employed in determining whether any
1
[Ayurvedic, Siddha or
Unani] drug is labelled with the true list of the ingredients which it is purported to contain;
(d) specify any substance as a poisonous substance;
(e) prescribe the forms of licences for the manufacture for sale of
1
[Ayurvedic, Siddha or Unani] drugs,
2
[and for
sale of processed Ayurvedic, Siddha or Unani drugs,] the form of application for such licences, the conditions
subject to which such licences may be issued, the authority empowered to issue the same and the fees payable
therefor;
2
[and provide for the cancellation or suspension of such licences in any case where any provision of this
Chapter or rules made thereunder is contravened or any of the conditions subject to which they are issued is not
complied with];
3
[(f) prescribe the conditions to be observed in the packing of Ayurvedic, Siddha and Unani drugs including the
use of packing material which comes into direct contact with the drugs, regulate the mode of labelling packed drugs
and prescribe the matters which shall or shall not be included in such labels;]
(g) prescribe the conditions subject to which small quantities of
1
[Ayurvedic, Siddha or Unani] drugs may be
manufactured for the purpose of examination, test or analysis;
2
[(gg) prescribe under clause (d) of section 33EE the colour or colours which an Ayurvedic, Siddha or Unani
drug may bear or contain for purposes of colouring;
(gga) prescribe the standards for Ayurvedic, Siddha or Unani drugs under section 33EEB
7
[***];]
8
[(ggb) prescribe the records, registers or other documents to be kept and maintained under section 33 KB; and]
(h) any other matter which is to be or may be prescribed under this Chapter.
33-O. Power to amend First Schedule.—The Central Government, after consultation with the Board and after
giving, by notification in the Official Gazette, not less than three months‘ notice of its intention so to do, may, by a like
notification, add to or otherwise amend the First Schedule for the purposes of this Chapter and thereupon the said
Schedule shall be deemed to be amended accordingly.]
4
[CHAPTER V
M
ISCELLANEOUS
5
[
6
[33P.] Power to give directions.—The Central Government may give such directions to any State Government
as may appear to the Central Government to be necessary for carrying into execution in the State any of the provisions of
this Act or of any rule or order made thereunder.]
34. Offences by companies.—(1) Where an offence under this Act has been committed by a company, every
person who at the time the offence was committed, was in charge of, and was responsible to the company for the conduct
of the business of the company, as well as the company shall be deemed to be guilty of the offence and shall be liable to
be proceeded against and punished accordingly:
Provided that nothing contained in this sub-section shall render any such person liable to any punishment provided
in this Act if he proves that the offence was committed without his knowledge or that he exercised all due diligence to
prevent the commission of such offence.
(2) Notwithstanding anything contained in sub-section (1), where an offence under this Act has been committed by
a company and it is proved that the offence has been committed with the consent or connivance of, or is attributable to
any neglect on the part of, any director, manager, secretary or other officer of the company, such director, manager,
secretary or other officer shall also be deemed to be guilty of that offence and shall be liable to be proceeded against and
punished accordingly:
1. Subs. by Act 68 of 1982, s. 2, for certain words (w.e.f. 1-2-1983).
2. Ins. by Act 68 of 1982, s. 35, (w.e.f. 1-2-1968).
3. Subs. by Act 68 of 1982, s. 35, for cl. (f) (w.e.f. 1-2-1968).
4. Subs. by Act 11 of 1955, s. 16, for Chapter V.
5
..
Ins. by Act 35 of 1960, s. 11 (w.e.f. 16-3-1961).
6. S. 33A re-numbered as s. 33P by Act 13 of 1964, s. 27 (w.e.f. 15-9-1964).
7. The word ―and‖ omitted by Act 26 of 2008, sec.18(i) (w.e.f. 10.08.2009)
8. Sub. by Act 26 of 2008, s. 18(ii) (w.e.f. 10.08.2009)
Drugs and Cosmetics Act, 1940
33
Explanation.—For the purposes of this section—
(a) ―company‖ means a body corporate, and includes a firm or other association of individuals; and
(b) ―director‖ in relation to a firm means a partner in the firm.
1
[34A. Offences by Government Departments.—Where an offence under Chapter 1V or Chapter 1VA has been committed
by any department of Government, such authority as is specified by the Central Government to be in charge of manufacture, sale or
distribution of drugs or where no authority is specified, the head of the department, shall be deemed to be guilty of the offence and
shall be liable to be proceeded against and punished accordingly:
Provided that nothing contained in this section shall render any such authority or person liable to any punishment provided in
Chapter 1V or Chapter 1VA, as the case may be, if such authority or person proves that the offence was committed without its or his
knowledge or that such authority or person exercised all due diligence to prevent the commission of such offence.]
2
[34AA. Penalty for vexatious search or seizure.—Any Inspector exercising powers under this Act or the rules
made thereunder, who,—
(a) without reasonable ground of suspicion searches any place, vehicle, vessel or other conveyance; or
(b) vexatiously and unnecessarily searches any person; or
(c) vexatiously and unnecessarily seizes any drug or cosmetic, or any substance or article, or any record,
register, document or other material object; or
(d) commits, as such Inspector, any other act, to the injury of any person without having reason to believe that
such act is required for the execution of his duty,
shall be punishable with fine which may extend to one thousand rupees.]
35. Publication of sentences passed under this Act.— (1) If any person is convicted of an offence under this Act,
3
[the Court
before which the conviction takes place shall, on application made to it by the Inspector, cause] the offender‘s name, place of
residence, the offence of which he has been convicted and the penalty which has been inflicted upon him, to be published at the
expense of such person in such newspapers or in such other manner as the Court may direct.
(2) The expenses of such publication shall be deemed to form part of the cost relating to the conviction and shall be recoverable
in the same manner as those costs are recoverable.
36. Magistrate‘s power to impose enhanced penalties.—Notwithstanding anything contained in
4
[***]
5
[the Code of
Criminal Procedure, 1973 (2 of 1974)] it shall be lawful for
6
[any Metropolitan Magistrate or any Judicial Magistrate of the first class]
to pass any sentence authorised by this Act in excess of his powers under
4
[* * *] the said Code.
7
[36A. Certain offences to be tried summarily.—Notwithstanding anything contained in the Code of Criminal
Procedure, 1973 (2 of 1974),
8
[all offences except the offences triable by the Special Court under Section 36-AB or Court
of Sessions under this Act,] punishable with imprisonment for a term not exceeding three years, other than an offence
under clause (b) of sub-section (1) of section 33-I, shall be tried in a summary way by a Judicial Magistrate of the first
class specially empowered in this behalf by the State Government or by a Metropolitan Magistrate and the provisions of
sections 262 to 265 (both inclusive) of the said Code shall, as far as may be, apply to such trial:
Provided that, in the case of any conviction in a summary trial under this section, it shall be lawful for the
Magistrate to pass a sentence of imprisonment for a term not exceeding one year:
Provided further that when at the commencement of, or in the course of, a summary trial under this section it
appears to the Magistrate that the nature of the case is such that a sentence of imprisonment for a term exceeding one
year may have to be passed or that it is, for any other reason, undesirable to try the case summarily, the Magistrate shall,
after hearing the parties, record an order to that effect and thereafter recall any witness who has been examined and
proceed to hear or rehear the case in the manner provided by the said Code.]
1. Ins. by Act 13 of 1964, s. 28 (w.e.f. 15-9-1964).
2. Ins. by Act 68 of 1982, s. 36 (w.e.f. 1-2-1983).
3. Subs. by Act 68 of 1982, s. 37, for certain words (w.e.f. 1-2-1983).
4. The words and figures ―section 32 of‖ omitted by Act 13 of 1964, s. 29 (w.e.f.15-9-1964).
5. Subs. by Act 68 of 1982, s. 38, for ―the Code of Criminal Procedure, 1898‖ (w.e.f. 1-2-1983).
6. Subs. by Act 68 of 1982, s. 38, for certain words (w.e.f. 1-2-1983).
7. Ins. by Act 68 of 1982, s. 38, (w.e.f. 1-2-1983).
8. Sub. by Act 26 of 2008, s. 19 for all offences (w.e.f. 10.08.2009)
Drugs and Cosmetics Act, 1940
34
3
[36-AB. Special Courts. – (1) The Central Government, or the State Government, in consultation with the Chief
Justice of the High Court, shall, for trial of offences relating to adulterated drugs or spurious drugs punishable under
clause (a) and (b) of Section 13, sub-section (3) of Section 22, clause (a) and (c) of Section 27, Section 28, Section 28-A,
Section 28-B and clause (b) of sub-section (1) of Section 30 and other offences relating to adulterated drugs or spurious
drugs, by notification, designate one or more Courts of Sessions as a Special Court or Special Courts for such area or for
such case or class or group of cases as may be specified in the notification.
Explanation.- In this sub-section, ―High Court‖ means the High Court of the State in which a Court of Sessions
designated as Special Court was functioning immediately before such designation.
(2) While trying an offence under this Act, a Special Court shall also try an offence, other than an offence referred
to in sub-section (1), with which the accused may, under the Code of Criminal Procedure, 1973 (2 of 1974), be charged at
the same trial.]
3
[36-AC. Offences to be cognizable and non-bailable in certain cases. –
(1) Notwithstanding anything contained in the Code of Criminal Procedure, 1973 (2 of 1974)-
(a) every offence, relating to adulterated or spurious drug and punishable under clause (a) and (c) of sub-
section (1) Section 13, clause (a) of sub-section (2) of Section 13, subsection (3) of Section 22, clause (a) and
(c) of Section 27, Section 28, Section 28A, 40 Section 28B and sub-section (1) and (2) of Section 30 and
other offences relating to adulterated drugs or spurious drugs, shall be cognizable.
(b) no person accused, of an offence punishable under clause (a) and (c) of sub-section (1) of Section 13,
clause (a) of sub-section (2) of Section 13, sub-section (3) of Section 22, clause (a) and (c) of Section 27,
Section 28, Section 28A, Section 28B and subsection (1) and (2) of Section 30 and other offences relating to
adulterated drugs or spurious drugs, shall be released on bail or on his own bond unless-
(i) the Public Prosecutor has been given an opportunity to oppose the application for such release; and
(ii) where the Public Prosecutor opposes the application, the court is satisfied that there are reasonable
grounds for believing that he is not guilty of such offence and that he is not likely to commit any
offence while on bail:
Provided that a person, who, is under the age of sixteen years,or is a woman or is sick or infirm, may be released
on bail, if the Special Court so directs.
(2) The limitation on granting of bail specified in clause (b) of sub-section (1) is in addition to the limitations under
the Code of Criminal Procedure, 1973 (2 of 1974) or any other law for the time being in force on granting bail.
(3) Nothing contained in this section shall be deemed to affect the Special powers of the High Court regarding bail
under Section 439 of the Code of Criminal Procedure, 1973 (2 of 1974) and the High Court may exercise such powers
including the power under clause (b) of sub-section (1) of that section as if the reference to ―Magistrate‖ in that section
includes also a reference to ―Special Court‖ designated under Section 36AB.]
3
[36-AD. Application Code of Criminal Procedure, 1973 to proceedings before Special Courts. – (1) Save as
otherwise provided in this Act, the provisions of the Code of Criminal Procedure, 1973 (2 of 1974) (including the
provisions as to bails and bonds), shall apply to the proceedings before a Special Courts and for the purpose of said
provisions, the Special Court shall be deemed to be a Court of Sessions and the person conducting the prosecution before
the Special Court, shall be deemed to be a Public Prosecutor:
Provided that the Central Government or the State Government may also appoint, for any case or cases or group of
cases, a Special Public Prosecutor.
(2) A person shall not be qualified to be appointed as Public Prosecutor or a Special Public Prosecutor under this
section unless he has been in practice as an advocate for not less than seven years, under the Union or a State, requiring
special knowledge of law.
(3) Every person appointed as a Public Prosecutor or a Special Public Prosecutor under this section shall be
deemed to be a Public Prosecutor within the meaning of clause (u) of 41 Section 2 of the Code of Criminal Procedure,
1973 (2 of 1974) and the provisions of that Code shall have effect accordingly.]
3
[36AE. Appeal and revision.- The High Court may exercise, so far as may be applicable, all the powers
conferred by Chapter XXIX or Chapter XXX of the Code of Criminal Procedure, 1973(2 of 1974), on a High Court, as if
a Special Court within the local limits of the jurisdiction of the High Court were a Court of Session trying cases within
the local limits of the jurisdiction of the High Court.]
37. Protection of action taken in good faith.—No suit, prosecution or other legal proceeding shall lie against any
person for anything which is in good faith done or intended to be done under this Act.
1
[38. Rules to be laid before Parliament.— Every rule made under this Act shall be laid as soon as may be after
it is made before each House of Parliament while it is in session for a total period of thirty days which may be comprised
in one session or in two or more successive sessions,
2
[and if, before the expiry of the session immediately following the
session or the successive sessions aforesaid], both Houses agree in making any modification in the rule or both Houses
agree that the rule should not be made, the rule shall thereafter have effect only in such modified from or be of no effect,
as the case may be; so however that any such modification or annulment shall be without prejudice to the validity of
anything previously done under that rule.]
1. Ins. by Act 13 of 1964, s. 30 (w.e.f. 15-9-1964).
2. Subs. by Act 68 of 1982, s. 40, for certain words (w.e.f. 1-2-1983).
3. Ins. by Act 26 of 2008, s. 20 (w.e.f. 10.08.2009)
Drugs and Cosmetics Act, 1940
35
1
[THE FIRST SCHEDULE
[See section 3(a)]
2
[A.—AYURVEDIC AND SIDDHA
SYSTEMS]
Serial No. Name of book
Ayurveda
1. Arogya Kalpadruma
2. Arka Prakasha
3. Arya Bhishak
4. Ashtanga Hridaya
5. Ashtanga Samgraha
6. Ayurveda Kalpadruma
7. Ayurveda Prakasha
8. Ayurveda Samgraha
9. Bhaishajya Ratnavali
10. Brihat Bhaishajya Ratnakara
11. Bhava Prakasha
12. Brihat Nighantu Ratnakara
13. Charaka Samihita
14. Chakra Datta
15. Gada Nigraha
16. Kupi Pakva Rasayana
17. Nighantu Ratnakara
18. Rasa Chandanshu
19. Rasa Raja Sundara
20. Rasaratna Samuchaya
21.
3
[Rasatantra Sara Va Siddha Prayoga Sangraha—Part 1]
4
[21 (a) Rasatantra Sara Va Siddha Prayoga Sangraha—Part II (Edition 2006)]
22. Rasa Tarangini
23. Rasa Yoga Sagara
24. Rasa Yoga Ratnakara
25. Rasa Yoga Samgraha
26. Rasendra Sara Samgraha
27. Rasa Pradipika
28. Sahasrayoga
29. Sarvaroga Chikitsa Ratnam
30. Sarvayoga Chikitsa Ratnam
31. Sharangadhara Samhita
32. Siddha Bhaishajya Manimala
33. Siddha Yoga Samgraha
34. Sushruta Samhita
35. Vaidya Chintamani
36. Vaidyaka Shabda Sindu
37. Vaidyaka Chikitsa Sara
38. Vidya Jiwan
39. Vasava Rajeeyam
40. Yoga Ratnakara
41. Yoga Tarangini
42. Yoga Chintamani
43. Kashyapasamhita
44. Bhelasamhita
45. Vishwanathachikitsa
46. Vrindachikitsa
1. Subs. by Act 13 of 1964, s. 31, for the Sch. The First Schedule came into force with effect from 1-2-1969 and the Second Schedule came into force
with effect from the 15
th
September, 1964.
2. Subs. by Act 68 of 1982, s. 41 (w.e.f. 1-2-1983).
3. Subs. by Notification No. G.S R. 658 (E), dated 31-08-1994.
4. Added by G.S R. 337 (E), dated 15-04-2010 (w.e.f. 20.4.2010).
Drugs and Cosmetics Act, 1940
36
Serial No. Name of book
47. Ayurvedachintamani
48. Abhinavachintamani
49. Ayurveda-Ratnakara
50. Yogaratnasangraha
51. Rasamrita
52. Dravyagunanighantu
53. Rasamanjari
54. Bangasena
1
[54A
6
[Ayurvedic Formulary of India and its Parts)
54B Ayurveda Sara Samgraha]
2
[54C Ayurvedic Pharmacopoeia of India.]
5
[54D. Ayurvedic Pharmacopoeia of India and its Parts.]
Siddha
55 Siddha Vaidya Thirattu
56 Therayar Maha Karisal
57 Brahma Muni Karukkadai (300)
58 Bhogar (700)
59 Pulippani (500)
60 Agasthiyar Paripuranam (400)
61 Therayar Yamagam
62 Agasthiyar Chenduram (300)
63 Agasthiyar (1500)
64 Athmarakshamrutham
65 Agasthiyar Pin (80)
66 Agasthiyar Rathna Churukkam
67 Therayar Karisal (300)
68 Veeramamuni Nasa Kandam
69 Agasthiyar (600)
70 Agasthiyar Kanma Soothiram
71 18 Siddar‘s Chillarai Kovai
72 Yog Vatha Kaviyam
73 Therayar Tharu
74 Agasthiyar Vaidya Kaviyam (1500)
75 Bala Vagadam
76 Chimittu Rathna (Rathna) Churukkam
77 Nagamuni (200)
78 Agasthiyar Chillarai Kovai
79 Chikicha Rathna Deepam
80 Agasthiyar Nayana Vidhi
81 Yugi Karisal (151)
82 Agasthiyar Vallathi (600)
83 Therayar Thaila Varkam
31
[84 Siddha Formulary of India (Part I)]
5
[85 Siddha Formulary of India and its Parts]
4
[B.—UNANI TIBB SYSTEM]
Serial No. Name of book
1 Karabadin Qadri
2 Karabadin Kabir
3 Karabadin Azam
4 Ilaj-ul-Amraz
5 Al Karabadin
6 Biaz Kabir Vol. II
7 Karabadin Jadid
8 Kitab-ul-Taklis
9 Sanat-ul-Taklis
10 Mifta-ul-Khazain
11 Madan-ul-Aksir
12 Makhzan-ul-murabhat
1
[13 National Formulary of Unani Medicine
7
[****]]
8
[14 Unani Pharmacopoeia of India]
1. Ins. by Notifn. No. G.S.R. 735 (E), dated the 28th August, 1987. 6. Subs. by G.S R. 337 (E), dated 15-04-2010 (w.e.f. 20.4.2010).
2. Ins. by Notifn. No. G.S.R. 423 (E), dated the 11th June, 2002. 7. Omitted by GSR 780(E), dt 25-11-2004.
3. Ins. by Notifn. No. G.S.R. 735 (E), dated the 28th August, 1987. 8. Ins by GSR 780 (E), dt. 25.11.20114.
4. Subs. by Act 68 of 1982, s. 41 (w.e.f. 1-2-1983).
5. Ins. by G.S R. 337 (E), dated 15-04-2010 (w.e.f. 20.4.2010).
Drugs and Cosmetics Act, 1940
37
4
[THE SECOND SCHEDULE
(See sections 8 and 16)
STANDARDS TO BE COMPLIED WITH BY IMPORTED DRUGS AND BY DRUGS MANUFACTURED FOR SALE,
SOLD,
STOCKED OR EXHIBITED FOR SALE OR
DISTRIBUTED
Class of drug Standard to be complied with
1 2
1. Patent or proprietary medicines
1
[other than
Homoeopathic medicines]
2.
2
[Substances commonly known as vaccines, sera
toxins, toxoids, antitoxins and antigens and
biological products of like nature, for human use or
for veterinary use.
3[* * * *]
4. Substances (other than food) intended to affect the
structure or any function of the human body or
intended to be used for the destruction of vermin or
insects which cause disease in human beings or
animals.
5
[
1
[4-A. Homoeopathic Medicines.
(a) Drugs included in the Homoeopathic
Pharmacopoeia of India.
(b) Drugs not included in the Homoeopathic
Pharmacopoeia of India but which are
included in the Homoeopathic
Pharmacopoeia of United States of
America or the United kingdom or the
German Homoeopathic Pharmacopoeia.
(c) Drugs not included in the Homoeopathic
Pharmacopoeia of India or the United
States of America, or the United
Kingdom or the German Homoeopathic
Pharmacopoeia.
The formula of list of ingredients displayed in the
prescribed manner on the label of the container and
such other standards as may be prescribed.
The standards maintained at the International
Laboratory for Biological Standards, Stantans Serum
Institute, Copenhagen and at the Central Veterinary
Laboratory, Weybridge Surrey, U.K., and such other
laboratories recognized by the World Health
Organization from time to time, and such further
standards of strength, quality and purity, as may be
prescribed.]
Such standards as may be prescribed.
Standards of identity, purity and strength specified in
the edition of the Homoeopathic Pharmacopoeia of
India for the time being and such other standards as
may be prescribed.
Standards of identity, purity and strength prescribed
for the drugs in the edition of such Pharmacopoeia
for the time being in which they are given and such
other standards as may be prescribed.
The formula or list of ingredients displayed in the
prescribed manner on the label of the containder and
such other standards as may be prescribed by the
Central Government].]
1. Ins. by Notifn. No. S.O. 887, dated the 19th March 1966, Gazette of India , Pt. II, Sec. 3 (ii), p. 819.
2. Subs. by Notifn. No. G.S.R. 299(E), dated the 23rd April 1984.
3. Entry 3 omitted by Notifn. No. G.S.R. 299(E), dated the 23rd April, 1984.
4. Subs. by Act 13 of 1964, S. 31, for the Schedule.
5. Subs. by G.S.R. 820 (E), dt. 6-6-1978, for item 4A, earlier Ins. by Notifn. No. S.O. 887, dated the 19th March 1966, Gazette of India , Pt.
II, Sec. 3 (ii), p. 819.
Drugs and Cosmetics Act, 1940
38
Class of drug Standard to be complied with
1 2
1
[5. Other drugs:
(a) Drugs included in the Indian Pharmacopoeia
(b) Drugs not included in the Indian
Pharmacopoeia but which are included in the
official Pharmacopoeia of any other country.
Standards of identity, purity and strength specified
in the edition of the Indian Pharmacopoeia for the
time being in force and such other standards as may
be prescribed.
In case the standards of identity, purity and strength
for drugs are not specified in the edition of the
Indian Pharmacopoeia for the time being in force
but are specified in the edition of the Indian
pharmacopoeia immediately preceding, the
standards of identity, purity and strength shall be
those occurring in such immediately preceding
edition of the Indian Pharmacopoeia and such other
standards as may be prescribed.
Standards of identity, purity and strength specified
for drugs in the edition of such official
Pharmacopoeia of any other country for the time
being in force and such other standards as may be
prescribed.
In case the standards of identity, purity and strength
for drugs are not specified in the edition of such
official Pharmacopoeia for the time being in force,
but are specified in the edition immediately
preceding, the standards of identity, purity and
strength shall be those occurring in such
immediately preceding of such official
Pharmacopoeia and such other standards as may be
prescribed.]]
1. Subs. by Notifn. No. G.S.R. 885, dated the 4
th
August, 1973, Gazette of India, Pt. II, s. 3(i), p. 1643, for item 5.
Drugs and Cosmetics Rules, 1945
39
[21st December
1945]
Notificaiton: No. F. 28-10/45-H (1).
_
In exercise of the powers conferred by
1
[sections 6(2),
12, 33 and 33N] of the Drugs and Cosmetics Act, 1940 (XXIII of 1940), the
Central
Government is pleased to make the following Rules:-
PART I
PRELIMINARY
1. Short title, extent and commencement.
Drugs
9
[and Cosmetics] Rules, 1945.
(2) They extend to the whole of India.
2
[***]
(1) These Rules may be called the
10
[***]
2. Definitions.
context
In these Rules, unless there is anything repugnant in the subject or
(a) ―the Act‖ means the Drugs and Cosmetics Act, 1940 (XXIII of 1940) as
amended from time to time;
3
[(b) ―Central Licence Approving Authority‖ means the Drugs Controller,
India, or the Joint Drugs Controller (India) or the Deputy Drugs Controller (India)
appointed by the Central Government;]
(c) ―Director‖ means the Director of the Central Drugs Laboratory;
(d) ―Form‖ means a form set forth in Schedule A;
4
[(dd) Homoeopathic medicines include any drug which is recorded in
Homoeopathic provings or therapeutic efficacy of which has been established
through long clinical experience as recorded in authoritative Homoeopathic
literature of India and abroad and which is prepared according to the techniques
of Homoeopathic pharmacy and covers combination of ingredients of such
Homoeopathic medicines but does not include a medicine which is
administered by parenteral route;]
(e) ―Laboratory‖ means the Central Drugs Laboratory;
5
[(ea) ―registered Homoeopathic medical practitioner‖ means a person who
is registered in the Central Register or State Register of Homoeopathy;]
8
[(eb)―Phytopharmaceutical drug‖ includes purified and standardised fraction
with defined minimum four bio-active or phyto-chemical compounds
(qualitatively and quantitatively assessed) of an extract of a medicinal plant or
its part, for internal or external use of human beings or animals for diagnosis,
treatment, mitigation or prevention of any disease or disorder but does not
include administration by parenteral route.]
6
[(ee) ―Registered medical practitioner‖ means a person
(i) holding a qualification granted by an authority specified or notified
under section 3 of the Indian Medical Degrees Act, 1916 (7 of 1916), or
specified in the Schedules to the Indian Medical Council Act, 1956 (102 of
1956); or
(ii) registered or eligible for registration in a medical register of a
State meant for the registration of persons practising the modern scientific
system of medicine
7
[excluding the Homoeopathic system of medicine]; or
1. Subs. by G.S.R. 370(E), dt. 7-4-1994. 2. Omitted by G.S.R. 358, dt. 15-3-1975.
3. Sub. by GSR. 579(E), dt. 20-9-2006, earlier Ins. by G.S.R. 923(E), dt. 14-12-1992.
4. Ins. by Notfn. No. F. 1-59 / 68-D, dt. 19-11-1969.
5. Ins. by G.S.R 680 (E), dt. 5-12-1980. 6. Ins. by Notfn. F. 1-22 / 59-D, dt. 9-4-1960.
7. Ins. by S.O. 2139, dt. 15-6-1972. 8.
Ins. By G.S.R 918(E), dt. 30-11-2015.
9. Ins. by GSR 1183(E), dt 17-8-1964. 10. Sub-rule (3) omitted by GSR 19, dt. 15-12-1977.
Drugs and Cosmetics Rules 1945
40
(iii) registered in a medical register,
1
[other than a register for the
registration of Homoeopathic practitioner], of a State, who although not falling
within sub-clause (i) or sub-clause (ii) is declared by a general or special order
made by the State Government in this behalf as a person practising the modern
scientific system of medicine for the purposes of this Act; or
(iv) registered or eligible for registration in the register of dentists for a
State under the Dentists Act, 1948 (16 of 1948); or
(v) who is engaged in the practice of veterinary medicine and who
possesses qualifications approved by the State Government;]
2
[(f) ―retail sale‖ means a sale
3
[whether to a hospital, or dispensary, or a
medical, educational or research institute or to any other person] other than a
sale by way of wholesale dealing];
4
[(g) ―sale by way of wholesale dealing‖ means sale to a person for the
purpose of selling again and includes sale to a hospital, dispensary, medical,
educational or research institution;]
5
[(h) ―Schedule‖ means a Schedule to these Rules;]
6
[(i) State Government in relation to a Union Territory means the
Administrator thereof;
9
[***]
PART
II
3. Functions.
THE CENTRAL DRUGS LABORATORY
It shall be the function of the Laboratory
(i) to analyse or test such samples of drugs as may be sent to it under sub-
section (2) of section 11, or under sub-section (4) of section 25 of the Act;
7
[* * * * *]
(iii) to carry out such other duties as may be entrusted to it by the Central
Government or, with the permission of the Central Government, by a State
Government after consultation with the Drugs Technical Advisory Board.
8
[3A. (1)The functions of the Laboratory in respect of the following drugs or
classes of drugs shall be carried out at the Central Research Institute, Kasauli, and the
functions of the Director in respect of the said drugs or classes of drugs shall be
exercised by the Director of the said Institute :
(1) Sera.
(2) Solution of serum proteins intended for injection.
(3)
Vaccines.
(4) Toxins.
(5) Antigens.
1. Ins. by S.O. 2139, dt. 5-6-1972.
2 Subs. by Notfn. No. F. 1-3/51-DS., dt. 15-11-1954.
3. Ins. by G.S.R 681 (E), dt. 6-6-1988.
4. Subs. by Notfn. F-1-16/57, dt. 15.6.1957.
5. Subs. by Notfn. No. F. 28-10/45-H (1), dt. 31-3-1957.
6. Subs. by Notfn. No. F-1-16/57-D, dt. 15-6-1957.
7. Cl. (ii) omitted, by Notfn. No. F-1-16/57-D, dt. 15-6-1957.
8 Ins. by Notfn. No. F. 4-1 / 60-D, dt. 15-5-1961.
9. Cl. (j) omitted by GSR 592(E), dt. 13-08-2008
Drugs and Cosmetics Rules 1945
41
(6) Anti-toxins.
(7) Sterilized surgical ligature and sterilised surgical suture.
(8) Bacteriophages:
1
[Provided that the functions of the Director in respect of Oral Polio Vaccine shall
be exercised by the Deputy Director and Head of the Polio Vaccine Testing
Laboratory in case of Central Research Institute, Kasauli only.]
2
[(1A) The functions of the Laboratory in respect of Oral Polio Vaccine shall be
carried out by the following Institutes and the functions of the Director in respect of
the said drugs shall be exercised by the Director of the respective Institutes :-
(a) Pasteur Institute of India, Coonoor.
(b) Enterovirus Research Centre (Indian Council of Medical Research),
Haffkin Institute Compound, Parel, Bombay-400012.]
3
[(c) The National Institute of Biologicals, NOIDA.]
4
[(2) The functions of the Laboratory in respect of the following drugs or classes of
drugs shall be carried out at the Indian Veterinary Research Institute, Izatnagar or
Mukteshwar and the functions of the Director in respect of the said drugs or classes of
drugs shall be exercised by the Director of either of the said institutes.
(1) Anti-sera for veterinary use.
(2) Vaccines for veterinary use.
(3) Toxoids for veterinary use.
(4) Diagnostic Antigens for veterinary use.]
5
[(3) The functions of the laboratory in respect of testing of condoms shall be
carried out at the Central Drugs Testing Laboratory, Chennai, and the functions of
the Director in respect of the said products shall be exercised by the Director of the
said Laboratory.]
6
[(4)] The functions of the Laboratory in respect of the following drug shall be
carried out at the Laboratory of the Serologist and Chemical Examiner to the
Government of India, Calcutta and the functions of the Director in respect of the said
drug shall be performed by the Serologist and Chemical Examiner of the said
Laboratory :
VDRL
Antigen.
7
[(5) The function of the Laboratory in respect of Intra-Utrine Devices and Falope
Rings shall be carried out at the Central Drugs Testing Laboratory, Thane,
Maharashtra and the functions of the Director in respect of the said devices shall be
exercised by the Director of the said Laboratory.]
1. Subs. by G.S.R.445(E), dt. 30-4-1992. Earlier Ins. by G.S.R.62(E), dt. 15-2-1982.
2. Ins. by G.S.R. 445(E), dt. 30-4-1992.
3. Ins. by G.S.R.249(E), dt. 4-4-2002.
4. Ins. by Notfn. No. F.-1-6/62-D, dt. 2-7-1969.
5. Sub. By G.S.R. 651(E), dt. 9-9-2009, earlier Ins. by S. O. No. 2139, dt. 12-8-1972.
6. Sub-rule (4) omitted and sub-rule (5) renumbered as sub-rule (4) by Notfn. No. G.S.R. 62(E),
dt. 15-2-1982.
7. Subs. by G.S.R 242(E), dt. 18-3-1998. Earlier Ins. by G.S.R. No. 865 (E), dt. 25-10-1990.
Drugs and Cosmetics Rules 1945
42
1
[(6) The functions of the Laboratory in respect of human blood and human blood
products including components, to test for freedom of HIV antibodies, shall be
carried out by the following Institutes/Hospitals and the functions of the Director in
respect of the above mentioned products shall be exercised by the head of the
respective Institute, namely:-
(a) National Institute for Communicable Disease, Department of
Microbiology,
Delhi.
(b) National Institute of Virology, Pune
(c) Centre of Advanced Research in Virology, Christian Medical College,
Vellore.]
2
[(7) The functions of the Laboratory in respect of Homoeopathic medicines shall
be carried out at the Homoeopathy Pharmacopoeia Laboratory, Ghaziabad and the
functions of the Director in respect of the Homoeopathic medicines shall be exercised
by the Director of the laboratory.]
3
[(8) (a) The functions of the Laboratory in respect of the following kits or class of
drugs shall be carried out at the National Institute of Biologicals, Noida and the
functions of the Director in respect of the said drugs or class of drugs shall be
exercised by the Director of the said institute.
(b) The kits or class of drugs referred to in clause (a) are-
(1) Blood grouping reagents.
(2) Diagnostic kits for human immunodeficiency virus, Hepatitis B Surface Antigen
and Hepatitis C Virus.
(3) Blood products-
(a) Human Albumin;
(b) Human Normal Immunoglobulin (intramuscular and intravenous);
(c) Human Coagulation Factor VIII;
(d) Human Coagulation Factor IX;
(e) Plasma Protein Fractionation;
(f) Fibrin Sealant Kit;
(g) Anti Inhibitor Coagulation complex.
(4) Recombinant products such as-
(a) Recombinant insulin and insulin analogue;
(b) r-erythropoietin (EPO);
(c) r-Granulocyte Colony stimulating Factor (G-CSF).
(5) Biochemical kits-
(a) Glucose Test Strips;
(b) Fully Automated analyzer based glucose reagents.]
4. Despatch of samples for test or analysis.- (1) Samples for test or analysis under
sub-section (4) of section 25 of the Act shall be sent by registered post in a sealed
packet, enclosed, together with a memorandum in Form 1, in an outer cover
addressed to the Director.
(2) The packet as well as the outer cover, shall be marked with a distinguishing
number.
(3) A copy of the memorandum in Form 1 and a specimen impression of the seal used
to seal the packet shall be sent separately by registered post to the Director.
5. Recording of condition of seals.
On receipt of the packet, it shall be opened by
an officer authorised in writing in that
behalf by the Director who shall record the condition of the seal on the packet.
1. Ins. by G.S.R 16(E), dt. 10-1-1990. 2. Ins. by G.S.R 246(E), dt. 1-5-1991.
3. Sub. by G.S.R. No. 908(E), dt. 4-4-2014. Earlier Ins. by G.S.R. No. 249 (E), dt. 4-4-2002.
Drugs and Cosmetics Rules 1945
43
6. Report of result of test or analysis.
After
test or analysis the result of the test or
analysis, together with full protocols of the tests applied, shall be supplied forthwith
to the sender in Form 2.
7. Fees.
The fees for test and analysis shall be those specified in Schedule B.
8. Signature of certificates.
Certificates issued under these Rules by the
Laboratory shall be signed by the Director or by an officer authorised by the
Central
Government by Notification in the Official Gazette to sign such certificates.
1
[PART
III
[RULES 9 to 20- omitted by SRO. 2136 dated 15-06-1957]
PART
IV
2
[IMPORT AND REGISTRATION
]
21. In this Part.–
3
[(a) ―import licence‖ means either a licence in Form 10 to import drugs
4
[* *
*]; excluding those specified in Schedule X, or a licence in Form 10-A to
import drugs specified in Schedule X;]
(b) ―licensing authority‖ means the authority appointed by the Central
Government to perform the duties of the licensing authority under these Rules and
includes any person to whom the powers of a licensing authority may be
delegated under Rule 22;
(c) ―licence for examination, test or analysis‖ means a licence in Form 11 to
import small quantities of drugs the import of which is otherwise prohibited, for
the purpose of examination, test or analysis;
5
[(d) ―manufacturer‖ includes a manufacturer of drugs, who may be a
Company or a unit or a body corporate or any other establishment in a country
other than India, having its drugs manufacturing facilities duly approved by the
National Regulatory Authority of that country, and who also has a free sale
approval of the drugs approved by the said authority in the concerned country, and
/or in other major countries;
(e) ―Registration Certificate‖ means a certificate issued under Rule 27A by
the licensing authority in Form 41 for registration of the premises and the drugs
manufactured by the manufacturer meant for import into and use in India.]
22. The licensing authority may with the approval of the Central Government by an
order in writing delegate the
2
[power to sign licences and Registration Certificate and]
such other powers as may be specified in the order to any other person under his
control.
1. Part III (Rules 9 to 20) omitted by Notfn. No. F. 1-16/57-D (SRO 2136), dt. 15-6-1957.
2. Sub. by G.S.R 604 (E), dt. 24-8-2001.
3. Subs. by G.S.R 462 (E),dt. 22-6-1982.
4. Omitted by G.S.R 604 (E), dt. 24-8-2001.
5. Ins. by G.S.R 604 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
44
1
[23. Import licences.–An import licence in Form 10 shall be required for
2
[import
of drugs], excluding those specified in Schedule X, and an import licence in Form 10-
A shall be required for the import of drugs specified in Schedule X.]
2
[24. Form and manner of application for import licence.– (1) An application for
an import licence shall be made to the licensing authority in Form 8 for drugs
excluding those specified in Schedule X, and in Form 8A for drugs specified in
Schedule X, either by the manufacturer himself having a valid wholesale licence for
sale or distribution of drugs under these Rules, or by the manufacturer‘s agent in
India either having a valid licence under the Rules to manufacture for sale of a drug
or having a valid wholesale licence for sale or distribution of drugs under these Rules,
and shall be accompanied by a licence fee of one thousand rupees for a single drug
and an additional fee at the rate of one hundred rupees for each additional drug and by
an undertaking in Form 9 duly signed by or on behalf of the manufacturer:
Provided that in the case of any subsequent application made by the same importer
for import licence for drugs manufactured by the same manufacturer, the fee to
accompany each such application shall be one hundred rupees for each drug:
(2) Any application for import licence in Form 8 or Form 8-A, as the case may be,
shall be accompanied by a copy of Registration Certificate issued in Form 41 under
Rule 27A:
Provided that in case of emergencies the licensing authority may, with the
approval of the Central Government, issue an import licence in Form 10 or 10A, as
the case may be, without the issuance of Registration Certificate under Rule 27A, for
reasons to be recorded in writing.
3
[Provided further that Registration certificate shall not be required to be
accompanied with an application for an import licence under the Rules for the import
of in-vitro diagnostic kits and regents, except for the diagnostic kits notified from
time to time under sub-clause (iv) of clause (b) of section 3.]
(3) A fee of two hundred and fifty rupees shall be paid for a duplicate copy of the
licence issued under this Rule, if the original is defaced, damaged or lost.]
4
[24A. Form and manner of application for Registration Certificate.—(1) An
application for issue of a Registration Certificate shall be made to the licensing
authority in Form 40, either by the manufacturer himself, having a valid wholesale
licence for sale or distribution of drugs under these rules, or by his authorised agent
in India, either having a valid licence under the rules to manufacture for sale of a drug
or having a valid wholesale licence for sale or distribution of drugs under these rules,
and shall be accompanied by the fee specified in sub-rule (3) and the informations and
undertakings specified in Schedules D-I and D-II duly signed by or on behalf of the
manufacturer.
1. Subs. by G.S.R. 462 (E), dt. 22-6-1982.
2. Subs. by G.S.R 604 (E), dt. 24-8-2001.
3. Ins. by G.S.R. 35(E), dt. 20.1.2005.
4. Ins. by G.S.R 604 (E), dt. 24-08-2001.
Drugs and Cosmetics Rules 1945
45
(2) The authorisation by a manufacturer to his agent in India shall be documented
by a power of attorney executed and authenticated either in India before a First Class
Magistrate, or in the country of origin before such an equivalent authority, the
certificate of which is attested by the Indian Embassy of the said country, and the
original of the same shall be furnished along with the application for Registration
Certificate.
(3) (i) A fee of one thousand and five hundred US dollars
1
[or its equivalent in
Indian rupees] shall be paid along with the application in Form 40 as registration fee
for his premises meant for manufacturing of drugs intended for import into and use in
India
(ii) A fee of one thousand US dollars
1
[or its equivalent in Indian rupees] shall be
paid along with the application in Form 40 for the registration of a single drug meant
for import into and use in India and an additional fee at the rate of one thousand US
dollars for each additional drug:
Provided that in the case of any subsequent application for registration of
additional drugs by the same manufacturer, the fee to accompany shall be one
thousand US dollars
1
[or its equivalent in Indian rupees] for each drug.
(4) The fees shall be paid through a Challan in the Bank of Baroda, Kasturba
Gandhi Marg, New Delhi-110001 or any other branch or branches of Bank of Baroda,
or any other bank, as notified, from time to time, by the Central Government, to be
credited under the Head of Account ―0210-Medical and Public Health, 04-Public
Health, 104-Fees and Fines‖:
Provided that in the case of any direct payment of fees by a manufacturer in the
country of origin, the fees shall be paid through Electronic Clearance System (ECS)
from any bank in the country of origin to the Bank of Baroda, Kasturba Gandhi Marg,
New Delhi, through the Electronic Code of the bank in the Head of Account ―0210-
Medical and Public Health, 04- Public Health, 104-Fee and Fines‖, and the original
receipt of the said transfer shall be treated as an equivalent to the bank challan,
subject to the approval by the Bank of Baroda that they have received the payment.
(5) The applicant shall be liable for the payment of a fee of five thousand US
dollars
1
[or its equivalent in Indian rupees] for expenditure as may be required for
inspection or visit of the manufacturing premises or drugs, by the licensing authority
or by any other persons to whom powers have been delegated in this behalf by the
licensing authority under Rule 22.
(6) The applicant shall be liable for the payment of testing fees directly to a testing
laboratory approved by the Central Government in India or abroad, as may be
required for examination, tests and analysis of drug.
(7) A fee of three hundred US dollars
1
[or its equivalent in Indian rupees] shall be
paid for a duplicate copy of the Registration Certificate, if the original is defaced,
damaged or lost.
(8) No Registration Certificate shall be required under these Rules in respect of an
inactive bulk substance to be used for a drug formulation, with or without
pharmacopoeial conformity.]
1. Ins. by G.S.R. 35(E), dt. 20.1.2005.
Drugs and Cosmetics Rules 1945
46
25. Licences for import of drugs manufactured by one manufacturer.– (1) A single
application may be made, and a single licence may be issued, in respect of the import
of more than one drug or class of drugs manufactured by the same manufacturer:
1
[Provided that the drugs or classes of drugs are manufactured at one factory or
more than one factory functioning conjointly as a single manufacturing unit:
Provided further that if a single manufacturer has two or more factories situated in
different places manufacturing the same or different drugs a separate licence shall be
required in respect of the drugs manufactured by each such factory.]
2
[
* * * * *]
3
[25A. Condition to be satisfied before a licence in Form 10 or Form 10-A is
granted.
(1) A licence in Form 10 or in Form 10-A shall be granted by the licensing
authority having regard to–
(i) the premises, where the imported substances will be stocked, are
equipped with proper storage accommodation for preserving the properties of the
drugs to which the licence applies; and
(ii) the occupation, trade or business ordinarily carried out by the
applicant:
Provided that the licensing authority may refuse to grant a licence in Form 10-A
in respect of any applicant where he is satisfied,--
(a) that the applicant has not complied with the provisions of the Act or
these rules; or
(b) that by reasons of—
4
[(i) his conviction under the Act or these Rules or the Narcotic Drugs
and Psychotropic Substances Act, 1985 (61 of 1985) or the rules made
thereunder;]
(ii) previous suspension or cancellation of the licence granted to him;
he is not a fit person to whom licence shall be granted.
(2) Any person who is aggrieved by the order passed by the licensing authority
under this Rule may, within thirty days of the receipt of the order, appeal to the
Central Government and the Central Government may after such enquiry into the
matter as it considers necessary and after giving the appellant an opportunity for
making a representation in the matter, make such orders in relation thereto as it thinks
fit.]
1. Ins. by Notfn. No. F. 1-19/48-D, dt. 27-10-1949.
2. Omitted Notfn. No.F. 1-16/57-D, dt. 15-6-1957.
3. Subs. by G.S.R 462(E), dt. 22-6-1982. Earlier Ins. by Notfn. No. F. 1-9/52-D. dt. 3-11-1958.
4. Subs. by G.S.R 604 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
47
1
[25B. Registration Certificate for import of drugs manufactured by one
manufacturer.--(1) A single application may be made, and a single Registration
Certificate in Form 41 may be issued in respect of the import of more than one drug
or class of drugs, manufactured by the same manufacturer:
Provided that the drug or classes of drugs, are manufactured at one factory or
more than one factory functioning conjointly as a single manufacturing unit:
Provided further that if a single manufacturer has two or more factories situated in
different places manufacturing the same or different drugs, separate Registration
Certificates shall be required in respect of the drugs manufactured by each such
factory.]
26. Conditions of import licence.
following conditions:
An import licence shall be subject to the
(i) the manufacturer shall at all times observe the undertaking given by him
or on his behalf in Form 9;
(ii) the licensee shall allow any Inspector authorised by the licensing
authority in that behalf to enter with or without notice any premises where the
imported substance is stocked, to inspect the means, if any, employed for
testing the substance and to take samples;
(iii) the licensee shall on request furnish to the licensing authority from
every batch of each substance or from such batch or batches as the licensing
authority may from time to time specify a sample of such amount as the
licensing authority may consider adequate for any examination required to be
made, and the licensee shall, if so required, furnish full protocols of the tests, if
any, which have been applied;
(iv) if the licensing authority so directs the licensee shall not sell or offer
for sale any batch in respect of which a sample is or protocols are furnished
under the last preceding sub-rule until a certificate authorising the sale of the
batch has been issued to him by or on behalf of the licensing authority;
(v) the licensee shall, on being informed by the licensing authority that any
part of any batch of the substance has been found by the licensing authority not
to conform with the standards of strength, quality and purity prescribed by
Chapter III of the Act, or the rules thereunder and on being directed so to do,
withdraw the remainder of that batch from sale and, so far as may in the
particular circumstances of the case be practicable, recall the issues already
made from that batch;
(vi) the licensee shall maintain a record of all sales by him of substances for
the import of which a licence is required, showing particulars of the substance
and of the person to whom sold and such further particulars, if any, as the
licensing authority may specify and such record shall be open to the inspection of
any Inspector authorised in that behalf by the licensing authority:
1. Ins. by G.S.R. No. 604(E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
48
1
[Provided that in respect of the sale or distribution of drugs specified in Schedule
X, the licensee shall maintain a separate record or register showing the following
particulars, namely:
1. Name of the Drug,
2. Batch number,
3. Name and address of the manufacturer,
4. Date of transaction,
5. Opening stock on the business day,
6. Quantity of drug received, if any, and the source from which received,
7. Name of the purchaser, his address and licence number,
8. Balance quantity of drug at the end of the business day,
9. Signature of the person under whose supervision the drugs have been
supplied.]
(vii) the licensee shall comply with such further requirements, if any,
applicable to the holders of import licenses, as may be specified in any rules,
subsequently made under Chapter III of the Act and of which the licensing
authority has given to him not less than four months‘ notice.
27. Grant of import licence.
On receipt of an application for an import licence
in the form and manner prescribed in Rule 24, the licensing authority shall, on being
satisfied that, if granted, the conditions of the licence will be observed, issue an
import licence in Form 10
1
[or From 10A, as the case may be].
2
[27A Grant of Registration Certificate.
(1) On receipt of an application for
Registration Certificate in the Form and manner specified in Rule 24A, the licensing
authority shall, on being satisfied, that, if granted, the conditions of the Registration
Certificate will be observed, issue a Registration Certificate in Form 41:
Provided further that if the application is complete in all respects and
informations specified in Schedules D-I and D-II are in order, the licensing authority
shall, within nine months from the date of receipt of an application, issue such
Registration Certificate, and in exceptional circumstances and for reasons to be
recorded in writing, the Registration Certificate may be issued within such extended
period, not exceeding three months, as the licensing authority may deem fit.
(2) If the applicant does not receive the Registration Certificate within the period
as specified in the proviso to sub-rule (1), he may appeal to the Central Government
and the Central Government may after such enquiry into the matter, as it considers
necessary, may pass such orders in relation thereto as it thinks fit.]
1. Ins. by G.S.R 462 (E), dt. 22-6-1982.
2. Ins. by G.S.R 604 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
49
1
[
28. Duration of import licence.
A licence unless, it is sooner suspended or
cancelled, shall be
2
[valid for a period of three years from the date of its issue:]
Provided that if application for a fresh licence is made three months before the
expiry of the existing licence the current licence shall be deemed to continue in force
until orders are passed on the application.]
3
[28A. Duration of Registration Certificate.—- A Registration Certificate, unless,
it is sooner suspended or cancelled, shall be valid for a period of three years from the
date of its issue:
Provided that if the application for a fresh Registration Certificate is made nine
months before the expiry of the existing certificate, the current Registration
Certificate shall be deemed to continue in force until orders are passed on the
application.]
4
[29. Suspension and cancellation of import licence.
If the manufacturer or
licensee fails to comply with any of the conditions of an import licence, the licensing
authority may after giving the manufacturer or licensee an opportunity to show cause
why such an order should not be passed, by an order in writing stating the reasons
therefor, suspend or cancel it for such period as it thinks fit, either wholly or in
respect of some of the substances to which it relates:
Provided that a person, who is aggrieved by the order passed by the licensing
authority under this rule may, within thirty days of the receipt of the order, appeal to
the Central Government, and the Central Government may, after such enquiry into the
matter as it considers necessary and after giving the appellant an opportunity for
representing his views in the matter, pass such orders in relation thereto as it thinks
fit.]
3
[29A. Suspension and cancellation of Registration Certificate. —If the
manufacturer fails to comply with any of the conditions of the Registration
Certificate, the licensing authority may after giving him an opportunity to show cause
why such an order should not be passed, by an order in writing stating the reasons
therefor, suspend or cancel the Registration Certificate for such period as it thinks fit
either wholly or in respect of some of the substances to which it relates:
Provided that a person, who is aggrieved by the order passed by the licensing
authority under this rule may, within thirty days of the receipt of the order, appeal to
the Central Government, and the Central Government may, after such enquiry into the
matter as it considers necessary and after giving the appellant an opportunity for
representing his views in the matter, pass such orders in relation thereto as it thinks
fit.]
1. Amended by Notfn. No. F. 1-10/62-D, dt. 19-4-1964.
2. Subs. by G.S.R 604 (E), dt. 24-8-2001.
3. Ins. by G.S.R 604 (E), dt. 24-8-2001.
4. Subs. by G.S.R 604 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
50
30. Prohibition of import after expiry of potency. —No biological or other special
product specified in Schedule C or C (I) shall be imported after the date shown on the
label, wrapper or container of the drug as the date up to which the drug may be
expected to retain a potency not less than, or not to acquire a toxicity greater than,
that required, or as the case may be, permitted by the prescribed test.
1
[* * * * *]
2
[30AA. Import of new Homoeopathic medicine.—(1) No new Homoeopathic
medicine shall be imported except under and in accordance with the permission in
writing of the Licensing Authority.
(2) The importer of a New Homoeopathic medicine when applying for permission
shall produce before the Licensing Authority such documentary and other evidence as
may be required by the Licensing Authority for assessing the therapeutic efficacy of
the medicine including the minimum provings carried out with it.]
3
[Explanation. —For the purpose of this rule, ‗New Homoeopathic Medicine‘
means—
(i) a Homoeopathic medicine which is not specified in the Homoeopathic
Pharmacopoeia of India or United States of America or of the United Kingdom
or the German Homoeopathic Pharmacopoeia; or
(ii) which is not recognized in authoritative Homoeopathic literature as
efficacious under the conditions recommended; or
(iii) a combination of Homoeopathic medicines containing one or more
medicines which are not specified in any of the Pharmacopoeias referred to in
clause (i) as Homoeopathic medicines and also not recognized in authoritative
Homoeopathic literature as efficacious under the conditions recommended.]
4
[30B. Prohibition of import of certain drugs.
No drug, the manufacture, sale
or distribution of which is prohibited in the country of origin, shall be imported under
the same name or under any other name except for the purpose of examination, test or
analysis.]
5
[31. Standard for certain imported drugs.—No drug shall be imported unless it
complies with the standard of strength, quality and purity, if any, and the test
prescribed in the Rules shall be applicable for determining whether any such imported
drug complies with the said standard:
Provided that the drugs intended for veterinary use, the standards of strength,
quality and purity, if any, shall be those that are specified in Schedule F(1) and the
test prescribed in that Schedule shall be applicable for determining whether any such
imported drug complies with the said standards and where no standards are specified
in Schedule F(1) for any veterinary drug, the standards for such drug shall be those
specified in the current edition, for the time being in force, of the British
Pharmacopoeia Veterinary:
1. Rule 30A omitted by G.S.R.944 (E), dt. 21-9-1988. Earlier rules 30A and 30AA ins. by Notfn. F. 1-
30/48-G, Dt. 14.4.1952.
2. Ins. by notification No. F 1-30/48, dt. 14-01-1952.
3. Subs. G.S.R. 680 (E) ,dt. 5-12-1980.
4. Ins. by Notfn. No. F. 1-45 4-1-1951.
5. Subs. G.S.R. 604 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
51
Provided further that the licensing authority shall not allow the import of any drug
having less than sixty per cent residual shelf-life period as on the date of import:
Provided also that in exceptional cases the licensing authority may, for reasons to
be recorded in writing, may allow, the import of any drug having lesser shelf-life
period, but before the date of expiry as declared on the container of the drug.]
1
[32. Packing and labelling of imported drugs.
No drug shall be imported unless
it is packed and labelled in conformity with the Rules in Parts IX and X
2
[
* * *] and
further conform to the standards laid down in Part XII provided that in the case of
drugs intended for veterinary use, the packing and labelling shall conform to the rules
in Parts IX and X and Schedule F(1)].
3
[32A Packing and Labelling of Homoeopathic medicine.
No Homoeopathic
medicine shall be imported unless it is packed and labelled in conformity with the
rules in Part IX-A.]
33. Import of drugs for examination, test or analysis
Small quantities of drugs
the import of which is otherwise prohibited under section 10 of the Act may be
imported for the purpose of examination, test or analysis subject to the following
conditions:
(a) No drug shall be imported for such purpose except under a licence in
Form 11;
(b) the licensee shall use the substances imported under the licence
exclusively for purposes of examination, test or analysis and shall carry on such
examination, test or analysis in the place specified in the licence, or in such other
places as the licensing authority may from time to time authorise;
(c) the licensee shall allow any Inspector authorized by the licensing authority
in this behalf to enter, with or without prior notice, the premises where the substances
are kept, and to inspect the premises, and investigate the manner in which the
substances are being used and to take samples thereof;
(d) the licensee shall keep a record of, and shall report to the licensing
authority, the substances imported under the licence, together with the quantities
imported, the date of importation and the name of the manufacturer;
(e) the licensee shall comply with such further requirements, if any, applicable
to the holders of licences for examination, test or analysis as may be specified in
any rules subsequently made under Chapter III of the Act and of which the
licensing authority has given to him not less than one month‘s notice.
1. Subs. by Notfn. No. F. 1-6/62-D (SO 2889), dt. 2-7-1969.
2. Certain words omitted by G.S.R. 661(E), dt. 3-7-1992.
3. Ins. by S. O. No. 2139, dt. 5-6-1972.
Drugs and Cosmetics Rules 1945
52
1
[33A Import of drugs by a Government Hospital or Autonomous Medical
Institution for the treatment of patients.—Small quantities of new drug, as defined in
Rule 122-E, the import of which is otherwise prohibited under section 10 of the Act,
may be imported for treatment of patients suffering from life threatening diseases, or
diseases causing serious permanent disability, or such disease requiring therapies for
unmet medical needs, by a Medical Officer of a Government Hospital or an
Autonomous Medical Institution providing tertiary care, duly certified by the Medical
Superintendent of the Government Hospital, or Head of the Autonomous Medical
Institution, subject to the following conditions, namely:-
(a) no new drug shall be imported for the said purpose except under a licence
in Form 11-A, and the said drug has been approved for marketing in the country
of origin;
(b) the licensee shall use the substances or drugs imported under the licence
exclusively for the purpose of treatment of patients suffering from life threatening
diseases, or diseases causing serious permanent disability, or such diseases
requiring therapies for unmet medical needs, under the supervision of its own
Medical Officers at the place, specified in the licence or at such other places, as
the licensing authority, may from time to time authorise;
(c) the licensee shall allow an Inspector authorised by the licensing authority
in this behalf to enter, with or without prior notice, the premises where the
substances or drugs are stocked, and to inspect the premises and relevant records
and investigate the manner in which the substances or drugs are being used and
to take, if necessary, samples thereof ;
(d) the licensee shall keep a record of, and shall submit the said report half
yearly to the licensing authority, the substances or drugs imported under the
licence, together with the quantities imported and issued to the patients, the date
of importation, the name of the manufacturer, the name and address of the patient
for whom the drug is prescribed and the name of disease;
(e) the licensee shall comply with such other requirements, if any, applicable
to the holders of import licences for import of new drugs for treatment of patients
by Government Hospitals, as may be specified from time to time in any rule
subsequently made under Chapter III of the Act and of which the licensing
authority has given to him not less than one month‘s notice;
(f) the drug shall be stocked under proper storage conditions and shall be
dispensed under the supervision of a registered pharmacist;
(g) the quantity of any single drug so imported shall not exceed 100 average
dosages per patient:
Provided that the licensing authority may, in exceptional circumstances, sanction
the import of drug of a larger quantity.]
34. Application for licence for examination, test or analysis.
(1) An application
for a licence for examination, test or analysis shall be made in Form 12 and shall be
made or countersigned by the head of the institution in which, or by a proprietor or
director of the company or firm by which the examination, test or analysis will be
conducted.
1. Ins. by G.S.R 604 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
53
(2) The licensing authority may require such further particulars to be supplied as
he may consider necessary.
1
[(3) Every application in Form 12 shall be accompanied by a fee of one hundred
rupees for a single drug and an additional fee of fifty rupees for each additional drug.
(4) The fees shall be paid through a challan in the Bank of Baroda, Kasturba
Gandhi Marg, New Delhi-110001 or any other branch or branches of Bank of Baroda,
or any other Bank, as notified, from time to time, by the Central Government, to be
credited under the Head of Account 0210-Medical and Public Health, 04- Public
Health, 104- Fees and Fines.]
2
[34A. Application for licence to import small quantities of new drugs by a
Government Hospital or Autonomous Medical Institution for the treatment of
patients.
(1) An application for an import licence for small quantities of a new drug,
as defined in Rule 122-E for the purpose of treatment of patients suffering from life
threatening diseases, or diseases causing serious permanent disability, or such
diseases requiring therapies for unmet medical needs, shall be made in Form 12-AA,
by a Medical Officer of the Government Hospital or Autonomous Medical Institution,
which shall be certified by the Medical Superintendent of the Government Hospital or
Head of the Autonomous Medical Institution, as the case may be.
(2) The licensing authority may require such further particulars to be supplied, as
he may consider necessary.
(3) Every application in Form 12-AA shall be accompanied by a fee of one
hundred rupees for a single drug and an additional fee of fifty rupees for each
additional drug.
(4) The fees shall be paid through a challan in the Bank of Baroda, Kasturba
Gandhi Marg, New Delhi-110001 or any other branch or branches of Bank of Baroda,
or any other Bank, as notified, from time to time, by the Central Government, to be
credited under the Head of Account 0210- Medical and Public Health, 04- Public
Health, 104- Fees and Fine.]
35. Cancellation of licence for examination, test or analysis.
(1) A licence for
examination, test or analysis may be cancelled by the licensing authority for breach of
any of the conditions subject to which the licence was issued.
(2) A licensee whose licence has been cancelled may appeal to the Central
Government within three months of the date of the order.
1. Subs. by G.S.R 604 (E), dt. 24-8-2001.
2. Ins. by G.S.R 604 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
54
1
[35A. Cancellation of licence for import of small quantities of new drugs.
(1) A
licence for import of small quantities of a new drug, defined in Rule122E, for the
purpose of the treatment of patients suffering from life threatening diseases, or diseases
causing serious permanent disability, or such diseases requiring therapies for unmet
medical needs, by a Government Hospital or an Autonomous Medical Institution may be
cancelled by the licensing authority for breach of any of the conditions subject to which
the licence was issued or for contravention of any of the provisions of the Act and rules
made thereunder.
(2) A licensee whose licence has been cancelled may appeal to the Central
Government within three months from the date of the receipt of the order, and the Central
Government may after such enquiry into the matter, as it considers necessary and after
giving the appellant an opportunity for representing his views, may pass such orders in
relation thereto, as it thinks fit.]
36. Import of drugs for personal use.
Small quantities of drugs, the import of which
is otherwise prohibited under section 10 of the Act, may be imported for personal use
subject to the following conditions:
(i) the drugs shall form part of a passenger‘s bona fide baggage and shall be the
property of, and be intended for, the exclusive personal use of the passenger;
(ii) the drugs shall be declared to the Customs authorities if they so direct;
(iii) the quantity of any single drug so imported shall not exceed one hundred
average doses :
Provided that the licensing authority may in an exceptional case in any individual
case sanction the import of a larger quantity:
2
[Provided further that any drug, imported for personal use but not forming part of
bona fide personal baggage, may be allowed to be imported subject to the following
conditions, namely:
(i) the licensing authority, on an application made to it in Form 12A is
satisfied that the drug is for bona fide personal use;
(ii) the quantity to be imported is reasonable in the opinion of the licensing
authority and is covered by prescription from a registered medical practitioner ;
and
(iii) the licensing authority grants a permit in respect of the said drug in Form
12B.]
3
[37. Packing of patent or proprietary medicine. —Patent or proprietary
medicines shall be imported in containers intended for retail sale:
4
[Provided that such medicines may be imported in bulk containers by any
person who holds a licence to manufacture, if such person has obtained permission in
writing to import such medicines from the licensing authority at least three months prior
to the date of import and the imports are made within a period of twelve months from
the date of issue of such permission].]
38. Statement to accompany imported drugs.
All consignments of drugs sought to be
imported shall be accompanied by an invoice or other statement showing the name and
address of the manufacturer and the name and quantities of the drugs.
39. Documents to be supplied to the Customs Collector.
Before drugs for the import
of which a licence is not required are imported a declaration signed by or on behalf of the
manufacturer or by or on behalf of the importer that the drugs comply with the provisions
of Chapter III of the Drugs and Cosmetics Act, 1940 and the Rules thereunder shall be
supplied to the Customs Collector.
1. Ins. by G.S.R 604 (E), dt. 24-8-2001.
2. Ins. by Notfn. No.F-1-36/54-D.S., (SRO 560), dt. 3-3-1955.
3. Ins. by Notfn. No.F-1-3/51-D.S., (SRO 3262), dt. 15-10-1954.
4. Ins. by Notfn. No.F-1-45/58-D, (SO 115), dt. 4-1-1961.
Drugs and Cosmetics Rules 1945
55
1
[
40. Procedure for the import of drugs.
(1) If the Customs Collector has reason
to doubt whether any drugs comply with the provisions of Chapter III of the Act and
Rules thereunder he may, and if requested by an officer appointed for this purpose by
the Central Government shall, take samples of any drugs in the consignment and
forward them to the Director of the laboratory appointed for this purpose by the
Central Government and may detain the drugs in the consignment of which samples
have been taken until the report of the Director of the said laboratory or any other
officer empowered by him on this behalf, subject to the approval of the Central
Government, on such samples is received:
Provided that if the importer gives an undertaking in writing not to dispose of the
drugs without the consent of the Customs Collector and to return the consignment or
such portion thereof as may be required, the Customs Collector shall make over the
consignment to the importer.
(2) If an importer who has given an undertaking under the proviso to sub-rule (1)
is required by the Customs Collector to return the consignment or any portion thereof
he shall return the consignment or portion thereof within ten days of receipt of the
notice.]
2
[41. (1) If the Director of the laboratory appointed for the purpose by the Central
Government or any other officer empowered by him on this behalf, subject to the
approval of the Central Government, reports to the Customs Collector that the
samples of any drug in a consignment are not of standard quality, or that the drug
contravenes in any other respect the provisions of Chapter III of the Act or the Rules
thereunder and that the contravention is such that it cannot be remedied by the
importer, the Customs Collector shall communicate the report forthwith to the
importer who shall, within two months of his receiving the communication either
export all the drugs of that description in the consignment, to the country in which
they were manufactured or forfeit them to the Central Government which shall cause
them to be destroyed :
Provided that the importer may within fifteen days of receipt of the report make a
representation against the report to the Customs Collector, and the Customs Collector
shall forward the representation with a further sample to the licensing authority, who
after obtaining, if necessary, the report of the Director of the Central Drugs
Laboratory, shall pass orders thereon which shall be final.
3
[(2) If the Director of the laboratory appointed for the purpose by the Central
Government or any other officer empowered by him on this behalf, subject to the
approval of the Central Government reports to the Customs Collector that the samples
of any drug contravene in any respect the provisions of Chapter III of the Act or the
Rules thereunder and that the contravention is such that it can be remedied by the
importer, the Customs Collector shall communicate the report forthwith to the
importer and permit him to import the drug on his giving an undertaking in writing
not to dispose of the drug without the permission of the officer authorised in this
behalf by the Central Government.]]
4
[
* * * * *
]
1. Subs. by Notifn. 1-99/52-D.S., dated 3-11-1953.
2. Subs. by Notfn. No. F. 7-7/47-D, dt. 5-1-1954.
3. Ins. by Notfn. No. 7-11/47-D, dt. 5-10-1951.
4. Rule 42 omitted by Notfn. No. F. 1-9/52-DS., dt. 3-11-1953.
Drugs and Cosmetics Rules 1945
56
43. The drugs specified in Schedule D shall be exempt from the provisions of
Chapter III of the Act and of the Rules made thereunder to the extent, and subject to
the conditions specified in that Schedule.
1
[43A. No drug shall be imported into India except through one of the following
places, namely:
Freozepore Cantonment and Amritsar Railway Stations:
In respect of drugs imported by rail across the frontier with Pakistan.
Ranaghat, Bongaon and Mohiassan Railways Stations:
In respect of drugs imported by rail across the frontier with Bangladesh.
5
[Petrapole Road in West Bengal, Sutarkandi in Assam, Old Raghna Bazar and Agartala in
Tripura :
In respect of drugs imported by Road from Bangladesh;]
2
[Raxaul:
In respect of drugs imported by road and railway lines connecting Raxaul in India
and Birganj in Nepal;]
4
[Chennai, Kolkata, Mumbai, Cochin, Nhava Sheva, Kandla and Inland Container
Depots at Tuglakabad and Patparganj in Delhi and Tuticorin in Tamil Nadu and
Marmugao port in Goa and Visakhapatnam in Andhra Pradesh:
In respect of drugs imported by sea into India;
Chennai, Kolkata, Mumbai, Delhi,Ahmedabad, Hyderabad, Goa, Bengaluru and
Visakhapatnam:
in respect of drugs imported by air into India.]
4
[43-B. Drugs, consignments of which are in transit through India to foreign
countries and which shall not be sold or distributed in India shall be exempted from
the requirements of Chapter III of the Drugs and Cosmetics Act, 1940 (23 of 1940)
and the Rules made thereunder:
Provided that if the Government of the countries to which the drugs are consigned
regulate their import by the grant of import licences, the importer shall at the time of
import into India, produce such import licences.]
1. Subs. by G.S.R 478 (E), dt. 6-8-1981. Earlier Ins. by Notfn No. F.7/7/47-D. dt. 5-1-1954.
2. Ins. by G.S.R 120 (E), dt. 5-3-1998.
3. Sub. by G.S.R 532 (E), dt. 18-05-2016. Earlier sub. by G.S.R 575 (E), dt. 17-11-2012, G.S.R 101 (E), dt.
18-2-2011, G.S.R 45 (E), dt. 21-1-2010, G.S.R 504 (E), dt. 18-7-2002, G.S.R 647 (E), dt. 28-10-1998.
4. Added by Notfn. No. E. 1-60/D, (SO 1056) dt. 19-3-1964.
5. Ins. by G.S.R. 116 (E), 24-01-2009.
Drugs and Cosmetics Rules 1945
57
PART
V
1
[GOVERNMENT ANALYSTS, INSPECTORS, LICENSING
AUTHORITIES
AND CONTROLLING
AUTHORITIES
]
2
[44. Qualifications of Government Analyst.
Government Analyst under the Act shall be a person who
A person appointed as a
(a) is a graduate in medicine or science or pharmacy or Pharmaceutical
Chemistry of a
3
[University established in India by law or has an equivalent
qualification recognized and notified by the Central Government for such
purpose] and has had not less than five years‘ post-graduate experience in the
testing of drugs in a laboratory under control of (i) a Government Analyst
appointed under the Act, or (ii) the head of an Institution or testing laboratory
approved for the purpose by the appointing authority,
4
[or has completed two
years‘ training on testing of drugs, including items stated in Schedule C, in
Central Drugs Laboratory], or
(b) possesses a post-graduate degree in medicine or science or pharmacy
or Pharmaceutical chemistry of a
3
[University established in India by law or
has an equivalent qualification recognized and notified by the Central
Government for such purpose] or possesses the Associateship Diploma of the
Institution of Chemists (India) obtained by passing the said examination with
‗Analysis of Drugs and Pharmaceuticals‘ as one of the subjects and has had
after obtaining the said post-graduate degree or diploma not less than three
years‘ experience in the testing of drugs in a laboratory under the control of
(i)
a Government Analyst appointed under the Act, or (ii) the head of an
Institution or testing laboratory approved for the purpose by the appointing
authority
4
[or has completed training on testing of drugs, including items stated
in Schedule C, in Central Drugs Laboratory]:
Provided that-
4
[(i) for purpose of examination of items in Schedule C,-
(ia) the persons appointed under clause (a) or (b) and having degree in
Medicine, Physiology, Pharmacology, Microbiology, Pharmacy should
have experience or training in testing of said items in an institution or
laboratory approved by the appointing authority for a period of not less than
six months;
(ib) the person appointed under clause(a) or (b) but not having degree in the
above subjects should have experience or training in testing of said
Schedule C drugs for a period of not less than three years in an institution or
laboratory approved by the appointing authority or have completed two
years training on testing of drugs including items stated in Schedule C in
Central Drugs Laboratory;]
1. Subs. by G.S.R 443 (E), dt. 12-4-1989.
2. Subs. by G.S.R. No. 1427, dt. 22-10-1977.
3. Subs. by G.S.R. 71(E), dt 30.1.1987.
4. Ins. by G.S.R 697(E) dt. 26-10-1995.
Drugs and Cosmetics Rules 1945
58
(ii) for a period of four years from the date on which Chapter IV of the Act
takes effect in the States, persons whose training and experience are regarded
by the appointing authority as affording, subject to such further training, if any,
as may be considered necessary, a reasonable guarantee of adequate knowledge
and competence, may be appointed as Government Analysts. The persons so
appointed may, if the appointing authority so desires, continue in service after
the expiry of the said period of four years;
(iii) no person who is engaged directly or indirectly in any trade or business
connected with the manufacture of drugs shall be appointed as a Government
Analyst for any area:
Provided further that for the purpose of examination of Anti-sera, Toxoid and
Vaccines and Diagnostic Antigens for Veterinary use, the person appointed shall be a
person who is a graduate in Veterinary Science, or general science, or medicine or
pharmacy and has had not less than five years‘ experience in the standardization of
biological products or person holding a post-graduate degree in Veterinary Science,
or general science, or medicine or pharmacy or pharmaceutical chemistry with an
experience of not less than three years in the standardization of biological products :
Provided also that persons, already appointed as Government Analysts may
continue to remain in service, if the appointing authority so desires, notwithstanding
the fact that they do not fulfil the qualifications as laid down in clause (a), clause (b)
or the preceding proviso.
45. Duties of Government
Analysts.
−
(1)
The Government Analyst shall cause to
be analysed or tested such samples or drugs
1
[and cosmetics] as may be sent to
him by Inspectors or other persons under the provisions of Chapter IV of the Act and
shall furnish reports of the results of test or analysis in accordance with these Rules.
(2) A Government Analyst shall from time to time forward to the Government
reports giving the result of analytical work and research with a view to their
publication at the discretion of Government.
46. Procedure on receipt of
sample.
−
O
n receipt of a package from an Inspector
containing a sample for test or analysis, the Government Analyst shall compare the
seals on the packet
2
[or on portion of sample or container] with the specimen
impression received separately and shall note the condition of the seals on the
3
[packet or on portion of sample or container]. After the test or analysis has been
completed, he shall forthwith supply to the Inspector a report in triplicate in Form 13
of the result of the test or analysis, together with full protocols of the tests or analysis
applied:
1. Ins. by S.O. 2139 dt. 5-6-1972.
2. Ins. by G.S.R. 59(E), dt. 7-2-1995.
3. Subs.by G.S.R. 59(E),dt. 7-2-1995.
Drugs and Cosmetics Rules 1945
59
1
[Explanation.
It shall be deemed to be full and sufficient compliance with the
requirement of the rule in respect of the supply of ―protocols of the tests or analysis
applied‖, if
(1) for pharmacopoeial drug, where the tests or methods of analysis
prescribed in the official pharmacopoeia are followed, references to the specific
tests or analysis in the pharmacopoeias are given in the report;
(2) for patent or proprietary medicines for which the tests and methods
prescribed in any of the official pharmacopoeias are applicable and are
followed, references to the specific tests or analysis in the pharmacopoeias are
given in the report;
(3 )for patent or proprietary medicines containing pharmacopoeial drugs for
which the official tests or analysis or methods of assays are modified and
applied, a description of the actual tests or, as the case may be, analysis or
methods of assays so applied is given in the report;
(4) for patent or proprietary medicines for which no pharmacopoeial tests or
methods of analysis are available or can be applied but for which tests or
methods of analysis given in standard books or journals are followed, a
description of such tests or methods of analysis applied together with the
reference to the relevant books or journals from which the tests or methods of
analysis have been adopted, is given in the report;
(5) for those drugs for which methods of test are not available and have
been evolved by the Government Analyst, a description of tests applied is
given in the report.]
47. Report of result of test or analysis.
An application from a purchaser for test
or analysis of a drug under section 26 of the Act shall be made in Form 14 A and the
report of test or analysis of the drug made on such application shall be supplied to the
applicant in Form 14B.
48. Fees.
The fees to be paid by a person submitting to the Government
Analyst under section 26 of the Act for test or analysis of a drug
3
[or cosmetic]
purchased by him shall be those specified in Schedule B.
2
[49. Qualifications of Inspectors. —A person who is appointed an Inspector
under the Act shall be a person who has a degree in Pharmacy or Pharmaceutical
Sciences or Medicine with specialisation in Clinical Pharmacology or Microbiology
from a University established in India by law:
Provided that only those Inspectors:
⎯
1. Ins. by No. F. 1-60/61-D, dt. 12-7-1962 (G.S.R 984 (E), dt. 12-7-1962).
2. Subs. by No. G.S.R 658 (E), dt. 19-10-1993.
3. Ins. by No. G.S.R 1140 (E), dt. 26-8-1978.
Drugs and Cosmetics Rules 1945
60
(i) Who have not less than 18 months‘ experience in the manufacture of
at least one of the substances specified in Schedule C, or
(ii) Who have not less than 18 months‘ experience in testing of at least
one of the substances in Schedule C in a laboratory approved for this purpose
by the licensing authority, or
(iii) Who have gained experiences of not less than three years in the
inspection of firms manufacturing any of the substances specified in Schedule
C during the tenure of their services as Drugs Inspectors;
shall be authorised to inspect the manufacture of the substances mentioned in Schedule
C:]
1
[Provided further that the requirement as to the academic qualification shall not
apply to persons appointed as Inspectors on or before the 18th day of October, 1993.]
2
[ 49A. Qualification of a Licensing Authority.—No person shall be qualified to be a
Licensing Authority under the Act unless:-
(i) he is a graduate in Pharmacy or Pharmaceutical Chemistry or in Medicine
with specialization in clinical pharmacology or microbiology from a University
established in India by law; and
(ii) he has experience in the manufacture or testing of drugs or enforcement of
the provisions of the Act for a minimum period of five years:
3
[ Provided that the requirements as to the academic qualification shall not apply
to those inspectors and the Government Analysts who were holding those positions
on the 12
th
day of April,1989.]]
4
[50. Controlling authority.
(1) All Inspectors appointed by the Central
Government shall be under the control of an officer appointed in this behalf by the
Central Government.
(2) All Inspectors appointed by the State Government shall be under the control
of an officer appointed in this behalf by the State Government.
(3) For the purposes of these rules an officer appointed by the Central Government
under sub-rule (1), or as the case may be, an officer appointed by the State
Government under sub-rule (2), shall be a controlling authority.]
1. Ins. by G.S.R 552 (E), dt. 4-12-1996.
2. Ins. by G.S.R 443 (E), dt. 12-4-1989.
3. Subs. by G.S.R. 532 (E), dt. 14.8.1991.
4. Subs. by S.O. 2139, dt. 5-6-1972.
Drugs and Cosmetics Rules 1945
61
1
[50A. Qualification of a Controlling Authority.
to be a Controlling Authority under the Act unless
(1) No person shall be qualified
(i) he is a graduate in Pharmacy or Pharmaceutical Chemistry or in
Medicine with specialization in Clinical Pharmacology or Microbiology from a
University established in India by law; and
(ii) he has experience in the manufacture or testing of drugs or enforcement of
the provisions of the Act for a minimum period of five years:
2
[Provided that the requirements as to the academic qualifications shall not apply
to those Inspectors and the Government Analysts who were holding those positions
on the 12th day of April, 1989.]
51. Duties of Inspectors of premises licensed for sale.
Subject to the
instructions of the controlling authority, it shall be duty of an Inspector authorized to
inspect premises licensed for the sale of drugs
(1) to inspect
3
[not less than once a year] all establishments licensed for the
sale of drugs within the area assigned to him;
(2) to satisfy himself that the conditions of the licences are being observed;
(3) to procure and send for test or analysis, if necessary, imported packages
which he has reason to suspect contain drugs being sold or stocked or exhibited
for sale in contravention of the provisions of the Act or Rules thereunder;
(4) to investigate any complaint in writing which may be made to him;
(5) to institute prosecutions in respect of breaches of the Act and Rules
thereunder;
(6) to maintain a record of all inspections made and action taken by him in the
performance of his duties, including the taking of samples and the seizure of
stocks, and to submit copies of such record to the controlling authority;
(7) to make such enquiries and inspections as may be necessary to detect the
sale of drugs in contravention of the Act;
1. Ins. by G.S.R 443 (E), dt. 12-04-1989.
2. Subs. by G.S.R 532 (E), dt. 14-8-1991.
3. Subs. by G.S.R. 700 (E), dt. 28-9-2001.
Drugs and Cosmetics Rules 1945
62
(8) when so authorized by the State Government, to detain imported packages
which he has reason to suspect contain drugs, the import of which is prohibited.
52. Duties of Inspectors specially authorized to inspect the manufacture of
1
[drugs or cosmetics].
Subject to the instructions of the controlling authority it shall
be the duty of an Inspector authorized to inspect the manufacture of drugs
(1) to inspect
2
[not less than once a year], all premises licensed for
manufacture of
1
[drugs or cosmetics] within the area allotted to him to satisfy
himself that the conditions of the licence and provisions of the Act and Rules
thereunder are being observed;
(2) in the case of establishments licensed to manufacture products specified
in Schedules C and C(1) to inspect the plant and the process of manufacture, the
means employed for standardizing and testing the
2
[drugs or cosmetics], the
methods and place of storage, the technical qualifications of the staff employed
and all details of location, construction and administration of the establishment
likely to affect the potency or purity of the product;
(3) to send forthwith to the controlling authority after each inspection a
detailed report indicating the conditions of the licence and provisions of the Act
and rules thereunder which are being observed and the conditions and
provisions, if any, which are not being observed;
(4) to take samples of the
1
[drugs or cosmetics] manufactured on the
premises and send them for test or analysis in accordance with these Rules;
(5) to institute prosecutions in respect of breaches of the Act and Rules
thereunder.
53. Prohibition of disclosure of information.
Except for the purposes of official
business or when required by a Court of Law, an Inspector shall not, without the
sanction in writing of his official superior, disclose to any person any information
acquired by him in the course of his official duties.
54. Form of order not to dispose of stock.
An order in writing by an Inspector
under clause (c) of section 22 of the Act requiring a person not to dispose of any
stock in his possession shall be in Form 15.
1. Subs. by G.S.R 504 (E), dt. 18-7-2002.
2. Subs. by G.S.R 700 (E), dt. 28-9-2001.
Drugs and Cosmetics Rules 1945
63
1
[54A. Prohibition of sale.
No person in possession of a drug
2
[or cosmetic] in
respect of which an Inspector has made an order under clause (c) of sub-section (1) of
section 22 of the Act shall in contravention of that order sell or otherwise dispose of
any stock of such drug
2
[or cosmetic].
3
[55. Forms of receipts for seized drug, cosmetic, record register, document or
any other material object.-- A receipt by an Inspector for the stock of any drug or
cosmetic or for any record, register, document or any other material object seized by
him under clause (c) or clause (cc) of sub-section (1) of section 22 of the Act shall be
in Form 16.]
4
[55A. Manner of certifying copies of seized documents.—The Drugs Inspector
shall return the documents , seized by him under clause (cc) or produced before him
under clause (cca), of sub-section (1) of section 22 of the Act, within a period of
twenty days of the date of such seizure or production, to the person from whom they
have seized or, as the case may be, the person who produced them, after copies
thereof of extracts therefrom have been signed by the concerned Drug Inspector and
the person from whom they have seized , or, as the case may be , who produced such
records.]
56. Form of intimation of purpose of taking samples.
When an Inspector takes a
sample of a drug for the purpose of test or analysis, he shall intimate such purpose in
writing in Form 17 to the person from whom he takes it.
5
[56A. Form or receipt for samples of drugs where fair price tendered is
refused.—Where the fair price, for the samples of drugs taken for the purpose of test
or analysis, tendered under sub-section (1) of section 23 has been refused, the
Inspector shall tender a receipt therefor to the person from whom the said samples
have been taken as specified in Form 17A.]
57. Procedure for despatch of sample to Government Analyst.
(1) The portion of
sample or the container sent by an Inspector to the Government Analyst for test or
analysis under sub-section (4) of section 23 of the Act shall be sent by registered post
or by hand in a sealed packet, enclosed together with a memorandum in Form 18, in
an outer cover addressed to the Government Analyst.
(2) A copy of the memorandum and a specimen impression of the seal used to
seal the packet shall be sent to the Government Analyst separately by registered post
or by hand.
1. Ins. by No. F. 1-19/59-D, dt. 13-6-1961.
2. Ins. by G.S.R 850(E), dt. 07-12-1994.
3. Subs. by G.S.R. No. 926 dt. 16-7-1977.
4. Ins. by G.S.R 89 (E), dt. 16-2-1985.
5. Ins. by G.S.R 292 (E), dt. 29-5-1997.
Drugs and Cosmetics Rules 1945
64
1
[58. Confiscation of drugs, implements, machinery etc.
(1) Where any person has
been convicted for contravening any of the provisions of Chapter IV of the Act or any
Rule made thereunder, the stock of the drug in respect of which the contravention has
been made shall be liable to confiscation.
(2) Where any person has been convicted for the manufacture of any drug
deemed to be misbranded under clause (a), clause (b), clause (c), clause (d), clause (f)
or clause (g) of section 17 of the Act, or adulterated drug under section 17B of the
Act, or for manufacture for sale, or stocking or exhibiting for sale or distribution of
any drug without a valid licence as required under clause (c) of section 18 of the Act,
any implements or machinery used in such manufacture, sale or distribution and any
receptacle, packages, or coverings in which such drug is contained and the animals,
vehicles, vessels or other conveyances used in carrying such drug shall also be liable
to confiscation.]
2
[58A. Procedure for disposal of confiscated drugs.
(1) The Court shall refer
the confiscated drugs to the Inspector concerned for report as to whether they are of
standard quality or contravene the provisions of the Act or the Rules in any respect.
(2) If the Inspector, on the basis of Government Analyst‘s report finds the
confiscated drugs to be not of standard quality or to contravene any of the provisions
of the Act or the Rules made thereunder, he shall report to the Court accordingly. The
Court shall thereupon order the destruction of the drugs. The destruction shall take
place under the supervision of the Inspector in the presence of such authority, if any,
as may be specified by the Court.
(3) If the Inspector finds that the confiscated drugs are of standard quality and do
not contravene the provisions of the Act or the Rules made thereunder, he shall report
to the Court accordingly.
3
[The Court may then order the Inspector to give the stocks
of confiscated drugs to hospital or dispensary maintained or supported by the
Government or by Charitable Institutions].]
1. Subs. by S. O. 289, dt. 3-2-1973.
2. Ins. by No. F. 1-9/62-D (GSR 6), dt. 2-12-1964.
3. Subs. by G.S.R 59 (E), dt. 7-2-1995.
Drugs and Cosmetics Rules 1945
65
PART
VI
SALE OF DRUGS OTHER THAN HOMOEOPATHIC MEDICINES
59. (1) The State Government shall appoint Licensing Authorities for the purpose
of this Part for such areas as may be specified.
1
[(2) Applications for the grant or renewal of a licence
2
[to sell, stock, exhibit or
offer for sale or distribute] drugs, other than those included in Schedule X,
3
[shall be
made in Form 19 accompanied by a fee of rupees one thousand and five hundred or
Form 19A accompanied by a fee of rupees five hundred, as the case may be, or in the
case of drugs included in Schedule X shall be made in Form 19C accompanied by a
fee of rupees five hundred, to the licensing authority:]
Provided that in the case of an itinerant vendor or an applicant who desires to
establish a shop in a village or town having population of 5,000 or less, the
application in Form 19-A shall be accompanied by a fee of rupees ten .
(3)
3
[A fee of rupees one hundred and fifty] shall be paid for a duplicate copy
of
a licence
2
[to sell, stock, exhibit or offer for sale or distribute] drugs, other than those
included in Schedule X, or for a licence
2
[to sell, stock, exhibit or offer for sale or
distribute] drugs, included in Schedule X, if the original is defaced, damaged or lost:
Provided that in the case of itinerant vendor or an applicant who desires to
establish a shop in a village or town having a population of 5,000 or less, the fee for a
duplicate copy of a licence if the original is defaced, damaged or lost, shall be rupees
two.
(4) Application for renewal of a licence
2
[to sell, stock, exhibit or offer for sale or
distribute] drugs, after its expiry but within six months of such expiry
3
[shall be
accompanied by a fee of rupees one thousand and five hundred plus an additional fee
at the rate of rupees five hundred per month or part thereof in Form 19, rupees five
hundred plus an additional fee at the rate of rupees two hundred and fifty per month
or part thereof in Form 19-A and rupees five hundred plus an additional fee at the rate
of rupees two hundred and fifty per month or part thereof in Form 19C:]
Provided that in the case of an itinerant vendor or an applicant desiring to open a
shop in a village or town having a population of 5,000 or less the application for such
renewal shall be accompanied by a fee of rupees ten, plus an additional fee at the rate
of rupees eight per month or part thereof.]
1. Subs. by G.S.R 462 (E), dt. 22-6-1982.
2. Subs. by G.S.R 788 (E), dt. 10-10-1985.
3. Subs. by G.S.R 601 (E), dt. 24-08-2001.
Drugs and Cosmetics Rules 1945
66
1
[60. A licensing authority may with the approval of the State Government by an
order in writing delegate the power to sign licences and such other powers as may be
specified in the order to any other person under his control.]
2
[61. Forms of licences to sell drugs.
(1) a licence
3
[ to sell, stock, exhibit or
offer for sale or distribute] drugs other than those specified in Schedules C, C (1) and
X and by retail on restricted licence or by wholesale, shall be issued in Form 20,
Form 20A or Form 20B, as the case may be:
Provided that a licence in Form 20A shall be valid for only such drugs as are
specified in the licence.
(2) A licence
3
[to sell, stock, exhibit or offer for sale or distribute] drugs specified
in Schedule C and C (1) excluding those specified in Schedule X, by retail on
restricted licence or by wholesale shall be issued in Form 21, Form 21A or Form 21B,
as the case may be:
4
[Provided that a licence in Form 21A shall not be granted for drugs specified in
Schedules C and shall be valid for only such Schedule C (1) drugs as are specified in
the licence.]
(3 )A licence
3
[to sell, stock, exhibit or offer for sale or distribute] drugs specified
in Schedule X by retail or by wholesale shall be issued in Form 20F or Form 20G as
the case may be.]
62. Sale at more than one place.
If drugs are sold or stocked for sale at more
than one place, separate application shall be made, and a separate licence shall be
issued, in respect of each such place:
5
[Provided that this shall not apply to itinerant vendors who have no specified
place of business and who will be licensed to conduct business in a particular area
within the jurisdiction of the licensing authority.]
1. Amended by F. 1-16/57-D, dt. 15-6-1957.
2. Subs. by G.S.R 462 (E), dt. 22-6-1982.
3. Subs. by G.S.R 788 (E), dt. 10-10-1985.
4. Subs. by G.S.R 487 (E), dt. 2-7-1984.
5. Added by Notfn. No. F. 10-21/49-D, dt. 10-3-1953.
Drugs and Cosmetics Rules 1945
67
1
[62A. Restricted licences in Forms 20A and 21A.
(a) Restricted licences in
Forms 20A and 21A shall be issued subject to the discretion of the Licensing
Authority, to dealers or persons in respect of drugs whose sale does not require the
supervision of a qualified person.
(b) Licences to itinerant vendors shall be issued only in exceptional circumstances
for bona fide travelling agents of firms dealing in drugs or for a vendor who
purchases drugs from a licensed dealer for distribution in sparsely populated rural
areas where other channels of distribution of drugs are not available.
(c) The licensing authority may issue a licence in Form 21A to a travelling agent
of a firm but to no other class of itinerant vendors for the specific purpose of
distribution to medical practitioners or dealers, samples of biological and other
special products specified in Schedule C:
Provided that travelling agents of licensed manufacturers, agents, of such
manufacturers and importers of drugs shall be exempted from taking out licence for
the free distribution of samples of medicines among members of the medical
profession, hospitals, dispensaries and the medical institution or research institutions.
1
[62-B. Conditions to be satisfied before a licence in Form 20A or Form 21A is
granted.
(1) A licence in Form 20A or Form 21A shall not be granted to any
person, unless the authority empowered to grant the licence is satisfied that the
premises in respect of which the licence is to be granted are adequate and equipped
with proper storage accommodation for preserving the properties of drugs to which
the licence applies:
Provided that this condition shall not apply in the case of licence granted to
itinerant vendors.
(2) In granting a licence under Rule 62A the authority empowered to grant it
shall have regard to:
(i) the number of licences granted in the locality during one year
immediately preceding; and
(ii) the occupation, trade or business carried on by such applicant :
1. Ins. by Notfn. No. F. 1-9/60-D, dt. 3-7-1961.
Drugs and Cosmetics Rules 1945
68
Provided that the licensing authority may refuse to grant or renew a licence to any
applicant or licensee in respect of whom it is satisfied that by reason of his conviction
of an offence under the Act or these Rules or the previous cancellation or suspension
of any licence granted thereunder, he is not a fit person to whom a licence should be
granted under this rule.
(3) Any person who is aggrieved by the order passed by the licensing authority in
sub-rule (1) may, within 30 days from the date of the receipt of such order appeal to
the State Government and the State Government may, after such enquiry into the
matter as it considers necessary and after giving the appellant an opportunity for
representing his views in the matter make such order in relation thereto as it thinks
fit.]
1
[62C. Application for licence to sell drugs by wholesale or to distribute the same
from a motor vehicle.
(1) Application for the grant or renewal of a licence to sell by
wholesale or to distribute from a motor vehicle shall be made to the Licensing
Authority in Form 19AA and shall be accompanied by
2
[a fee of rupees five
hundred]:
Provided that if the applicant applies for the renewal of a licence after its expiry
but within six months of such expiry , the fee payable for renewal of such licence
shall be
2
[rupees five hundred plus an additional fee at the rate of rupees two hundred
and fifty per month or part thereof].
(2) A fee of
2
[rupees one hundred and fifty] shall be paid for a duplicate copy of a
licence issued under this rule, if the original is defaced, damaged or lost.]
3
[62D. Form of licences to sell drugs by wholesale or distribute drugs from a
motor vehicle.
A licence shall be issued for sale by wholesale or for distribution
from a motor vehicle of drugs other than those specified in Schedule and Schedule
C(1) in Form 20BB and of drugs specified in Schedule C and Schedule C(1) in Form
21BB :
Provided that such a licence shall not be required in a case where a public carrier
or a hired vehicle is used for transportation or distribution of drug.]
3
[63. Duration of licence.
An original licence or a renewed licence to sell drugs,
unless sooner suspended or cancelled, shall be
2
[valid for a period of five years on
and from the date on which] it is granted or renewed:
1. Ins. by Notfn. No. 1-9/60-D dt. 3-7-1961.
2. Subs. by Notfn. No. G.S.R 601 (E), dt. 24-8-2001.
3. Amended by Notfn. No. F. 1-10/62-D, dt. 10-4-1964.
Drugs and Cosmetics Rules 1945
69
1
[
Provided that if the application for renewal of licence in force is made before its
expiry or if the application is made within six months of its expiry, after payment of
additional fee, the licence shall continue to be in force until orders are passed on the
application. The licence shall be deemed to have expired if application for its renewal
is not made within six months after its expiry].]
2
[63A. Certificate of renewal of a sale licence.
The certificate of renewal of a
sale licence in Forms 20, 20A, 20B,
3
[20F, 20G], 21, 21A and 21B shall be
issued in Form 21C.]
4
[63B. Certificate of renewal of licence.
A certificate of renewal of a licence in
Form 20BB or Form 21BB shall be issued in Form 21CC.]
5
[64. Conditions to be satisfied before a licence in Form
8
[20, 20B, 20F,20G,
21 or 21B] is granted .
(1)A licence in Form
3
[20, 20B, 20F, 20G, 21 or 21B]
6
[to sell, stock, exhibit or offer for sale or distribute] drugs shall not be granted
7
[or
renewed] to any person unless the authority empowered to grant the licence is
satisfied that the premises in respect of which the licence is to be granted
7
[or
renewed] are adequate, equipped with proper storage accommodation for preserving
the properties of the drugs to which the licence applies and are in charge of a person
competent in the opinion of the licensing authority to supervise and control the sale,
distribution and preservation of drugs :
Provided that in the case of a pharmacy a licence in Form 20 or 21 shall not be
granted
7
[or renewed] unless the licensing authority is satisfied that the requirements
prescribed for a pharmacy in Schedule N have been complied with:
3
[Provided further that licence in Form 20F shall be granted
7
[or renewed] only
to a pharmacy and in areas where a pharmacy is not operating, such licence may be
7
[granted or renewed] to a chemist and druggist.]
Explanation.
For the purpose of this rule the term ‗Pharmacy‘ shall be held to
mean to include every store or shop or other place : (1) where drugs are dispensed,
that is, measured or weighed or made up and supplied ; or (2) where prescriptions are
compounded; or (3) where drugs are prepared; or (4) which has upon it or displayed
within it, or affixed to or used in connection with it, a sign bearing the word or words
―Pharmacy‖, ―Pharmacist‖, ―Dispensing Chemist‖ or ―Pharmaceutical Chemist‖; or
(5) which, by sign, symbol or indication within or upon it gives the impression that
the operations mentioned at (1), (2) and (3) are carried out in the premises; or (6)
which is advertised in terms referred to in (4) above.
1. Amended by S. O. No. 2139, dt. 12-8-1972.
2. Ins. by Notfn. No. F. 1-10/62-D, dt. 10-4-1964.
3. Ins. by G.S.R 462 (E), dt. 22-6-1982.
4. Ins. by Notfn. No. F.1-10/62-D,dt. 10-4-1964.
5. Subs. by Notfn. No.F.1-16/57-D,dt. 15-6-1957 and No. F. 1-19/59-D, dt. 13-6-1961.
6. Subs. by G.S.R 788 (E), dt. 10-10-1985.
7. Subs. by No. G.S.R 681(E), dt. 6-6-1988.
8. Subs. by G.S.R 462 (E), dt. 22-6-1982.
Drugs and Cosmetics Rules 1945
70
(2) In granting
1
[or renewing] a licence under sub-rule (1) the authority empowered
to grant it shall have regard
2
[(i) to the average number of licences granted
1
[or renewed] during the
period of 3 years immediately preceding, and]
(ii) to the occupation, trade or business ordinarily carried on by such
applicant during the period aforesaid:
Provided that the licensing authority may refuse to grant or renew a licence to any
applicant or licensee in respect of whom it is satisfied that by reason of his conviction
of an offence under the Act or these rules, or the previous cancellation or suspension
of any licence granted
1
[or renewed] thereunder, he is not a fit person to whom a
licence should be granted
1
[or renewed] under this rule. Every such order shall be
communicated to the licensee as soon as possible:
3
[Provided further that in respect of an application for the grant of a licence in
Form 20B or Form 21B or both, the licensing authority shall satisfy himself that the
premises in respect of which a wholesale licence is to be granted
1
[or renewed] are:-
(i) of an area of not less than ten square meters; and]
4
[(ii) in the charge of a competent person, who—
(a) is a Registered Pharmacist, or
(b) has passed the matriculation examination or its equivalent
examination from a recognised Board with four years‘ experience in dealing
with sale of drugs, or
(c) holds a degree of a recognised University with one year‘s
experience in dealing with drugs:]
5
[Provided also that,-
(i) in respect of an application for the grant of a licence in Form 20 or Form
21 or both, the licensing authority shall satisfy itself that the premises are of an
area] of not less than 10 square meters, and
(ii) in respect of an application for the grant of a licence
(A) In Form 20 or Form 21 or both, and
(B) In Form 20 B or Form 21B or both,
the licensing authority shall satisfy itself that the premises are of an area not less than
15 square meters:
1. Ins. by G.S.R 681(E), dt. 6.6.1988.
2. Subs. by Notfn. No. F. 1-19/59-D, dt. 13-6-1961.
3. Ins. by G.S.R 681(E), dt. 6.6.1980.
4. Substituted. G.S.R 351(E), dt. 26-4-2000.
5. Ins. by G.S.R 91(E), dt. 25-2-1997.
Drugs and Cosmetics Rules 1945
71
Provided also that the provisions of the preceding proviso shall not apply to the
premises for which licences have been issued by the licensing authority before the
commencement of the Drugs and Cosmetics (1st Amendment) Rules, 1997.]
1
[(3) Any person who is aggrieved by the order passed by the licensing authority
in sub-Rule (1) may, within 30 days from the date of receipt of such order, appeal to
the State Government and the State Government may, after such enquiry into the
matter as it considers necessary and after giving the appellant an opportunity for
representing his views in the matter, make such an order in relation thereto as it thinks
fit.]
65. Condition of licences.
Licences in
2
[Forms 20, 20-A, 20-B, 20-F, 20-G, 21
and 21-B] shall be subject to the conditions stated therein and to the following general
conditions
2
[(1) Any drug shall, if compounded or made on the licensee‘s premises be
compounded or made by or under the direct and personal supervision of a
3
[registered
Pharmacist].]
(2) The supply, otherwise than by way of wholesale dealing,
4
[* * *] of any drug
supplied on the prescription of a Registered Medical Practitioner shall be effected
only by or under the personal supervision of a
3
[registered Pharmacist].
5
[(3) (1) The supply of any drug
6
[other than those specified in Schedule X] on a
prescription of a Registered Medical Practitioner shall be recorded at the time of
supply in a prescription register specially maintained for the purpose and the serial
number of the entry in the register shall be entered on the prescription. The following
particulars shall be entered in the register:
_
(a) serial number of the entry,
(b) the date of supply,
(c) the name and address of the prescriber,
7
[(d) the name and address of the patient, or the name and address of the
owner of the animal if the drug supplied is for veterinary use,
(e) the name of the drug or preparation and the quantity or in the case of a
medicine made up by the licensee, the ingredients and quantities thereof,
(f) in the case of a drug specified in
2
[Schedule C or
8
[Schedule H and
Schedule H1]] the name of the manufacturer of the drug, its batch number and
the date of expiry of potency, if any,
(g) the signature of the
3
[registered Pharmacist] by or under whose
supervision the medicine was made up or supplied:
1. Amended by F.1-9/60-D dt. 3-7-1961.
2. Subs. by G.S.R 462 (E), dt. 22-6-1982.
3. Subs. by G.S.R 676 (E), dt. 6-9-1994.
4. Omitted by No. G.S.R 462(E), dt. 22-6-1982.
5. Subs. by S. O. 2139, dt. 5-6-1972.
6. Ins. by G.S.R. 462(E), dt. 22-6-1982.
7. Subs. by G.S.R. 926 dt. 16-7-1977.
8. Subs. by G.S.R 588 (E), dt. 30-08-2013.
Drugs and Cosmetics Rules 1945
72
Provided that in the case of drugs which are not compounded in the premises and
which are supplied from or in the original containers, the particulars specified in
items (a) to (g) above may be entered in a cash or credit memo book, serially
numbered and specially maintained for this purpose:
Provided further that if the medicine is supplied on a prescription on which the
medicine has been supplied on a previous occasion and entries made in the
prescription register, it shall be sufficient if the new entry in the register includes a
serial number, the date of supply, the quantity supplied and a sufficient reference to
an entry in the register recording the dispensing of the medicine on the previous
occasion:
Provided also that it shall not be necessary to record the above details in the
register or in the cash or credit memo particulars in respect of−
(i) any drugs supplied against prescription under the Employees State
Insurance Scheme if all the above particulars are given in that prescription, and
(ii) any drug other than that specified in
1
[Schedule C or
4
[Schedule H and Schedule
H1]] if it is supplied in the original unopened container of the manufacturer and
if the prescription is duly stamped at the time of supply with the name of the supplier
and the date on which the supply was made and on condition that the provisions of
sub-rule (4)(3) of this rule are complied with.
5
[(h) the supply of a drug specified in Schedule H1 shall be recorded in a separate
register at the time of the supply giving the name and address of the prescriber, the
name of the patient, the name of the drug and the quantity supplied and such records
shall be maintained for three years and be open for inspection.]
(2) The option to maintain a prescription register or a cash or credit memo book
in respect of drugs and medicines which are supplied from or in the original container,
shall be made in writing to the Licensing Authority at the time of application for the
grant or renewal of the licence to sell by retail:
Provided that the Licensing Authority may require records to be maintained only
in prescription register if it is satisfied that the entries in the carbon copy of the cash
or credit memo book are not legible.]
2
[(4) (1) The supply by retail, otherwise than on a prescription of a drug specified
in Schedule C
3
[
* * *] shall be recorded at the time of supply
either
−
1. Subs. by G.S.R 462 (E), dt. 22-6-1982.
2. Ins. by Notfn. No. 1-63/61-D, dt. 17-7-1963.
3. Omitted by G.S.R 462 (E), dt. 22-6-1982.
4. Subs. by G.S.R 588 (E), dt. 30-08-2013.
5. Ins. by G.S.R 588 (E), dt. 30-08-2013.
Drugs and Cosmetics Rules 1945
73
(i) in a register specially maintained for the purpose in which the following
particulars shall be entered :
(a) serial number of the entry,
(b) the date of supply,
(c) the name and address of the purchaser,
(d) the name of the drug and the quantity thereof,
(e) in the case of a drug specified in Schedule C, the name of the
manufacturer, the batch number and the date of expiry of potency,
(f) the signature of the person under whose supervision the sale was
effected, or
(ii) in a cash or credit memo book, serially numbered containing all the
particulars specified in items (b) to (f) of sub-clause (i) above.
NOTE: The entries in the carbon copy of the cash or credit memo which is retained
by the licensee shall be maintained in a legible manner.
(2) The option to maintain a register or a cash or credit memo book shall be made
in writing to the Licensing Authority at the time of application for the grant or
renewal of a licence to sell by retail:
Provided that the Licensing Authority may require records to be maintained in a
register if it is satisfied that the entries in the carbon copy of the cash/credit memo
book are not legible.
(3)(i) The supply by retail of any drug shall be made against a cash/credit memo
which shall contain the following particulars :
(a) Name, address and sale licence number of the dealer,
1
[(b) Serial number of the cash/credit memo,
(c) the name and quantity of the drug supplied.]
(ii) Carbon copies of cash/credit memos shall be maintained by the licensee as
record.
1. Ins. by G. S. R. No. 245, dt. 21-2-1976.
Drugs and Cosmetics Rules 1945
74
1
[(4)(i) Records of purchase of a drug intended for sale or sold by retail shall be
maintained by the licensee and such records shall show the following particulars,
namely:
(a) the date of purchase,
(b) the name and address of the person from whom purchased and the
number of the relevant licence held by him,
(c) the name of the drug, the quantity and the batch number, and
(d) the name of the manufacturer of the drug.
(ii) Purchase bills including cash or credit memo shall be serially numbered by the
licensee and maintained by him in a chronological order.]
2
[(5)(1) Subject to the other provisions of these Rules the supply of a drug by
wholesale shall be made against a cash or credit memo bearing the name and address
of the licensee and his licence number under the Drugs and Cosmetics Act in which
the following particulars shall be entered
(a) the date of sale,
(b) the name, address of the licensee to whom sold and his sale licence
number. In case of sale to an authority purchasing on behalf of Government, or
to a hospital, medical, educational or research institution or to a Registered
Medical Practitioner for the purpose of supply to his patients the name and
address of the authority, institution or the Registered Medical Practitioner as
the case may be,
(c) the name of the drug, the quantity and the batch number,
(d) the name of the manufacturer,
3
[(e) the signature of the competent person under whose supervision the sale
was effected.]
(2) Carbon copies of cash or credit memos specified in clause (1) shall be
preserved as records for a period of three years from the date of the sale of the drug.
1. Subs. by G.S.R 1242 (E), dt. 17-9-1979.
2. Amended by F. 1-63/62-D, dt. 17-7-1963.
3. Ins. by G.S.R 496 (E), dt. 9-6-1995.
Drugs and Cosmetics Rules 1945
75
1
[(3) (i) Records of purchase of a drug intended for resale or sold by wholesale
shall be maintained by the licensee and such records shall show the following
particulars, namely:-
(a) the date of purchase,
(b) the name, address and the number of the relevant licence held by the
person from whom purchased,
(c) the name of the drug, the quantity and the batch number, and
(d) the name of the manufacturer of the drug.
(ii) Purchase bills including cash or credit memos shall be serially numbered by
the licensee and maintained by him in a chronological order.]
(6) The licensee shall produce for inspection by an Inspector appointed under the
Act on demand all registers and records maintained under these Rules, and shall
supply to the Inspector such information as he may require for the purpose of
ascertaining whether the provisions of the Act and Rules thereunder have been
observed.
(7) Except where otherwise provided in these Rules, all registers and records
maintained under these Rules shall be preserved for a period of not less than two
years from the date of the last entry therein.
(8) Notwithstanding anything contained in this Rule it shall not be necessary to
record particulars in a register specially maintained for the purpose if the particulars
are recorded in any other register specially maintained under any other law for the
time being in force.
2
[(9) (a) Substances specified in
3
[Schedule H and Schedule H1] or Schedule X
shall not be sold by retail except on and in accordance with the prescription of a
Registered Medical Practitioner and in the case of substances specified in Schedule
X, the prescriptions shall be in duplicate, one copy of which shall be retained by the
licensee for a period of two years.
(b) The supply of drugs specified in
3
[Schedule H and Schedule H1] or
Schedule X to Registered Medical Practitioners, Hospitals, Dispensaries and Nursing
Homes shall be made only against the signed order in writing which shall be
preserved by the licensee for a period of two years.]
1. Subs. by G.S.R 1242(E), dt. 17-9-1979.
2. Subs. by G.S.R 462(E), dt. 22-6-1982.
3. Subs. by G.S.R 588(E), dt. 30-8-2013.
Drugs and Cosmetics Rules 1945
76
(10) For the purposes of clause (9) a prescription shall
(a) be in writing and be signed by the person giving it with his usual
signature and be dated by him;
1
[(b) specify the name and address of the person for whose treatment it is
given, or the name and address of the owner of the animal if the drug is meant
for veterinary use;]
(c) indicate the total amount of the medicine to be supplied and the dose to
be taken.
(11) The person dispensing a prescription containing a drug specified in
5
[Schedule H and Schedule H1]
2
[and Schedule X] shall comply with the following
requirements in addition to other requirement of these rules.
(a) the prescription must not be dispensed more than once unless the
prescriber has stated thereon that it may be dispensed more than once;
(b) if the prescription contains a direction that it may be dispensed a stated
number of times or at stated intervals it must not be dispensed otherwise than
in accordance with the directions;
(c) at the time of dispensing there must be noted on the prescription above
the signature of the prescriber the name and address of the seller and the date
on which the prescription is dispensed.
4
[(11-A) No person dispensing a prescription containing substances specified in
3
[
5
[Schedule H and Schedule H1] or X], may supply any other preparation, whether
containing the same substance or not, in lieu thereof.
3
[(12) Substances specified in Schedule X kept in retail shop or premises used in
connection therewith shall be stored—
(a) under lock and key in cupboard or drawer reserved solely for the storage
of these substances; or
(b) in a part of the premises separated from the remainder of the premises
and to which only responsible persons have access;]
1. Subs. by G. S. R. No. 926, dt. 24-6-1977.
2. Ins. by G.S.R 462 (E), dt. 22-6-1982.
3. Subs., by G.S.R 462 (E), dt. 22-6-1982.
4. Ins. by SO 2139, dt. 5-6-1972.
5. Subs. by G.S.R 588(E), dt. 30-8-2013.
Drugs and Cosmetics Rules 1945
77
1
[* * * * *]
2
[(15)(a) The description ―Drugstore‖ shall be displayed by such licensees who do
not require the services of a
3
[Registered Pharmacist].
(b) The description ―Chemists and Druggists‖ shall be displayed by such
licensees who employ the services of a
3
[Registered Pharmacist] but who do not
maintain a ―Pharmacy‖ for compounding against prescriptions.
(c) The description ―Pharmacy‖, ―Pharmacist‖, ―Dispensing Chemist‖ or
―Pharmaceutical Chemist‖ shall be displayed by such licensees who employ the
services of a
3
[Registered Pharmacist] and maintain a ―Pharmacy‖ for compounding
against prescriptions:
3
[Explanation:- For the purpose of this rule,-
(i) ―Registered Pharmacist‖ means a person who is a registered
Pharmacist as defined in clause (i) of section (2) of the Pharmacy Act, 1948
(Act No. 8 of 1948):
Provided that the provisions of sub-clause (i) shall not apply to those
persons who are already approved as ―qualified person‖ by the licensing
authority on or before 31st December, 1969:
(ii) ―Date of Expiry of potency‖ means the date that is recorded on the
container, label or wrapper as the date up to which the substance may be
expected to retain a potency not less than or not to acquire a toxicity greater
than that required or permitted by the prescribed test].]
4
[(16) The licensee shall maintain an Inspection Book in Form 35 to enable an
Inspector to record his impressions and the defects noticed.]
1. Sub-Rules (13) and (14) omitted by G.S.R 462 (E), dt. 22-6-1982.
2. Subs. by Notfn. No. F. 1-16/57-D, dt. 15-6-1957.
3. Subs. by G.S.R 676 (E), dt. 6-9-1994.
4. Subs. by Notfn. No. F. 1-14/68-D dt. 26-10-1968.
Drugs and Cosmetics Rules 1945
78
1
[(17) No drug shall be sold or stocked by the licensee after the date of expiration
of potency recorded on its container, label or wrapper, or in violation of any statement
or direction recorded on such container, label or wrapper:
Provided that any such drugs in respect of which the licensee has taken steps with
the manufacturer or his representative for the withdrawal, reimbursement or disposal
of the same, may be stocked after the date of expiration of potency pending such
withdrawal, reimbursement or disposal, as the case may be, subject to the condition
that the same shall be stored separately from the trade stocks
2
[and all such drugs
shall be kept in packages or cartons, the top of which shall display prominently, the
words ―Not for sale‖].]
3
[(18) No drug intended for distribution to the medical profession as free sample
which bears a label on the container as specified in clause
4
[(ix)] of sub-rule (1) of rule
96, and no drug meant for consumption by the Employees‘ State Insurance
Corporation, the Central Government Health Scheme, the Government Medical
Stores Depots, the Armed Forces Medical Stores or other Government institutions,
which bears a distinguishing mark or any inscription on the drug or on the label
affixed to the container thereof indicating this purpose shall be sold or stocked by the
licensee on his premises:]
5
[Provided that this sub-rule shall not be applicable to licensees who have been
appointed as approved chemists, by the State Government in writing, under the
employees‘ State Insurance Scheme, or have been appointed as authorised agent or
distributor, by the manufacturer in writing, for drugs meant for consumption under
the Central Government Health Scheme, the Government Medical Stores Depots, the
Armed Forces Medical Stores or other Government Institutions for drugs meant for
consumption under those schemes
6
[or have been appointed as authorised Depots or
Carrying and Forwarding agent by the manufacturer in writing, for storing free
samples meant for distribution to medical profession] subject to the conditions that
the stock shall be stored separately from the trade stocks and shall maintain separate
records of the stocks received and distributed by them.]
1. Ins. by Notfn. No. F. 1-55/61-D, dt. 22-8-1964.
2. Ins. by S. O. No. 903, dt. 28-2-1976.
3. Ins. by Notfn. No. 1-113/69-D, dt. 23-12-1969.
4. Subs. by G.S.R. 676(E) dt. 6-9-1994.
5. Subs. by G.S.R. 496(E) dt. 9-6-1995.
6. Ins. by G.S.R 352(E), dt. 26-4-2000.
Drugs and Cosmetics Rules 1945
79
1
[(19) The supply by retail of any drug in a container other than the one in which
the manufacturer has marketed the drug, shall be made only by dealers who employ
the services of a
2
[Registered Pharmacist] and such supply shall be made under the
direct supervision of the
2
[Registered Pharmacist] in an envelope or other suitable
wrapper or container showing the following particulars on the label:
(a) name of the drug,
(b) the quantity supplied,
(c) the name and address of the dealer.]
3
[(20) The medicines for treatment of animals kept in a retail shop or premises
shall be labelled with the words ‗Not for human use
and shall be stored
for treatment of animals only‘
(a) in a cupboard or drawer reserved solely for the storage of veterinary
drugs, or
(b) in a part of the premises separated from the remainder of the premises
to which customers are not permitted to have access.]
4
[(21) (a) The supply of drugs specified in Schedule X shall be recorded at the
time of supply in a register (bound and serially page numbered) specially maintained
for the purpose and separate pages shall be allotted for each drug.
(b) The following particulars shall be entered in the said register, namely:--
(i) Date of transaction;
(ii) Quantity received, if any, the name and address of the supplier and the
number of the relevant licence held by the supplier;
(iii) Name of the drug;
(iv) Quantity supplied;
(v) Manufacturer‘s name;
(vi) Batch No. or Lot No;
(vii) Name and address of the patient/purchaser;
(viii) Reference Number of the prescription against which supplies were
made;
(ix) Bill No and date in respect of purchases and supplies made by him;
(x) Signature of the person under whose supervision the drugs have been
supplied.]
1. Ins. by G. S. R. 444 dt. 28-4-1973.
2. Subs. by G.S.R 676 (E), dt. 6-9-1994.
3. Added by G. S. R. No. 926 dt. 16-7-1977.
4. Ins. by G.S.R 462 (E), dt. 22-6-1982.
Drugs and Cosmetics Rules 1945
80
1
[65A. Additional information to be furnished by an applicant for liscence or a
licensee to the Licensing Authority.
The applicant for the grant of a licence or any
person granted a licence under this Part shall, on demand, furnish to the licensing
authority, before the grant of the licence or during the period the licence is in force,
as the case may be, documentary evidence in respect of the ownership of occupation
or rental or other basis of the premises, specified in the application for licence or in
the licence granted, constitution of the firm, or any other relevant matter which may
be required for the purpose of verifying the correctness of the statements made by the
applicant or the licensee, while applying for or after obtaining the licence, as the case
may be.]
66. Cancellation and suspension of licences.
(1) The Licensing Authority may,
after giving the licensee an opportunity to show cause why such an order should not
be passed by an order in writing stating the reasons therefor, cancel a licence issued
under this Part or suspend it for such period as he thinks fit, either wholly or in
respect of some of the substances to which it relates, if in his opinion, the licensee has
failed to comply with any of the conditions of the licence or with any provisions of
the Act or Rules thereunder:
1
[Provided that, where such failure or contravention is the consequence of an act
or omission on the part of an agent or employee, the licence shall not be cancelled or
suspended if the licensee proves to the satisfaction of the licensing authority−
(a) that the act or omission was not instigated or connived at by him or, if the
licensee is a firm or company, by a partner of the firm or a director of the
company, or
(b) that he or his agent or employee had not been guilty of any similar act or
omission within twelve months before the date on which the act or omission in
question took place, or where his agent or employee had been guilty of any such act
or omission the licensee had not or could not reasonably have had, knowledge of that
previous act or omission, or
(c) if the act or omission was a continuing act or omission, he had not or could
not reasonably have had knowledge of that previous act or omission, or
(d) that he had used due diligence to ensure that the conditions of the licence or
the provisions of the Act or the Rules thereunder were observed.]
2
[(2) A licensee whose licence has been suspended or cancelled may, within three
months of the date of order under sub-rule (1), prefer an appeal against that order to
the State Government, which shall decide the same.]
3
[66A. Procedure for disposal of drugs in the event of cancellation of licence.—
(1) In case a licensee, whose licence has been cancelled, desires to dispose of the
drugs he has in his possession in the premises in respect of which the licence has been
cancelled, he shall apply in writing to the licensing authority for this purpose, giving
the following particulars, namely:—
1. Ins. by S. O. 2139, dt. 12-8-1972.
2. Subs. by G. S. R. 926 dt. 16-7-1977.
3. Ins. by G.S.R 1242 (E), dt. 17-9-1979.
Drugs and Cosmetics Rules 1945
81
(a) the name and address of the person to whom the drugs are proposed to
be sold or supplied together with the number of the licence for sale or
manufacture, as the case may be, held by him,
(b) the names of drugs together with their quantities, batch numbers, the
names and addresses of their manufacturers and the dates of their expiry, if any,
proposed to be sold to the person mentioned in clause (a).
(2) The licensing authority may, after examination of the particulars referred to in
sub-rule (1) and, if necessary, after inspection by an Inspector of the premises where
the drugs are stocked, grant the necessary permission for their disposal.]
6
[****]
1
[PART
VIA
SALE OF HOMOEOPATHIC
MEDICINES
67A. (1) The State Government shall appoint Licensing Authorities for the
purpose of this Part for such areas as may be specified.
(2) Application for the grant or renewal of a licence
2
[to sell, stock or exhibit or
offer for sale or distribute] Homoeopathic medicines shall be made in Form 19-B to
the Licensing Authority and shall be accompanied by a
3
[fee of rupees two hundred
and fifty]:
4
[Provided that if the applicant applies for renewal of licence after its expiry but
within six months of such expiry the fee payable for renewal of such licence shall be
3
[rupees two hundred and fifty plus an additional fee at the rate of rupees fifty or part
thereof].
5
[(3) If the original licence is either defaced, damaged or lost, a duplicate copy
thereof may be issued on payment of a
3
[fee of rupees fifty].]
67B. A Licensing Authority may, with the approval of the State Government, by
an order in writing, delegate the power to sign licences and such other powers, as may
be specified, to any other person under his control.
67C. Forms of licences to sell drugs.
(1) A licence
2
[to sell, stock or exhibit or
offer for sale or distribute] Homoeopathic medicines by retail or by wholesale shall
be issued in Form 20C or 20D as the case may be.
1. Added by Notfn. No. F. 1-35/64-D, dt. 18-8-1964.
2. Subs. by G.S.R 788(E) dt. 10-10-1985.
3. Subs. by G.S.R 601 (E), dt. 24-8-2001.
4. Amended by S. O. 2139 dt. 12-8-1972.
5. Added by G. S. R. 665, dt. 28-5-77.
6. Rule 67 omitted by SO 289 (E), dt. 20-12-1972.
Drugs and Cosmetics Rules 1945
82
67D. Sale at more than one place.
If drugs are sold or stocked for sale at more
than one place, a separate application shall be made and a separate licence shall be
obtained in respect of each place.
67E. Duration of licences.
An original licence or a renewed licence unless it is
sooner suspended or cancelled shall be
1
[valid for a period of five years on and from
the date on which] it is granted or renewed :
2
[Provided that if the application for renewal of a licence in force is made before
its expiry or if the application is made within six month of its expiry, after payment of
additional fee, the licence shall continue to be in force until orders are passed on the
application and the licence shall be deemed to have expired if application for its
renewal is not made within six months after its expiry.]
3
[67EE. Certificate of renewal.
The certificate of renewal of a sale licence in
Forms 20C and 20D shall be issued in Form 20E.]
67F. Condition to be satisfied before a licence in Form 20C or Form 20D is
granted.-(1) A licence in Form 20C or Form 20D to
4
[to sell, stock or exhibit or
offer for sale or distribute] Homoeopathic medicines shall not be granted to any
person unless the authority empowered to grant the licence is satisfied that the
premises in respect of which the licence is to be granted are clean and in the case of a
licence in Form 20C the sale premises is in charge of a person who is or has been
dealing in Homoeopathic medicines and who is in the opinion of the Licensing
Authority competent to deal in Homoeopathic medicines:
5
[Provided that no registered Homoeopathic medical practitioner who is
practising Homoeopathy in the premises where Homoeopathic medicines are sold
shall deal in Homoeopathic medicines.]
(2) Any person who is aggrieved by the order passed by the Licensing Authority
under sub-rule (1) may within 30 days from the date of the receipt of such order
appeal to the State Government and the State Government may, after such enquiry
into the matter as it considers necessary and after giving the appellant an opportunity
for representing his case, make such order in relation thereto as it thinks fit.
1. Subs. by G.S.R 601 (E), dt. 24-8-2001.
2. Subs. by S. O. 2139 dt. 5-6-1972.
3. Added by Notfn. No. F. 1-14/67-D, dt. the 3-2-1969.
4. Subs. by G.S.R 788 (E), dt. 10-10-1985.
5. Ins. by Notfn. No. G.S.R 680 (E), dt. 5-12-1980.
Drugs and Cosmetics Rules 1945
83
67G. Conditions of licence.
Licence in Form 20C or 20D shall be subject to
the conditions stated therein and to the following further conditions, namely:
(1) The premises where the Homoeopathic medicines are stocked for sale or
sold are maintained in a clean condition.
(2) The sale of Homoeopathic medicines shall be conducted under the
supervision of a person, competent to deal in Homoeopathic medicines.
(3) The licensee shall permit an Inspector to inspect the premises and
furnish such information as he may require for ascertaining whether the
provisions of the Act and the Rules made thereunder have been observed.
(4) The licensee in Form 20D shall maintain records of purchase and sale
of Homoeopathic medicines containing alcohol together with names and
addresses of parties to whom sold.
1
[(5) The licensee in Form 20C shall maintain records of purchase and sale
of Homoeopathic medicines containing alcohol. No records of sale in respect
of Homoeopathic potentised preparation in containers of 30 ml. or lower
capacity and in respect of mother tinctures made up in quantities up to 60 ml.
need be maintained.]
2
[(6) The licensee shall maintain an Inspection Book in Form 35 to enable
an Inspector to record his impressions and the defects noticed.]
3
[67GG. Additional information to be furnished by an applicant for licence or a
licensee to the Licensing Authority.
The applicant for the grant of a licence or any
person granted a licence under this Part shall, on demand furnish to the Licensing
Authority, before the grant of the licence or during the period the licence is in force
as the case may be, documentary evidence in respect of the ownership or occupation
or rental or other basis of the premises, specified in the application for licence or in
the licence granted, constitution of the firm, or any other relevant matter, which
may be required for the purpose of verifying the correctness of the statements made
by the applicant or the licensee, while applying for or after obtaining the licence, as
the case may be.]
1. Ins. by Notfn. No. F. 1-59/68-D, dt. the 19-11-1969.
2. Ins. by G.S.R 331 (E), dt. 8-5-1984.
3. Ins. by S. O. 2139 dt. 5-6-1972.
Drugs and Cosmetics Rules 1945
84
67-H. Cancellation and suspension of licences.
(1) The Licensing Authority
may, after giving the licensee an opportunity to show cause why such an order should
not be passed by an order in writing stating the reasons therefor, cancel a licence
issued under this Part or suspend it for such period as he thinks fit, if in his opinion,
the licensee has failed to comply with any of the conditions of the licence or with any
provisions of the Act or Rules made thereunder:
1
[Provided that, where such failure or contravention is the consequence of an act
or omission on the part of an agent or employee, the licence shall not be cancelled or
suspended if the licensee proves to the satisfaction of the Licensing
Authority
−
(a) that the act or omission was not instigated or connived at by him or, if
the licensee is a firm or company, by a partner of the firm or a director of the
company, or
(b) that he or his agent or employee had not been guilty of any similar act
or omission within twelve months before the date on which the act or omission
in question took place, or where his agent or employee had been guilty of any
such act or omission, the licensee had not or could not reasonably have had,
knowledge of that previous act or omission, or
(c) if the act or omission was a continuing act or omission that he had not
or could not reasonably have had knowledge of that previous act or omission,
or
(d) that he had used due diligence to ensure that the conditions of the
licence or the provisions of the Act or the Rules thereunder were observed.]
2
[(2) A licensee whose licence has been suspended or cancelled may, within three
months of the date of the order under sub-rule (1), prefer an appeal against that order
to the State Government, which shall decide the same.]
1. Ins. by S. O. 2139 dt. 5-6-1972.
2. Amended by G.S.R. 926 dt. 16-7-1977.
Drugs and Cosmetics Rules 1945
85
PART
VII
1
[MANUFACTURE FOR SALE OR FOR DISTRIBUTION] OF DRUGS
OTHER THAN HOMOEOPATHIC MEDICINES
68. Manufacture on more than one set of premises.
If drugs are manufactured
on more than one set of premises a separate application shall be made and a separate
licence shall be issued in respect of each such set of premises.
2
[68-A. Grant or Renewal of Licences by the Central Licence Approving
Authority.— (1) Notwithstanding anything contained in this Part, on and from the
commencement of the Drugs and Cosmetics (Amendment) Rules,1992, a licence for
the manufacture for sale or distribution of drugs as specified from time to time by the
Central Government by notification in the Official Gazette, for the purpose of this
rule, shall be granted or renewed, as the case may be, by the Central Licence
Approving Authority (appointed by the Central Government):]
Provided that the application for the grant or renewal of such licence
shall be made to the Licensing Authority.
(2) On receipt of the application for grant or renewal of a licence, the licensing
authority shall,-
(i) verify the statement made in the application form;
(ii) cause the manufacturing and testing establishment to be inspected in
accordance with the provisions of rule 79; and
(iii) in case the application is for the renewal of licence, call for the
information(s) of the past performance of the licensee.
(3) If the licensing authority is satisfied that the applicant is in a position to fulfil
the requirements laid down as in these Rules, he shall prepare a report to that effect
and forward it along with the application
3
[and the licence (in triplicate) to be
granted and renewed, duly completed] to the Central Licence Approving Authority:
Provided that if the licensing authority is of the opinion that the applicant is not
in
a position to fulfil the requirements laid down in these Rules, he may, by order, for
reasons to be recorded in writing, refuse to grant or renew the licence, as the case may
be.
(4) If on receipt of the application and the report of the licensing authority
referred to in sub-rule (3) and after taking such measures including inspection of the
premises by the Inspector, appointed by the Central Government under section
21 of the Act, with or without an expert in the concerned field if deemed
necessary, the Central Licence Approving Authority, is satisfied that the applicant
1. Subs. by G.S.R 788 (E), dt. 10-10-1985.
2. Ins. by G.S.R 923 (E), dt. 14-12-1992.
3. Subs. by G.S.R 89 (E), dt. 14-2-1996.
Drugs and Cosmetics Rules 1945
86
is in a position to fulfil the requirements laid down in these Rules, he may grant or
renew the licence, as the case may be:
Provided that if the Central Licence Approving Authority is of the opinion that
the applicant is not in a position to fulfil the requirements laid down in these rules, he
may, notwithstanding the report of the licensing authority, by order, for reasons to be
recorded in writing, reject the application for grant or renewal of licence, as the case
may be.]
1
[68B. Delegation of Powers by the Central Licence Approving Authority.—The
Central Licence Approving Authority may with the approval of the Central
Government, by notification delegate his powers of signing licences and any other
powers under the rules to any person under his control having same qualifications as
prescribed for controlling authority under Rule 50A for such areas and for such
periods as may be specified.]
2
[69. Application for licence to manufacture drugs other than those specified in
Schedules C and C(I) to the Drugs and Cosmetics Rules.
3
[(1) Application for grant
or renewal of
4
[licence to manufacture for sale or for distribution] of drugs, other than
those specified in Schedules C and C(I) shall be made to the licensing authority
appointed by the State Government for the purpose of this Part (hereinafter in this
Part referred to as the licensing authority) and shall be made
(a) in the case of repacking of drugs excluding those specified in Schedule
X for sale or distribution in, Form 24B;
(b) in the case of manufacture of drugs included in Schedule X, in Form
24F;
(c) in any other case, in Form 24.]
5
[(2)(a) Every application in Form 24B shall be made up to ten items for each
category of drugs categorised in Schedule M and shall be accompanied by a licence
fee of rupees five hundred plus and an inspection fee of rupees two hundred for every
inspection or for the purpose of renewal of the licence.
1. Ins. by G.S.R 89 (E), dt. 14-02-1996.
2. Amended by Notfn. F. 1-22/59-D, dt. 9-4-1960.
3. Subs. by G.S.R 462 (E), dt. 22-06-1982.
4 Subs. by G.S.R.788 (E), dt. 10-10-1985.
5. Subs. by G.S.R 601(E), dt. 21-8-2001.
Drugs and Cosmetics Rules 1945
87
(b) Every application in Form 24F shall be made up to ten items for each
category of drugs categorised in Schedule M and shall be accompanied by a licence
fee of rupees six thousand and an inspection fee of rupees one thousand and five
hundred for every subsequent inspection or for the purpose of renewal of licence.
(c) Every application in Form 24 shall be made up to ten items for each category
of drugs
3
[referred to in Schedule M relating to pharmaceuticals products and
Schedule MIII relating to medical devices and in-vitro diagnostics] and shall be
accompanied
by
a licence fee of rupees six thousand and an inspection fee of one
thousand and five hundred for every inspection or for the purpose of renewal of the
licence.]
1
[(3) If a person applies for the renewal of a licence after the expiry thereof but
within six months of such expiry the fee payable for the renewal of such licence shall
be
−
]
2
[(i) in the case of Form 24B a licence fee of rupees five hundred plus an
additional fee at the rate of rupees two hundred and fifty per month or part
thereof in addition to an inspection fee of rupees two hundred;
(ii) in the case of Form 24F a licence fee of rupees six thousand plus an
additional fee at the rate of rupees one thousand per month or part thereof in
addition to an inspection fee of rupees one thousand;
(iii) in the case of Form 24 a licence fee of rupees six thousand plus an
additional fee at the rate of rupees one thousand per month or part thereof in
addition to an inspection fee of rupees one thousand and five hundred.]
1
[(4) A fee
2
[rupees one thousand shall be paid] for a duplicate copy of the
licence issued under clause (a), clause (b) or clause (c) of sub-Rule (1) if the original
is defaced, damaged or lost.]
2
[(5) Applications for manufacture of more than ten items of each category of
drugs as categorized under Schedule M and M-III or for manufacture of additional
items of drugs by licensees in Form 24 or Form 24F shall be accompanied by an
additional fee at the rate of rupees three hundred for each additional item of drug.
Applications in Form 24B for licence to manufacture for sale and distribution for
repacking for more than 10 items of each category or for manufacture of additional
item of drug shall be accompanied by additional fee of rupees one hundred for each
additional item of drugs as cetegorized in Schedule M and M-III].
1. Subs. by G.S.R 462 (E), dt. 22-6-1982.
2. Subs. by G.S.R 26 (E), dt. 19-1-2006.
3. Subs. by G.S.R 640 (E), dt. 29-6-2016.
Drugs and Cosmetics Rules 1945
88
1
[(6) Where an application under this Rule is for the manufacture of drug
formulations falling under the purview of new drug as defined in rule 122E, such
application shall also be accompanied with approval, in writing in favour of the
applicant, from the licensing authority as defined in clause (b) of rule 21.]
2
[69A. Loan
Licences.
⎯
3
[(1)
Application for the grant or renewal of loan
licences to manufacture for sale or for distribution of drugs other than those specified
in Schedule C, Schedule C (1) and Schedule X shall be made up to ten items for each
category of drugs
5
[referred to in Schedule M relating to pharmaceuticals products and
Schedule M-III relating to medical devices and in-vitro diagnostics] and shall be made
in Form 24A accompanied by a licence fee of rupees six thousand and an inspection
fee of rupees one thousand and five hundred to the licensing authority:
Provided that if the applicant applies for the renewal of a licence after its expiry
but within six months of such expiry, the fee payable for renewal of such licence shall
be accompanied by a licence fee of rupees six thousand and an inspection fee of
rupees one thousand and five hundred plus an additional fee at the rate of rupees one
thousand per month or part thereof.]
4
[Explanation.- For the purpose of this rule a loan licence means a licence which
the Licensing Authority may issue to an applicant who does not have his own
arrangements for manufacture but who intends to avail himself of the manufacturing
facilities owned by a licensee in Form 25.]
(2) The Licensing Authority shall, before the grant of a loan licence, satisfy
himself that the manufacturing unit has adequate equipment, staff, capacity for
manufacture, and facilities for testing, to undertake the manufacture on behalf of the
applicant for a loan licence.
3
[(3) Subject to the provisions of sub-rule (2), application for manufacture of
more than ten items for each category of drug on a loan licence shall be accompanied
by an additional fee of rupees three hundred per additional item specified
5
[referred to
in Schedule M relating to pharmaceuticals products and Schedule MIII relating to
medical devices and in-vitro diagnostics].
1. Ins. by G.S.R 311 (E), dt. 1-5-2002.
2. Amended by Notfn. No. F. 1-16/57-D, dt. 15-6- 1957.
3. Subs. by G.S.R 601(E) dt. 24-8-2001.
4. Subs. by G.S.R 724(E) dt. 07-11-2013.
5. Subs. by G.S.R 640 (E), dt. 29-6-2016.
Drugs and Cosmetics Rules 1945
89
1
[(4) If the Licensing Authority is satisfied that a loan licence is defaced,
damaged or lost or otherwise rendered useless, he may, on payment of a
2
[fee of
rupees one thousand] issue a duplicate licence.]
3
[* * * *
*]
4
[70. Form of licence to repack or manufacture drugs other than those specified
in Schedules C and C(1).-
Licences for repacking of drugs against application in Form 24-B shall be granted in
Form 25-B, licences for manufacture of drugs included in Schedule X and against
application in Form 24-F shall be granted in Form 25-F and licences for manufacture
of drugs against application in Form 24 shall be granted in Form 25.]
5
[70A. Form of loan
6
[licence to manufacture for sale or for distribution] of drugs
other than those
7
[specified in Schedules C, C(1) and
X].
⎯
A loan
6
[licence to manufacture for sale or for distribution] or drugs other than those
7
[specified in Schedules C, C(1) and X] shall be issued in Form 25A.]
8
[71. Conditions for the grant or renewal of a licence in Form 25
9
[or Form
25F].
⎯
Before a licence in Form 25
9
[or Form 25F] is granted or renewed, the
following conditions shall be complied with by the applicant.-
(1) The manufacture shall be conducted under the active direction and
personal supervision of competent technical staff consisting at least of one person
who is a whole-time employee and who is
(a) a graduate in Pharmacy or Pharmaceutical Chemistry of
10
[a
University established in India by law or has an equivalent qualification
recognised and notified by the Central Government for such purpose] and
has had at least eighteen months practical experience after the graduation in
the manufacture of drugs. This period of experience may, however, be
reduced by six months if the person has undergone training in manufacture of
drugs for a period of six months during his University course; or
(b) a graduate in Science of
10
[a University established
in India by law or has an equivalent qualification recognized and
notified by the Central Government for such purpose] who for the purpose
of his degree has studied Chemistry as a principal subject and has
1. Ins. by Notfn. No. F.1-20/64-D, dt. 26.10.1968.
2. Subs. by Notfn. No. G.S.R. 601 (E), dt. 24.8.2001.
3. Rule 69 omitted by G.S.R. 944 (E), dt. 21-9-1988.
4. Subs. by Notfn. No. G.S.R. 462 (E), dt. 22.6.1982.
5. Ins. by Notfn. No. F.1-16/57 D, 15-6-1957 & No. F.1/22/59-D, dt. 9.4.1960.
6. Subs. by Notfn. No. G.S.R. 788 (E), dt. 10-10-1985.
7. Subs. by Notfn. No. G.S.R. 462 (E), dt. 22-6-1982.
8. Subs. by Notfn. No. F.1-16/57-D, dt. 15-6-1957.
9. Ins. by G.S.R. 462(E), dt. 22-6-1982.
10. Subs. by Notfn. No. G.S.R. 71 (E), dt. 30-1-1987.
Drugs and Cosmetics Rules 1945
90
had at least three years practical experience in the manufacture of drugs after
his graduation; or
(c) a graduate in Chemical Engineering or Chemical Technology or Medicine
of
1
[a University established in India by law or has an equivalent qualification
recognised and notified by the Central Government for such purpose] with
general training and practical experience, extending over a period of not less
than three years in the manufacture of drugs, after his graduation; or
2
[(d) holding any foreign qualification the quality and content of training of
which are comparable with those prescribed in clause (a), clause (b) or clause
(c) and is permitted to work as competent technical staff under this Rule by the
Central Government:]
Provided that any person who was immediately before the 29th June, 1957,
actively directing and personally supervising the manufacture of drugs and whose
name was accordingly entered in any licence granted in Form 25
3
[or Form 25F] as it
existed before the date shall be deemed to be qualified for the purposes of this rule:
4
[Provided further that for drugs other than those specified in Schedules C, C(1)
and X and meant for veterinary use, the whole-time employee under whose
supervision the manufacture is conducted shall be a graduate in Veterinary Science or
Pharmacy or General Science or Medicine of a University recognized by the Central
Government and who has had at least three years practical experience in the
manufacture of drugs excluding graduate in Pharmacy who shall have at least
eighteen months practical experience in the manufacture of drugs:]
5
[Provided
6
[also] that the Licensing Authority may, in the matter of manufacture
of disinfectant fluids, insecticides, liquid paraffin, medicinal gases, non-chemical
contraceptives, plaster of Paris and surgical dressings, for the manufacture of which
the knowledge of Pharmaceutical Chemistry or Pharmacy is not essential, permit the
manufacture of the substance under the active direction and personal supervision of
the competent technical staff, who, although not having any of the qualifications
included in clause (a), (b) or (c) of this rule, has, in the opinion of the Licensing
Authority, adequate experience in the manufacture of such substance.]
1. Subs. by G.S.R. 71(E), dt. 30-1-1987.
2. Added by Notfn. NO. F. 1-19/59-D, dt. 13-6-1961.
3. Ins. by. G.S.R. 462 (E), dt. 22-6-1982.
4. Ins. by. G.S.R. 93 (E), dt. 24-2-1999.
5. Added Notfn. No. F. 1-14/68-D, dt. the 26-10-1968.
6. Sub. by. G.S.R. 93 (E), dt. 24-2-1999.
Drugs and Cosmetics Rules 1945
91
(2) The factory premises shall comply with the conditions prescribed in
Schedule M.
(3) The applicant shall provide adequate space, plant and equipment for the
manufacturing operations; the space, plant and equipment recommended for various
operations are given in Schedule M.
1
[(4) The applicant shall provide and maintain adequate staff, premises and
laboratory equipment for carrying out tests of the strength, quality and purity of the
substances at a testing unit, which shall be separate from the manufacturing unit and
the head of the testing unit shall be independent of the head of the manufacturing
unit :
Provided that the manufacturing units, which, before the commencement of the
Drugs and Cosmetics (Amendment) Rules, 1977, were making arrangements with
institutions approved by the Licensing Authority for such tests to be carried out on
their behalf may continue such arrangements up to the 30th June, 1977 :
Provided further that for tests requiring sophisticated instrumentation techniques
or biological or microbiological methods other than sterility the Licensing Authority
may permit such tests to be conducted by institutions approved by it
4
[ under
Part XV(A) of these rules] for this purpose.]
2
[(4A) The head of the testing unit referred to in condition (4) shall possess a
degree in Medicine or Science or Pharmacy or Pharmaceutical Chemistry of a
University recognized for this purpose and shall have experience in the testing of
drugs, which in the opinion of the licensing authority is considered adequate.]
(5) The applicant shall make adequate arrangements for the storage of drugs
manufactured by him.
3
[(6) The applicant shall, while applying for a licence to manufacture patent or
proprietary medicines, furnish to the Licensing Authority evidence and data justifying
that the patent or proprietary medicines
(i) contain the constituent ingredients in therapeutic/prophylactic quantities
as determined in relation to the claims or conditions for which the medicines
are recommended for use or claimed to be useful;
1. Subs. by G.S.R. 926 dt. 16-7-1977.
2. Ins. by G.S.R. 681(E), dt. 5-12-1980.
3. Ins. by G.S.R. 515 dt. 10-4-1976.
4. Ins. by G.S.R. 1172 dt. 23-8-1977.
Drugs and Cosmetics Rules 1945
92
(ii) are safe for use in the context of the vehicles, excipients, additives and
pharmaceutical aids used in the formulation and under the conditions in which
the formulation for administration and use are recommended;
(iii) are stable under the conditions of storage recommended;
(iv) contain such ingredients and in such quantities for which there is
therapeutic justification; and]
1
[(v) have the approval, in writing, in favour of the applicant to manufacture
drugs formulations falling under the purview of new drug as defined in Rule
122-E, from the Licensing Authority as defined in clause (b) of rule 21.]
2
[(7) The licensee shall comply with the requirements of Good Manufacturing
Practices as laid down in Schedule M.]
6
[(8) The applicant shall make application for grant of licence for a drug formulation
containing single active ingredient only in proper name.]
3
[71A. Conditions for the grant or renewal of a licence in Form 25B. Before a licence in
Form 25B is granted or renewed the following conditions shall be complied with by the
applicant :-
(1) the repacking operation shall be carried out under hygienic conditions and
under the supervision of a competent person;
4
[(2) the factory premises shall comply with the conditions prescribed in
Schedule M; and]
5
[(3) the applicant shall have adequate arrangements in his own premises for
carrying out tests for the strength, quality and purity of the drugs at a testing unit
which shall be separate from the repacking unit:]
6
[(4) The application for grant of licence for a drug formulation containing single
active ingredient shall be made only in proper name:]
Provided that the repacking units, which before the commencement of the Drugs
and Cosmetics (Second Amendment) Rules, 1977, were making arrangements with
institutions approved by the licensing authority for such tests to be carried out on their
behalf, may continue such arrangements up to the 31st July, 1977:
1. Ins. by G.S.R. 311 (E), dt. 1-5-2002.
2. Ins. by G.S.R. 735 (E), dt. 24-6-1988.
3. Ins. by No. F.1-22/59-D, dt. 9-4-1960.
4. Amended by S.O. 2139 dt. 12-8-1972.
5. Amended by G.S.R. 926 dt. 16-7-1977.
6. Ins. by G.S.R. 570 (E), dt. 7-8-2014.
Drugs and Cosmetics Rules 1945
93
Provided further that for tests requiring sophisticated instrumentation techniques
or biological or microbiological methods the licensing authority may permit such test
to be conducted by institutions approved by it under Part XV(A) of these Rules for
this purpose.]
Explanation.−A person who satisfies the following minimum qualifications shall
be deemed to be a ―competent person‖ for the purposes of rule 71A or 74A of these
rules, namely: −
(a) a person who holds the Diploma in Pharmacy approved by the Pharmacy
Council of India under the Pharmacy Act, 1948 (VIII of 1948) or a person who is
registered under the said Act, or
(b) a person who has passed the Intermediate examination with Chemistry
as one of the principal subjects or an examination equivalent to it or an
examination recognized by the Licensing Authority as equivalent to it; or
(c) a person who has passed the Matriculation examination or an
examination recognized by the Licensing Authority as equivalent to it and has
had not less than four years‘ practical experience in the manufacture,
dispensing or repacking of drugs.]
1
[71B. Conditions for the grant of renewal of a licence in Form 25A.− Before a
licence in Form 25A is granted or renewed, the applicant shall, while applying for a
licence to manufacture patent or proprietary medicines, furnish to the Licensing
Authority evidence and data justifying that the patent or proprietary medicines:-
(i) contain the constituent ingredients in therapeutic/prophylactic quantities as
determined in relation to the claims or conditions for which the medicines are
recommended for use or claimed to be useful;
(ii) are safe for use in the context of the vehicles, recipients, additives and
pharmaceutical aids used in the formulations and under conditions in which the
formulations for administration and use are recommended;
(iii) are stable under the conditions of storage recommended; and
(iv) contain such ingredients and in such quantities for which there is
therapeutic justification.
2
[Provided that the application for grant of a licence for a drug formulation
containing single active ingredient shall be made only in proper name.]
1. Ins. by G.S.R. 515 (E), dt. 24-3-1976.
2. Ins. by G.S.R. 570 (E), dt. 7-8-2014.
Drugs and Cosmetics Rules 1945
94
1
[72. Duration of licence.–An original licence or a renewed licence in
Form 25,
2
[Form 25B or Form 25F] unless sooner suspended or cancelled shall be
3
[valid for a period of five years on and from the date on which] it is granted or
renewed:
4
[
Provided that if the application for the renewal of a licence is made before its
expiry, or if the application is made within six months of its expiry, after payment of
additional fee, the licence shall continue to be in force until orders are passed on the
application and the licence shall be deemed to have expired if the application for its
renewal is not made within six months of its expiry.]
2
[73. Certificate of renewal.– The certificate of renewal of a licence in Form 25 or
Form 25F shall be issued in Form 26 or Form 26E respectively].
5
[73A. A certificate of renewal of loan licence.- The certificate of renewal of a
loan licence in Form 25A shall be issued in Form 26A.]
5
[73AA. Duration of loan licence.– An original loan licence in Form 25A or a
renewed loan licence in Form 26A, unless sooner suspended or cancelled, shall be
3
[valid for a period of five years on and from the date on which] it is granted or
renewed:]
6
[Provided that if the application for the renewal of a licence is made before its
expiry, or if the application is made within six months of its expiry, after payment of
additional fee, the licence shall continue to be in force until orders are passed on the
application and the licence shall be deemed to have expired if the application for its
renewal is not made within six months of its expiry.]
7
[73B. Certificate of renewal of licence in Form 25B.–The certificate of renewal
of a licence in Form 25B shall be issued in Form 26B.]
1. Subs. by Notfn. No. F.1-10/62-D, dt. 10-4-1964.
2. Subs. by G.S.R. 462 (E), dt. 22-6-1982.
3. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
4. Amended by S.O. 2139 dt. 12-8-1972.
5. Amended by Notfn. No. F.1-10/62-D, dt. 10-4-1964.
6. Amended by S.O. 2139 dt. 12-8-1972.
7. Ins. by S.O. 1196, dt. 6-5-1960.
Drugs and Cosmetics Rules 1945
95
1
[74. Conditions of licence in Form 25.−A licence in
2
[Form 25 and Form
25F] shall be subject to the conditions stated therein and to the following
further conditions, namely :
(a) the licensee shall provide and maintain staff, premises and the
equipment as specified in rule 71;
(b) the licensee shall comply with the provisions of the Act and of these
rules and with such further requirements, if any, as may be specified in any
rules subsequently made under Chapter IV of the Act; provided that where
such further requirements are specified in the Rules, these would come into
force, four months after publication in the Official Gazette;
(c) the licensee shall either in his own laboratory or in any other laboratory
approved by the Licensing Authority
4
[under Part XV (A) of these rules]
test each batch or lot of the raw material used by him for the manufacture of
his products and also each batch of the final product and shall maintain records
or registers showing the particulars in respect of such tests as specified
in Schedule U. The records or registers shall be retained for a period of 5
years from the date of manufacture;
(d) the licensee shall keep records of the details of manufacture as per
particulars given in Schedule U of each batch of the drugs manufactured by
him and such records shall be retained for a period of five years;
(e) the licensee shall allow an
3
[Inspector appointed under the Act], to
enter, with or without prior notice, any premises and to inspect the plant and
the process of manufacture and the means employed in standardizing and
testing the drugs;
(f) the licensee shall allow an
3
[Inspector appointed under the Act] to
inspect all registers and records maintained under these rules and to take
samples of the manufactured drugs and shall supply to such Inspector such
information as he may require for the purpose of ascertaining whether the
provisions of the Act and the rules thereunder have been observed;
(g) the licensee shall, from time to time, report to the Licensing Authority
any changes in the expert staff responsible for the manufacture or testing of the
drugs and any material alterations in the premises or plant used for the purpose
which have been made since the date of the last inspection made on behalf
of the licensing authority;
1. Subs. by Notfn. No. F. 1-20/64-D (S.O. 3868), dt. 26-10-1968.
2. Subs. by G.S.R. 462 (E), dt. 22-6-1982.
3. Amended by G.S.R. 444 dt. 28-4-1973.
4. Ins. by G.S.R. 1172 (E), dt. 23-8-1977.
Drugs and Cosmetics Rules 1945
96
1
[(h) the licensee shall, on request, furnish to the Licensing Authority, the
Controlling Authority or to such authorities as the Licensing Authority or the
Controlling Authority may direct from every batch, or batches of drugs as the
Licensing Authority or the Controlling Authority may from time to time
specify, a sample of such quantity as may be considered adequate by such
authority for any examination and, if so required, also furnish full protocols of
tests which have been applied;]
(i) if the Licensing Authority
2
[or the Controlling Authority] so directs and
if requested by the licensee who had also furnished prima facie reasons for
such directions, the licensee shall not sell or offer for sale any batch in respect
of which a sample is or protocols are furnished under clause (h) until a
certificate authorizing the sale of the batch has been issued to him by or on
behalf of the Licensing Authority
2
[or the Controlling Authority;
(j) the licensee shall on being informed by the Licensing Authority
2
[or the
Controlling Authority] that any part of any batch of the drug has been found by
the Licensing Authority
2
[or the Controlling Authority]not to conform with the
standards of strength, quality or purity specified in these rules and on being
directed so to do, withdraw the remainder of the batch from sale, and, so far as
may in the particular circumstances of the case be practicable, recall all issues
already made from that batch;
(k) the licensee shall maintain an Inspection Book in Form 35 to enable an
Inspector to record his impressions and the defects noticed;
1
[(l) the licensee shall maintain reference samples from each batch of the
drugs manufactured by him in a quantity which is at least twice the quantity of
the drug required to conduct all the tests performed on the batch. In case of
drugs bearing an expiry date on the label, the reference samples shall be
maintained for a period of three months beyond the date of expiry or potency.
In case of drugs where no date of expiry of potency is specified on the label,
the reference samples shall be maintained for a period of three years from the
date of manufacture;]
2
[(m) the licensee, who has been granted a licence in Form 25F, shall-
(i) forward to the licensing authority of the concerned States of
manufacture and supply of the drug a statement of the sales effected to
manufacturers, wholesalers, retailers, hospitals, dispensaries and nursing
homes and Registered Medical Practitioners every three months;
(ii) maintain accounts of all transactions giving details as
indicated below in a register bound and serially page numbered and such
records shall be retained for a period of five years or one year after the
expiry of potency, whichever is later:-
1. Subs. by G.S.R. No. 444 dt. 31-3-1973.
2. Ins. by G.S.R. No. 444 dt. 31-3-1973.
3. Ins. by G.S.R. 462 (E), dt. 22-6-1982.
Drugs and Cosmetics Rules 1945
97
A. Accounts of the drugs specified in Schedule X used for the
manufacture:
1. Date of issue.
2. Name of the drug.
3. Opening balance of stock on the production day.
4. Quantity received, if any, and source from where received.
5. Quantity used in manufacture.
6. Balance quantity on hand at the end of the production day.
7. Signature of the person in charge.
B. Accounts of production:
1. Date of manufacture.
2. Name of the drug.
3. Batch Number.
4. Quantity of raw material used in manufacture.
5. Anticipated yield.
6. Actual yield,
7 Wastage,
8. Quantity of the manufactured goods transferred.
C. Accounts of the manufactured
drugs:
1. Date of manufacture.
2. Name of the drug.
3. Batch Number.
4. Opening Balance.
5. Quantity manufactured.
6. Quantity sold.
7. Name of the purchaser and his address.
8. Balance quantity at the end of the day.
9. Signature of the person in charge.
(n) the licensee shall store drugs specified in Schedule X in bulk form
and when any of such drug is required for manufacture in a place other than
its place of storage it shall be kept in a separate place under the direct
custody of a responsible person;]
1
[(o) the licensee shall comply with the requirements of
2
[Good
Laboratory Practices as laid down in Schedule L-I and] ‗Good
Manufacturing Practices‘ as laid down in Schedule M.]
3
[(p) No advertisement of the drugs specified in Schedule H, Schedule
H1 and Schedule X shall be made except with the previous sanction of the
Central Government.]
1. Ins. by G.S.R. 735 (E), dt. 24-6-1988.
2. Ins by G.S.R. 780 (E), dt. 10-11-2008.
3. Ins by G.S.R. 289 (E), dt. 15-04-2015.
Drugs and Cosmetics Rules 1945
98
74A. Conditions for licence in Form 25B.
_
A licence in Form 25B shall be
subject to the conditions stated therein and to the following conditions:
_
(a) the repacking of drugs shall at all times be conducted under the personal
supervision of at least one person who is approved as a competent person by
the Licensing Authority;
(b) the licensee shall either provide and maintain adequate arrangements in
his own premises for carrying out tests of the strength, quality and purity of the
drugs repacked or make arrangements with some institution approved by the
Licensing Authority
3
[under Part XV (A) of these rules] for such tests to be
regularly carried out on his behalf by the institution;
(c) the licensee shall make adequate arrangements for the storage of drugs;
2
[(d) the licensee shall comply with the provisions of the Act and of these
rules and with such further requirements, if any, as may be specified in any
rules subsequently made under Chapter IV of the Act:
Provided that where such further requirements are specified in the Rules,
these would come into force four months after publication in the Official
Gazette.]
(e) the licensee shall allow any
4
[Inspector appointed under the Act] to
enter with or without notice, any premises where the packing of drugs in
respect of which the licence is issued is carried on, to inspect the premises and
to take samples of repacked drugs;
2
[(f) the licensee shall, either in his own laboratory or, in any other laboratory
approved by the Licensing Authority, test each batch or lot of raw material
used by him for repacking and also each batch of the product thus repacked
and shall maintain records or registers showing the particulars in respect of
such tests as specified in Schedule U. The records or registers shall be
retained for a period of five years from the date of repacking. The licensee
shall allow the Inspector to inspect all registers and records maintained under
these rules and shall supply to the Inspector such information as he may require
for the purpose of ascertaining whether the provisions of the Act and these
rules have been observed;]
1. Ins. by G.S.R. 735 (E), dt. 24-6-1988.
2. Subs. by Notfn. No. F.1-20/64-D, dt. 26-10-1968.
3. Ins. by G.S.R. 1172 (E), dt. 23-8-1977.
4. Subs. by G.S.R. 444 (E), dt. 31-3-1973.
Drugs and Cosmetics Rules 1945
99
1
[(g) the licensee shall maintain an Inspection Book, in Form 35, to enable
an Inspector to record his impressions and the defects noticed;]
2
[(h) the licensee shall maintain reference samples from each batch of the
drugs manufactured by him in a quantity which is at least twice the quantity of
the drug required to conduct all the tests performed on the batch. In case of
drugs bearing an expiry date on the label, the reference sample shall be
maintained for a period of three months beyond the date of expiry of potency.
In case of drugs where no date of expiry of potency is specified on the label,
the reference samples shall be maintained for a period of three years from the
date of manufacture.
4
[(i) No advertisement of the drugs specified in Schedule H, Schedule H1 or
Schedule X shall be made
except
with the previous sanction of the Central
Government.]
3
[74B.Conditions of licence in Form 25A.
(1) The licence in Form 25A
shall be deemed to be cancelled or suspended, if the licence owned by the
licensee in Form 25, whose manufacturing facilities have been availed of by
the licensee, is cancelled or suspended, as the case may be, under these rules.
(2) The licensee shall comply with the provisions of the Act and of these rules
and with such further requirements if any, as may be specified in any rules
subsequently made under Chapter IV of the Act; provided that where such further
requirements are specified in the rules, these would come into force four months after
publication in the Official Gazette.
(3) The licensee shall test each batch or lot of the raw material used by him for
the manufacture of his products and also each batch of the final product and shall
maintain records or registers showing the particulars in respect of such tests as
specified in Schedule U. The records or registers shall be retained for a period of five
years from the date of manufacture. The licensee shall allow an Inspector to inspect
all registers and records maintained under these rules and shall supply to the Inspector
such information as he may require for the purpose of ascertaining whether the
provisions of the Act and these rules have been observed.
1. Ins. by Notfn. No. 1-14/68-D, dt. 26-10-1968.
2. Ins. by G.S.R. 444 (E) dt. 31-3-1973 .
3. Subs. by Notfn. No. F. 1-14/68-D, dt. the 26-10-1968.
4. Ins. by G.S.R. 289 (E) dt. 15-4-2015.
Drugs and Cosmetics Rules 1945
100
(4) The licensee shall either-
(i) provide and maintain to the satisfaction of the Licensing Authority
adequate staff and adequate laboratory facilities for carrying out test of the
strength, quality and purity of the substances manufactured by him, or
(ii) make arrangements with some institution approved by the Licensing
Authority
7
[under Part XV (A) of these rules] for such tests to be regularly
carried out on his behalf by the institution.
1
[(5) The licensee shall maintain reference samples from each batch of the drugs
manufactured by him in a quantity which is at least twice the quantity of the drug
required to conduct all the tests performed on the batch. In case of drugs bearing an
expiry date on the label the reference samples shall be maintained for a period of
three months beyond the date of expiry of potency. In case of drugs where no date of
expiry of potency is specified on the label, the reference samples shall be maintained
for a period of three years from the date of manufacture.]
2
[(6) The licensee shall maintain an Inspection Book in Form 35 to enable an
Inspector to record his impressions and the defects noticed.]
8
[(7)
No advertisement of the drugs specified in Schedule H, Schedule H1 or
Schedule X shall be made
except
with the
previous
sanction of the Central
Government.]
3
[75. Form of application for licence to manufacture for sale or distribution of
drugs specified in Schedules C and C(1) and X
4
[excluding those specified in Part XB
and Schedule X].
_
(1) Applications for the grant or renewal of licence to manufacture
for sale or distribution of drugs specified in Schedules C and C(1)
4
[excluding those
specified in Part X-B and Schedule X], shall be made to the Licensing Authority in
Form 27 and
5
[shall be made up to ten items for each category of drugs
6
[referred to in
Schedule M relating to pharmaceuticals products and Schedule M-III relating to
medical devices and in-vitro diagnostics] and shall be accompanied by a licence fee
of rupees six thousand and an inspection fee of rupees one thousand and five hundred
for every inspection or for the purpose of renewal of licences:]
Provided that if the applicant applies for renewal of licence after its expiry but
within six months of such expiry, the fee payable for renewal of the licence shall be
5
[a licence fee of rupees six thousand plus an additional fee of rupees one thousand
per month or a part thereof in addition to an inspection fee of rupees one thousand
and five hundred.]
(2) Application for grant or renewal of licence to manufacture for sale or
distribution of drugs specified in Schedules C, C(1) and X shall be made to the
licensing authority in Form 27-B, and
5
[shall be made up to ten items for each
category of drugs
6
[referred to in Schedule M relating to pharmaceuticals products
and Schedule M-III relating to medical devices and in-vitro diagnostics] and shall
be accompanied by a licence fee of rupees six thousand and an inspection fee of
rupees one thousand five hundred for every inspection or for the purpose of renewal
of licences]:
1. Ins. by G.S.R.. No. 444, dt. 28-4-1973. 7. Subs. by G.S.R. 1172(E), dt. 23-8-1977.
2. Ins. by G.S.R. 331 (E), dt. 8-5-1984. 8. Ins. by G.S.R. 289(E), dt. 15-4-2015.
3. Subs. by G.S.R. 462 (E), dt. 22-6-1982.
4. Subs. by G.S.R. 28(E), dt. 22-1-1993.
5. Subs. by G.S.R. 601(E), dt. 24-8-2001.
6. Subs. by G.S.R. 640(E), dt. 29-6-2016.
Drugs and Cosmetics Rules 1945
101
Provided that the applicant shall possess a licence in Form 28 to manufacture
such drugs:
Provided further that if the application for renewal of a licence is made after its
expiry but within six months of such expiry, the fee payable for renewal of the licence
shall be
1
[rupees six thousand plus an additional fee of rupees one thousand per
month or part thereof in addition to an inspection fee of rupees one thousand five
hundred.]
2
[(3) The application for grant or renewal of licence to manufacture for sale or for
distribution of drugs in
4
[Large Volume Parenterals, Sera and Vaccine and
Recombinant DNA (r-DNA) derived drugs] shall be made to the licensing authority
appointed under this Part in Form 27D and
1
[shall be made up to ten items for each
category of drugs categorized in Schedule M and shall be accompanied by a licence
fee of rupees six thousand and an inspection fee of rupees one thousand five
hundred for every inspection or for the purposes of renewal of licences:]
Provided that if the application for renewal of a licence is made after its expiry
but within six months of such expiry, the fee payable for renewal of the licence
1
[shall
be rupees six thousand plus an additional fee of rupees one thousand per month or a
part thereof in addition to the inspection fee of rupees one thousand and five
hundred.]
1
[(4) A fee of rupees one thousand shall be paid for duplicate copy of the licence
issued under sub-rule (1), sub-rule (2) or sub-rule (3), as the case may be, if the
original licence is defaced, damaged or lost.
(5) If the licensee applies for manufacture of more than ten items of each category
of drugs, the application shall be accompanied by an additional fee at the rate of
rupees three hundred for each additional item of drugs
5
[referred to in Schedule M
relating to pharmaceuticals products and Schedule M-III relating to medical devices
and in-vitro diagnostics].]
3
[(6) Where an application under this Rule is for the manufacture of drug
formulations falling under the purview of new drugs as defined in Rule 122-E, such
application shall also be accompanied with approval, in writing, in favour of the
applicant, from the licensing authority as defined in clause (b) of Rule 21.]]
1. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
2. Ins. by G.S.R. 119 (E), dt. 11-3-1996.
3. Ins. by G.S.R. 311 (E), dt. 1-5-2002.
4. Subs. by G.S.R. 26 (E), dt. 19-1-2006.
5. Subs. by G.S.R. 640 (E), dt. 29-6-2016.
Drugs and Cosmetics Rules 1945
102
1
[75A. Loan licences.−(1)
Applications for the grant or renewal of loan
2
[licences for the manufacture for sale or for distribution] of drugs specified in
Schedules C and C(1)
3
[excluding those specified in Part X-B and Schedule X] shall
be made in Form 27-A to the licensing authority and
4
[shall be made upto ten items
for each category of drugs
14
[referred to in Schedule M relating to pharmaceuticals
products and Schedule M-III relating to medical devices and in-vitro diagnostics] and
shall be accompanied by a fee of rupees six thousand and an inspection fee of rupees
one thousand and five hundred for every inspection or for the purpose of renewal
of licences:]
5
[Provided that if the applicant applies for the renewal of a licence after its expiry
but within six months of such expiry the fee payable for renewal of the licence shall
be
4
[rupees six thousand and an inspection of fee of rupees one thousand five hundred
plus an additional fee at the rate of rupees one thousand] per month or a part thereof.]
11
[Explanation. − For the purpose of this rule a loan licence means a licence which
a licensing authority may issue to an applicant who intends to avail the manufacturing
facilities owned by a licensee in Form 28.]
12
[(1A) The application for grant or renewal of loan license to manufacture for
sale or distribution of drugs in ‗Large Volume Parenterals‘, ‗Sera and Vaccine‘ and
‗Recombinant DNA (r-DNA) derived drugs‘ shall be made to the licensing authority
appointed under this Part, in Form 27DA and be made upto ten items for each
category of drugs categorized in Schedule M and accompanied by a license fee of six
thousand rupees and an inspection fee of one thousand five hundred rupees for every
inspection or for the purpose of renewal of licenses:
Provided that if the application for renewal of a license is made after its expiry but
within six months of such expiry, the fee payable for renewal of the license shall be
six thousand rupees plus an additional fee of one thousand rupees per month or a part
thereof in addition to the inspection fee of one thousand and five hundred rupees;]
(2) The licensing authority, shall, before the grant of a loan licence, satisfy
himself that the manufacturing unit has adequate equipment, staff, capacity for
manufacture and facilities for testing to undertake the manufacture on behalf of the
applicant for a loan licence.
13
[***]
4
[(3) Subject to the provisions of sub-rule (2), the application for manufacture of
more than ten items of each category of drugs on a loan license, shall be accompanied
by an additional fee at the rate of rupees three hundred for each additional item of
drugs.
(4) If the licensing authority is satisfied that a loan licence is defaced, damaged
or lost, he may, on payment of a fee of rupees one thousand, issue a duplicate copy of
loan licence.]
6
[* * * * *]
7
[76.
8
[Forms of licence to manufacture drugs specified in Schedules C and C(1),
9
[excluding those specified in Part XB and Schedule X], or drugs specified in
Schedules C, C(1) and X and the conditions for the grant or renewal of such
licences.-
10
[A licence to manufacture for sale or for distribution of drugs specified in
1. Ins. by F.1-16/57-D, dt. 15-6-1957.
2. Subs. by G.S.R 788 (E), dt. 10-10-1985.
3. Subs. by G.S.R 28 (E), dt. 22-1-1993.
4. Subs. by G.S.R 601 (E), dt. 24-8-2001.
5. Amended by S.O.2139 dt. 13-8-1972.
6. Rule 75B omitted by G.S.R. 944 (E), dt. 21-9-1988.
7. Amended by F- 1- /57-D, dt. 15-6-1969.
8. Subs. by G.S.R. 462 (E), dt. 22-6-1982.
9. Subs. by G.S.R. 28 (E) , dt. 22.1.1993.
10. Subs. by G.S.R. 119 (E), dt. 11-3-1996.
11. Subs. by G.S.R. 724 (E), dt. 7-11-2013.
12. Ins. by G.S.R. 574 (E) , dt. 17.7.2012.
13. Proviso omitted by G.S.R. 574 (E) , dt. 17.7.2012.
14. Subs. by G.S.R. 640 (E), dt. 29-06-2016.
Drugs and Cosmetics Rules 1945
103
Schedules C and C(1) other than
4
[Large Volume Parenterals, Sera and Vaccine
and Recombinant DNA (r-DNA) derived drugs] specified in Part X B and Schedule
X shall be issued in Form 28 and a licence to manufacture for sale or distribution of
drugs specified under Schedules C and C(1) (other than
4
[Large Volume Parenterals,
Sera and Vaccine and Recombinant DNA (r-DNA) derived drugs] specified in Part
X-B) and Schedule X shall be issued in Form 28B. A licence to manufacture for
sale or for distribution of
4
[Large Volume Parenterals, Sera and Vaccine and
Recombinant DNA (r-DNA) derived drugs] shall be issued in Form 28-D. Before a
licence in Form 28 or Form 28B or Form 28D is granted or renewed, the following
conditions shall be complied with by the applicant:-
(1) The manufacture will be conducted under the active direction and personal
supervision of competent technical staff consisting at least of one person who is a
whole time employee and who is
(a) a graduate in Pharmacy or Pharmaceutical Chemistry of
1
[a University
established in India by law or has an equivalent qualification recognized and
notified by the Central Government for such purpose] and has had at least
eighteen months‘ practical experience after the graduation in the manufacture
of drugs to which this licence applies; this period of experience may however
be reduced by six months if the person has undergone training in manufacture
of drugs to which the licence applies for a period of six months during his
University course; or
(b) a graduate in Science of
1
[a University established in India by law or
has an equivalent qualification recognized and notified by the Central
Government for such purpose] who for the purpose of his degree has studied
Chemistry
3
[or Microbiology] as a principal subject and has had at least three
years‘ practical experience in the manufacture of drugs to which this licence
applies after his graduation; or
(c) a graduate in Medicine of
1
[a University established in India by law or
has an equivalent qualification recognized and notified by the Central
Government for such purpose] with at least three years‘ experience in the
manufacture and pharmacological testing of biological products after his
graduation; or
2
[(d) a graduate in Chemical Engineering of a University recognised by the
Central Government with at least three years‘ practical experience in the
manufacture of drugs to which this licence applies after his graduation; or
(e) holding any foreign qualification the quality and content of training of
which are comparable with those prescribed in clause (a), clause (b), clause (c)
or clause (d) and is permitted to work as competent technical staff under this
Rule by the Central Government.]
1. Subs. by G.S.R. 71(E), dt. 30-1-1987.
2. Ins. by F.1-19/59-D, dt. 13-6-1967.
3. Ins. by G.S.R. 245(E), dt. 3-2-1976.
4. Subs. by G.S.R. 26 (E), dt. 19-1-2006.
Drugs and Cosmetics Rules 1945
104
Provided that any person who was approved by the licensing authority as an
expert responsible for the manufacture of drugs for the purpose of rule 76 read with
Rule 78 as these Rules were in force immediately before the 29th June, 1957, shall be
deemed to be qualified for the purposes of this rule:
1
[Provided that for the drugs specified in Schedules C and C(1) meant for
veterinary use, the whole time employee under whose supervision the manufacture is
conducted may be a graduate in Veterinary Science or general science or medicine or
pharmacy of a University, recognized by the Central Government and who has had at
least three years‘ experience in the manufacture of biological products:
5
[Provided also that for medical devices, the whole time employee under whose
supervision the manufacture or testing is conducted shall be—
(i) a graduate in Pharmacy or Engineering (in appropriate branch) from a
University recognised by the Central Government for such purposes and has
had at least eighteen months practical experience in the manufacturing or
testing of devices to which this licence applies after his graduation; or
(ii) a graduate in science, from a University recognised by the Central
Government for such purposes, with Physics or Chemistry or Microbiology
as one of the subject and has had at least three years practical experience in
the manufacturing or testing of devices to which this licence applies after his
graduation; or
(iii) a diploma in Pharmacy or Engineering (in appropriate branch) from a Board
or Institute recognised by the Central Government or the State Government,
as the case may be, for such purposes and has had at least four years practical
experience in the manufacturing or testing of devices to which this licence
applies after his diploma; or
(iv) having a foreign qualification, the quality and content of training of which
are comparable with those specified in clause (i), clause (ii) and clause (iii)
and is permitted to work as competent technical staff under this rule by the
Central Government.]
6
[(2) The applicant proposing to manufacture pharmaceutical products shall comply
with the provisions referred to in Schedule M.
(2A) The applicant proposing to manufacture medical devices and in-vitro
diagnostics shall comply with the quality management system as referred to in
Schedule M-III.
(3) The applicant shall provide adequate space, plant and equipment for
pharmaceutical products as referred to in Schedule M and for Medical devices and in-
vitro diagnostics as referred to in Schedule M-III.]
3
[(4) The applicant shall provide and maintain adequate staff, premises and
laboratory equipment for carrying out such tests of the strength, quality and purity of
the substances as may be required to be carried out by him under the provisions of
Part X of these rules including proper housing for animals used for the purposes of
such tests, the testing unit being separate from the manufacturing unit and the head of
the testing unit being independent of the head of the manufacturing unit:
Provided that the manufacturing units which before the commencement of the
Drugs and Cosmetics (Amendment) Rules, 1977
4
, were making arrangements with
institutions approved by the Licensing Authority for such tests to be carried out on
their behalf may continue such arrangements upto the 30th June, 1977 :
Provided further that for tests requiring sophisticated instrumentation techniques
or biological or microbiological methods other than sterility the Licensing Authority
may permit such tests to be conducted by institutions approved by it
2
[under Part
XV (A) of these rules] for this purpose.
1. Ins. by F.1-6/62-D (SO 2889), dt. 2-7-1969.
2. Ins. by G.S.R 1172 (E), dt. 23-8-1977.
3. Sub. by G.S.R 926 (E), dt. 24-6-1977.
4. These rules came in to force on 28
th
May, 1977 vide G.S.R 665 (E), dt. 6-5-1977.
5. Sub. by G.S.R 690 (E), dt. 25-9-2014. Earlier Ins. by G.S.R 109 (E), dt. 22-2-1994.
6. Sub. by G.S.R 640 (E), dt. 29-6-2016.
Drugs and Cosmetics Rules 1945
105
1
[(4A) The head of the testing unit referred to in condition (4) shall possess a
degree in Medicine or Science or Pharmacy or Pharmaceutical Chemistry of a
University recognized for this purpose and shall have experience in the testing of
drugs, which in the opinion of the Licensing authority is considered adequate.]
(5) The applicant shall make adequate arrangements for the storage of drugs
manufactured by him.
2
[(6) The applicant shall furnish to the Licensing Authority, if required to do so,
data on the stability of drugs which are likely to deteriorate for fixing the date of
expiry which shall be printed on the labels of such drugs on the basis of the data so
furnished.]
3
[(7) The applicant shall, while applying for licence to manufacture patent or
proprietary medicines, furnish to the Licensing Authority evidence and data justifying
that the patent or proprietary medicines−
(i) contain the constituent ingredients in therapeutic/prophylactic quantities
as determined in relation to the claims or conditions for which the medicines are
recommended for use or claimed to be useful;
(ii) are safe for use in the context of the vehicles, excipients, additives and
pharmaceutical aids used in the formulations and under the conditions in which the
formulations for administration and use are recommended;
(iii) are stable under the conditions of storage recommended;
(iv) contain such ingredients and in such quantities for which there is
therapeutic justification.;] and
4
[(v) have the approval, in writing, in favour of the applicant to manufacture drug
formulations falling under the purview of new drug as defined in Rule 122E, from the
licensing authority as defined in clause (b) of rule 21.]
5
[(8) The licensee of pharmaceutical products shall comply with the requirements
of ‗Good Manufacturing Practices‘ as laid down in Schedule M and the licensee of
Medical Devices and in-vitro diagnostics shall comply with the requirements of
―Quality Management System‖ as laid down in Schedule M-III.
.]
1. Ins. by G.S.R 681 (E), dt. 5-12-1980.
2. Ins. by G.S.R 444 dt. 31-3-1973.
3. Ins. by G.S.R 515 dt. 24-3-1976.
4. Ins. by G.S.R 311 (E), dt. 1-5-2002.
5. Subs. by G.S.R 640 (E), dt. 29-06-2016. Previously Ins. by G.S.R 735 (E), dt. 24-6-1988.
Drugs and Cosmetics Rules 1945
106
1
[Explanation:-
For the purpose of this rule,
6
[―Large Volume Parenterals‖ sera and
vaccines and recombinant DNA (r-DNA) derived drugs,] shall mean the sterile solutions
intended for parenteral administration with a volume of 100 ml. or more (and shall include
anti-coagulant solutions) in one container of the finished dosage form intended for single
use.]
7
[(9) The applicant shall make application for grant of licence for a drug formulation
containing single active ingredient only in proper name.]
2
[76A. Forms of loan licenses to manufacture for sale or for distribution drugs
specified in Schedule C and C(1) excluding drugs specified in Schedule X or of Large
Volume Parenterals, Sera and Vaccine and recombinant DNA (r-DNA) derived drugs,
and conditions for the grant or renewal of such license.— A loan license to manufacture
for sale or for distribution of drugs specified in Schedules C and C(1), excluding drugs specified
in Schedule X, and Large Volume Parenterals, Sera and Vaccine and Recombinant DNA(r-
DNA) derived drugs specified in Part XB shall be issued in Form 28A and a loan license to
manufacture for sale or for distribution of Large Volume Parenterals, Sera and Vaccine and
Recombinant DNA (r-DNA) derived drugs shall be issued in Form 28DA, and the applicant shall,
while applying for a licence to manufacture patent or proprietary medicines, furnish to the
Licensing Authority evidence and data justifying that the patent or proprietary medicines-
(i) contain the constituent ingredients in therapeutic/prophylactic quantities as
determined in relation to the claims or conditions for which the medicines are
recommended for use or claimed to be useful;
(ii) are safe for use in the context of the vehicles, excipients, additives and
pharmaceutical aids used in the formulations, and under the conditions in
which the formulations for administration and use are recommended;
(iii) are stable under the conditions of storage recommended; and
(iv) contain such ingredients and in such quantities for which there is
therapeutic justification.]
7
[Provided that the application for grant of a licence for a drug formulation
containing single active ingredient shall be made only in proper name.]
3
[
77. Duration of licence.
An original licence in
4
[Form 28, Form 28B and
Form 28D or renewed licence in Forms 26, 26F, and Form 26H], unless sooner
suspended or cancelled shall be
5
[valid for a period of five years on and from the date
on which] it is granted or renewed:
1. Ins. by G.S.R. 119 (E), dt. 11-3-1996.
2. Subs. by G.S.R. 574 (E), dt. 17-7-2012.Earlier Subs. by G.S.R. 788 (E), dt. 10-10-1985 and Subs. by G.S.R.
462 (E), dt. 22-6-1982.
3. Amended by No. G.1-10/62-D, dt. 10-4-1964.
4. Subs. by G.S.R. 119 (E), dt. 11-3-1996.
5. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
6. Subs. by G.S.R. 26 (E), dt. 19-1-2006.
7. Ins. by G.S.R. 570 (E) dt. 7-8-2014.
Drugs and Cosmetics Rules 1945
107
1
[Provided that if the application for the renewal of a licence is made before its
expiry, or if the application is made within six months of its expiry after payment
of additional fee, the licence shall continue to be in force until orders are passed on
the application and the licence shall be deemed to have expired if the application for
its renewal is not made within six months of its expiry.]]
2
[78. Conditions of licence.−A licence in
3
[Form 28, Form 28B or Form 28D]
shall be subject to the special conditions, if any, set out in Schedule F or
ScheduleF(1), as the case may be, which relate to the substance in respect of which
the licence
is granted and to the following general
conditions:
−
(a) (i) The licensee shall provide and maintain an adequate staff and
adequate premises and plant for the proper manufacture and storage of the
substances in respect of which the licence is issued;
(ii) Without prejudice to the generality of the foregoing requirement, every
holder of a licence who for any purpose engaged in the culture or manipulation
of pathogenic spore-bearing micro-organisms shall provide to the satisfaction
of the Licensing Authority separate laboratories and utensils and apparatus
required for the culture or manipulation of such micro-organisms, the
laboratories, utensils and apparatus so provided not being used for the
manufacture of any other substance;
4
[(b) The licensee shall provide and maintain staff, premises and equipment
as specified in Rule 76;]
5
[(c)(i) The licensee shall maintain records of manufacture as per
particulars given in Schedule U;
(ii) The licensee shall either in his own laboratory or in any laboratory
approved by the Licensing Authority
6
[under Part XV (A) of these rules]
test each batch or lot of the raw material used by him for the manufacture of
his product and also each batch of the final product and shall maintain records
or registers showing the particulars in respect of such tests as specified
in Schedule U. The records or registers shall be retained in the case of
a substance for which a potency date is fixed for a period of two years from
the expiry of such date, and in the case of other substances for a period of
five years from the date of manufacture;]
(d) The licensee shall allow an
7
[Inspector appointed under the Act] to
enter, with or without prior notice, any premises where the manufacture is
carried on and to inspect the premises, and in the case of substances specified
in Schedules C and C(1), to inspect the plant and the process of manufacture
and the means employed for standardizing and testing the substance;]
1. Amended by S.O. 2139 dt. 12-8-1972.
2. Amended by F.1-6/62-B, dt. 2-6-1969.
3. Subs. by G.S.R. 119 (E), dt. 11-3-1996.
4. Amended by F.1-16/57-D (SO 2136), dt. 15-6-1957.
5. Amended by F.1-20/64-D (SO 3868), dt. 26-10-1968.
6. Ins. by G.S.R. 1172 (E), dt. 23-8-1977.
7. Subs. by G.S.R. 444 (E), dt. 31-3-1973.
Drugs and Cosmetics Rules 1945
108
(e) The licensee shall allow an
1
[Inspector appointed under the Act] to
inspect all registers and records maintained under these Rules and to take
samples of the manufactured product and shall supply to such Inspector such
information as he may require for the purpose of ascertaining whether the
provisions of the Act and Rules thereunder have been observed;]
(f) The licensee shall from time to time report to the Licensing Authority
any changes in the expert staff responsible for the manufacture or testing of the
substance and any material alterations in the premises or plant used for that
purpose which have been made since the date of the last inspection made on
behalf of the Licensing Authority before the issue of the licence;
1
[(g) The licensee shall on request furnish to the Licensing Authority,
Controlling Authority or to such authorities as the Licensing Authority or the
Controlling Authority may direct, from every batch of drug as the Licensing
Authority or the Controlling Authority may from time to time specify, a sample
of such quantity as may be considered adequate by such Authority for any
examination and, if so required, also furnish, full protocols of the tests which
have been applied;]
2
[(h) If the Licensing Authority or the Controlling Authority so directs, the
licensee shall not sell or offer for sale any batch in respect of which a sample
is, or protocols are furnished under the last preceding sub-paragraph until a
certificate authorising the sale of the batch has been issued to him by or on
behalf of the Licensing Authority or the Controlling Authority;]
1
[(i) The licensee shall on being informed by the Licensing Authority or the
Controlling Authority that any part of any batch of the substance has been
found by the Licensing Authority or the Controlling Authority not to conform
with the standards of strength, quality or purity specified in these rules and on
being directed so to do, withdraw the remainder of that batch from sale and so
far as may in the particular circumstances of the case be practicable recall all
issues already made from that batch;]
(j) No drug manufactured under the licence shall be sold unless the
precautions necessary for preserving its properties have been observed
throughout the period after manufacture;
3
[(k) The licensee shall comply with the provisions of the Act and of these
rules and with such further requirements, if any, as may be specified in any
rules subsequently made under Chapter IV of the Act, provided that where
such further requirements are specified in the rules, these would come into
force four months after publication in the Official Gazette;]
1. Subs. by G.S.R 444, dt. 28-4-1973.
2. Amended by F.1-16/57-D, dt. 15-6-1957.
3. Amended by F.1-14/68-B (SO 3868), dt. 26-10-1968.
Drugs and Cosmetics Rules 1945
109
1
[(l) The licensee shall maintain an Inspection Book in Form 35 to enable an
Inspector to record his impression and defects
noticed.]
2
[(m) The licensee shall maintain reference samples from each batch of the drugs
manufactured by him in a quantity which is at least twice the quantity of the drug
required to conduct all the tests performed on the batch. In case of drugs bearing an
expiry date on the label, the reference samples shall be maintained for a period of
three months beyond the date of expiry of potency. In case of drugs where no date of
expiry is specified on the label the reference samples shall be maintained for a period
of three years from the date of manufacture.]
3
[(n) The licensee, who has been granted a license in Form 28B
shal
l
−
(i) forward to the licensing authority of the concerned States of
manufacture and supply of the drug a statement of the sales effected to
manufacturers, wholesalers, retailers, hospitals, dispensaries and Nursing
Homes and Registered Medical Practitioners every three months;
(ii) maintain accounts of all transactions giving details as indicated below
in a register bound and serially page numbered and such records shall be
retained for a period of five years or one year after the expiry of potency,
whichever is later.
A. Accounts of the drugs specified in Schedule X used for the manufacture:-
1. Date of issue.
2. Name of the drug.
3. Opening balance of stock on the production day.
4. Quantity received, if any, and source from where received.
5. Quantity used in manufacture.
6. Balance quantity on hand at the end of the production day.
7. Signature of the person in charge.
1. Subs. by F.1-14/68-B (SO3868), dt. 26-10-1968.
2. Ins. by G.S.R. 444, dt. 28-4-1973.
3. Ins. by G.S.R. 462 (E), dt. 22-6-1982.
Drugs and Cosmetics Rules 1945
110
B. Accounts of Production:
1. Date of manufacture.
2. Name of the drug.
3. Batch Number.
4. Quantity of raw material used in manufacture.
5. Anticipated yield.
6. Actual yield.
7 Wastage.
8. Quantity of the manufactured goods transferred.
C. Accounts of the manufactured drugs:
1. Date of manufacture.
2. Name of the drug.
3. Batch Number.
4. Opening Balance.
5. Quantity manufactured.
6. Quantity sold.
7. Name of the purchaser and his address.
8. Balance quantity at the end of the day.
(o) The licensee shall store drugs specified in Schedule X in bulk form
and when any of such drug is required for manufacture in a place other than its
place of storage it shall be kept in a separate place under the direct custody of a
responsible person.]
1
[(p) The licensee shall comply with the requirements of
3
[‗Good
Manufacturing Practices‘ as laid down in Schedule L-1 and Good Manufacturing
Practices‘ as laid down in Schedule M.]
4
[(q) No advertisement of the drugs specified in Schedule H, Schedule H1 or
Schedule X shall be made except with the previous sanction of the Central
Government.]
2
[78A. Conditions of license in
5
[Form 28A or Form 28DA]- (1) The license in
5
[Form 28A of Form 28DA] shall be deemed to be cancelled or suspended, if the
licence owned by the licensee in
6
[
5
[Form 28 or Form 28D] whose manufacturing
facilities have been availed of by the licensee is cancelled or suspended, as the case
may be, under these rules.
1. Ins. by G.S.R. 735 (E), dt. 24-6-1998.
2. Amended by F.1-14/68-D (S.O. 3868), dt. 26-10-1968.
3. Ins. by G.S.R. 780 (E), dt. 10-9-2008.
4. Ins. by G.S.R. 289 (E), dt. 15-4-2015.
5. Subs. by G.S.R. 574 (E), dt. 17-7-2012.
6. Subs. by G.S.R. 592 (E), dt. 13-8-2008.
Drugs and Cosmetics Rules 1945
111
(2) The licensee shall comply with the provisions of the Act, and of these rules
and with such further requirements if any, as may be specified in any rules
subsequently made under Chapter IV of the Act, provided that where such further
requirements are specified in the rules, those would come into force four months after
publication in the Official Gazette.
(3) The licensee shall test each batch or lot of the raw material used by him for
the manufacture of his products and also each batch of the final product and shall
maintain records or registers showing the particulars in respect of such tests as
specified in Schedule U. Records or registers shall be retained, in the case of a
substance for which a potency date is fixed, for a period of two years from the expiry
of such date and in the case of other substances, for a period of five years from the
date of manufacture. The licensee shall allow an Inspector to inspect all registers and
records maintained under these rules and shall supply to the Inspector such
information as he may require for the purpose of ascertaining whether the provisions
of the Act and these rules have been observed.
(4) The licensee shall either (i) provide and maintain to the satisfaction of the
Licensing Authority adequate staff and adequate laboratory facilities for carrying out
tests of the strength, quality and purity of the substances manufactured by him, or (ii)
make arrangements with some institution approved by the Licensing Authority for
such tests to be regularly carried out on his behalf by the institution.]
1
[(5) The licensee shall furnish to the Licensing Authority, if required to do so,
data on the stability of drugs which are likely to deteriorate for fixing the date of
expiry which would be printed on the labels of such drugs on the basis of the data so
furnished.]
2
[(6) The licensee shall maintain reference samples from each batch of the drug
manufactured by him in a quantity which is at least twice the quantity of the drug
required to conduct all the tests performed on the batch. In case of drugs bearing an
expiry date on the labels, the reference samples shall be maintained for a period of
three months beyond the date of expiry of potency. In case of drugs where no date of
expiry of potency is specified on the label, the reference samples shall be maintained
for a period of three years from the date of manufacture.]
3
[(7) The licensee shall maintain an Inspection Book in Form 35 to enable an
Inspector to record his impressions and the defects noticed.]
4
[(8) No advertisement of the drugs specified in Schedule H, Schedule H1 or
Schedule X shall be made except with the previous sanction of the Central
Government.
5
[79. Inspection before grant or renewal of
licence
.
−
Before
a licence under
1. Ins. by G.S.R. 444, dt. 28-4-1973.
2. Subs. by G.S.R. 574 (E), dt. 17-7-2012.
3. Ins. by G.S.R. 331 (E), dt. 8-5-1984.
4. Ins. by G.S.R. 289 (E), dt. 15-4-2015.
5. Subs. by G.S.R. 923 (E), dt. 14-12-1992.
Drugs and Cosmetics Rules 1945
112
this Part is granted or renewed the Licensing Authority or Central Licence Approving
Authority, as the case may be, shall cause the establishment in which the
manufacture is proposed to be conducted or being conducted to be inspected by one
or more Inspectors appointed under this Act with or without an expert in the
concerned field. The Inspector or Inspectors shall examine all portions of the
premises, plant and appliances and also inspect the process of manufacture intended
to be employed or being employed along with the means to be employed or being
employed for standardizing and testing the drugs to be manufactured or being
manufactured and enquire into the professional qualifications of the technical staff to
be employed. He shall also examine and verify the statements made in the application
in regard to their correctness, and the capability of the applicant to comply with the
requirements of competent technical staff, manufacturing plants, testing equipments
and the ‗Requirements of Good Manufacturing Practices‘ and the ‗Requirements of
Plant and Equipment‘ as laid down in Schedule M read with the Requirements of
Maintenance of Records as laid down in Schedule U.]
1
[80. Report by
Inspector
.
−
The
Inspector shall forward a detailed descriptive
report giving his findings on each aspect of inspection along with his
recommendations after completion of his inspection in accordance with the provisions
of Rule 79, to the Licensing Authority or Central Licence Approving Authority, as
the case may be.]
81. Procedure of Licensing
Authority
.
−
(1)
If the Licensing Authority
5
[or
Central Licence Approving Authority, as the case may be,] after such further enquiry,
if any, as he may consider necessary, is satisfied that the requirements of the Rules
under the Act have been complied with and that the conditions of the licence and the
Rules under the Act will be observed, he
2
[shall issue a licence under this Part].
(2) If the Licensing Authority
5
[or Central Licence Approving Authority, as the
case may be,] is not so satisfied, he shall reject the application and shall inform the
applicant of the reasons for such rejection and of the conditions which must be
satisfied before a licence can be granted and shall supply the applicant with a copy of
the inspection report.
3
[82. Further application after rejection.
−
If
within a period of six months from
the rejection of an application for a licence the applicant informs the Licensing
Authority
5
[or Central Licence Approving Authority, as the case may be,] that the
conditions laid down have been satisfied and deposits an inspection
4
[fee of rupees
two hundred and fifty] the Licensing Authority
5
[or Central Licence Approving
Authority, as the case may be,] may, if after causing a further inspection to be made,
he is satisfied that the conditions for the grant of a licence have been complied with,
5
[in respect of drugs notified under Rule 68-A] issue a licence in Form 28
2
[or Form
28-B].
1. Subs. by G.S.R. 923 (E), dt. 14-12-1992.
2. Ins. by G.S.R. 462 (E), dt. 22-6-1982.
3. Ins. by F.1-16/57-D, dt. 15-6-1957.
4. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
5. Ins. by G.S.R. 923 (E), dt. 14-12-1992.
Drugs and Cosmetics Rules 1945
113
83. Renewal.−On application being made for renewal, the licensing authority
may cause an inspection to be made and, if satisfied that the condition of the licence
and the Rules under the Act are, and will continue to be observed,
1
[he shall prepare a
report to that effect in respect of those drugs which have been notified by the Central
Government under Rule 68-A and forward it along with the application to the Central
Licence Approving Authority], and shall issue a certificate of renewal
3
[under this
Part].
3
[83-A. Certificate of renewal of a loan licence
.
−
The
certificate of renewal of a
loan licence in
8
[Form 28A or Form 28DA] shall be issued in Form 26A or Form 26J
respectively.]
4
[83-AA. Duration of loan licence
.
−
An
original loan licence in
8
[Form 28A or
Form 28DA] or a renewed loan licence in
8
[Form 26A or Form J], unless sooner
suspended or cancelled, shall be
5
[valid for a period of five years on and from the
date on which] it is granted or renewed:
6
[Provided that if the application for the renewal of a licence is made before its
expiry, or if the application is made within six months of its expiry, after payment of
the additional fee, the licence shall continue to be in force until orders are passed on
the application and the licence shall be deemed to have expired if the application for
its renewal is not made within six months of its expiry].]
84. The provisions of this Part shall apply to the manufacture of drugs for sale
notwithstanding that such drugs are manufactured for sale outside India.
7
[
6
[84-A. Provision for appeal to the State Government or Central Government
by party whose licence has not been granted or
renewed.
−
Any person who is aggrieved by the order passed by the Licensing Authority or the
Central Licence Approving Authority, as the case may be, refusing to
2
[grant or renew
a licence under this Part], may within thirty days from the date of receipt of such
order, appeal to the State Government or Central Government, as the case may
be, and the State
Government or the Central Government may, after such enquiry
into the matter,]
as is considered necessary and after giving the said person an
opportunity for representing his views, may pass such order in relation thereto as it
thinks fit.]
1. Ins. by G.S.R. 923 (E), dt. 14-12-1992.
2. Subs. by G.S.R. 119 (E), dt. 11-3-1996..
3. Ins. by F1-16/57-B, dt. 15-6-1957.
4. Ins. by Notfn. No. F. 1-10/62-D, dt. 10-4-1964.
5. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
6. Subs. by S.O. 2139, dt. 12-8-1972.
7. Subs. by G.S.R. 923 (E), dt. 14-12-1992 as corrected by G.S.R. 373 (E), dt. 13-4-1993.
8. Subs. by G.S.R. 574 (E), dt. 17-5-2012.
Drugs and Cosmetics Rules 1945
114
6
[84AA. Additional information to be furnished by an applicant for licence or a
licensee to the licensing authority.
The applicant for the grant of a licence or any
person granted a licence under this Part shall, on demand, furnish to the Licensing
Authority, before the grant of the licence or during the period the licence is in force,
as the case may be, documentary evidence in respect of the ownership or occupation
on rental or other basis of the premises, specified in the application for licence or in
the licence granted, constitution of the firm or any other relevant matter which may
be required for the purpose of verifying the correctness of the statements made by the
applicant or the licensee, while applying for or after obtaining the licence, as the case
may be.]
1
[84B. Prohibition for the manufacture for sale of cyclamates and preparations
containing cyclamates.
No person shall manufacture for sale cyclamates and
preparations containing cyclamates.]
2
[85. Cancellation and suspension of licences.
(1) The Central Licence
Approving Authority may, after giving the licensee an opportunity to show cause why
such an order should not be passed, by an order in writing stating the reasons therefor,
cancel a licence issued under this Part, or suspend it for such period as he thinks fit
either wholly or in respect of any of the drugs to which it relates
3
[or direct the
licensee to stop manufacture, sale or distribution of the said drugs and
4
[thereupon
order the destruction of drugs and] the stock thereof in the presence of an Inspector],
if in his opinion, the licensee has failed to comply with any of the conditions of the
licencee or with any provisions of the Act or rules made thereunder.
(2) The Licensing Authority may, for such licences granted or renewed by him,
after giving the licensee an opportunity to show cause why such an order should not
be passed, by an order in writing stating the reasons therefor, cancel a licence issued
under this Part or suspend it for such period as he thinks fit, either wholly or in
respect of some of the substances to which it relates,
3
[or direct the licensee to stop
manufacture, sale or distribution of the said drugs and
4
[thereupon order the
destruction of drugs and] the stock thereof in the presence of an Inspector] if, in his
opinion, the licensee has failed to comply with any of the conditions of the licence or
with any provisions of the Act or rules made thereunder.]
5
[(3) A licensee whose licence has been suspended or cancelled by the Central
Licence Approving Authority or Licensing Authority under sub-rule (1) or sub-rule
(2), as the case may be, may within ninety days of the receipt of a copy of the order
by him prefer an appeal to the Central Government or the State Government, as the
case may be, and the Central Government or the State Government may after giving
the licensee an opportunity of being heard, confirm, reverse or modify such order.]
1. Ins. by S.O.2358, dt. 26-8-1972.
2. Subs. by G.S.R. 923 (E), dt. 14-12-1992 as corrected by G.S.R. 373 (E), dt. 13-4-1993.
3. Ins. by G.S.R. 20 (E), dt. 11-1-1996.
4. Ins. by (Corrigenda) G.S.R. 514 (E), dated 5.11.1996.
5. Ins. by 615 (E), dt. 9-8-1994 as corrected by G.S.R. 55 (E), dt. 7-2-1995.
6. Ins. by S.O. 2139, dt. 5-6-1972.
Drugs and Cosmetics Rules 1945
115
1
[PART
VIIA
2
[MANUFACTURE FOR SALE OR FOR DISTRIBUTION]
OF
HOMOEOPATHIC
MEDICINES
85A
.
Manufacture on more than one set of premises.
If Homoeopathic
medicines are manufactured in more than one set of premises a separate application
shall be made and a separate licence shall be obtained in respect of each such set of
premises.
85B. Application for licence to manufacture Homoeopathic medicines.
(1)
Application for grant or renewal of
2
[licence to manufacture for sale or for
distribution] of Homoeopathic medicines shall be made to the Licensing Authority
appointed by the State Government for the purpose of this Part (hereinafter in this
Part referred to as the Licensing Authority) and shall be made in Form 24-C.
3
[(2) The application in Form 24-C shall be accompanied–
(a) by a fee of
4
[rupees two hundred] for the manufacture of
Homoeopathic mother tinctures and potentised preparations and an inspection
fee of
4
[rupees one hundred] for the first inspection or
4
[rupees fifty] in case of
inspection for renewal of licence;
(b) by a fee of
4
[rupees two hundred] for the manufacture of Homoeopathic
potentised preparations only, and an inspection fee of
4
[rupees one hundred] for
the first inspection or
4
[rupees fifty] in case of inspection for renewal of
licence;
(c) by a fee of
4
[rupees two hundred] for the manufacture of potentised
preparations from back potencies by pharmacies which are already licensed to
sell Homoeopathic medicines by retail and an inspection fee of
4
[rupees one
hundred] for the first inspection or
4
[rupees fifty] in case of inspection for
renewal of licence.
1. Ins. under G.S.R. 1185 (E), dt. 18-8-1964.
2. Sub. by G.S.R. 788 (E), dt. 10-10-1985.
3. Sub. by G.S.R. 245, dt. 11-2-1976.
4. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
116
1
[(3) If a person applies for renewal of a licence after its expiry but within six
months of such expiry, the fee payable for the renewal of such a licence shall be
_
(a)
2
[rupees two hundred] plus an additional fee at the rate of
2
[rupees
one hundred] per month or part thereof and an inspection fee of
2
[rupees fifty]
for the manufacture of Homoeopathic mother tinctures and potentised
preparations;
4
[(b)
2
[rupees two hundred] plus an additional fee at the rate of
2
[rupees
one hundred] per month or part thereof and an inspection fee of
2
[rupees fifty]
for the manufacture of Homoeopathic potentised preparations only;]
(c)
2
[rupees two hundred] plus an additional fee at the rate of
2
[rupees one
hundred] per month or part thereof and an inspection fee of
2
[rupees fifty] for
the manufacture of Homoeopathic mother tinctures and potentised preparations
from back potencies by pharmacies who are already licensed to sell
Homoeopathic medicines by retail.]
(4) A fee of
2
[rupees fifty] shall be paid for a duplicate copy of the licence for the
manufacture of Homoeopathic mother tinctures and potentised preparations issued
under sub-rule (1) if the original is defaced, damaged or lost, while the fee to be paid
for such a duplicate copy of the licence for the manufacture of Homoeopathic
potentised preparations only shall be
2
[rupees fifty].
3
[(5) Applications by licensee to manufacture additional items of Homoeopathic
medicines shall be made to the Licensing Authority and such applications shall be
accompanied by a fee of
2
[rupees fifty] for each additional item.]
85C. Application to manufacture ‗New Homoeopathic medicines.‘
the other provisions of these Rules
Subject to
(1) no ‗New Homoeopathic medicine‘ shall be manufactured unless it is
previously approved by the Licensing Authority mentioned in Rule 21;
(2) the manufacturer of ‗New Homoeopathic medicine‘, when applying
to the Licensing Authority mentioned in sub-rule (1) shall produce such
documentary and other evidence as may be required by the Licensing Authority
for assessing the therapeutic efficacy of the medicine including the minimum
provings carried out with it.
1. Subs. by G.S.R. 245, dt. 3-2-1976.
2. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
3. Ins. by G.S.R. 13 (E), dt. 7-1-1983.
4. Subs. by G.S.R. 779 (E), dt. 18-7-1980.
Drugs and Cosmetics Rules 1945
117
(3) While applying for a licence to manufacture a ‗New Homoeopathic
medicine‘ an applicant shall produce along with his application evidence that the
‗New Homoeopathic medicine‘ for the manufacture of which application is made has
already been approved.
Explanation.−The term ‗New Homoeopathic medicine‘ in this rule shall have the
same meaning as in rule 30AA.
1
[85D. Form of licence to manufacture Homoeopathic medicines.—Licence for
manufacture of Homoeopathic medicines is a licence to manufacture potentised
preparations from back potencies by Pharmacies who are already licensed to sell
Homoeopathic medicines by retail and shall be granted in Form 25C.]
85E.
Conditions for the grant or renewal of a licence in Form
25C
−
Before
a
licence in Form 25C is granted or renewed the following conditions shall be complied
with by the applicant:—
(1) The manufacture of Homoeopathic medicines shall be conducted under the
direction and supervision of competent technical staff consisting at least of one
person who is a whole time employee
2
[and who is—
(a) a graduate in Science with Chemistry as one of the subjects with three
years‘ experience in manufacture of Homoeopathic Medicines; or
(b) a graduate in Pharmacy with 18 months of experience in the manufacture
of Homoeopathic medicines; or
(c) holds qualification as defined under sub-clause (g) of clause (1) of
section 2 of Homoeopathy Central Council Act, 1973 (59 of 1973) with 18
months of experience in the manufacture of Homoeopathic medicines:
Provided that the persons who are already in employment with five years‘
experience in the manufacture of Homoeopathic medicines and whose name
was accordingly entered in any licence granted in Form 25C for manufacture of
different classes of Homoeopathic medicines included in them shall be deemed
to be qualified for the purpose of this rule.]
3
[(2) The factory premises shall comply with the requirements and
conditions specified in Schedule M-I:
1. Amended by F.1-59/68-D (SO 4816), dt. 19-11-1969.
2. Subs. by G.S.R. 812 (E), dt. 14-11-1994 as corrected by G.S.R. 517 (E), dt. 26-6-1995.
3. Subs. by G.S.R. 570 (E), dt. 12-6-1987.
Drugs and Cosmetics Rules 1945
118
Provided that where the Licensing Authority considers it necessary or
expedient so to do, it may having regard to the nature and extent of
manufacturing operations, relax or suitably alter the said requirements or
conditions in any particular case for reasons to be recorded in writing.]
(3) The applicant for manufacture of Homoeopathic mother tinctures shall
either (i) provide and maintain adequate staff, premises and laboratory
equipment for identifying the raw materials and for testing the mother tinctures
wherever possible, or (ii) make arrangements with some institution approved
by the Licensing Authority
2
[under Part XV(A) of these rules] for such tests,
wherever possible, to be regularly carried out on his behalf by that institution.
(4) The premises where Homoeopathic medicines are manufactured shall be
distinct and separate from the premises used for residential purposes.
(5) Homoeopathic medicines shall not be manufactured simultaneously with
drugs pertaining to other systems of medicine.
(6) The applicant shall make arrangements for proper storage of
Homoeopathic medicines manufactured by him:
1
[Provided that in case potentised preparations are made in a Pharmacy holding
licence in Form 20-C, the conditions (2) and (3) shall not apply. The licensee shall
ensure to the satisfaction of the Licensing Authority that the products manufactured
by it, conform to the claims made on the label.]
3
[85-EA. Inspection before grant or renewal of licence.-- Before a licence under
this Part is granted or renewed in Form 25C or Form 26C, the Licensing Authority
shall cause the establishment, in which the manufacture is proposed, to be conducted
or being conducted, to be inspected by one or more Inspectors shall examine all
portions of the premises, plant and appliances and also inspect the process of
manufacture intended to be employed or being employed along with the means to be
employed or being employed for standardizing and testing the substances to be
manufactured and inquire into the professional qualifications of the technical staff to
be employed. He shall also examine and verify the statements made in the application
in regard to their correctness, and the capability of the applicant to comply with the
requirements of competent technical staff, manufacturing plants, testing equipments
and the requirements of plant and equipment as laid down in Part I of Schedule M
read with the requirements of maintenance of records as laid down in Schedule U.
1. Amended by F.1-59/68-D (SO 4816), dt. 19-11-1969.
2. Ins. by G.S.R. 1172 (E), dt. 23-8-1977.
3. Ins. by G.S.R. 493 (E), dt. 9-6-1995.
Drugs and Cosmetics Rules 1945
119
85EB. Report by Inspector.–The Inspector or Inspectors shall forward a detailed
descriptive report giving his or their findings on each aspect of inspection along with
his or their recommendations after completion of his or their inspection to the
Licensing Authority.
85EC. Grant or refusal of licence.– (1) If the Licensing Authority after such
further enquiry, if any, as he may consider necessary is satisfied that the requirements
of the rules under the Act have been complied with and that conditions of the licence
and the rules under the Act shall be observed, he shall grant or renew a licence in
Form 25C or Form 26C.
(2) If the Licensing Authority is not so satisfied, he shall reject the application
and shall inform the applicant of the reasons for such rejection and of the conditions
which must be satisfied before a licence can be granted or renewed and shall supply
the applicant with a copy of inspection report.]
85ED. Further application after rejection. .–If within a period of six months
from the rejection of an application for a licence, the applicant informs the Licensing
Authority that the conditions laid down have been fulfilled and deposits an inspection
fee of
1
[rupees two hundred and fifty], the Licensing Authority may, if, after causing
further inspection to be made, he is satisfied that the conditions for the grant of
licence have been complied with, issue a licence in Form 25C or Form 26C.
85EE. Appeal to the State Government.–Any person who is aggrieved by the
order passed by the Licensing Authority refusing to grant or renew a licence under
this Part may within ninety days from the date of receipt of such order, appeal to the
State Government and the State Government may, after such enquiry into the matter
as is considered necessary and after giving the said person an opportunity for
representing the case, pass such order as it thinks fit.]
85F. Duration of licence.–An original licence or a renewed licence unless it is
sooner suspended or cancelled shall be
1
[valid for a period of five years on and from
the date on which] it is granted or renewed:
2
[Provided that if the application for renewal of a licence in force is made before
its expiry or if the application is made within six months of its expiry, after payment
of additional fee, the licence shall continue to be in force until orders are passed on
the application and the licence shall be deemed to have expired if application for its
renewal is not made within six months of its expiry.]
85G. Certificate of renewal.–The certificate of renewal of a licence in Form 25-C
shall be issued in Form 26-C.
1. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
2. Subs. by S.O. 2139, dt. 12-8-1972.
Drugs and Cosmetics Rules 1945
120
85H. Conditions of licence.–A licence in Form 25-C shall be subject to the
conditions stated therein and to the following further conditions, namely :
(a) the licensee shall provide and maintain staff and premises as specified in
Rule 85-E;
(b) the licensee shall allow an
1
[Inspector appointed under the Act] to enter,
with or without prior notice, any premises where the manufacture of a
Homoeopathic medicine in respect of which the licence is issued is carried on, to
inspect the premises and to take samples of the manufactured Homoeopathic
medicines;
(c) the licensee shall allow an Inspector to inspect all registers and records
maintained under these rules and shall supply to the Inspector such information
as he may require for the purpose of ascertaining whether the provisions of the
Act and the rules made thereunder have been observed;
2
[(d) the licensee shall maintain an Inspection Book in Form 35 to enable an
Inspector to record his impressions and defects noticed;]
(e) the licensee shall comply with the following conditions in respect of
mother tinctures manufactured by him
_
(i) the crude drug used in the manufacture of the mother tincture shall be
identified and records of such identification shall be kept
3
[for a period of
five years];
(ii) the total solids in the mother tincture shall be determined and
records of such tests shall be kept
3
[for a period of five years];
(iii) the alcohol content in the mother tincture shall be determined and
records of the same shall be maintained
3
[for a period of five years];
(iv) the containers of mother tinctures shall preferably be of glass and
shall be clean and free from any sort of impurities or adhering matter. The
glass shall be neutral as far as possible;
(v) in the process of manufacture of mother tinctures hygienic
conditions shall be scrupulously observed by the licensee. Storage and
handling conditions shall also be properly observed by the licensee according
to Homoeopathic principles;
1. Amended by G. S. R. 444, dt. 28-4-1973.
2. Amended by F-1-14/ 68-D, dt. 26-10-1968.
3. Ins. by G.S.R. 13(E), dt. 7-1-1983.
Drugs and Cosmetics Rules 1945
121
1
[(ea) no colour shall be added to any Homoeopathic medicines :
Provided that caramel may be added to combination of Homoeopathic
preparations with syrup base;]
(f) records shall be maintained of Homoeopathic medicines containing
alcohol and the quantities sold together with names and addresses of parties to
whom sold.
2
[Such records shall be maintained for a period of five years.]
3
[85HH. Additional information to be furnished by an applicant for the licence or a
licensee to the Licensing Authority.–The applicant for the grant of licence or any
other person granted a licence under this Part shall, on demand, furnish to the
Licensing Authority, before the grant of the licence or during the period the licence is
in force, as the case may be, documentary evidence in respect of the ownership or
occupation in rental or other basis of the premises, specified in the application for
licence or in the licence granted, constitution of the firm or any other relevant matters
which may be required for the purpose of verifying the correctness of the statements
made by the applicant or the licensee, while applying for or after obtaining the
licence, as the case may be.]
85-I. Cancellation and suspension of licences.– (1) The Licensing Autority may,
after giving the licensee an opportunity to show cause why such an order should not
be passed, by an order in writing stating the reasons therefor, cancel a licence issued
under this Part or suspend it for such period as he thinks fit, either wholly or in respect
of some of the substances to which it relates if, in his opinion, the licensee has failed
to comply with any of the conditions of the licence or with any provisions of the Act
or Rules made thereunder.
4
[(2) A licensee whose licence has been suspended or cancelled may, within three
months of the date of the order under sub-rule (1), prefer an appeal against that order
to the State Government, which shall decide the same.]
PART
VIII
MANUFACTURE FOR EXAMINATION, TEST OR
ANALYSIS
86. Conditions relating to manufacture for examination, test or analysis.–The
provisions of Section 18 of the Act shall not apply to the manufacture of any drug in
small quantities for the purpose of examination, test or analysis if the conditions
prescribed in this Part are fulfilled.
87. Labelling.–Any drug manufactured for the purpose of examination, test or
analysis shall be kept in containers bearing labels indicating the purpose for which it
has been manufactured.
88. Labelling of drugs supplied to other persons.–If any drug manufactured for
the purpose of examination, test or analysis is supplied by the manufacturer to any
other person, the container shall bear a label on which shall be stated the name and
address of the manufacturer, the accepted scientific name of the substance if known,
or if not known a reference which will enable the substance to be identified and the
purpose for which it has been manufactured.
1. Ins. by G.S.R. 680 (E), dt. 5-12-1980.
2. Ins. by G.S.R. 13 (E), dt. 7-1-1983.
3. Ins. by S. O. 2139, dt. 12-8-1972.
4. Subs. G.S.R. 926, dt. 16-7-1977.
Drugs and Cosmetics Rules 1945
122
89. Licence.–If the person proposing to manufacture a drug for the purpose of
examination, test or analysis does not hold a licence in Form 25 or Form 28 in respect
of such drugs he shall, before commencing such manufacture, obtain a licence in
Form 29:
1
[Provided that in the case of a drug the composition of which is such that the drug
is not generally recognized among experts qualified by scientific training and
experience to evaluate the safety of drugs as safe for use, no licence in Form 29 shall
be granted unless the applicant produces a certificate from the ―Licensing Authority‖
mentioned in Rule 21, to the effect that there would be no objection to such licence
being granted.
90. Form of application.–
2
[(1)] An application for a licence in Form 29 shall
be made to the Licensing Authority appointed by the State Government for the
purpose of this Part (hereafter in this Part referred to as the Licensing Authority) in
Form 30 and shall be made by or countersigned by the head of the institution in
which, or a director of the firm or company by which, the substance will be
manufactured.
4
[(2) Every application in Form 29 shall be accompanied by a fee of
3
[rupees two
hundred fifty].
91. Duration of licence.–A licence in Form 29 shall, unless sooner cancelled, be
in force for a period of one year from the date of issue, and may thereafter be renewed
for periods of one year at a time.
92. Conditions of licence. −A licence in Form 29 shall be subject to the following
conditions
(a) the licensee shall use the drugs manufactured under the licence
exclusively for purpose of examination, test or analysis, and shall carry on the
manufacture and examination, test or analysis at the place specified in the
licence;
(b) the licensee shall allow any
3
[inspector appointed under the Act]
to enter, with or without notice, the premises where the drugs are manufactured
and to satisfy himself that only examination, test or analysis work is being
conducted;
(c) the licensee shall keep a record of the quantity of drugs manufactured
for examination, test or analysis and of any person or persons to whom the
drugs have been supplied;
(d) the licensee shall comply with such further requirements, if any,
applicable to the holders of licences in Form 29 as may be specified in any
rules subsequently made under the Act and of which the Licensing Authority
has given him not less than one month‘s notice;
(e) the licensee shall maintain an Inspection Book to enable an Inspector to
record his impressions and defects noticed.
93.
Cancellation
of licences.-
(1) The Licensing Authority may after giving the
licensee an opportunity to show
cause why such an order should not be passed, by an order in writing stating the
reasons therefor, cancel a licence issued under this Part, either wholly or in respect of
some of the substances to which it relates, if, in his opinion, the licensee has failed to
comply with any of the conditions of the licence or with any provision of the Act or
Rules thereunder
1. Ins. under F. 1-19/59-D (SO 1449), dt. 13-6-1961.
2. Re-numbered by S.O. 903, dt. 28-2-1976.
3. Subs. by G.S.R. by 444, dt. 31.3.1973.
4. Ins. by S.O 903, dt. 28-2-1976.
Drugs and Cosmetics Rules 1945
123
1
[(2) A licensee whose licence has been suspended or cancelled may appeal to the
State Government within three months of the date of the order.]
PART
IX
LABELLING AND PACKING OF DRUGS OTHER THAN
HOMOEOPATHIC MEDICINES
94. Exemption of certain drugs from certain provisions of this Part.— (1) Labels
on packages or containers of drugs for export shall be adapted to meet the specific
requirements of the law of the country to which the drug is to be exported but the
following particulars shall appear in a conspicuous position on the innermost
container in which the drug is packed and every other covering in which that
container is packed:
(a) name of the drug;
(b) the name, address of the manufacturer and the number of the licence under
which the drug has been manufactured;
(c) batch or lot number;
(d) date of expiry, if any:
2
[Provided that where a drug, not classified under Schedule F, Schedule F(1) and
Schedule X,
5
[or blood products defined under rule 122EA] is required by the
consignee to be not labelled with the name and address of the manufacturer, the labels
on packages or containers shall bear a code number as approved by the Licensing
Authority mentioned in Rule 21.]
4
[Provided further that where a drug classified as Narcotic Drug or Psychotropic
Substance is to be exported under a code number, the same may be permitted by the
said licensing authority on the following conditions, namely:-
(i) Each consignment of export shall be accompanied with requisite import license from
the importing country;
(ii) The applicant shall obtain a no objection certificate from the Drugs Controller, India for
manufacture of such formulations to be exported with code number against each export
order along with certificate from the regulatory authority of the importing country
controlling Narotic Drugs and Psychotropic Substances that they do not have any
objection for the import of the drug with code number;
(iii) The State Licensing Authority shall issue the manufacturing license for these
formulations on each export order on the basis of a No Objection Certificate from Drugs
Controller, India;
(iv) A no objection certificate shall be obtained from the drugs Controller, India for export
of each consignment; and
(v) A no objection certificate shall be obtained from the Narcotic Commissioner of India,
Gwalior for export of each consignment of the drug.]
3
[(2) The provisions of Rules 96 to 101 inclusive, shall not apply to a medicine
made up ready for treatment, whether after or without dilution, which is supplied on
the prescription of a registered practitioner provided that:
(i) the medicine is labelled with the following particulars : –
(a) the name and address of the supplier;
(b) the name of the patient and the quantity of the medicine;
(c) the number representing serial number of the entry in the prescription
register;
1. Subs. by F.1-10/68-D (S.O 2482), dt. 17-6-1969.
2. Ins. by G.S.R. 676 (E), dt. 2-6-1988.
3. Subs. by F.1-19/59-D, dt. 13-6-1961.
4. Ins. by G.S.R. 592 (E), dt. 13-8-2008.
5. Subs. by 592 (E), dt. 13-8-2008.
Drugs and Cosmetics Rules 1945
124
(d) the dose, if the medicine is for internal use;
1
[(e) the words ―FOR EXTERNEL USE ONLY‖ shall be printed on the
label if the medicine is for external application].
(ii) Condition (3) of the conditions in Rule 65 is satisfied.]
95. Prohibition of sale or distribution unless labelled.—Subject to the other
provisions of these Rules, no person shall sell or distribute any drug (including a
patent or proprietary medicine) unless it is labelled in accordance with these Rules.
2
[96. Manner of Labelling .— (1) Subject to the other provisions of these Rules,
the following particulars shall be either printed or written in indelible ink and shall
appear in a conspicuous manner on the label of the innermost container of any drug
and on every other covering in which the container is packed, namely :—
(i) the name of the drug−
3
[(A) for this purpose, the proper name of the drug shall be printed or
written in a more conspicuous manner than the trade name, if any, which
shall be shown immediately after or under the proper name and shall be]—
(a) for drugs included in the Schedule F or Schedule F (1), the name
given therein;
(b) for drugs included in the Indian Pharmacopoeia or the official
pharmacopoeias and official compendia of drug standards prescribed in
Rule 124, the name or synonym specified in the respective official
pharmacopoeias and official compendia of drug standards followed by
the letters ‗I.P., or, as the case may be, by the recognized abbreviations
of the respective official pharmacopoeias and official compendia of drug
standards;
(c) for drugs included in the National Formulary of India, the name
or synonym specified therein followed by the letters ‗N.F.I.‘;
(d) for other drugs, the international non-proprietary name, if any,
published by the World Health Organisation or where an international
non-proprietary name is not published, the name descriptive of the true
nature or origin of the substance;
4
[* * * * *]
(ii) A correct statement of the net content in terms of weight, measure,
volume, number of units of contents, number of units of activity, as the case may
be, and the weight, measure and volume shall be expressed in Metric system.
1. Subs. by G.S.R. 462 (E), dt. 22-6-1982.
2 Amended under G.S.R.19, dt. 15-12-1977.
3. Subs. by G.S.R. 27(E), dt. 17-1-1981.
4. Sub-clause (B) omitted by G.S.R. 94 (E), dt. 8-2-2000. Earlier ins. by G.S.R. 27 (F), dt.-1-1981.
Drugs and Cosmetics Rules 1945
125
(iii) The content of active
ingredients
−
This shall be expressed−
(a) for oral liquid preparations in terms of the content per single
dose, being indicated in 5 millilitres
1
[** *]:
Provided that where the dose is below 5 millilitres the contents of
active ingredients may be expressed in terms of 1 millilitre;
2
[or fraction
thereof:]
3
[Provided further that where the single dose is more than 5
millilitres, the content of active ingredients shall be expressed in terms
of minimum single dose as approved by the licensing authority;]
(b) for liquid parenteral preparations ready for administration in
terms of 1 millilitre or percentage by volume or per dose in the case of
single dose container :
Provided that if the preparation is contained in an ampoule it will be enough
if the composition is shown on the label or wrapper affixed to any package in
which such ampoule is issued for sale;
(c) for drugs in solid form intended for parenteral administration, in terms of
units or weight per milligram or gram;
(d) for tablets, capsules, pills and the like, in terms of the content in each
tablet, capsule, pill or other unit, as the case may be;
(e) for other preparations, in terms of percentage by weight or volume or in
terms of unitage per gram or millilitre, as the case may be:
Provided that clause (iii) shall not apply to the pharmacopoeial preparations
where the composition of such preparation is specified in the respective
pharmacopoeia and to a preparation included in the National Formulary of India.
(iv)
4
[The name of the manufacturer and the address of the premises of the
manufacturer where the drug has been manufactured:]
Provided that if the drug is contained in an ampoule or a similar small container,
it shall be enough if only the name of the manufacturer and his principal place of
5
[manufacture] is shown.
(v) A distinctive batch number, that is to say, the number by reference to which
details of manufacture of the particular batch from which the substance in the
container is taken are recorded and are available for inspection, the figure
representing the batch number being preceded by the words ‗Batch No.‘ or ‗B. No.‘
or ‗Batch‘ or ‗Lot No.‘ or ‗Lot‘.
NOTES
(1) In the case of drugs manufactured by a continuous process, like
manufacture of magnesium sulphate, pharmaceutical chemicals etc., the
production resulting in one homogenous mix of the finished products shall be
considered as one ―Batch‖.
1. Omitted by G.S.R. 285 (E), dt. 16-7-1996.
2. Ins. by G.S.R. 681(E), dt. 5-12-1980.
3. Ins. by G.S.R. 285 (E), dt. 16-7-1996.
4. Subs. by G.S.R. 491 (E), dt. 25-7-1991.
5. Subs. by G.S.R. 17 (E), dt. 7-1-1986.
Drugs and Cosmetics Rules 1945
126
(2) In the case of powders, liquid orals, ointments etc., one ―Batch Number‖
shall be assigned to all the containers filled from one homogenous bulk.
(3) In the case of tablets, capsules, lozenges, troches, etc., one ―Batch
Number‖ shall be assigned to the products manufactured from one homogenous
mix ready for compression or filling.
(4) In the case of parenteral preparations sterilized by steam under pressure,
one ―Batch Number‖ shall be assigned to all containers filled from one
homogenous bulk solution and sterilized in one sterilizer load.
(5) In the case of containers of parenteral preparations filled from one
homogenous bulk solution and sterilized in more than one sterilizer load, the
―Batch Number‖ assigned to the containers in the different sterilizer loads shall
be the same ―Batch Number‖ as is assigned to the homogenous bulk solution,
provided the samples taken from all the sterilizer loads pass the sterility test, and
are kept separate from one another until the report of the sterility test is available.
Explanation.— For the purpose of chemical and other tests, representative
samples from all containers filled from the homogenous bulk solution should be
taken.
(6) In the case of parenteral and other sterile products filled aseptically, a
―Batch Number‖ shall be assigned to all containers filled from one homogenous
mix during one filling operation, the filling operation being completed in a period
of not more than a day and during which no schedule change in the filling
assembly is made.
When containers are filled from one homogenous mix, in a number of filling
operations, the ―Batch Number‖ assigned to the containers filled in individual
filling operations shall be the same ―Batch Number‖ as is assigned to the
homogenous mix, provided the samples taken from all the different filling
operations pass the sterility tests, and are kept separate from one another until the
report of the sterility test is available.
Explanation.-For the purpose of chemical and other tests, representative
samples from all containers filled from the homogenous mix should be taken.
(7) In the case of medicinal gases produced by a continuous process of
operation a week‘s production from one tank load shall be considered as a Batch.
(vi) Every drug manufactured in India shall bear on its label the number of the
licence under which the drug is manufactured, the figure representing the
manufacturing licence number being preceded by the words ―Manufcaturing Licence
Number‖ or ―Mfg. Lic. No.‖ or ―M.L.‖.
(vii) Drugs specified in Schedule P and their preparations including combinations
with other drugs shall bear on their labels the date of manufacture, and the date of
expiry of potency, and the period between the date of manufacture
Drugs and Cosmetics Rules 1945
127
and the date of expiry shall not exceed that laid down in the said Schedule
1
[under the conditions of storage specified therein.
2
[Drugs and their
preparations not included in Schedule P], shall bear on their labels the date of
their manufacture and also the date of their expiry which shall not exceed sixty
months from the date of manufacture:]
Provided that this period may be extended by the Licensing Authority
specified in clause (b) of Rule 21 in respect of any specified drug if satisfactory
evidence is produced by the manufacturer to justify such an extension.
7
[(viii) Drugs specified in Schedule C(I) and their preparations including
combinations in other drugs shall bear on their labels (a) the date of
manufacture, and (b) date of expiry of potency fixed by the manufacturer:
3
[
4
[Provided that drugs in bulk form included in Schedule C(I) which are
not ready for use and not included in Schedule P need not bear on the label the
date of expiry of potency:]
Provided further that no reference shall be made to any other licence
number granted by any authority outside India on any label or container or in
any covering in which the container is packed or in any other matter or
advertisement enclosed therewith].
(ix) Every drug intended for distribution to the medical profession as a free
sample shall, while complying with the labelling provisions under clauses (i) to
(viii), further bear on the label of the container the words ‗Physician‘s
Sample—Not to be sold‘ which shall be overprinted.
5
[(x)
If any preparation contains not less than 3 per cent by volume of
alcohol the quantity of alcohol shall be stated in terms of the average
percentage by volume of absolute alcohol in the finished products.]
6
[(xi) In addition to the other particulars which are required to be printed or
written under these Rules, the label of innermost container of the following
categories of drugs and every other covering in which the container is packed
shall bear a conspicuous red vertical line on the left side running throughout the
body of the label which should not be less than 1mm in width and without
disturbing the other conditions printed on the label under these
rules, namely: —
1. Subs. by G.S.R. 17 (E), dt. 7-1-1986.
2. Subs. by G.S.R. 285 (E), dt. 16-7-1996.
3. Subs. by G.S.R. 487(E), dt. 2-7-1984.
4. Subs. by G.S.R. 813 (E), dt. 27-7-1988.
5. Ins. by G.S.R. 462 (E), dt. 22-6-1982.
6. Ins. by G.S.R. 597 (E), dt. 17-6-1992.
7. Subs. by G.S.R. 592 (E), dt. 13-8-2008.
Drugs and Cosmetics Rules 1945
128
Narcotic analgestics, hypnotics, sedatives, tranquillisers, corticosteroids,
hormones, hypoglycemics, antimicrobials, antiepileptics, antidepressants,
anticoagulants, anti-cancer drugs and all other drugs falling under
Schedules ‗G‘, ‗H‘, and ‗X‘ whether covered or not in the above list:
Provided that the provisions of this clause shall not apply to: −
(a) preparations intended for animal
treatment;
(b) preparations intended for external use;
(c) ophthalmic preparations and ear drops; and
(d) sterile preparations such as sutures, surgical dressings and preparations
intended for parenteral use.]
1
[(xii) Drugs and their preparations including combinations with other drugs
imported into the country shall also bear on the label, the license number under
which the drug is imported, preceded by the words ―Import License‖ and the
name and address of the importer.]
(2)(i) The particulars to be printed or written on the label of a mechanical
contraceptive shall be as specified in Schedule R.
(ii) The following particulars, in addition to those specified under sub-rule (1)
shall be either printed or written in indelible ink and shall appear in a conspicuous
manner on the label of the innermost container and on every other covering in which
the container of a contraceptive, other than a mechanical contraceptive, is packed,
namely : −
(a) the date of manufacture;
(b) the date upto which the contraceptive is expected to retain its
properties;
(c) the storage conditions necessary for preserving the properties of the
contraceptive upto the date indicated in sub-clause (b) :
Provided that for oral contraceptives it shall be sufficient to display on the label
of the container the date of manufacture only.
(3)(i) The particulars prescribed in sub-rule (1) shall be printed or written in
indelible ink either on the label borne by a container of vaccine lymph or on a label or
wrapper affixed to any package in which the container is issued for sale. The said
particulars shall be indelibly marked on the sealed container of surgical ligature or
suture or printed or written in indelible ink on a label enclosed therein.
(ii) Nothing in these rules shall be deemed to require the labelling of any
transparent cover or of any wrapper, case or other covering used solely for the
purpose of packing, transport or delivery.
(4) Where by any provision of these rules any particulars are required to be
displayed on a label on the container, such particulars may, instead of being
displayed on a label, be etched, painted or otherwise indelibly marked on the
container:
1. Ins. by G.S.R. 592 (E), dt. 13-08-2008.
Drugs and Cosmetics Rules 1945
129
Provided that, except where otherwise provided in these rules, the name of the
drug or any distinctive letters intended to refer to the drug shall not be etched, painted
or otherwise indelibly marked on any glass container other than ampoules.
Explanation.— For the purpose of this rule, the date of expiry shall be in terms of
month and year and it shall mean that the drug is recommended till the last day of the
month. The date of expiry shall be preceded by the words ‗Expiry date‘.]
97. Labelling of medicines.—
1
[(1) The container of a medicine for internal use
shall—
(a) if it contains a substance specified in Schedule G, be labelled with the
words ―Caution: it is dangerous to take this preparation except under medical
supervision‖ – conspicuously printed and surrounded by a line within which
there shall be no other words;
(b) if it contains a substance specified in Schedule H, be labelled with the
symbol Rx and conspicuously displayed on the left top corner of the label and
be also labelled with the following words:
‗Schedule H drug- Warning: To be sold by retail on the prescription of a
Registered Medical Practitioner only‘,
(c) if it contains a substance specified in Schedule H, and comes within
the purview of the
2
[Narcotic Drugs and Psychotropic Substances Act, 1985
(61 of 1985)] be labelled with the symbol NRx which shall be in red and
conspicuously displayed on the left top corner of the label, and be also labelled
with the following words:
‗Schedule H drug -Warning: To be sold by retail on the prescription of a
Registered Medical Practitioner only‘;
(d) If it contains a substance specified in Schedule X, be labelled with the
symbol XRx which shall be in red conspicuously displayed on the left top
corner of the label and be also labelled with the following words : -
‗Schedule X drug -Warning: To be sold by retail on the prescription of
a Registered Medical Practitioner only‘.
4
[(e) if it contains a drug substance specified in Schedule H1, the drug
formulation shall be labeled with the symbol Rx which shall be in red conspicuously
displsyed on the left top corner of the label, and shall also be labelled with the
following words in a box with a red border:
“SCHEDULE H1 DRUG – WARNING.
- It is dangerous to take this preparation except in accordance with the
medical advice.
- Not to be sold by retail without the prescription of a Registered Medical
Practitioner.]
(2) The container of an embrocation, liniment, lotion,
3
[ointment, antiseptic
cream,] liquid antiseptic or other liquid medicine for external application shall be
labelled with the words:
―FOR EXTERNAL USE ONLY‖.
1. Subs. by G.S.R. 462 (E), dt. 22-6-1982.
2. Subs. By G.S.R. 282(E), dt. 16.7.1996. As corrected by G.S.R. 241(E), dt. 15.4.1998.
3. Ins. by G.S.R. 850 (E), dt. 7-12-1994.
4. Subs. by G.S.R. 588 (E), dt. 30-8-2013.
Drugs and Cosmetics Rules 1945
130
1
[(3) The container of a medicine made up ready only for treatment of an animal
shall be labelled conspicuously with the words ‗Not for human use; for animal
treatment only‘ and shall bear a symbol depicting the head of a domestic animal.]
2
[* * * * *]
10
[(3A) The container of a medicine for treatment of food producing animals shall
be labeled with the withdrawal period of the drug for the species on which it is
intended to be used:
Provided that if the specific withdrawal period has not been validated, the
withdrawal period shall not be less than seven days for eggs or milk, twenty eight
days for meat from poultry and mammals including fat and offal, five hundred degree
days for fish meat.
Explanation:- For the purpose of this Rule, the withdrawal period is the period of
interval between the last administration of a veterinary medicine to animals under the
normal conditions of use and the production of food stuff from such animals to
ensure that food stuffs do not contain residues in quantities in excess of the maximum
residue limits laid down.]
3
[(4)] The container of a medicine prepared for treatment of human ailments shall
if the medicine contains industrial methylated spirit, indicate this fact on the label and
be labelled with the words :
―For External Use only‖.
4
[(5) Substances specified in Schedule X in bulk form shall bear a label wherein
the symbol as specified in sub-Rule (1) shall be given conspicuously in red letters.]
5
[* * * * *]
6
[102. Non-Sterile Surgical Ligature and Suture.- Every container of, and
wrapper enclosing surgical ligature or suture other than a ligature or suture offered or
intended to be offered for sale as sterile, shall bear a label on which are printed or
written in a conspicuous manner in indelible red ink the words ―Non-sterile surgical
ligature (suture) – not to be used for operations upon the human body unless
efficiently sterilized‖.]
103.
7
[* * * * *]
(2) The name and address of the manufacturer shall be printed on the label of the
container of a patent or proprietary medicine.
8
[(3) The true formula or list of the ingredients shall be printed or written in
indelible ink on the outer label of every package containing patent or proprietary
medicine.]
9
[104 Use of letter I.P. etc.--The letters ‗I.P‘. and recognized abbreviations of
pharmacopoeias and official compendia of drug standards prescribed under these
Rules shall be entered on the label of the drug only for the purpose of indicating that
the drug is in accordance with standards set out in the Indian Pharmacopoeia or in any
such pharmacopoeia or official compendium of drug standards recognized under the
Rules.]
1. Subs. by notification No. F.1-6/62-D(S.O.2889),, dt. 2.7.1969.
2. Subs. (4) omitted by G.S.R. 462 (E), dt. 22-1-1982.
3. Sub-rule (5) re-numbered as sub-Rule (4), by G.S.R. 462 (E), dt. 22-6-1982.
4. Ins. by G.S.R. 462 (E), dt. 22-6-1982.
5. Rules 98, 99,100 and 101 omitted, by G.S.R. 462 (E), dt. 22-6-1982.
6. Sub. by F. No. F1-3/51-DS, dt. 15.10.1954.
7. Sub-rule (1) omitted by S.O. 2136, dt. 15.6.1957.
8. Sub. by S.O. 2136, dt. 15.6.1957.
9. Sub. by G.S.R. 19, dt. 15.12.1977.
10. Ins. by G.S.R. 128 (E), dt. 17.1.2012.
Drugs and Cosmetics Rules 1945
131
1
[104A. Prohibition against altering inscriptions on containers, labels or wrappers of
drug. –No person shall alter, obliterate or deface any inscription or mark made or recorded by
the manufacturer on the container, label or wrapper of any drug:
Provided that nothing in this rule shall apply to any alteration, any inscription or mark
made on the container, label or wrapper of any drug at the instance or direction or with the
permission of the Licensing Authority.]
2
[105. Packing of drugs.–(1) The pack sizes of drugs meant for retail sale shall be as
prescribed in Schedule P1 to these rules.
(2) The pack sizes of drugs not covered by Schedule P-1 shall be as given below: –
Unless specified otherwise in Schedule P-1,
(i) The pack sizes for Tablets/Capsules shall be–
Where the number of Tablets (coated or uncoated)/Capsules (hard or soft
gelatin) is less than 10, such packing shall be made by the integral number. For
numbers above 10, the pack size of Tablets/Capsules shall contain multiples of 5.
(ii) The pack sizes for liquid Oral preparations shall be 30 ml (paediatric only)/60
ml/100 ml/200 ml/450 ml.
(iii) The pack sizes for Paediatric Oral Drops shall be 5 ml/10 ml/15 ml.
(iv) The pack sizes for Eye/Ear/Nasal drops shall be 3 ml/5 ml/10 ml.
(v) The pack size for Eye Ointment shall be 3 gm/5 gm/ 10 gm:
Provided that the provisions of the pack sizes covered under this rule shall not apply to: –
1. Pack sizes or dosage forms not covered by the foregoing provisions of this rule.
2. The imported formulations in finished form.
3. Preparations intended for Veterinary use.
4 Preparations intended for Export.
5. Vitamins/Tonics/Cough Preparations/Antacids/Laxatives in Liquid Oral forms,
Unit dose (including applicaps).
6. Pack sizes of dosage forms meant for retail sale to Hospitals, Registered
Medical Practitioners, Nursing
Homes.
7. Physician‘s Samples.
8. Pack sizes of large volume Intravenous Fluids:
4
[Provided further that] pack sizes of any of the new drug as and when approved by the
Licensing Authority appointed under Rule 21 and if not covered under this rule, shall be
examined for the purpose of approval with specific justification by the said Licensing
Authority:
3
[
4
[Provided also that] Oxytocin injection meant for sale shall be in single unit blister
pack only:]
5
[Provided also that Diclofenac injection for human use shall be in single unit dose pack
only.]
1. Ins. by G.S.R. 1242 (E), dt. 17-9-1979.
2. Ins. by G.S.R. 796 (E), dt. 1-10-1992.
3. Sub. by G.S.R. 242 (E), dt. 3-4-2001.
4. Sub. by G.S.R. 558 (E), dt. 17-7-2015.
5. Ins. by G.S.R. 558 (E), dt. 17-7-2015.
Drugs and Cosmetics Rules 1945
132
1
[105A. Packings of drugs specified in Schedule X.- The drugs specified in Schedule X
shall be marketed in packings not exceeding-
(i) 100 unit doses in the case of tablets/capsules;
(ii) 300 ml in the case of oral liquid preparations; and
(iii) 5 ml in the case of injections:
Provided that nothing in this rule shall apply to packing meant for use of a hospital or a
dispensary subject to the conditions that–
(i) such supplies are made by the manufacturers or distributors direct to the
hospital/dispensaries; and
(ii) hospital packs shall not be supplied to a retail dealer or to a Registered Medical
Practitioner.]
2
[106. Diseases which a drug may not purport to prevent or cure.—(1) No drug may
purport or claim to prevent or cure or may convey to the intending user thereof any idea that it
may prevent or cure one or more of the diseases or ailments specified in Schedule J.
(2) No drug may purport or claim to procure or assist to procure, or may convey to the
intending user thereof any idea that it may procure or assist to procure, miscarriage in women.
3
[* * * *]
4
[PART
IXA
LABELLING AND PACKINGOF HOMOEOPATHIC
MEDICINES
106-A. Manner of labelling of Homoeopathic medicines.—(A) The following particulars
shall be either printed or written in indelible ink and shall appear in a conspicuous manner on
the label of the innermost container of any Homoeopathic medicine and on every other
covering in which the container is packed—
(i) The words ‗Homoeopathic medicine‘,
(ii) The name of the medicine—
5
[(a) For drugs specified in the Homoeopathic Pharmacopoeias of India or
the United States of America or the United Kingdom, or the German Homoeopathic
Pharmacopoeia, the name specified in that Pharmacopoeia.]
(b) For other drugs, the name descriptive of the true nature of the drugs.
1. Ins. by G.S.R. 462 (E), dt. 22-6-1982.
2. Sub. by notification F. 1-16/52-DC (SO 2122), dt. 22-6-1954.
3. Omitted by G.S.R. 462(E), dt. 22.6.1982.
4. Ins. by G.S.R. 1185 (E), dt. 18.8.1964.
5. Subs. by G.S.R. 680 (E), dt. 5-12-1980.
Drugs and Cosmetics Rules 1945
133
(iii) The potency of the Homoeopathic medicine—For this purpose the potency
shall be expressed either in decimal, centesimal or millisimal systems.
1
[(iiiA) In case of Homoeopathic medicine containing two or more ingredients the
name of each ingredient together with its potency and proportion expressed in metric
system shall be stated on the label.]
2
[(iv) Name and address of the manufacturer when sold in original containers of the
manufacturer. In case a Homoeopathic medicine is sold in a container other than that
of the manufacturer—the name and address of the seller:]
5
[Provided that where such medicines are imported, the name and address of the
importer shall also be mentioned on the label.]
(v) In case the Homoeopathic medicine contains alcohol, the alcohol content in
percentage by volume in terms of ethyl alcohol shall be stated on the label:
3
[Provided that in case the total quantity of the pharmacopoeial homoeopathic
medicine in the container is 30 millilitres or less, it will not be necessary to state the
content of alcohol on the label.]
(B) In addition to the above particulars the label of a Homoeopathic mother tincture shall
display the following particulars: −
(i) A distinctive batch number, that is to say, the number by reference to which
details of manufacture of the particular batch from which the substance in the container
is taken are recorded and are available for inspection, the figures representing the batch
number being preceded by the words ―Batch No.‖ or ―Batch‖ or ―Lot Number‖ or ―Lot
No.‖ or ―Lot‖ or any distinguishing prefix.
(ii) Manufacturing licence number, the number being preceded by the words
―Manufacturing Licence Number‖ or ―Mfg. Lic. No.‖ or ―M.L.‖.
4
[Explanation.−This clause shall not apply to a Homoeopathic mother tincture
manufactured outside India.
(C) No Homoeopathic medicine containing a single ingredient shall bear a proprietary
name on its label.]
1. Subs. by G.S.R. 466 (E), dt. 17-5-1994.
2. Sub. by notification F.1-59/68-D, dt. 19-11-1969.
3. Subs. by G.S.R. 108 (E), dt. 22-2-1994.
4. Ins. by S.O. 2139, dt. 12-8-1972.
5. Ins. by G.S.R. 263 (E), dt. 20-4-2009.
Drugs and Cosmetics Rules 1945
134
1
[106-B. Prohibition of quantity and percentage.–No Homoeopathic medicine containing
more than 12% alcohol v/v (Ethyl alcohol) shall be packed and sold in packing or bottles of
more than 30 millilitres, except that it may be sold to hospitals/dispensaries in packings or
bottles of not more than 100 millilitres.]
PART
X
SPECIAL PROVISIONS RELATING TOBIOLOGICAL
AND
OTHER SPECIAL
PRODUCTS
2
[107. Name of substance.—If any substance specified in Schedule C is advertised or sold
as a proprietary medicine or is contained in a medicine so advertised or sold, the proper name
of the substance shall appear on the label in the manner prescribed in this Part.
3
[Explanation.−For the purpose of this rule the expression ―proper name‖ means the
proper name stated in Schedule F or if no such name is stated, the name descriptive of the true
nature and origin of the substance:
Provided that in the case of veterinary biological product the expression ―proper name‖
means the proper name stated in Schedule F (1) or if no such name is stated, the name or
synonym given in the current edition for the time being of the
4
[British Pharmacopoea
(Veterinary)] , or, if no such name is stated either in Schedule F (1) or the
4
[British
Pharmacopoea (Veterinary)], the name descriptive of the true nature and origin of the
substance approved by the Licensing Authority.
108. Container.—
5
[(1) No substance specified in Schedule C shall be sold or offered for
sale unless it has been sealed in a previously sterilized container made of glass or any other
suitable material approved for the purpose by the Licensing Authority appointed under rule
21, in such manner as may, in the opinion of the Licensing Authority, suffice to preclude the
access of bacteria:
Provided that it shall not be necessary to use a previously sterilized container if the filled
and sealed container is to be sterilized after the sealing and such sterilizing procedure would
render the product sterile. However, the Licensing Authority may, for any special reasons,
direct the licensee to pre-sterile such containers.]
(2) When any such substance is issued in liquid form in containers which are sealed in
such a manner that portions of the contents can be withdrawn for use on different occasions,
the liquid shall contain a sufficient proportion of some antiseptic to prevent the growth of any
organism which may be accidentally introduced in the process of removing a portion of the
contents of the container:
6
[Provided that nothing in this sub-rule shall apply to a penicillin suspension in oil
and wax.]
1. Ins. by G.S.R. 108 (E), dt. 22-2-1994.
2. Subs. by F. 1-5/47-D (SRO 2889), dt. 25-11-1949.
3. Subs. by F. 1-6/62-D, dt. 2-7-1969.
4. Subs. by G.S.R.647 (E), dt. 28-10-1998.
5. Subs. by G.S.R. 245, dt. 21-2-1976.
6. Ins. by SO 115, dt. 04-1-1961.
Drugs and Cosmetics Rules 1945
135
1
[(3) The container shall comply with such further requirements, if any, as are specified in
Schedule F or Schedule F (1) as the case may be, in that behalf.
(4) The Licensing Authority may in the case of any particular preparation of any such
substance dispense with any of the requirements of this Rule or Schedule F or Schedule F (1)
as the case may be, and may make such additional requirements, as having regard to the
nature of the preparation, they may deem necessary.]
2
[109. Labelling.–(1) The following particulars and such further particulars, if any, as are
specified in Schedule F or Schedule F (1), as the case may be, shall be printed or written in
indelible ink on the label of every phial, ampoule or other container of a substance specified
in Schedule C and on every other covering in which such phial, ampoule or container is
packed—
(a) where a drug is imported, the number of licence under which it is imported,
preceded by the words ‗Import Licence‘:
Provided that no reference shall be made to any other import licence number granted
by any authority outside India on any label or container or in any covering in which the
container is packed or in any other matter of advertisement enclosed therein;
(b) where a test for potency in units is required by these rules, a statement of the
potency in units defined in terms of relation to the standard preparation specified in
Schedule F or F (1), as the case may be :
Provided that this clause shall not apply in the case of vaccine lymph;
(c) where a test for potency or maximum toxicity is required the date upto which the
substance if kept under suitable conditions may be expected to retain a potency not less
than stated on the label of the container or not to acquire a toxicity greater than that
permitted by the test, as the case may be. The date of expiry shall be in terms of month
and year and it shall mean that the drug is recommended for use till the last day of the
month. The date of expiry shall be preceded by the words ‗Expiry date‘ :
Provided that nothing in these rules shall be deemed to require the labelling of any
transparent cover or any wrapper, case or other covering used solely for the purpose of
packing, transport or delivery.
(2) The particulars prescribed in clause (a) of the preceding sub-rule shall be printed or
written in indelible ink either on the label borne by a container of vaccine lymph or on a label
or wrapper affixed to any package in which the container is issued for sale. The said
particulars shall be indelibly marked on the sealed container of surgical ligature or suture or
printed or written in indelible ink on a label enclosed therein.
1. Subs. by F.1-6/62-D (SO 2889), dt. 2-7-1969.
2. Subs. by G.S.R.19, dt. 15-12-1977.
Drugs and Cosmetics Rules 1945
136
(3) The following particulars, and such further particulars, if any, as are specified in
Schedule F or Schedule F (1), as the case may be, shall be printed or written in indelible ink
either on the label borne by the container of any substance specified in Schedule C or on a
label or wrapper affixed to any package in which any such container is issued for sale,
namely:–
(a) the date on which the manufacture of the particular batch from which the
substance in the container is taken was completed as defined in Schedule F or Schedule
F(1), or if there is no definition in Schedule F or Schedule F(1) as hereafter defined in this
rule and in the case of vaccine prepared from concentrates, the date of completion of the
final products and the bottling for issue;
(b) where an antiseptic substance has been added, the nature and the percentage
proportion introduced;
(c) the precaution necessary for preserving the properties of the contents up to the
date indicated in clause (c) of sub-rule (1).
(4) For the purpose of clause (a) of sub-rule (3), the date on which the manufacture of a
batch is completed shall be—
(a) in cases where a test for potency or toxicity is required by these rules or not being
so required, is accepted by the Licensing Authority as sufficient for the purpose of fixing
the date of completion of manufacture, the date on which the substance was removed
from cold storage after having been kept at a temperature not exceeding 5° C
continuously for a period not exceeding two years from the time when the last test was
completed,
(b) in cases where no such test is required or accepted−
(i) if the substance is a serum obtained from a living animal, the earliest date on
which any material contributing to the batch was removed from the animal;
(ii) if the substance was obtained by the growth of organisms or artificial media,
the earliest date on which growth was terminated in any of the material contributing
to the batch:
Provided that if a batch of the substance (including all material contributing to
this batch) has for a period of not more than three years been kept in cold storage at
a temperature not exceeding 5°C continuously from the earliest practicable date
after that on which growth was terminated in the material as the case may be, the
date of removal from cold storage shall be treated as the date on which the
manufacture of the batch is completed;
(c) in all other cases, the date on which the substance is filled in the container.
1
[109-A. Labelling of Medical Devices.– Subject to the other provisions of these rules, the
following particulars shall be printed in indelible ink on the label or sticker on the shelf pack of
the medical device or on the outer cover of such medical device and on every outer covering in
which the medical device is packed, namely:––
(a) proper name of the medical device;
(b) the details necessary for the user to identify the device and its use;
(c) the name of the manufacturer and address of the manufacturing premises where the
device has been manufactured;
(d) the correct statement of the net quantity in terms of weight, measure, volume, number
of units, as the case may be, and the number of the devices contained in the package shall be
expressed in metric system; and
(e) the date of manufacture and date of expiry; alternately the label shall bear the shelf life
of the product:
1. Sub. by G.S.R. 690 (E), dt. 25-9-2014. Earlier Ins. by G.S.R. 109 (E), dt. 22-2-1994.
Drugs and Cosmetics Rules 1945
137
Provided that in the case of sterile devices the date of sterilisation may be given as
date of the manufacture of the device:
Provided further that the device is made up of stable materials such as stainless steel
or titanium, and supplied non-sterile, date of expiry may not be necessary;
(f) to provide, wherever required, an indication that the device contains medicinal or
biological substance;
(g) to provide, a distinctive batch number or lot number preceded by the word ―Lot No.‖
or ―Lot‖ or ―Batch No.‖ or ―B. No.‖;
(h) to indicate, wherever required, any special storage or handling conditions applicable to
the device;
(i) to indicate, if the device is supplied as a sterile product, its sterile state and the
sterilisation method;
(j) to give, if considered relevant, warnings or precautions for the attention of the user of
the medical device;
(k) to label the device, if the device is intended for single use;
(l) to overprint on the label of the container, the words ―FOR CLINICAL
INVESTIGATION ONLY‖, if the device is intended for clinical investigation;
(m) to overprint on the label of the device, the words ―Physician‘s Sample—Not to be
sold‖, if a medical device is intended for distribution to the medical professional as a free
sample;
(n) to provide, except for imported devices, the manufacturing licence number by
preceding the words ―Manufacturing Licence Number‖ or ―Mfg. Lic. No.‖ or ―M. L‖;
(o) Devices or In-vitro diagnostics which are not sold to customer or patient directly and
are sold for use by hospitals or diagnostic labs shall provide the information affixing additional
label or sticker on outer shelf pack;
(p) to provide on the label, in case of imported devices, with the approval of the licensing
authority mentioned in rule 21, the import licence number, name and address of the importer
and address of the actual manufacturing premises, date of manufacture, (if not already printed
at the time of import):
Provided that the label may bear symbols recognised by the Bureau of Indian
Standards or International Organisation for Standardisation (ISO) in lieu of text and the device
safety is not compromised by a lack of understanding on the part of the user in case the
meaning of the symbol is not obvious to the device user.]
1
[109B. Exemption of certain labelling requirements for medical devices for export from
India.–– The labels on packages or container of devices for export shall be adopted to meet
specific requirements of the law of the country to which the device is to be exported, but the
following particulars shall appear in conspicuous manner on the label of the shelf pack of the
medical device in which the device is packed and every other outer covering in which the
container is packed-
(a) name of the Device;
(b) the distinctive batch number or lot number preceded by the word ―Lot No.‖ or ―Lot‖
or ―Batch No.‖ or ―B.No.‖;
(c) the date of expiry, if any;
(d) the name and address of the manufacturer and address of actual premises where the
device has been manufactured;
(e) the manufacturing Licence No. preceded by the letters ―M.L. No‖ or
―Manufacturing Licence No‖;
(f) the internationally recognised symbols in lieu of text, wherever required:
1. Ins. by G.S.R. 690 (E), dt. 25-9-2014.
Drugs and Cosmetics Rules 1945
138
Provided that where a device is required by the consignee not to be labeled with the
name and address of the manufacturer, the label on the packages or container shall bear a code
number as approved by the licensing authority and the code number shall bear the name of the
State or Union territory, in abbreviation, followed by the word ―Device‖ and ―manufacturing
licence number:
Provided further that where a device is required by the consignee not to be labeled with the
code number also, the label on the packages or container shall bear a special code number, as
requested by the consignee, and approved by the licensing authority under rule 21.]
1
[109C. Shelf life of the medical devices.–– The shelf life of the medical devices shall not
exceed sixty months from the date of manufacture:
Provided that this period may be extended by the licensing authority, in respect of
any specified medical device, if satisfactory evidence is produced by the manufacturer to
justify such an extension.]
110. Prohibition of sale of substance after prescribed date.–No person shall sell, or
exhibit for sale any substance specified in Schedule C after the date recorded on the container,
label or wrapper as the date upto which the substance may be expected to retain a potency not
less than, or not to acquire a toxicity greater than that required or permitted by the prescribed
test as the case may be.
2
[
* * * * *]
1. Ins. by G.S.R. 109 (E), dt. 22-2-1994.
2. Rule 110A omitted by G.S.R. 1242(E), dt. 17.9.1979.
Drugs and Cosmetics Rules 1945
139
1
[111. Standards.–Every substance specified in Schedules C and C (1) intended for sale
shall conform with the standards of strength, quality and purity specified in these Rules and in
Schedule F or F(1), as the case may be, and the tests for determining such conformity shall be
applied to samples taken from the final product after every manufacturing process has been
completed.]
2
[112. Tests for strength and quality.–The tests, if any, required for determining the
strength and quality of each of the substances specified in Schedules C and C (1) shall be
those set out in Schedule F or Schedule F (1)
4
[or as specified, as the case may be].]
3
[* * * * *]
115. Application of tests for sterility.–The tests shall be applied−
(a) to samples taken from each batch of the substance before the operation of filling
and sealing the containers in which it is to be issued has commenced except preparations,
which after being sealed in the containers are to be sterilized by heat, in a manner
satisfactory to the Licensing Authority; and
(b) to the contents of sample containers when ready for issue.
4
[
* * * * *]
119.−(1) If at this examination no growth of micro-organisms is found in any tube, the
sample may be treated as having passed the test.
(2) If at the examination a growth of micro-organisms is visible, further samples may be
taken and the tests may be repeated on the further samples taken; but no container the
contents of which form part of the batch shall be issued until such further samples have
passed the test. The process of taking samples from the batch for a test may be repeated
twice:
Provided that if the same organism is visible in more than one test the batch shall be
treated as not sterile and the material contained in the batch shall not be issued or used as part
of a further batch unless and until it has been re-sterilized and has passed the tests.
120
.−
Notwithstanding anything contained in the last preceding rule, in any case where—
(a) a substance is required in an emergency by a registered medical practitioner, but
the licensee has no filled containers in stock; or
1. Amended by F.1-6/62-D (SO 2889), dt. 2-7-1969.
2 Subs. by G.S.R. 663(E), dt. 3.7.1992.
3. Rules 113 and 114 omitted by G.S.R. 663(E),dt. 3.7.1992.
4. Rules 116, 117 and 118 omitted by G.S.R. 663 (E), dt. 3-7-1992.
Drugs and Cosmetics Rules 1945
140
(b) a substance which in the opinion of the Licensing Authority is so unstable in
solution that the delay occasioned by the completing of the sterility test on filled
containers would render its issue in active form impossible, the licensee may issue the
substance from a batch which has already passed the tests for sterility and freedom from
abnormal toxicity, without completing the sterility test on the filled containers, provided
that he complies with the following conditions—
(i) the licensee shall before the issue take samples in the required proportion
from the containers into which the batch is filled, and after the required inoculation
shall examine the tube every day for five days;
(ii) if at any examination any growth is visible in any of the tubes, he shall
immediately notify the Licensing Authority;
(iii) he shall keep available for inspection a record of all issues made under this
Rule containing such particulars of the circumstances in which the issue is made as
the Licensing Authority may require.
1
[121. Test for freedom from abnormal toxicity. –The test for freedom from abnormal
toxicity shall be carried out as per the current edition of Indian Pharmacopoeia in the case of
each batch of the serum tested by the licensee or by an institution approved by the Licensing
Authority for the purpose of carrying out the test on its behalf.]
2
[121A. Test for pyrogens–Solution of substances intended for parenteral administration in
large volumes (10 ml or more at a time) shall be pyrogen-free and tested for pyrogens. If
water or any other aqueous solvent is supplied along with the substances for preparing such
solutions, it shall also be pyrogen-free and tested for pyrogens.]
122. Substances specified in Schedule C(1). –The following provisions shall apply in the
case of a substance specified in Schedule C (1): –
3
[
(a) The container shall comply with the requirements, if any, specified in Schedule
F or Schedule F (1)
4
[or as specified], as the case may be.]
5
[* * * * *]
(c) The substance shall conform to the standards of strength, quality and purity
specified in Schedule F or Schedule F (1)
4
[or as specified], as the case may be and the
tests for determining the strength, quality and purity of the substance shall be those
specified in Schedule F or Schedule F
(1)
4
[or as specified,] as the case may be.
(d) The tests for determining the strength, quality and purity of a substance specified
in Schedule F or Schedule F (1)
3
[or as specified] as the case may be shall be applied to
samples taken from the final product after each manufacturing process has been
completed.
(e) The substance should be stored in a cool place and away from light.
1. Subs. by G.S.R. 834 (E), dt. 29-12-1999.
2. Subs. by SO 1449, dt. 13-06-1961. Earlier Ins. by F.1-27/56-D, dt. 18-12-1956
3. Subs. by F.1-6/62-D, dt. 2-7-1969
4. Subs. by G.S.R. 663 (E), dt. 3-7-1992
5. Omitted by G.S.R. 19, dt. 15.12.1977.
Drugs and Cosmetics Rules 1945
141
1
[PART
X A.
IMPORT OF MANUFACTURE OFNEW DRUG FOR CLINICAL
TRIALS OR MARKETING
122-A. Application for permission to import new drug.-
2
[(1) (a) No new drug shall be
imported, except under, and in accordance with, the permission granted by the Licensing
Authority as defined in clause (b) of rule 21.
(b) An application for the grant of permission to import a new drug shall be made in
Form
44 to the Licensing Authority, accompanied by a fee of fifty thousand rupees:
Provided that where a subsequent application by the same applicant for that drug, whether
in modified dosage form or with new claims, is made, the fee to accompany such application
shall be fifteen thousand rupees.
Provided further that any application received after one year of the grant of approval for
the import and sale of new drug, shall be accompanied by a fee of fifteen thousand rupees and
such information and data as required by
3
[Appendix I or Appendix IA or Appendix IB] of
Schedule Y, as the case may be].
(2) The importer of a new drug when applying for permission under sub-rule (1), shall
submit data as given in
3
[Appendix I or Appendix IA or Appendix IB] to Schedule Y
including the results of local clinical trials carried out in accordance with the guidelines
specified in that Schedule and submit the report of such clinical trials in the format given in
appendix II to the said Schedule:
Provided that the requirement of submitting the results of local clinical trials may not be
necessary if the drug is of such a nature that the Licensing Authority may, in public interest,
decide to grant such permission on the basis of data available from other countries:
Provided further that the submission of requirements relating to Animal Toxicology,
Reproduction studies, Teratogenic studies, Perinatal studies, Mutagenicity and
Carcinogenicity may be modified or relaxed in case of new drugs approved and marketed for
several years in other countries if he is satisfied that there is adequate published evidence
regarding the safety of the drug, subject to the other provisions of these rules.
2
[(3) The Licensing Authority, after being satisfied that the drug if permitted to be
imported as raw material (bulk drug substance) or as finished formulation shall be effective
and safe for use in the country, may issue an import permission in Form 45 and/or Form 45-
A, subject to the conditions stated therein:
Provided that the Licensing Authority shall, where the data provided or generated on the
drug is inadequate, intimate the applicant in writing, and the conditions, which shall be
satisfied before permission could be considered.]
122-B. Application for approval to manufacture new drug
4
[***].-
2
[(1)(a) No new
drug shall be manufactured for sale unless it is approved by the Licensing Authority as defined
in clause (b) of rule 21.
1. Ins. by G.S.R. 944 (E), dt. 21-9-1988.
2. Subs. by G.S.R. 900 (E), dt. 12.12.2001.
3. Subs. by G.S.R. 918 (E), dt. 30.11.2005.
4. Omitted by G.S.R. 26 (E), dt. 19.01.2006.
Drugs and Cosmetics Rules 1945
142
(b) An application for the grant of approval to manufacture the new drug and its
formulations shall be made in Form 44 to the Licensing Authority as defined in clause (b) of
Rule 21 and shall be accompanied by a fee of fifty thousand rupees:
Provided that where the application is for permission to import a new drug (bulk drug
substance) and grant of approval to manufacture its formulation/s, the fee to accompany such
application shall be fifty thousand rupees only.
Provided further that where a subsequent application by the same applicant for that drug,
whether in modified dosage form or with the new claims, is made, the fee to accompany such
subsequent application shall be fifteen thousand rupees:
Provided also that any application received after one year of the grant of approval for the
manufacture for sale of the new drug, shall be accompanied by a fee of fifteen thousand
rupees and such information and data as required by
4
[Appendix 1 or Appendix 1A or
Appendix IB] of Schedule Y, as the case may be.]
(2) The manufacturer of a new drug under sub-rule (1) when applying for approval to the
Licensing Authority mentioned in the said sub-rule, shall submit data as given in
4
[Appendix
1 or Appendix 1A or Appendix IB] to Schedule Y including the results of clinical trials
carried out in the country in accordance with the guideline specified in Schedule Y and
submit the report of such clinical trials in the same format given in Appendix II to the said
Schedule.
1
[(2A) The Licensing authority as defined in clause (b) of rule 21 after being satisfied that
the drug if approved to be manufactured as raw material (bulk drug substance) or as finished
formulation shall be effective and safe for use in the country, shall issue approval in Form 46
and/or Form 46A, as the case may be, subject to the conditions stated therein:
Provided that the Licensing Authority shall, where the data provided or generated on the
drug is inadequate, intimate the applicant in writing, and the conditions, which shall be
satisfied before permission could be considered.]
(3) When applying for approval to manufacture a new drug under sub-rule (1) or its
preparations, to the State Licensing Authority, an applicant shall produce along with his
application, evidence that the drug for the manufacture of which application is made has
already been approved
5
[in the name of the applicant] by the Licensing Authority mentioned in
Rule 21:
Provided that the requirement of submitting the results of local clinical trials may not be
necessary if the drug is of such nature that the
6
[Licensing Authority in Rule 21] may, in
public interest, decide to grant such permission on the basis of data available from other
countries:
Provided further that the submission of requirements relating to Animal Toxicology,
Reproduction studies, Teratogenic studies, Perinatal studies, Mutagenicity and
Carnicogenicity may be modified or relaxed in case of new drugs approved and marketed for
several years in other countries if he is satisfied that there is adequate published evidence
regarding the safety of the drug, subject to the other provisions of these rules.
2
[* * * * *]
3
[122D. Permission to import or manufacture fixed dose combination.- (1) An
application for permission to import or manufacture fixed dose combination of two or more
drugs as defined in clause (c) of rule 122-E shall be made to the Licensing Authority as
defined in clause (b) of Rule 21 in Form 44, accompanied by a fee of fifteen thousand rupees
and shall be accompanied by such information and data as is required in Appendix VI of
Schedule Y.
1. Ins. by G.S.R. 900(E), dt. 12-12-2001.
2. Rules 122-C omitted, by G.S.R. 900(E), dt. 12-12-2001.
3. Subs. by G.S.R. 900(E), dt. 12-12-2001.
4. Subs. by G.S.R. 918(E), dt. 30-11-2015.
5. Ins. by G.S.R. 26 (E), dt. 19-01-2006.
6. Subs. by G.S.R. 26 (E), dt. 19-01-2006.
Drugs and Cosmetics Rules 1945
143
(2) The Licensing Authority after being satisfied that the fixed dose combination if
approved to be imported or manufactured as finished formulation shall be effective and safe
for use in the country, shall issue permission in Form 45 or Form 46, as the case may be,
subject to the conditions stated therein:
Provided that the Licensing Authority shall, where the data provided or generated on the
fixed dose combination is inadequate, intimate the applicant in writing, and the conditions
which shall be satisfied before grant of approval/permission could be considered.
122DA. Application for permission to conduct clinical trials for New
Drug/Investigational New Drug.− (1) No clinical trial for a new drug, whether for clinical
investigation or any clinical experiment by any institution, shall be conducted except under,
and in accordance with, the permission, in writing, of the Licensing Authority defined in
clause (b) of Rule 21.
(2) An application for grant of permission to conduct−
(a) human clinical trials (Phase-I) on a new drug shall be made to the Licensing
Authority in Form 44 accompanied by a fee of fifty thousand rupees and such
information and data as required under Schedule Y.
(b) exploratory clinical trials (Phase-II) on a new drug shall be made on the
basis of data emerging from Phase-I trial, accompanied by a fee of twenty-five
thousand rupees;
(c) confirmatory clinical trials (Phase-III) on a new drug shall be made on the
basis of the data emerging from Phase-II and where necessary, data emerging from
Phase-I also, and shall be accompanied by a fee of twenty-five thousand rupees:
Provided that no separate fee shall be required to be paid along with application for
import/manufacture of a new drug based on successful completion of phases clinical trials by
the applicant:
Provided further that no fee shall be required to be paid along with the application by
Central Government or State Government Institutes involved in clinical research for
conducting trials for academic or research purposes.
(3) The Licensing Authority after being satisfied with the clinical trials, shall grant
permission in Form 45 or Form 45-A or Form 46 or Form 46-A, as the case may be, subject to
the conditions stated therein:
Provided that the Licensing Authority shall, where the data provided on the clinical trials
is inadequate, intimate the applicant in writing, within six months from the date of such
intimation or such extended period, not exceeding a further period of six months, as the
Licensing Authority may, for reasons to be recorded in writing, permit, intimating the
conditions which shall be satisfied before permission could be considered.
1
[(4) No permission for conduct of clinical trial intended for academic purposes in respect
of approved drug formulation shall be required for any new indication or new route of
administration or new dose or new dosage form where,-
(a) the trial is approved by the Ethics Committee; and
(b) subject to the provisions of sub-rule 5, the data generated is not intended for submission to
licensing authority.
Drugs and Cosmetics Rules 1945
144
1. Ins. by G.S.R. 313(E), dt. 16-03-2016.
(5) The Ethics Committee shall however inform the licensing authority about the cases
approved by it and also about cases where there could be an overlap between the clinical trial
for academic and regulatory purposes and where the said authority does not convey its
comments to the Ethics Committee within a period of thirty days from the date of receipt of
communication from the Ethics Committee, it shall be presumed that no permission from the
licensing authority is required.]
1
[Explanation:- —For the purposes of these rules,—
(a) ―Clinical Trial‖ means a systematic study of any new drug(s) in human subject(s) to
generate data for discovering and/or verifying the clinical, pharmacological (including
pharmacodynamic and pharmacokinetic), and/or adverse effects with the objective of
determining safety and/or efficacy of the new drug;
(b) ―Global Clinical Trial‖ means any clinical trial which is conducted as part of multi-
national clinical development of a drug;
(c) ―Investigational New Drug‖ means a new chemical entity or a product having therapeutic
indication but which has never been tested earlier on human being;
(d) ―New Chemical Entity‖ means an active substances in developmental stage which may be
specified as a drug under the Act, after undergoing any clinical trial.]
2
[****]
3
[122-DAB- Compensation in case of injury or death during clinical trial.-
4
[(1) In case of an injury occurring to the subject during the clinical trial, free medical
management shall be given as long as required or till such time it is established that the injury
is not related to the clinical trial, whichever is earlier.]
(2) In case, the injury occurring to the trial subject is related to the clinical trial, such
subject shall also be entitled for financial compensation as per order of the Licensing
Authority defined under clause (b) of Rule 21, and the financial compensation will be over and
above any expenses incurred on the medical management of the subject.
5
[(2A) In case, there is no permanent injury, the quantum of compensation shall be
commensurate with the nature of the non-permanent injury and loss of wages of the subject.]
(3) In the case of clinical trial related death of the subject, his / her nominee(s) would be
entitled for financial compensation, as per the order of the Licensing Authority defined under
clause (b) of Rule 21 and the financial compensation will be over and above any expenses
incurred on the medical management of such subject.
(4) The expenses on medical management and financial compensation in the case of
clinical trial injury or death of the trial subject shall be borne by the sponsor of the clinical
trial.
(5) Any injury or death of the subject occurring in clinical trial due to following reasons
shall be considered as clinical trial related injury or death and the subject or his/her
nominees(s), as the case may be, are entitled for financial compensation for such injury or
death:
(a) Adverse effect of investigational product(s);
(b) Violation of the approved protocol, scientific misconduct or negligence by the
sponsor or his representative or the investigator;
1. Subs. by G.S.R. 826 (E), dt. 30-10-2015 with following explanation.
―Explanation.−For the purpose of these rules Investigational New Drug means a new chemical entity or a
product having therapeutic indication but which have never been earlier tested on human beings.‖
2. Omitted rule 122DAA by G.S.R. 826 (E), dt. 30-10-2015, before omission it stood as under:
―122DAA. Definition of Clinical trial.--For the purpose of this Part, ―Clinical trial‖ means a systematic study
of new drug(s) in human subject(s) to generate data for discovering and/or verifying the clinical, pharmacological
(including pharmacodynamic and pharmacokinetic) and/or adverse effects with the objective of determining
safety and / or efficacy of the new drug.‖
3. Ins. by G.S.R. 53 (E), dt. 30-01-2013.
4. Subs. by G.S.R. 889 (E), dt. 12-12-2014.
5. Ins. by G.S.R. 889 (E), dt. 12-12-2014.
Drugs and Cosmetics Rules 1945
145
(c) Failure of investigational product to provide intended therapeutic effect, where, the
standard care, though available, was not provided to the subject as per the clinical trial
protocol;
(d) Use of placebo in a placebo-controlled trial where, the standard care, though
available, was not provided to the subject as per the clinical trial protocol;
(e) Adverse effects due to concomitant medication excluding standard care,
necessitated as part of approved protocol;
(f) For injury to a child in-utero because of the participation of parent in clinical trail;
(g) Any clinical trial procedures involved in the study.
(6) The sponsor, whether a pharmaceutical company or an institution shall give an
undertaking along with the application for clinical trail permission to the Licensing Authority
defined in clause (b) of Rule 21, to provide compensation in the case of clinical trial related
injury or death for which subjects are entitled to compensation.
(7) In case, the sponsor fails to provide medical management for the injury to the subject
and / or financial compensation to the trial subject for clinical trial related injury or financial
compensation to the subject‘s nominee(s) in case of clinical trial related death of the subject,
the Licensing Authority may after giving an opportunity to show cause why such an order
should not be passed, by an order in writing, stating the reasons thereof, suspend or cancel the
clinical trial and / or restrict Sponsor including his representative(s) to conduct any further
clinical trials in the country or take any other action deemed fit under the rules.]
1
[122 DAC. Permission to conduct clinical trial:- (1) The Licensing Authority as defined
in clause (b) of Rule 21, on being satisfied that the data submitted along with the application in
support of the proposed clinical trial is adequate in all respects, issue permission for conduct
of clinical trial, subject to the following conditions, namely:-
(a) Clinical trial shall be conducted in compliance with the approved protocols,
requirements of Schedule Y annexed to these rules, Good Clinical Practice Guidelines for
conduct of clinical trials in India and other applicable regulations;
(b) Approval of the Ethics Committee shall be obtained before initiation of the study;
(c) Clinical trial shall be registered at Clinical Trials Registry of India before enrolling
the first patient for the study;
(d) Annual status report of each clinical trial, as to whether it is ongoing, completed or
terminated, shall be submitted to the Licensing Authority and in case of termination of any
clinical trial the detailed reasons for the same shall be communicated to the said Licensing
Authority;
(e) Any report of serious adverse event occurring during clinical trial to the subject,
after due analysis, shall be forwarded within ten days of its occurrence as per Appendix XI
and in compliance with the procedures prescribed in Schedule Y;
(f) In case of an injury or death during the clinical trial to the subject of the clinical trial
the applicant shall provide complete medical management and compensation in the case of
trial related injury or death in accordance with Rule 122 DAB and the procedures prescribed
under Schedule Y, and the details of compensation provided in such cases shall be intimated to
the Licensing Authority within thirty days of the receipt of the order of the said authority;
(g) The premises of Sponsor including their employees, subsidiaries and branches,
their agents, contractors and sub-contractors and clinical trial sites shall be open to
inspection by the officers authorized by the Central Drugs Standard Control Organization,
who may be accompanied by an officer of the State Drug Control Authority concerned, to
verify compliance to the requirements of Schedule Y, Good Clinical Practices guidelines for
conduct of clinical trials in India and other applicable regulations;
1. Ins. by G.S.R. 63 (E), dt. 01-02-2013.
Drugs and Cosmetics Rules 1945
146
(h) The Sponsor including their employees, subsidiaries and branches, their agents,
contractors and sub-contractors and clinical trial sites and the investigator shall allow officers
authorized by the Central Drug Standard Control Organization, who may be accompanied by
an officer of the State Drug Control Authority concerned, to enter with or without prior notice,
any premises of sponsor including their employees, subsidiaries and branches, their agents,
contractors and sub-contractors and clinical trial sites to inspect, search and seize any record,
data, document, books, investigational drugs etc. related to clinical trials and provide adequate
replies to any queries raised by the inspecting authority in relation to the conduct of clinical
trial;
(2) Notwithstanding the conditions specified in sub-Rule (1), the Licensing Authority, on
being satisfied that the data submitted along with the application in support of the proposed
clinical trial is adequate in all respect, may also impose such additional conditions for issuance
of permission in respect of specific clinical trials, if considered necessary, regarding the
objective, design, subject population, subject eligibility, assessments, conduct and treatment
of such clinical trial.
(3) If any Sponsor including their employees, subsidiaries and branches, their agents,
contractors and sub-contractors, Investigators conducting clinical trial and clinical trial sites
fail to comply with any of the above conditions, the Licensing Authority, may, after giving an
opportunity to show cause why such an order should not be passed, by an order in writing
stating the reasons thereof,-
(a) Issue warning letter giving details of deficiency found during the inspection, which
might affect the right or well-being of the clinical trial subject or the validity of the study
conducted at that site;
(b) Recommend that study may be rejected or discontinued;
(c) Suspend or cancel the clinical trial permission;
(d) Debar the Investigator(s), Sponsor including their employees, subsidiaries and
branches, their agents, contractors and sub-contractors to conduct any clinical trial in future.
(4) The Sponsor including their employees, subsidiaries and branches, their agents,
contractors and sub-contractors and clinical trial Investigators, against whom action as
mentioned in sub- Rule (3) has been taken by the Licensing Authority, may, within ninety
days of the receipt of the copy of the order of the Licensing Authority prefer an appeal to the
Central Government, and the Central Government may, after giving such appellant an
opportunity of being heard, confirm, reverse or modify such order.]
122DB. Suspension or cancellation of Permission/Approval.- If the importer or
manufacturer under this Part fails to comply with any of the conditions of the permission or
approval, the Licensing Authority may, after giving an opportunity to show cause why such
an order should not be passed, by an order in writing stating the reasons therefor, suspend or
cancel it.
122DC. Appeal.- Any person aggrieved by an order passed by the Licensing Authority
under this Part, may within sixty days from the date of such order, appeal to the Central
Government, and the Central Government may, after such enquiry into the matter as is
considered necessary, pass such order in relation thereto as it thinks fit.
1
[122 DD. Registration of Ethics Committee:- (1) No Ethics Committee shall review and
accord its approval to a clinical trial protocol without prior registration with the Licensing
Authority as defined in clause (b) of Rule21:
Provided that any Ethics Committee, existing on the date of commencement of the
Drugs and Cosmetics (Third Amendment) Rules, 2013, who has already reviewed and
accorded approval to clinical trial protocol, shall obtain registration within a period of forty-
five days from the date of commencement of Drugs and Cosmetics (Third Amendment) Rules,
2013.
1. Ins. by G.S.R. 72 (E), dt. 08-02-2013.
Drugs and Cosmetics Rules 1945
147
(2) An application for registration of Ethics Committee shall be made to the Licensing
Authority in accordance with the requirements as specified in the Appendix VIII of Schedule
Y.
(3) The Licensing Authority after being satisfied that the requirements have been
complied with, may grant registration to the Ethics Committee subject to such conditions as
may be stated therein.
(4) The Ethics Committee shall review and accord its approval to a clinical trial and also
carry ongoing review of the trial at appropriate intervals, as specified in Schedule Y, and the
Good Clinical Practice Guidelines for Clinical Trials in India and other applicable regulatory
requirements for safeguarding the rights, safety and well-being of the trial subjects.
(5) In the case of any serious adverse event occurring to the clinical trial subjects during
the clinical trial, the Ethics Committee shall analyze and forward its opinion as per procedure
specified under APPENDIX XII of Schedule Y.
(6) The Ethics Committee shall allow inspectors or officials authorized by the Central
Drugs Standard Control Organization to enter its premises to inspect any record, data or any
document related to clinical trial and provide adequate replies to any query raised by such
inspectors or officials, as the case may be in relation to the conduct of clinical trial.
(7) The registration, unless it is suspended or cancelled, shall be valid for a period of three
years from the date of issue:
Provided that if the application for re-registration is received by the Licensing Authority
within three months before the expiry, the registration shall continue to be in force until orders
are passed by the said authority:
Provided further that the Licensing Authority shall be informed in writing in case of any
change in the membership or the constitution of the Ethics Committee takes place.
(8) If the Licensing Authority is not satisfied, he shall reject the application and shall
inform the applicant of the reasons for such rejection and the conditions which must be
satisfied before the registration can be granted.
(9) If the Ethics Committee fails to comply with any of the conditions of registration, the
Licensing Authority may, after giving an opportunity to show cause why such an order should
not be passed, by an order in writing stating the reasons therefor, suspend or cancel the
registration of the Ethics Committee for such period as considered necessary.
(10) The Ethics Committee whose registration has been suspended or cancelled by the
Licensing Authority, may, within ninety days of the receipt of the copy of the order, prefer an
appeal to the Central Government and the Central Government may after giving an opportunity
of being heard, confirm, reverse or modify such order.
Explanation:- For the purpose of this Rule an Ethics Committee is a committee
comprising of medical, scientific, non-medical and nonscientific members, whose
responsibility is to ensure the protection of the rights, safety and will-being of human subjects
involved in a clinical trial and it shall be responsible for reviewing and approving the protocol,
the suitability of the investigators, facilities, methods and adequacy of information to be used
for obtaining and documenting informed consent of the study subjects and adequacy of
confidentiality safeguards.]
122E. Definition of new drug.- For the purpose of this Part, new drug shall mean and
include-
1
[(a) A drug, as defined in the Act including bulk drug substance
2
[or
phytopharmaceutical drug] which has not been used in the country to any significant extent
under the conditions prescribed, recommended or suggested in the labelling thereof and has
not been recognized as effective and safe by the licensing authority mentioned under rule 21
for the proposed claims:
1. Ins. by G.S.R. 591 (E), dt. 17-8-1999.
2. Ins. by G.S.R. 918 (E), dt. 30-11-2015.
Drugs and Cosmetics Rules 1945
148
Provided that the limited use, if any, has been with the permission of the licensing
authority.]
(b) A drug already approved by the Licensing Authority mentioned in Rule 21 for
certain claims, which is now proposed to be marketed with modified or new claims, namely,
indications, dosage, dosage form (including sustained release dosage form) and route of
administration.
(c) A fixed dose combination of two or more drugs, individually approved earlier for
certain claims, which are now proposed to be combined for the first time in a fixed ratio, or if
the ratio of ingredients in an already marketed combination is proposed to be changed, with
certain claims, viz. indications, dosage, dosage form (including sustained release dosage
form) and route of administration. (See items (b) and (c) of Appendix VI to Schedule Y.)
Explanation.- For the purpose of this rule−
1
[(i) all vaccines and Recombinant DNA (r-DNA) derived drugs shall be new drugs
unless certified otherwise by the Licensing Authority under Rule 21;]
(ii) a new drug shall continue to be considered as new drug for a period of four years
from the date of its first approval
2
[***].]
1. Ins. by G.S.R. 45(E), dt. 24.01.2011.
2. Omitted by G.S.R. 724(E), dt. 7.11.2013, the following words,-
―or its inclusion in the Indian Pharmacopoeia Whichever is earlier‖.
Drugs and Cosmetics Rules 1945
149
1
[PART
XB
REQUIREMENTS FOR THE COLLECTION,
STORAGE,
PROCESSING
AND DISTRIBUTION OF WHOLE HUMAN BLOOD,
HUMAN
BLOOD
COMPONENTS BY BLOOD BANKS
ANDMANUFACTURE
OF
BLOOD
PRODUCTS
2
[122EA. Definitions.- (1) In this Part and in the Forms contained in Schedule A and in
Part XII-B,
3
[Part XII-C and Part XIID] of Schedule F, unless there is anything repugnant in
the subject or context−
(a) ―apheresis‖ means the process by which blood drawn from a donor, after
separating plasma or platelets, or leucocytes, is re-transfused simultaneously into the said
donor;
(b) ―autologous blood‖ means the blood drawn from the patient for re-transfusion
unto himself later on;
(c) ―blood‖ means and includes whole human blood, drawn from a donor and mixed
with an anti-coagulant;
(d) ―blood bank‖ means a place or organization or unit or institution or other
arrangements made by such organization, unit or institution for carrying out all or any of
the operations for collection, apheresis, storage, processing and distribution of blood
drawn from donors and/or for preparation, storage and distribution of blood components;
(e) ―blood component‖ means a drug prepared, obtained, derived or separated from a
unit of blood drawn from a donor;
(f) ―blood product‖ means a drug manufactured or obtained from pooled plasma of
blood by fractionation, drawn from donors;
4
[(fa) ―cord blood bank‖ means a place or organization or unit for carrying out and
responsible for operations of collection, processing, testing, banking, selection and
release of cord blood units;]
(g) ―donor‖ means a person who voluntarily donates blood after he has been declared
fit after a medical examination, for donating blood, on fulfilling the criteria given
hereinafter, without accepting in return any consideration in cash or in kind from any
source but does not include a professional or a paid donor.
Explanation.- For the purposes of this clause, benefits or incentives like pins, plaques,
badges, medals, commendation certificates, time-off from work, membership of blood
assurance programme, gifts of little or intrinsic monetary value shall not be construed as
consideration;
(h) ―leucapheresis‖ means the process by which the blood drawn from a donor, after
leucocyte concentrates have been separarated is re-transfused simultaneously into the
said donor;
(i) ―plasmapheresis‖ means the process by which the blood drawn from a donor, after
plasma has been separated, is re-transfused during the same sitting into the said donor;
(j) ―plateletpheresis‖ means the process by which the blood drawn from a donor, after
platelet concentrates have been separated, is re-transfused simultaneously into the said
donor;
(k) ―professional donor‖ means a person who donates blood for a valuable
consideration, in cash or kind, from any source, on behalf of the recipient-patient and
includes a paid donor or a commercial donor;
(l) ―replacement donor‖ means a donor who is a family friend or a relative of the
patient-recipient.]
1. Ins. by G.S.R. 28(E), dt. 22-1-1993.
2. Ins. by G.S.R. 245 (E), dt. 5-04-1999.
3. Subs. by G.S.R. 899 (E), dt. 27-12-2011.
4. Ins. by G.S.R. 899 (E), dt. 27-12-2011.
Drugs and Cosmetics Rules 1945
150
4
[(m) ―umbilical cord blood‖ is the whole blood including Hematopoietic Progenitor Cells
collected from placental and or Umbilical cord blood vessels after the umbilical cord have
been clamped.]
122-F. Form of application for licence for operation of Blood Bank/processing of
whole human blood for components/manufacture of blood products for sale or
distribution
4
[, collection, processing, testing, storage, banking and release of umbilical cord
blood stem cells.]- (1) Application for the grant and/or renewal of licence for the operation
of a Blood Bank/processing of human blood for components/manufacture of blood
products
4
[ collection, processing, testing, storage, banking and release of umbilical cord blood
stem cells] shall be made to the Licensing Authority appointed under Part VII in
1
[Form 27-
C or
5
[Form 27-E or Form 27-F], as the case may be], and shall be accompanied by
3
[licence
fee of rupees six thousand and an inspection fee of rupees one thousand and five hundred for
every inspection thereof or for the purpose of renewal of licence]:
Provided that if the applicant applies for renewal of licence after its expiry but within six
months of such expiry the fee payable for the renewal of the licence
3
[shall be rupees six
thousand and inspection fee of rupees one thousand and five hundred plus an additional fee at
the rate of rupees one thousand per month or a part thereof in addition to the inspection fee]:
5
[Provided further that a licensee holding a license in Form 28-C, Form 28-E or Form 28-
F as the case may be, for operation of Blood Bank/ processing of whole human blood for
components / manufacture of blood products / collection, processing testing storage, banking
and release of umbilical cord blood stem cells shall apply for grant of license under sub Rule
(1) before the expiry of the said license in Form 27-C, Form 27-E or Form 27-F as the case
may be and he shall continue to operate the same till the orders on his application are
communicated to him.]
2
[***]
(2) A fee of
3
[rupees one thousand] shall be paid for a duplicate copy of a licence issued
under this rule, if the original is defaced, damaged or lost.
(3) Application by a licensee to manufacture additional drugs listed in the application
shall be accompanied by a fee of
3
[rupees three hundred] for each drug listed in the
application.
(4) On receipt of the application for the grant or renewal of such licence, the Licensing
Authority shall,–
(i) verify the statements made in the application form;
(ii) cause the manufacturing and testing establishment to be inspected in accordance
with the provision of rule 122-I; and
(iii) in case the application is for renewal of licence, call for information of past
performance of the licensee.
(5) If the Licensing Authority is satisfied that the applicant is in a position to fulfil the
requirements laid down in the rules, he shall prepare a report to that effect and forward it
6
[along with the application and the licence (in triplicate) to be granted or renewed, duly
completed] to the Central Licence Approving Authority:
Provided that if the Licensing Authority is of the opinion that the applicant is not in a
position to fulfil the requirements laid down in these rules, he may, by order, for reasons to be
recorded in writing, refuse to grant or renew the licence, as the case may be.
(6) If, on receipt of the application and report of the Licensing Authority referred to in
sub-rule
7
[(5)] and after taking such measures including inspection of the premises by the
Inspector, appointed by the Central Government under section 21 of the Act, and/or along
1. Subs. by G.S.R. 245(E), dt. 5.4.1999. 4. Ins. by G.S.R. 899 (E), dt. 27-12-2011.
2. Explanation omitted by G.S.R. 733 (E), dt. 21.12.2005 earlier Ins. by G.S.R. 89(E), dt. 14-2-1996.
3. Subs. by G.S.R. 601(E), dt. 24-8-2001. 5. Subs. by G.S.R. 899 (E), dt. 27-12-2011.
6. Ins. by G.S.R. 89 (E), dt. 14.2.1996.
7. Corrected by corrigendum G.S.R. 447 (E), dt. 10-06-1993.
Drugs and Cosmetics Rules 1945
151
with the Expert in the field concerned if deemed necessary, the Central Licence Approving
Authority is satisfied that the applicant is in a position to fulfil the requirements laid down in
these rules, he may grant or renew the licence, as the case may be:
Provided that if the Central Licence Approving Authority is of the opinion that the
applicant is not in a position to fulfil the requirements laid down in these rules he may,
notwithstanding the report of the Licensing Authority, by order, for reasons to be recorded in
writing, reject the application for grant or renewal of licence, as the case may be, and shall
supply the applicant with a copy of the inspection report.
122G. Form of Licence for the operation of a Blood Bank/processing of whole
human blood for components and manufacture of blood products
3
[/manufacture of blood
products/collection, processing, testing, storage, banking and release of umbilical cord
blood stem cells] and the conditions for the grant or renewal of such licence.−
2
[(1)] A
licence for the operation of a Blood Bank or for processing whole human blood for
components and
3
[/manufacture of blood products/collection, processing, testing, storage,
banking and release of umbilical cord blood stem cells] shall be issued in
1
[Form 28C or Form
28E or
3
[Form 28F or Form 26G or Form26-I or Form 26J, as the case may be, before a
license in Form 28C or Form 28E or Form28-F or Form 26G or Form 26-I or Form 26-J], as
the case may be,] is granted or renewed the following conditions shall be complied with by the
applicant:-
1
[(i) The operation of Blood Bank and/or processing of whole human blood for
components shall be conducted under the active direction and personal supervision of
competent technical staff consisting of at least one person who is whole time employee
and who is Medical Officer, and possessing-
(a) Postgraduate degree in Medicine - M.D (Pathology/Transfusion
Medicines); or
(b) Degree in Medicine (M.B.B.S.) with Diploma in Pathology or Transfusion
Medicines having adequate knowledge in blood group serology, blood group
methodology and medical principles involved in the procurement of blood and/or
preparation of its components; or
(c) Degree in Medicine (M.B.B.S.) having experience in Blood Bank for one
year during regular service and also has adequate knowledge and experience in
blood group serology, blood group methodology and medical principles involved in
the procurement of blood and/or preparation of its components,
the degree or diploma being from a University recognized by the Central Government.
Explanation.- For the purposes of this condition, the experience in Blood Bank for
one year shall not apply in the case of persons who are approved by the Licensing
Authority and/or Central Licence Approving Authority prior to the commencement of
the Drugs and Cosmetics (Second Amendment) Rules, 1999].
(ii) The applicant shall provide adequate space, plant and equipment for any or all
the operations of blood collection or blood processing. The space, plant and equipment
required for various operation is given in Schedule ‗F‘, Part XIIB and/or XIIC
4
[or XIID].
(iii) The applicant shall provide and maintain adequate technical staff as specified in
Schedule F, Part XIIB and/or XIIC
4
[or XIID].
(iv) The applicant shall provide adequate arrangements for storage of whole
human blood, human blood components and blood products.
(v) The applicant shall furnish to the Licensing Authority, if required to do so,
data on the stability of whole human blood, its components or blood products
which are likely to deteriorate, for fixing the date of expiry which shall be printed
on the labels of such products on the basis of the data so furnished.
1. Ins. by GSR 245(E), dt. 5-4-1999.
2. Renumbered as sub-rule (1) by GSR 733(E), dt. 21-12-2005.
3. Subs. by GSR 899(E), dt. 27-12-2011. 4. Ins. by GSR 899(E), dt. 27-12-2011.
Drugs and Cosmetics Rules 1945
152
3
[(2) Application for grant or renewal of a licence for operation of Blood Bank or processing
of human blood components shall be made by the Blood Bank run by the Government, Indian
Red Cross Society, hospital, charitable trust or voluntary organization approved by a State/
Union Territory Blood Transfusion Council only.
Explanation.– For the purpose of this sub-rule, ―renewal‖ shall include renewal of any
licenceissued prior to the commencement of the Drugs and Cosmetics (……..Amendment)
Rules,2005.]
122H. Duration of licence.- An original licence in
1
[Form 28C or Form 28E
4
[or Form
28F] or a renewed licence in Form 26G or Form 26-I]
4
[or Form 26J] unless sooner
suspended or cancelled shall be
2
[valid for a period of five years on and from the date on
which] it is granted or renewed.
122-I. Inspection before grant or renewal of licence for operation of Blood Bank,
processing of whole human blood for components and manufacture of blood
products.- Before a licence in
1
[Form 28C or Form 28E
4
[or Form 28F] is granted or a
renewal of licence in form 26G or Form 26-I
4
[or Form 26J] is made, as the case may be,] the
Licensing Authority or the Central Licence Approving Authority, as the case may be, shall
cause the establishment in which Blood Bank is proposed to be operated/whole human blood
for components is processed/ blood products are manufactured to be inspected by one or
more Inspectors, appointed under the Act and/or along with the Expert in the field concerned.
The Inspector or Inspectors shall examine all portions of the premises and
appliances/equipments and inspect the process of manufacture intended to be employed or
being employed along with the means to be employed or being employed for operation of
blood bank/processing of whole human blood for components/manufacture of blood
products together with their testing facilities and also enquire into the professional
qualification of the expert staff and other technical staff to be employed.
122J. Report by Inspector.-The Inspector or Inspectors shall forward a detailed
descriptive report giving his findings on each aspect of inspection along with his
recommendation in accordance with the provisions of rule 122-I to the Licensing Authority or
to the Central Licence Approving Authority.
122K. Further application after rejection.- If within a period of six months from the
rejection of application of a licence the applicant informs the Licensing Authority that the
conditions laid down have been satisfied and deposits an inspection
2
[fee of rupees two
hundred and fifty] the Licensing Authority may, if after causing further inspection to be made
is satisfied that the conditions for the
1
[grant or renewal of a licence have been complied with,
shall grant or renew the licence in Form 28C or Form 28E
4
[or Form 28F]:
Provided that in the case of a drug notified by the Central Government under rule 68-A,
the application, together with the inspection report and the Form of licence (in triplicate to be
granted or renewed), duly completed shall be sent, to the Central Licence Approving
Authority, who may approve the same and return it to the Licensing Authority for issue of the
licence.]
122L. Delegation of powers by the Central Licence Approving Authority.- The Central
Licence Approving Authority may, with the approval of the Central Government, by
notification delegate his powers of signing licences and any other power under rules to
persons under his control having same qualifications as prescribed for Controlling Authority
under rule 50-A, for such areas and for such periods as may be specified.
122M. Provision for appeal to the State Government by a party whose licence has not
been granted or renewed.- Any person who is aggrieved by the order passed by the Licensing
Authority or Central Licence Approving Authority, as the case may be, may within thirty
days from the date of receipt of such order, appeal to the State Government or Central
Government, as the case may be, after such enquiry into the matter as it considers necessary
and after giving the said person an opportunity for representing his view in the matter may
pass such order in relation thereto as it thinks fit.
1. Ins. by G.S.R 245(E), dt. 5-4-1999. 3. Ins. by G.S.R 733(E), dt. 21-12-2005.
2. Subs. by G.S.R 601(E), dt. 24-8-2001. 4. Ins. by GSR 899(E), dt. 27-12-2011.
Drugs and Cosmetics Rules 1945
153
122-N. Additional information to be furnished by an applicant for licence or by a
licensee to the Licensing Authority.- The applicant for the grant of licence or any person
granted a licence under the Part shall, on demand furnish to the Licensing Authority, before
the grant of the licence or during the period the licence is in force, as the case may be,
documentary evidence in respect of the ownership or occupation, rental or other basis of the
premises, specified in the application for licence or in the licence granted, constitution of the
firm or any other relevant matter, which may be required for the purpose of verifying the
correctness of the statement made by the applicant or the licensee, while applying for or after
obtaining the licence, as the case may be.
122-O. Cancellation and suspension of licences.− (1) The Licensing Authority or Central
Licence Approving Authority may for such licences granted or renewed by him after giving
the licensee an opportunity to show cause why such an order should not be passed by an order
in writing stating the reason thereof, cancel a licence issued under this part or suspend it for
such period as he thinks fit, either wholly or in respect of some of the substances to which it
relates
1
[or direct the licensee to stop collection, storage, processing, manufacture and
distribution of the said substances and
2
[thereupon order the destruction of substances and]
stocks thereof in the presence of an Inspector], if in his opinion, the licensee has failed to
comply with any of the conditions of the licence or with any provisions of the Act or Rules
thereunder.
(2) A licensee whose licence has been suspended or cancelled may, within three months
of the date of the order under sub-rule (1) prefer an appeal against the order to the State
Government or Central Government, which shall decide the same.
122-P. Conditions of licence.-
3
[A licence in Form 28C, Form 28E,
4
[Form 28F, Form
26G, Form 26-I or Form 28J shall be subject to the special conditions set out in Schedule F,
Part XII-B and Part XII C, Part XIID,] as the case may be, which relate to the substance in
respect of which the licence is granted or renewed and to the following general conditions,
namely:-]
(i) (a) The licensee shall provide and maintain adequate staff, plant and premises
for the proper operation of a Blood Bank for processing whole human blood, its
components and/or manufacture of blood products.
(b) The licensee shall maintain staff, premises and equipment as specified in Rule
122-G. The licensee shall maintain necessary records and registers as specified in
Schedule F, Parts XII-B and XII-C.
(c) The licensee shall test in his own laboratory whole human blood, its
components and blood products and maintain records and registers in respect of such tests
as specified in Schedule F, Parts XIIB and XIIC
5
[or XIID]. The records and register shall
be maintained for a period of five years from the date of manufacture.
(d) The licensee shall maintain/preserve reference sample and supply to the
Inspector the reference sample of the whole human blood collected by him in an adequate
quantity to conduct all the prescribed tests. The licensee shall supply to the Inspector the
reference sample for the purpose of testing.
1. Subs. by G.S.R. 20(E), dt. 11-1-1996.
2. Ins. by (Corrigenda) G.S.R. 514 (E), dt. 6-11-1996.
3. Subs. by G.S.R. 245(E), dt. 5-4-1999.
4. Subs. by GSR 899(E), dt. 27-12-2011.
5. Ins. by GSR 899(E), dt. 27-12-2011.
Drugs and Cosmetics Rules 1945
154
(ii) The licensee shall allow an Inspector appointed under the Act to enter, with or
without prior notice, any premises where the activities of the Blood Bank are being
carried out for the processing of Whole Human Blood and/or Blood Products, to inspect
the premises and plant and the process of manufacture and the means employed for
standardizing and testing the substance.
(iii) The licensee shall allow an Inspector appointed under the Act to inspect all
registers and records maintained under these rules and to take samples of the
manufactured product and shall supply to the Inspector such information as he may
require for the purpose of ascertaining whether the provisions of the Act and rules
thereunder have been observed.
(iv) The licensee shall from time to time report to the Licensing Authority any
changes in the expert staff responsible for the operation of a Blood Bank/processing of
whole human blood for components and/or manufacture of blood products and any
material alterations in the premises or plant used for that purpose which have been made
since the date of last inspection made on behalf of the Licensing Authority before the
grant of the licence.
(v) The licensee shall on request furnish to the Licensing Authority, or Central
Licence Approving Authority or to such Authority as the Licensing Authority, or the
Central Licence Approving Authority may direct, from any batch unit of drugs as the
Licensing Authority or Central Licence Approving Authority may from time to time
specify, sample of such quantity as may be considered adequate by such Authority for
any examination and, if so required, also furnish full protocols of the test which have
been applied.
(vi) If the Licensing Authority or the Central Licence Approving Authority so
directs, the licensee shall not sell or offer for sale any batch/unit in respect of which a
sample is, or protocols are furnished under the last preceding sub-paragraph until a
certificate authorizing the sales of batch/unit has been issued to him by or on behalf of the
Licensing Authority or the Central Licence Approving Authority.
(vii) The licensee shall on being informed by the Licensing Authority or the
Controlling Authority that any part of any batch/unit of the substance has been found by
the Licensing Authority or the Central Licence Approving Authority not to conform with
the standards of strength, quality or purity specified in these Rules and on being directed
so to do, withdraw, from sales and so far as may in the particular circumstances of the
case be practicable recall all issues already made from that batch/unit.
(viii) No drug manufactured under the licence shall be sold unless the precautions
necessary for preserving its properties have been observed throughout the period after
manufacture. Further no batch/unit manufactured under this licence shall be
supplied/distributed to any person without prescription of a Registered Medical
Practitioner.
(ix) The licensee shall comply with the provisions of the Act and of these Rules and
with such further requirements, if any, as may be specified in any Rules subsequently
made under Chapter IV of the Act, provided that where such further requirements are
specified in the Rules, these would come in force four months after publication in the
Official Gazette.
(x) The licensee shall maintain an Inspection Book in Form 35 to enable an Inspector
to record his impression and defects noticed.
(xi) The licensee shall destroy the stock of batch/unit which does not comply
with standard tests in such a way that it would not spread any disease/infection by
way of proper disinfection method.
Drugs and Cosmetics Rules 1945
155
1
[(xii) All bio-medical waste shall be treated, disposed of or destroyed as per
the provisions of the Bio-Medical Wastes (Management and Handling) Rules,
1996.
(xiii) The licensee shall neither collect blood from any professional donor or
paid donor nor shall he prepare blood components and/or manufacture blood
products from the blood drawn from such a donor.]
PART
XI
EXEMPTIONS
123. The drugs specified in Schedule K shall be exempted from the provisions of Chapter
IV of the Act and the Rules made thereunder to the extent and subject to the conditions
specified in that Schedule.
PART
XII
2
[
124. Standards of drugs: –
STANDARDS
(1) For drugs included in the Indian Pharmacopoeia—
(a) The standards for identity, purity and strength shall be those as may be
specified in the edition of the Indian Pharmacopoeia for the time being in force.
(b) In case the standards for identity, purity and strength for drugs are not
specified in the edition of the Indian Pharmacopoeia for the time being in force but
are specified in the edition of the Indian Pharmacopoeia immediately preceding, the
standards for identity, purity and strength shall be those occurring in such
immediately preceding edition of the Indian Pharmacopoeia.
(2) For other drugs–
(a) The standards for identity, purity and strength shall be those as may be
specified in the edition of the official pharmacopoeia, for the time being in force, of
any country to which the drug claims to comply with,
(b) In case the standards for identity, purity and strength for drugs are not
specified in the edition of such official pharmacopoeia for the time being in force,
but are specified in the edition immediately preceding, the standards for identity,
purity and strength shall be those occurring in such immediately preceding edition
of such official pharmacopoeia to which the drug claims to comply with.
(c) For drugs for which standards are not included in the edition of the official
pharmacopoeia, for the time being in force, of any country or in edition
immediately preceding, but included in the official compendia of drug standards,
namely, the British Pharmaceutical Codex or the National Formulary of the United
States, for the time being in force, to which the drug claims to comply with.]
3
[124A. Standards for veterinary drugs. –For drugs intended for veterinary use,
the standards shall be those given in the current edition for the time being in force of the
4
[British Pharmacopoeia (Veterinary)].
1. Subs. by G.S.R. 245(E), dt. 5-4-1999.
2. Subs. by G.S.R. 19, dt. 15-12-1977.
3. Ins. by notification F. 1-6/62-D (SO 2889), dt. 2-7-1969.
4. Subs. by G.S.R. 647 (E), dt. 28-10-1998.
Drugs and Cosmetics Rules 1945
156
1
[124B. Standards for patent or proprietary medicines.— The standards for patent or
proprietary medicines shall be those laid down in Schedule V and such medicines shall also
comply with the standards laid down in the Second Schedule to the Act.
2
[124C. Standards for Surgical Dressings.-The standards for Surgical Dressings shall be
such as are laid down in Schedule F (II).]
3
[124D. Standards for Sterilised Umbilical tapes.- The standards for Sterilised Umbilical
tapes shall be as laid down in Schedule F(III).]
4
[125. Standards for substances (other than food) intended to affect the structure or
any function of human body—contraceptives.—(1) The standards for mechanical
contraceptives shall be such as are laid down in Schedule R.
(2) The standards which other contraceptives will have to comply with shall be in
conformity with the formulae approved as safe and efficacious by the Central Government.
Such formula shall be displayed on the label of every container of such contraceptive.
5
[125A. Standards for Medical Devices. —The standards for the Medical Devices shall be
such as are laid down in Schedule R-1.]
6
[126. Standards for substances intended to be used for the destruction of vermin
or insects which cause
9
[***] disease in human beings or animals.- Disinfectants.
The standards of disinfectants shall be such as are laid down in Schedule O.]
7
[126A Standards for ophthalmic preparations
8
[including Homoeopathic ophthalmic
preparations].—The standards for ophthalmic preparations
8
[including Homoeopathic
ophthalmic preparations] shall be those laid down in Schedule FF, and such preparations shall
also comply with the standards set out in the Second Schedule to the Act.]
1. Ins. by G.S.R. 665, dt. 28-5-1977.
2. Ins. by G.S.R. 318 (E), dt. 1-5-1984.
3. Ins. by G.S.R. 1115 (E), dt. 30-9-1986.
4. Amended by F-1-28/65D (SO 886), dt. 8-3-1966.
5. Ins. by G.S.R. 109 (E), dt. 22-2-1994.
6. Amended by F.1-20/60-D, dt. 24-1-1964.
7. Ins. by F 1-113/60-D (SO 23), dt. 23-12-1969.
8. Subs. by G.S.R. 245 (E), dt. 17-6-1996.
9. Subs heading ―Insecticides‖ and the entry relating thereto omitted by GSR 139, dt. 8-1-1976.
Drugs and Cosmetics Rules 1945
157
1
[127. List of colours permitted to be used in drugs.−(1) No drug shall contain a colour
other than specified below :-
(1) Natural Colours
Annatto
Carotene
Chlorophyll
Cochineal
Curcumin
Red Oxide of iron
Yellow Oxide of iron
2
[Titanium Oxide]
3
[Black Oxide of iron]
6
[Titanium dioxide coated mica pearlescent pigments]
(2) Artificial
Colours
Caramel
4
[Riboflavin]
(3) Coal Tar
Colours
Common name of the colour Colour Index
Number
Chemical Name
1
2
3
GREEN
Quinazarine Green S.S.
61565
1, 4-bis (p-Toluino) anthraquinone.
Alizarin Cyanine Green F.
61570
Disodium salt of 1, 4-bis (O-sulfo-p-
Toluino) anthra-quinone.
2
[Fast Green F.C.F.
42053
Disodium salt of 4-{[4-(N-ethyl-p
Sulfobenzylamino)-phenyl-]-(4-hydroxy-
2- sulfoniumphenyl)-methylene}
[1-(N-ethyl-N-p-sulfobenzyl]∆
2, 5-cyclohexadienimine].
5
[** * * *]
YELLOW
Tartrazine 19140 Trisodium salt of 3-carboxy-5- hydroxy-l-
p-sulfophenyl-4-p- Sulfophenyl
azopyrazole.
Sunset Yellow FCF 15985 Disodium salt of 1-p-sulfophenyl azo-2-
naphthol-6-sulfonic acid.
1. Amended by S.O. 289, dt. 20-12-1972.
2. Ins. by X.11013/3/76-DM.S (SO 1074), dt. 19-8-1978.
3. Ins. by G.S.R. 370 (E), dt. 7-4-1994.
4. Ins. by G.S.R. 681 (E), dt. 6-6-1988.
5. ―Green S‖ omitted by G.S.R. 753 (E), dt. 4-11-1999.
6. Ins. by G.S.R. 76 (E), dt. 8-2-2012.
Drugs and Cosmetics Rules 1945
158
(1) (2) (3)
1
[Quinoline Yellow WS 47005 Disodium salt of disulfonic acid of 2(2-
quinolyl)-1, 3-indandione.]
RED
2
[** ** *]
Erythrosine 45430 Disodium salt of 9-0-carboxyphenyl 6-hydroxy
2,4-5,7-tetriodo-3-isoxanthone
Eosin YS or Eosine G 45380 Disodium of salt of 2,4,5, 7-Tetrabromo- 9-p-
carboxyphenyl-6-hydroxy
3-isoxanthone.
Toney Red or Sudan III 26100 1-p-phenylazophenylaze-2-naphthol.
Ponceau 4 R 16255 Trisodium salt of 1-(4-sulpho-1-1- Napthylazo)-
2 napthol-6 : 8-disulphonic acid.
Carmoisine 14720 Disodium salt of 2-(4-sulpho-1-napthylazo)-1
napthol-4 sulphonic acid.
3
[
*** * *]
BLUE
Indigo Carmine
73015 Disodium salt of indigotin-5 : 5 Disu lphonic
Acid
4
[Brilliant Blue FCF 42090 Disodium salt of 4-[ {4-(N-ethyl-p-
sulfobenzylamino)-phenyl
}-](2- sulfonium
phenyl)-methylene)-1-(N-
ethyl-N-p-
sulfobenzyl)- ∆ 2, 5-cyclohexadienimine.
ORANGE
Orange G
16230 Disodium salt of 1-phenylazo-2- naphthol-6, 8-
disulfonic acid.
BROWN
Resorcin Brown
20170 Monosodium salt of 4-p-sulfophenylazo-2-(2, 4-
xylylazo-1, 3 resorcinol.
BLACK
Naphthol Blue Balck
20470 Disodium salt of 8-amino-7-p-nitro- phenylazo-
2-phenylazo-1-naphthol-3,
6-disulfonic acid.
1. Subs. by G.S.R. 11(E), dt. 7-1-1991.
2. ‗Amaranth‘ omitted by G.S.R. 753(E) dt. 4.11.1999.
3. Fast Red omitted by G.S.R. 753, dt. 4-11-1999.
4. Ins. by X.11013/3/76-DM.S, dt. 19-8-1978.
Drugs and Cosmetics Rules 1945
159
(4) LAKES
The aluminum or calcium salts (lakes) of any of the water-soluble colours listed
above:
5
[Provided that disinfectants may also contain colours specified under Schedule
Q, which are non-staining.]
(2) The label on the container of a drug containing a permitted colour shall indicate the
common name of the colour.]
128. The following rules are hereby repealed except as respects things done or omitted to
be done under these rules, namely :---
Andhra Pradesh Drugs Rules, 1945.
Assam Drugs Rules, 1945.
Bihar Drugs Rules, 1945.
Bombay Drugs Rules, 1946.
East Punjab Drugs Rules, 1945.
C.P. & Berar Drugs Rules, 1945.
Madras Drugs Rules, 1945.
Orissa Drugs Rules, 1945.
Rajasthan Drugs Rules, 1953.
Saurashtra Drugs Rules, 1953.
Travancore-Cohin Drugs Rules, 1953.
United Provinces Drugs Rules, 1945.
West Bengal Drugs Rules, 1946.
2
[Mysore Drugs Rules, 1954].
1
[PART
XIII
3
[IMPORT AND REGISTRATION OF
COSMETICS]
4
[129. Registration of cosmetic products imported into the country.- No cosmetic shall
be imported into India unless the product is registered under the rules by the licensing
authority appointed by the Central Government under rule 21 or by any person to whom such
powers may be delegated under rule 22.
129A. Form and manner of application for Registration Certificate.- (1) An application
for issue of a Registration Certificate for cosmetics intended to be imported into India shall
be made in Form 42 either by the manufacturer himself or by his authorised agent or importer
in India or by the subsidiary in India authorised by the manufacturer and shall be accompanied
by a fee of two hundred and fifty US dollars or its equivalent to Indian rupees for each brand
of cosmetic. The application shall be accompanied by a treasury challan as specified in sub-
rule (3) along with the information and undertaking as specified in Schedule D (III) duly
signed by or on behalf of the manufacturer or by his authorised agent or importer in India or
by the subsidiary in India authorised by the manufacturer.
1. Ins. by G.S.R. 1183 dt. 17-8-1964. 5. Ins. by G.S.R. 76 (E), dt. 8-2-2012.
2. Added by notification F. 1-37/58-D, dt. 21-7-1958.
3. Subs. by G.S.R. 426 (E), dt. 19-5-2010.
4. Rules 129 to 129H subs. by G.S.R. 426 (E), dt. 19-5-2010.
Drugs and Cosmetics Rules 1945
160
(2) An authorisation by the manufacturer to his agent in India shall be duly authenticated
either in India before a First Class Magistrate or in the country of origin before such an
equivalent authority.
(3) The fees shall be paid through a challan in the designated branches of Bank of Baroda
either in US dollars or in equivalent Indian rupees under Head of Account ―0210-MEDICAL
AND PUBLIC HEALTH, 04 PUBLIC HEALTH, 104-FEES AND FINES‖ and the original
copy of the treasury challan shall be submitted along with the application for product
registration.
Provided that in the case of any direct payment of fees by a manufacturer in the country of
origin, the fees shall be paid through Electronic Clearance System (ECS) from any bank in the
country of origin to the Bank of Baroda, Kasturba Gandhi Marg, New Delhi, through the
Electronic Code of the bank in the Head of Account ―0210-MEDICALAND PUBLIC
HEALTH, 04 PUBLIC HEALTH, 104-FEES AND FINES‖ and the original receipt of the said
transfer shall be treated as an equivalent to the bank challan subject to the approval by the
Bank of Baroda that they have received the payment.
(4) The applicant shall be liable for the payment of testing fees directly to a testing
laboratory approved by the Central Government, as may be, required for examination, tests
and analysis of cosmetics.
(5) A fee of one hundred US dollars or its equivalent shall be paid for a duplicate copy of
the Registration Certificate, if the original is defaced, damaged or lost.
129B. Registration Certificate for the import of cosmetics manufactured by one
manufacturer.-A single application may be made and a single Registration Certificate in Form
43 may be issued in respect of import of one or more than one cosmetics manufactured by the
same manufacturer: Provided that the cosmetics are manufactured at one factory or more than
one factory functioning conjointly as a single manufacturing unit.
129C. Grant of Registration Certificate.- (1) On receipt of an application for Registration
Certificate in the form and manner specified in rule 129A, the licensing authority shall, if
satisfied, issue a Registration Certificate in form 43 subject to the conditions of the registration
certificates in form 43:
Provided that if the application is complete in all respects and information specified in
Schedule D III is in order, the licensing authority shall, within six months from the date of
receipt of an application, issue such Registration Certificate, and in exceptional circumstances
and for reasons to be recorded in writing, the Registration Certificate may be issued within
such extended period, not exceeding three months, as the licensing authority may deem fit.
(2) If the applicant does not receive the Registration Certificate within the period as
specified above, he may appeal to the Central Government and the Central Government may
after such enquiry into the matter, as it considers necessary, may pass such orders in relation
thereto as it thinks fit.
129D. Duration of Registration Certificate.- A Registration Certificate, unless it is sooner
suspended or cancelled, shall be valid for a period of three years from the date of its issue:
Provided that if application for a fresh Registration Certificate is made within six months
before the expiry of the said certificate, the existing Registration Certificate shall be deemed to
continue to remain in force until orders are passed on the application.
129E. Suspension and cancellation of Registration Certificate.- If the manufacturer fails
to comply with any of the conditions of the Registration Certificate, the licensing authority
may after giving him an opportunity to show cause why such an order should not be passed,
by an order in writing, stating the reasons therefor, suspend or cancel the Registration
Certificate for such period as it thinks fit either wholly or in respect of some of the cosmetics
to which it relates: Provided that a person who is aggrieved by the order passed by the
licensing authority under this rule may, within thirty days of the receipt of the order, appeal to
the Central Government and the Central Government may after such enquiry into the matter as
it considers necessary and after giving the said appellant an opportunity of being heard pass
orders as it thinks fit.
Drugs and Cosmetics Rules 1945
161
129F. Prohibition of import of certain cosmetic.- No cosmetic, the manufacture, sale or
distribution of which is prohibited in the county of origin, shall be imported under the same
name or under any other name except for the purpose of examination, test or analysis.
129G. Standard for imported cosmetics.- No cosmetic shall be imported unless it complies
with the specifications prescribed under Schedule S and Schedule Q or any other standards of
quality and safety, applicable to it, and other provisions under the rules. In case the cosmetic
is not included under Schedule S, it shall meet with specifications under the rules and
standards applicable to it in the country of origin.
129H. Labeling and Packing of Cosmetics.- No cosmetic shall be imported unless it is
packed and labeled in conformity with the rules in Parts XV. Further the label of imported
cosmetics shall bear registration certificate number of the product and the name and address of
the registration certificate holder for marketing the said product in India.]
130. Documents to be supplied to the Collector of Customs.− Before any cosmetics are
imported, a declaration signed by or on behalf of the manufacturer or by on behalf of the
importer that the cosmetics comply with the provisions of Chapter III of the Act, and the
Rules made there under, shall be supplied to the Collector of Customs.
131. Procedure for the import of cosmetics.− (1) If the officer appointed at the post of
entry by the Central Government has reason to believe that any cosmetic contravenes any of
the provisions of the Act or the rules made thereunder he may take sample of the cosmetic
from the consignment for inspection. If on examination of the sample defects are noticed the
officer shall advise the Collector of Customs for further action to be taken.
If the suspected contravention of the provisions of the Act or the Rules is such as may have
to be determined by test, the officer shall send the sample to the laboratory established for
the purpose for performing such tests. The consignment of the said cosmetic shall be detained
till such time that the test report on such sample is received from the Director of the said
laboratory or any other officer of the laboratory empowered by him in this behalf with the
approval of the Central Government:
Provided that if the importer gives an undertaking in writing not to dispose of the
cosmetic without the consent of the Collector of Customs and to return the consignment or
such portion thereof as may be required, the Collector of Customs shall make over the
consignment to the importer.
(2) If the importer who has given an undertaking under the proviso to sub-rule (1) is
required by the Collector of Customs to return the consignment or portion thereof, he shall
return the consignment or portion thereof within ten days of receipt of the notice.
Further procedure on receipt of the report of analysis
(3) If the Director of the Laboratory established for the purpose by the Central
Government or any other officer of the laboratory empowered by him in this behalf with the
approval of the Central Government, reports to the Collector of Customs or to the officer
mentioned in sub-rule (1) above that the sample of any cosmetic in a consignment
contravenes the provisions of Chapter III of the Act or the Rules made thereunder and that the
contravention is such that it cannot be remedied by the importer, the Collector of Customs
shall communicate the report forthwith to the importer who shall within two months of
receiving such a communication either send back all the cosmetic of that description to the
country in which it was manufactured or to the country from which it was imported or hand it
over to the Central Government which shall cause it to be destroyed:
Provided that the importer may within thirty days of receipt of the report make a
representation against the report to the Collector of Customs who shall forward the
representation with a fresh sample of the cosmetic to the Drugs Controller, India, who after
Drugs and Cosmetics Rules 1945
162
obtaining, if necessary, the report of the Director of the Central Drugs Laboratory shall pass
orders thereon which shall be final.
(4) If the Drugs Controller or any other officer empowered by him in this behalf with the
approval of Central Government reports to the Collector of Customs after the inspection of
the sample of cosmetic and if necessary, after obtaining a test report thereon that the sample
of the said cosmetic contravenes in any respect the provisions of Chapter III of the Act or the
Rules made thereunder but that the contravention is such that it can be remedied by the
importer, the Collector of Customs shall communicate the report forthwith to the importer and
permit him to import the cosmetic on his giving an undertaking in writing not to dispose of
the cosmetic without the permission of the officer authorised in this behalf by the Central
Government.
132. Exemption of cosmetics—Cosmetics as may be specified in Schedule D shall be
exempted from the provisions of Chapter III of the Act and the Rules made thereunder to the
extent and subject to the conditions specified in that Schedule.
133. Import through points of entry—No cosmetic shall be imported into India except
through the points of entry specified in rule 43A.
1
[134. Cosmetic to contain Dyes, Colours and Pigments.- No Cosmetic shall contain
Dyes, Colours and Pigments other than those specified by the Bureau of Indian Standards
(IS:4707 Part 1 as amended) and Schedule Q.
The permitted Synthetic Organic Colours and Natural Organic Colours used in the
Cosmetic shall not contain more than:-
(i) 2 parts per million of arsenic calculated as arsenic trioxide.
(ii) 20 parts per million of lead calculated as lead.
(iii) 100 parts per million of heavy metals other than lead calculated as the
total of the respective metals.]
2
[134-A Prohibition of import of cosmetic containing Hexachlorophene.— No cosmetic
containing hexachlorophene shall be imported.
135. Import of cosmetic containing Lead or Arsenic compound prohibited.—No
cosmetic shall be imported in which a Lead or Arsenic compound has been used for purposes
of colouring.
3
[135-A. Import of cosmetics containing mercury compounds prohibited.–No
cosmetic shall be imported which contains mercury compounds.]
5
[135-B. Prohibition of import of cosmetics tested on animals.–No cosmetic that has
been tested on animals after the commencement of the Drugs and Cosmetics (Fifth
Amendment) Rules, 2014 shall be imported into the country.]
136. Import of cosmetic for personal use—Small quantities of cosmetics the import of
which is otherwise prohibited under section 10 of the Act, may be imported for personal use
subject to the following conditions: —
(i) The cosmetics shall form part of a passenger‘s baggage and shall be the property of
and intended for, the bona fide use of the passenger; and
(ii) The cosmetics shall be declared to the Customs authorities, if they so direct.
4
[PART
XIV
MANUFACTURE OF COSMETIC FOR SALE
OR
FOR
DISTRIBUTION
]
137. Manufacture on more than one set of premises. — If cosmetics are
manufactured
on
more than one premises, a separate application for each such premises
shall be made and a
separate licence obtained for each such premises.
1. Subs. by G.S.R. 811 (E), dt. 14-11-1994. 2. Added by G.S.R. 116, dt. 25-1-1975.
3. Ins. by X.11013/76-D & MS, dt. 19-8-1978. 4. Subs. by G.S.R. 788 (E), dt. 10-10-1985.
5. Ins. by G.S.R. 718 (E), dt. 13-10-2014.
Drugs and Cosmetics Rules 1945
163
138. Application for
5
[licence to manufacture cosmetics for sale and distribution]—
3
[(1) Application for grant or renewal of
5
[licence to manufacture any cosmetic for sale or
for distribution]
1
[shall be made up to ten items of each category of cosmetics categorized in
Schedule MII to the Licensing Authority appointed by the State Government for the purpose
of this Part (hereinafter in this Part referred to as the Licensing Authority) in Form 31 and
shall be accompanied by a licence fee of rupees two thousand and five hundred and an
inspection fee of rupees one thousand for every inspection
thereof or for the purpose of renewal of licence].
2
[* * * **]
3
[
(2) If a person applies for the renewal of licence after expiry but within six months of
such expiry, the fee payable for the renewal of such licence shall be
1
[rupees two thousand
five hundred plus an additional fee at the rate of rupees four hundred per month or part
thereof in addition to an inspection fee of rupees one thousand.]
2
[
* * * * *]
(3) Application by a licensee to manufacture additional items of cosmetics shall be
accompanied by a fee of
1
[rupees one hundred for each item subject to a maximum of rupees
three thousand for each application.]
2
[
* * * * *]
6
[(4) A fee of
1
[rupees two hundred and fifty] shall be paid for a duplicate copy of a
licence under sub-rule (1), if the original is defaced, damaged or lost.]
4
[138A. Application for loan licence to manufacture cosmetics.−(1) Application for grant
or renewal of a loan licence for the manufacture for sale of cosmetics
1
[shall be made up to
ten items of each category of cosmetics categorized in Schedule M-II in Form 31-A to the
Licensing Authority and shall be accompanied by a licence fee of rupees two thousand and
five hundred and an inspection fee of rupees one thousand for every inspection thereof].
Explanation.--For the purpose of this rule a ‗loan licence‘ means a licence, which a
Licensing Authority may issue to an applicant who does not have his own arrangements to
manufacture but who intends to avail himself of the manufacturing facilities owned by a
licensee in Form 32.
(2) If a person applies for the renewal of a loan licence after the expiry but within
six months of such expiry, the fee payable for the renewal of such a licence shall be
1. Subs. by G.S.R. 601(E), dt. 24-8-2001.
2. Omitted by G.S.R. 331(E),dt. 8.5.1984.
3. Amended by G.S.R. 245, dt. 21.2.1976.
4. Ins. by G.S.R. 444, dt. 28-4-1973.
5. Subs. by G.S.R. 788 (E), dt. 10-10-1985.
6. Subs. by G.S.R. 331(E),dt. 8.5.1984.
Drugs and Cosmetics Rules 1945
164
1
[rupees two thousand and five hundred plus an additional fee at the rate of rupees four
hundred for each month or part thereof.]
(3) The Licensing Authority shall before the grant of a loan licence satisfy
himself that the manufacturing unit has adequate equipment, staff, capacity for
manufacture and facilities to undertake the manufacture on behalf of the applicant for a
loan licence.
(4) The loan licence shall be granted by the Licensing Authority to only such
applicants who propose to avail of the facilities of manufacture of cosmetics in the
premises of a manufacturer located in the same State where the applicant is located. In
case the manufacture of cosmetic involves any special process of manufacture or use of
equipment which are not available in the State where the applicant is located, the
Licensing Authority after consulting the Licensing Authority where the manufacturing
unit is located, may grant the loan licence.
(5) Subject to the provisions of sub-rule (2), application for manufacture of
additional items on a loan licence shall be accompanied by a fee of
1
[rupees one
hundred for each item subject to a maximum of rupees three thousand per application.]
(6) A fee of
1
[rupees two hundred and fifty] shall be paid for a duplicate copy of
a licence issued under sub-rule (1) if the original is defaced, damaged or lost.
139. Conditions for the grant or renewal of a licence in Form 32—Before a licence in
Form 32 is granted or renewed, the following conditions shall be complied with by
applicant:-
(1) The manufacture shall be conducted under the direction and personal supervision
of a competent technical staff consisting of at least one person who is a whole time
employee and who possesses any one of the following qualifications:
(a) holds a Diploma in Pharmacy approved by the Pharmacy Council of India
under the Pharmacy Act, 1948 (8 of 1948), or
(b) is registered under the Pharmacy Act, 1948 (8 of 1948),
or
(c) has passed the Intermediate Examination with Chemistry as one of the
subjects or an examination recognized by the Licensing Authority as equivalent
to it.
2
[
* * * *
*]
1. Subs. by G.S.R. 601(E), dt. 24-8-2001.
2. Omitted by. G.S.R. 331(E), dt. 8.5.1984
Drugs and Cosmetics Rules 1945
165
1
[(2) The factory premises shall comply with the requirements and conditions specified in
Schedule M-II.]
2 [
* * * *
*]
(5) The applicant shall either--
(i) provide and maintain adequate staff, premises and laboratory equipment for testing
the cosmetic manufactured, and the raw materials used in the manufacture; or
(ii) make arrangements with some institution approved by the Licensing Authority
3
[under Part XV (A) of these rules] for such tests to be regularly carried out in this behalf
by the institution.
4
[
139A. Form of
5
[licence to manufacture cosmetics for sale or for distribution].—A
5
[licence to manufacture cosmetics for sale or for distribution] against application in
Form 31, shall be granted in Form 32.]
6
[139AA. Inspection before grant or renewal of licence.- Before a licence under this Part
is granted or renewed in Form 32, Form 32A or Form 33, the Licensing Authority shall cause
the establishment, in which the manufacture is proposed to be conducted or being conducted,
to be inspected by one or more Inspectors appointed under the Act. The Inspector or
Inspectors shall examine all portions of the premises, plant and appliances and also inspect
the process of manufacture intended to be employed or being employed along with the means
to be employed or being employed for standardizing and testing the substances to be
manufactured and enquire into the professional qualifications of the technical staff to be
employed. He shall also examine and verify the statements made in the application in regard
to their correctness, and the capability of the applicant to comply with the requirements of
competent technical staff, manufacturing plant, testing equipments and the requirements of
plant and equipments as laid down in Schedule M-II read with requirements of maintenance
of records as laid down in Schedule U-1.]
6
[139AB. Report by Inspector.- The Inspector or Inspectors shall forward a detailed
descriptive report giving his or their findings on each aspect of inspection along with his or
their recommendations after completion of his or their inspection to the Licensing Authority.]
6
[139AC. Grant or refusal of licence.- (1) If the Licensing Authority after such further
enquiry, if any, as he may consider necessary is satisfied that the requirements of the rules
under the Act have been complied with and that the conditions of the licence and the rules
under the Act shall be observed, he shall grant or renew a licence in form 32, Form 32-A or
Form 33.
1. Subs. by G.S.R. 723 (E), dt. 11-8-1992.
2. Omitted condition (3) and (4) by G.S.R. 723 (E), dt. 11-8-1992.
3. Ins. by G.S.R. 1172 (E), dt. 23-8-1977.
4. Ins. by G.S.R. 444, dt. 28-4-1973.
5. Subs. by G.S.R. 788 (E), dt. 10-10-1985.
6. Ins. by G.S.R. 493 (E), dt. 9-6-1995.
Drugs and Cosmetics Rules 1945
166
(2) If the Licensing Authority is not so satisfied, he shall reject the application and shall
inform the applicant of the reasons for such rejection and of the conditions which must be
satisfied before a licence can be granted or renewed and shall supply the applicant with a
copy of inspection report.]
1
[139AD. Further application after rejection.–If within a period of six months from the
rejection of an application for a licence, the applicant informs the Licensing Authority that the
conditions laid down have been fulfilled and deposits an inspection
2
[fee of rupees two
hundred and fifty], the Licensing Authority may, if, after causing further inspection to be
made, he is satisfied that the conditions for the grant of licence have been complied with,
issue a licence in Form 32, Form 32-A or Form 33.]
1
[139AE. Appeal to the State Government.- Any person who is aggrieved by the order
passed by the Licensing Authority refusing to grant or renew a licence under this Part may,
within ninety days from the date of receipt of such order, appeal to the State Government and
the State Government may, after such enquiry into the matter as is considered necessary and
after giving the said person an opportunity for representing the case, pass such order as it
thinks fit.]
3
[139B. Form of loan
4
[licence to manufacture cosmetics for sale or for
distribution].−A loan
4
[licence to manufacture cosmetics for sale or for distribution]
against application in Form 31-A shall be granted in Form 32-A.
140. Duration of licence.- An original licence or a renewed licence shall unless sooner
suspended or cancelled be
2
[valid for a period of five years on and from the date on which] it
is granted or renewed:
5
[Provided that if the application for renewal of a licence in force is made before its
expiry or if the application is made within six months of its expiry, after payment of
additional fee, the licence shall continue to be in force until orders are passed on the
application and the licence shall be deemed to have expired, if application for its renewal is
not made within six months of its expiry.]
141. Certificate of renewal.−The certificate of renewal of a licence in Form 32 shall be
issued in Form 33.
1. Ins. by G.S.R. 493 (E), dt. 9-6-1995.
2. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
3. Ins. by G.S.R. 444, dt. 28-4-1973.
4. Subs. by G.S.R. 493 (E), dt. 9-6-1995.
5. Amended by S.O. 2139, dt. 12.8.1972.
Drugs and Cosmetics Rules 1945
167
1
[141A. Certificate of renewal of a loan licence—The certificate of renewal of a licence
in Form 32-A shall be issued in Form 33-A.]
1
[141AA. Duration of a loan licence.–An original loan licence in Form 32A or a renewed
loan licence in Form 33-A, unless sooner suspended or cancelled, shall be
2
[valid for a period
of five years on and from the date on which] it is granted or renewed:
Provided that if the application for the renewal of a licence is made before its expiry, or if
the application is made within six months of its expiry, after payment of the additional fee,
the licence shall continue to be in force until orders are passed on the application. The licence
shall be deemed to have expired if the application for its renewal is not made within six
months of its expiry.]
142. Conditions of licence—A licence in Form 32 shall be subject to the conditions stated
therein and to the following other conditions, namely: –
(a) the licensee shall provide and maintain staff, premises and equipment as
specified in rule 139;
(b) the licensee shall comply with the provisions of the Act and the Rules made
thereunder and with such further requirements, if any, as may be specified in any rules to
be made hereafter under Chapter IV of the Act;
3
[(b1) the licensee shall keep records of the details of each batch of cosmetic
manufactured by him and of raw materials used therein as per particulars specified in
Schedule U(1) and such records shall be retained for a period of three years;]
(c) the licensee shall test each batch or lot of the raw materials used by him for the
cosmetics and also each batch of the final product and shall maintain records or registers
showing the particulars in respect of such tests. The records or registers shall be retained
for a period of three years from the date of manufacture;
(d) the licensee shall allow any
1
[Inspector appointed under the Act] to enter with
or without prior notice any premises where the manufacture of a substance in respect of
which the licence is issued is carried on, to inspect the premises and to take samples of
the manufactured products under a receipt;
1. Ins. by G.S.R. 444, dt. 28-4-1973.
2. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
3. Ins. by G.S.R. 1594, dt. 28-10-1976.
Drugs and Cosmetics Rules 1945
168
(e) the licensee shall allow an Inspector to inspect all registers and records
maintained under these rules and shall supply to the Inspector such information as
he may require for the purpose of ascertaining whether the provisions of the Act
and the Rules made thereunder have been complied;
1
[(f) the licensee shall maintain an Inspection Book in Form 35 to
enable an Inspector to record his impression and the defects noticed:
2
[Provided that clauses (b-1) and (c) shall not apply to the manufacture of
soap and the procedure for testing of raw materials and the records to be
maintained by the manufacturer of soap shall be such as are approved by the
Licensing Authority.]
4
[142A. Additional information to be furnished by an applicant for licence or a licensee
to the Licensing Authority.—The applicant for the grant of a licence or any person granted a
licence under this Part shall, on demand, furnish to the Licensing Authority, before the grant
of the licence or during the period the licence is in force, as the case may be, documentary
evidence in respect of the ownership or occupation on rental or other basis of the premises,
specified in the application for licence or in the licence granted, constitution of the firm, or
any other relevant matter, which may be required for the purpose of verifying the correctness
of the statements made by the applicant or the licensee, while applying for or after obtaining
the licence as the case may be.]
1
[142B. Conditions of licence in Form 32-A.–
(a) A licence in Form 32-A shall be deemed to be cancelled or suspended, if the
licence owned by the licensee, in Form 32, whose manufacturing facilities are
cancelled or suspended, as the case may be under these rules.
(b) The licensee shall comply with the provisions of the Act and these rules and
with each further requirements, if any, as may be specified from time to time in
Chapter IV of the Act, provided that where such further requirements are specified in
the rules, these would come into force four months after publication in the Official
Gazette.
3
[(b1) The licensee shall keep records of the details of each batch of cosmetic
manufactured by him and of raw materials used therein as per particulars specified in
Schedule U(1) and such records shall be retained for a period of three years.]
(c) The licensee shall test each batch or lot of the raw materials used by him for
the manufacture of the cosmetics and also each batch of the final product and shall
maintain records of registration showing the particulars in respect of such tests. The
records or registers shall be retained for a period of three years from the date of
manufacture.
1. Ins. by G.S.R. 444, dt. 28-4-1973.
2. Ins. by G.S.R. 681 (E), dt. 6-6-1988.
3. Ins. by G.S.R. 1594, dt. 28-10-1976.
4. Ins. by S.O.2139, dt. 12-8-1972.
Drugs and Cosmetics Rules 1945
169
(d) The licensee shall allow an Inspector appointed under the Act to enter with or
without prior notice any premises where the manufacture of a substance in respect of
which licence is issued is carried on, to inspect the premises and to take samples of
the manufactured products under a receipt.
(e) The licensee shall allow an Inspector to inspect all registers and records
maintained under these rules and shall supply to the Inspector such information as he
may require for the purpose of ascertaining whether the provisions of the Act, and the
rules made thereunder have been complied.
(f) The licensee shall maintain an Inspection Book in Form 35 to enable an
Inspector to record his impressions and the defects noticed.]
143. Cancellation and suspension of licence.−(1) The Licensing Authority may, after
giving the licensee an opportunity to show cause why such an order should not be passed, by
an order in writing stating the reasons therefor, cancel a licence issued under this Part or
suspend it for such period as he thinks fit, either wholly or in respect of some of the
substances to which it relates, if in his opinion, the licensee has failed to comply with any of
the conditions of the licence or with any provisions of the Act or the rules made thereunder.
(2) A licensee whose license has been suspended or cancelled may appeal within a period
of three months from the date of the order to the State Government which shall after
considering the appeal, pass orders, and such orders shall be final.
1
[144. Prohibition of manufacture of cosmetics containing colours other than
those prescribed.- No Cosmetic shall be manufactured which contains Dyes, Colours and
Pigments other than the one specified by the Bureau of Indian Standards (IS: 4707 Part I as
amended) and Schedule Q.
The permitted Synthetic Organic colours and Natural Organic colours used in the
Cosmetic shall not contain more than−
(i) 2 parts per million of arsenic calculated as arsenic trioxide.
(ii) 20 parts per million of lead calculated as lead.
(iii) 100 parts per million of heavy metals other than lead calculated as the total of the
respective metals.]
2
[144A. Prohibition of manufacture of cosmetics containing Hexachlorophene.—No
cosmetic containing Hexachlorophene shall be manufactured:]
1. Subs. by G.S.R. 811(E), dt. 14-11-1994.
2. Ins. by G.S.R. 116, dt. 15.1.1975.
Drugs and Cosmetics Rules 1945
170
1
[Provided that in the case of soaps Hexachlorophene may be used in concentrations not
exceeding one per cent weight by weight:
Provided further that the following cautionary note shall be printed and shall appear in a
conspicuous manner on the wrapper of package of each soap, namely:-
―Contains Hexachlorophene – not to be used on babies‖.]
145. Use of Lead and Arsenic compounds for the purpose of colouring cosmetics
prohibited.—The use of Lead and Arsenic compounds for the purpose of colouring cosmetics
is prohibited.
2
[145A. Form of intimation for purpose of taking samples of cosmetics.—Where
an Inspector takes a sample of a cosmetic for the purpose of test or analysis, he shall
intimate such purpose in writing in Form 17 to the person from whom he takes it.]
3
[145AA. Form of receipt of samples of cosmetics where fair price tendered is refused.-
Where the fair price, for the samples of Cosmetics taken for the purpose of test or analysis,
tendered under sub-section (1) of section 23 has been refused, the Inspector shall tender a
receipt therefor to the person from whom the said samples have been taken as specified in
Form 17A.]
2
[145B. Form of receipt for seized cosmetics.−A receipt by an Inspector for the stock
of any cosmetic seized under clause (c) of sub-section (1) of section 22 of the Act shall be in
Form 15.]
4
[145BA. Manner of certifying copies of seized documents.-The Drugs Inspector shall
return the documents, seized by him under clause (cc), or produced before him under clause
(cca), of sub-section (1) of section 22 of the Act, within a period of twenty days of the date of
such seizure or production, to the person from whom they were seized or, as the case may be,
the person who produced them, after copies thereof or extracts therefrom have been signed by
the Drugs Inspector concerned and the person from whom they were seized, or, as the case
may be, who produced such records.]
5
[145C. Form of order not to dispose of stocks of cosmetics—An order in writing by an
Inspector under clause (c) of sub-section (1) of section 22 of the Act requiring a person not to
dispose of any stock of cosmetics in his possession shall be in Form 15.]
6
[145D. Prohibition of manufacture of cosmetics containing mercury compounds.–
No cosmetics containing mercury compounds shall be manufactured.]
1. Ins. by G.S.R. 1049 (E), dt. 29-8-1986.
2. Ins. by S.O. 2139, dt. 5.6.1972.
3. Ins. by G.S.R. 292 (E), dt. 29-5-1997.
4. Ins. by G.S.R. 89(E), dt. 16-2-1985.
5. Ins. by G.S.R. 1594, dt. 28-10-1976.
6. Ins. by G.S.R. 1074, dt. 19.8.1978 (w.e.f. 2.9.1978).
Drugs and Cosmetics Rules 1945
171
PART XV
1
[LABELLING, PACKING AND STANDARDS OF COSMETICS
]
146. Prohibition of sale or distribution.–Subject to other provisions of these rules, no
person shall sell or distribute any cosmetic unless the cosmetic, if of Indian origin is
manufactured by a licensed manufacturer and labelled and packed in accordance with these
rules.
2
[147. Exemption of cosmetics not manufactured for consumption or sale in India
from the provisions of this Part.– Labels on packages or containers of cosmetics not
manufactured for consumption or sale in India shall be adopted to meet the specific
requirements, if any, of the consignee:
Provided that where a cosmetic is required by the consignee to be not labelled with the
name and address of the manufacturer, the labels on packages or containers shall bear a code
number as approved by the Licensing Authority mentioned in rule 21.]
148. Manner of labelling.–Subject to other provisions of the rules, a cosmetic shall
carry.–
(1) on both the inner and outer labels;
(a) the name of the cosmetic,
3
[(b) the name of the manufacturer and complete address of the premises of the
manufacturer where the cosmetic has been manufactured.
Provided that if the cosmetic is contained in a very small size container
where the address of the manufacturer cannot be given, the name of the manufacturer
and his principal place of manufacture shall be given along with pin code.]
(2) On the outer label.–
A declaration of the net contents expressed in terms of weight for solids, fluid
measure for liquids, weight for semi-solids, combined with numerical count if the content is
sub-divided:
Provided that this statement need not appear in case of a package of perfume, toilet water
or the like the net content of which does not exceed 60 ml or any package of solid or semi-
solid cosmetic the net content of which does not exceed 30 grams.
(3) On the inner label, where a hazard exists–
(a) adequate direction for safe use,
(b) any warning, caution or special direction required to be observed by the
consumer,
(c) a statement of the names and quantities of the ingredients that are hazardous or
poisonous.
1. Subs. by S.O. 3408, dt. 1.11.1996.
2. Subs. by G.S.R. 682 (E), dt. 5-12-1980.
3. Subs. by G.S.R. 352 (E), dt. 26-4-2000.
Drugs and Cosmetics Rules 1945
172
1
[(4) A distinctive batch number, that is to say, the number by reference to which details of
manufacture of the particular batch from which the substance in the container is taken are
recorded and are available for inspection, the figures representing the batch number being
preceded by the letter ―B‖:
Provided that this clause shall not apply to any cosmetic containing 10 grams or less
if the cosmetic is in solid or semi-solid state, and 25 millilitres or less if the cosmetic is in a
liquid state:
2
[Provided further that in the case of soaps, instead of the batch number, the month and
year of manufacture of soap shall be given on the label.]
1
[(5) manufacturing licence number, the number being preceded by the letter ‗M‘.]
(6) Where a package of a cosmetic has only one label, such label shall contain all the
information required to be shown on both the inner and the outer labels, under these Rules.
5
[(7) The list of ingredients, present in concentration of more than one percent shall be
listed in the descending order of weight or volume at the time they are added, followed by
those inconcentration of less than or equal to one percent, in any order, and preceded by the
words ‗INGREDIENTS‘.
Provided that this statement need not appear for packs of less than 60 ml of liquid
and30 gm of solid and semi-solids.
(8) Labeling requirement, if any, specified in the relevant Indian standard as laid down
by the ‗Bureau of Indian Standards‘ for the cosmetics covered under Schedule S.]
3
[148A. Prohibition against altering inscriptions on containers, labels or wrappers of
cosmetics.- No person shall alter, obliterate or deface any inscription or mark made or
recorded by the manufacturer on the container, label or wrapper of any cosmetic:
Provided that nothing in this rule shall apply to any alteration, inscription or mark made
on the container, label or wrapper of any cosmetic at the instance or direction or with the
permission of the licensing authority.]
5
[148B - Prohibition against false or misleading claims :- No cosmetic may purport or
claimto purport or convey any idea which is false or misleading to the intending user.]
149.
4
[Labelling of Hair dyes containing Dyes, Colours and Pigments.—Hair dyes
containing Para-Phenylenediamine or other Dyes, Colours and Pigments] shall be labelled
with the following legend in English and local languages and these shall appear on both the
inner and the outer labels.
―Caution—This product contains ingredients which may cause skin irritation in
certain cases and so a preliminary test according to the accompanying direction should
first be made. This product should not be used for dyeing the eye-lashes or eye-brows;
as such a use may cause blindness‖.
Each package shall also contain instructions in English and local languages on the
following lines for carrying out the test:
―This preparation may cause serious inflammation of the skin in some cases and so a
preliminary test should always be carried out to determine whether or not special
sensitivity exists. To make the test, cleanse a small area of skin behind the ear or upon
the inner surface of the forearm, using either soap and water or alcohol. Apply a small
quantity of the hair dye as prepared for use to the area and allow it to dry.
After twenty-four hours, wash the area gently with soap and water. If
no irritation or inflammation is apparent, it may be assumed that
1. Subs. by G.S.R. 245, dt. 3-2-1976.
2. Ins. by. 681(E), dt. 6-8-1988.
3. Ins. by G.S.R. 351 (E), dt. 26-4-2000.
4. Subs. by G.S.R. 811 (E), dt. 14-11-1994.
5. Ins. by. 46 (E), dt. 22-1-2009.
Drugs and Cosmetics Rules 1945
173
no hypersensitivity to the dye exists. The test should, however, be carried out before each
and every application. This preparation should on no account be used for dyeing eye-
brows or eye-lashes as severe inflammation of the eye or even blindness may result.]
1
[149A. Special provisions relating to toothpaste containing fluoride.-
(i) Fluoride content in tooth paste shall not be more than 1000 ppm and the content
of fluoride in terms of ppm shall be mentioned on the tube and carton.
(ii) Date of expiry should be mentioned on tube and carton
.]
150. Report of result of test or analysis of cosmetics.—Test reports on samples of
cosmetics taken for test or analysis under these rules shall be supplied in Form 34.
2
[150-A. Standard for cosmetics.- Subject to the provisions of these rules, the standards
for cosmetics shall be such as may be prescribed in Schedule S.]
3
[PART XV
(A)
APPROVAL OF INSTITUTIONS FOR CARRYING OUT TESTS
ON
DRUGS, COSMETICS AND RAW MATERIALS USED IN
THEIR
MANUFACTURE ON BEHALF OF LICENSEES
FOR
MANUFACTURE FOR SALE OF DRUGS /
COSMETICS
150-B. Application for grant of testing drugs/cosmetics— (1) Application for grant or
renewal of approval for carrying out tests for identity, purity, quality and strength on drugs or
cosmetics or the raw materials used in the manufacture thereof on behalf of licensees for
manufacture for sale of drugs or cosmetics, shall be made in Form 36 to the Licensing
Authority appointed by the State Government for the purposes of Part VII, VII (A) or XIV of
these Rules, as the case may be and referred to as the ―approving authority‖ under this Part
and shall be accompanied by an inspection fee of
2
[rupees six thousand] in the case of testing
of drugs specified in Schedules C and C (1) and
2
[rupees one thousand five hundred] in the
case of testing of drugs other than those specified in Schedules C and C (1), homoeopathic
drugs and cosmetics:
Provided that the applicant shall furnish to the approving authority such additional
information as may be required by him in connection with the application in Form 36:
4
[Provided further that if the applicant applies for renewal of approval after its expiry
but within six months of such expiry, the inspection fee payable shall be rupees six thousand
in the case of testing of drugs specified in Schedules C and C (1) and rupees one thousand
five hundred in the case of testing of drugs other than those specified in Schedules C and C
(1), Homoeopathic medicines and cosmetics plus an additional fee at the rate of rupees one
thousand per month.]
4
[(2) A separate application shall be made for grant of approval for carrying out tests
on additional categories of drugs or items of cosmetics and shall be accompanied by an
inspection fee of rupees one thousand five hundred in the case of drugs specified in Schedule
C and Schedule C(1) and rupees one thousand each in case of drugs other than those specified
in Schedule C and Schedule C(1), homeopathic medicines and cosmetics.
1. Ins. by G.S.R. 223 (E), dt. 19-4-1991.
2. Ins. by G.S.R. 510 (E), dt. 26-7-1982.
3. Ins. rule 150B to 150K by X.1104/7/76-D&M, dt. 23-8-1977.
4. Subs. by G.S.R. 601(E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
174
Explanation—For the purpose of this Part, the words ‗drugs‘ and ‗cosmetics‘ shall also
mean and include the raw materials used in the manufacture of drugs including Homoeopathic
drugs or cosmetics, as the case may be.]
150-C. Form in which approval to be granted for carrying out tests on drugs / cosmetics
on behalf of licensees for manufacture of drugs/cosmetics and conditions for grant or
renewal of such approval.– (1) Approval for carrying out such tests of identity, purity,
quality and strength of drugs or cosmetics as may be required under the provisions of
these rules, on behalf of licensee for manufacture of drugs or cosmetics shall be granted in
Form 37.
(2) Before approval in Form 37 is granted or renewed, the following conditions
shall be complied with by the applicant–
(1) The premises where the tests are being carried out shall be well lighted and
properly ventilated except where the nature of tests of any drug or cosmetic warrants
otherwise. Wherever necessary, the premises shall be air conditioned so as to
maintain the accuracy and functioning of laboratory instruments or to enable the
performance of special tests such as sterility tests, microbiological tests, etc.
(2) The applicant shall provide adequate space having regard to the nature and
number of samples of drugs or cosmetics proposed to be tested.
Provided that the approving authority shall determine from time to time whether
the space provided continues to be adequate.
(3) If it is intended to carry out tests requiring the use of animals, the applicant
shall provide for an animal house and comply with the following requirements–
(a) The animal house shall be adequate in area, well lighted and properly
ventilated and the animals undergoing tests shall be kept in air conditioned area.
(b) The animals shall be suitably housed in hygienic surroundings and
necessary provisions made for removal of excreta and foul smell.
(c) The applicant shall provide for suitable arrangements for preparation of animal
feed.
(d) The applicant shall provide for suitable arrangements for quarantining of all
animals immediately on their receipt in the institution.
(e) The animals shall be periodically examined for their physical fitness.
(f) The applicant shall provide for isolation of sick animals as well as animals
under test.
(g) The applicant shall ensure compliance with the requirements of the
Prevention of Cruelty to Animals Act, 1960 (59 of 1960).
(h) The applicant shall make proper arrangements for the disposal of the carcasses
of animals in a manner as not to cause hazard to public health.
(4) The applicant shall provide and maintain suitable equipment having regard to
the nature and number of samples of drugs or cosmetics intended to be tested which shall
be adequate in the opinion of the approving authority.
(5) The testing of drugs or cosmetics, as the case may be, shall be under the active
direction of a person whose qualifications and experience are considered adequate in the
opinion of the approving authority and who shall be held responsible for the reports of
test or analysis issued by the applicant.
Drugs and Cosmetics Rules 1945
175
(6) The testing of drugs or cosmetics, as the case may be, for identity,
purity, quality and strength shall be carried out by persons whose qualifications
and experience of testing are adequate in the opinion of the approving authority.
(7) The applicant shall provide books of standards recognized under the
provisions of the Act and the Rules made thereunder and such books of reference
as may be required in connection with the testing or analysis of the products for
the testing of which approval is applied for.
150D. Duration of approval. –An approval granted in Form 37 or renewed in Form 38,
unless sooner suspended or withdrawn, shall be
1
[valid for a period of five years on and from
the date on which] it is granted or renewed:
Provided that if an application for the renewal of an approval in Form 37 is made before
its expiry or if the application is made within six months of its expiry after the payment of the
additional fee, the approval shall continue to be in force until orders are passed on the
applications and the approval shall be deemed to have expired if the application for its
renewal is not made within six months of its expiry.
150E. Conditions of approval –An approval in Form 37 shall be subject to the following
general conditions: —
(a) The institution granted approval under this Part (hereinafter referred to as the
approved institution) shall provide and maintain an adequate staff and adequate premises
and equipment as specified in rule 150-C
2
[and Schedule L-1].
(b) The approved institution shall provide proper facilities for storage so as to
preserve the properties of the samples to be tested by it.
(c) The approved institution shall maintain records of tests for identity, purity,
quality and strength carried out on all samples of drugs or cosmetics and the results
thereof together with the protocols of tests showing the readings and calculation in such
form as to be available for inspection and such records shall be retained in the case of
substances for which an expiry date is assigned for a period of two years from the expiry
of such date and in the case of other substances for a period of six years.
(d) The approved institution shall allow the Inspector appointed under this Act to
enter with or without prior notice the premises where the testing is carried on and to
inspect the premises and the equipment used for test and the testing procedures employed.
The institution shall allow the Inspectors to inspect the registers and records maintained
under these Rules and shall supply to such Inspectors such information as they may
require for the purpose of ascertaining whether the provisions of the Act and Rules made
thereunder have been observed.
(e) The approved institution shall from time to time report to the approving
authority any changes in the person-in-charge of testing of drugs or cosmetics or in the
expert staff responsible for testing as the case may be and any material alteration in the
premises or changes in the equipment used for the purposes of testing which have been
made since the date of last inspection made on behalf of the approving authority before
the grant or renewal of approval.
1. Subs. by G.S.R. 601 (E), dt. 24-8-2001.
2. Ins. by G.S.R. 780 (E), dt. 10-11-2008.
Drugs and Cosmetics Rules 1945
176
(f) The approved institution shall furnish reports of the results of test or analysis
in Form 39.
(g) In case any sample of a drug or a cosmetic is found on test to be not of
standard quality, the approved institution shall furnish the approving authority
1
[and
the licensing authority of the State where the manufacturer and/or sender of the drug
or cosmetic is located] with copy of the test report on the sample with the protocols of
tests applied.
(h) The approved institution shall comply with the provisions of the Act and
Rules made thereunder and with each further requirements, if any, may be specified
in the rules subsequently made under Chapter IV of the Act of which the approving
authority has given the approved institution not less than four months notice.
(i) The approved institution shall maintain an Inspection Book to enable the
Inspectors to record his impression or defects noticed.
150F. Inspection before grant of approval.— Before an approval in Form 37 is granted,
the approving authority shall cause the institution at which the testing of drugs or cosmetics,
as the case may be, is proposed to be carried out to be inspected jointly by the Drugs
Inspectors of the Central Drugs Standard Control Organisation and the State Drugs Control
Organisation who shall examine the premises and the equipment intended to be used for
testing of drugs or cosmetics and inquire into the professional qualifications of the expert staff
to be employed.
150G. Report of Inspection.— The Drug Inspector mentioned in rule 150-F shall forward
to the approving authority a detailed report of the result of the inspection.
150H. Procedure of approving authority.— (1) If the approving authority after such
further enquiry, if any, as he may consider necessary, is satisfied that the requirements of the
rules made under the Act have been complied with and that the conditions of the approval and
the rules made under the Act will be observed, he shall grant an approval in Form 37.
(2) If the approving authority is not so satisfied, he shall reject the application and shall
inform the applicant of the reasons for such rejection and of the conditions which must be
satisfied before an approval could be granted.
150-I. Further application after rejection.— If within a period of six months from the
rejection of an application for approval, the applicant informs the approving authority that the
conditions laid down have been satisfied and deposits inspection fee of
2
[rupees two hundred
and fifty], the approving authority may, if, after causing a further inspection to be made, he is
satisfied that the conditions for grant of approval have been complied with, grant the approval
in Form 37.
1. Ins. by G.S.R 93 (E), dt. 24-2-1995.
2. Subs.by G.S.R 601 (E), dt. 24-8-2001.
Drugs and Cosmetics Rules 1945
177
150J. Renewal. – On an application being made for renewal the approving authority may
cause an inspection to be made and if satisfied that the conditions of the approval and the
rules made under the Act are and shall continue to be observed shall issue a certificate of
renewal in Form 38.
150K. Withdrawal and suspension of approvals – (1) The approving authority may, after
giving the approved institution an opportunity to show cause why such an order should not be
passed, by an order in writing stating the reasons therefor, withdraw an approval granted
under this Part or suspend it for such period as he thinks fit either wholly or in respect of
some of the categories of drugs or items of cosmetics to which it relates, if in his opinion the
approved institution has failed to comply with any of the conditions of the approval or with
any provisions of the Act or the Rules made thereunder.
(2) Any approved institution whose approval has been suspended or withdrawn may
within three months of the date of the order, appeal to the State Government which shall
dispose of the appeal in consultation with a panel of competent persons appointed by it in this
behalf and notified in the Official Gazette.]
1
[PART XVI
MANUFACTURE FOR SALE OF
AYURVEDIC
(INCLUDING SIDDHA) OR
UNANI
DRUGS
151. Manufacture on more than one set of premises.—If Ayurvedic (including Siddha)
or Unani drugs are manufactured on more than one set of premises, a separate application
shall be made and a separate licence shall be obtained in respect of each such set of premises.
152. Licensing Authorities.—For the purpose of this Part the State Government shall
appoint such Licensing Authorities and for such areas as may be specified in this behalf by
notification in the Official Gazette.
153. Application for licence to manufacture Ayurvedic (including Siddha) or
Unani drugs.— (1) An application for the grant or renewal of a licence to manufacture for
sale any Ayurvedic (including Siddha) or Unani drugs shall be made in Form 24-D to the
Licensing Authority along with
2
[a fee of rupees one thousand]:
Provided that in the case of renewal the applicant may apply for the renewal of the licence
before its expiry or within one month of such expiry:
Provided further that the applicant may apply for renewal after the expiry of one month
but within three months of such expiry in which case the
2
[fee payable for renewal of such
licence shall be rupees one thousand and two hundred plus an additional fee of rupees six
hundred].
(ii)
2
[A fee of rupees three hundred] shall be payable for a duplicate copy of a licence
issued under this rule, if the original licence is defaced, damaged or lost.
1. Parts XVI, XVII and XVII added by S.O. 642, dt. the 2-2-1970 (w.e.f. 21.2.1970)
2. Subs. by G.S.R 79 (E), dt. 14-2-2005.
Drugs and Cosmetics Rules 1945
178
1
[153A. Loan Licence.—(i) An application for the grant of renewal of a loan licence to
manufacture for sale of any Ayurvedic (including Siddha) or Unani drugs shall be made in
Form 25-E to the Licensing Authority along with
2
[a fee of rupees six hundred.]
Explanation—For the purpose of this rule, a loan licence means a licence which a
Licensing Authority may issue to an applicant who does not have his own arrangements for
manufacture but intends to avail himself of the manufacturing facilities owned by a licence in
Form 25-D:
Provided that in the case of renewal the applicant may apply for the renewal of the licence
before its expiry or within one month of such expiry:
Provided further that the applicant may apply for renewal after the expiry of one month,
but within three months of such expiry in which case
2
[the fee payable for renewal of such
licences shall be rupees six hundred plus an additional fee of rupees three hundred.]]
(ii)
2
[A fee of rupees one hundred and fifty] shall be payable for a duplicate copy of a
licence issued under this rule, if the original licence is defaced, damaged or lost.]
154. Form of licence to manufacture Ayurvedic (including Siddha) or Unani drugs.
— (1) Subject to the conditions of rule 157 being fulfilled, a licence to manufacture for sale
any Ayurvedic (including Siddha) or Unani drugs shall be issued in Form 25-D. The licence
shall be issued within a period of three months from the date of receipt of the application.
(2) A licence under this rule shall be granted by the licensing authority after consulting
such expert in Ayurvedic (including Siddha) or Unani Systems of medicine as the case may
be, which the State Government may approve in this behalf.
1
[154A. Form of loan licence to manufacture for sale of Ayurvedic (including Siddha)
or Unani drugs.—
(1) A loan licence to manufacture for sale of any Ayurvedic (including Siddha) or
Unani drugs shall be issued in Form 25E.
(2) A licence under this rule shall be granted by the Licensing Authority after
consulting such expert in Ayurvedic (including Siddha) or Unani systems of medicine,
as the case may be, which the State Government may approve in this behalf.
(3) The Licensing Authority shall, before the grant of a loan licence, satisfy himself
that the manufacturing unit has adequate equipment, staff, capacity for manufacture and
facilities for testing, to undertake the manufacture on behalf of the applicant for a loan
licence.]
155. Certificate of renewal—The certificate of renewal of a licence in Form 25-D shall
be issued in Form 26-D.
1. Ins. by G.S.R. 376(E), dt. 20-7-1978.
2. Subs. by G.S.R 79 (E), dt. 14-2-2005.
Drugs and Cosmetics Rules 1945
179
1
[155A. Certificate of renewal of a loan licence.—The certificate of renewal of a loan
licence in Form 25-E shall be issued in Form 26-E.]
2
[155B. Certificate of award of G.M.P. of Ayurveda, Siddha and Unani Drugs.—
3
[(1)]The certificate of Good Manufacturing Practices to manufacturers of Ayurveda, Siddha
or Unani drugs shall be issued to licensees who comply with the requirements of Good
Manufacturing Practice of Ayurveda, Siddha and Unani drugs as laid down in Schedule T.]
4
[(2) The certificate referred to in sub-rule (1) shall be issued for a period of five years
from the date of issuance of the license.]
156. Duration of licence—An original licence in Form 25-D or a renewed licence in
Form 26-D, unless sooner suspended or cancelled shall be
5
[valid for a period of
6
[five
years] from the date of its issue]:
Provided that if the application for the renewal of a licence is made before its expiry or
within one month of its expiry after payment of the additional fee of rupees thirty, the licence
shall continue to be in force until orders are passed on the application. The licence shall be
deemed to have expired, if the application for its renewal is not made within three months of
its expiry.]
1
[156A. Duration of loan licence.—An original loan licence in Form 25-E or a renewed
loan licence in Form 26-E, unless sooner suspended or cancelled, shall be valid up to the 31st
December of the year following the year in which it is granted or renewed:
Provided that if the application for the renewal of a loan licence is made in accordance
with rule 153-A, the loan licence shall continue to be in force until orders are passed on the
application. The licence shall be deemed to have expired, if the application for its renewal is
not made within three months of its expiry.]
157. Conditions for the grant or renewal of a licence in Form 25-D.—Before a licence
in Form 25-D is granted or renewed in Form 26-D the following conditions shall be complied
with by the applicant, namely: —
(1) The manufacture of Ayurvedic (including Siddha) or Unani drugs shall be carried
out in such premises and under such hygienic conditions as are specified in Schedule T.
2
[(IA) For issuing of the certificate of Good Manufacturing Practices, the Licensing
Authority shall verify the requirements as per schedule T and issue the Good
Manufacturing Practices certificate in form 26 E-I, simultaneously along with grant or
renewal of licence in form 25D].
7
[(IB) No manufacturer shall use any prefix or suffix with the name of any Ayurvedic,
Siddha or UnaniTibb drug falling under clause (a) of section 3 of the Act, except as
described in the authoritative books specified in the First Schedule to the Act:
Provided that a formulation without any specific name, described in the
authoritative books may be named on the basis of the ingredients of the formulation.
(IC) The name of any Ayurvedic, Siddha or UnaniTibb drug falling under clause (a)
of section 3 of the Act shall not be used for naming any patent or proprietary medicine
relating to Ayurvedic, Siddha or UnaniTibb systems of medicine referred to in sub-clause
(i) of clause (h) of the said section:
Provided that this rule shall not be applicable for single plant-ingredient based
Ayurvedic, Siddha or UnaniTibb formulation licensed or to be licensed as patent or
proprietary medicine under sub-clause (i) of clause (h) of section 3 of the Act.]
1. Ins. by G.S.R. 376 (E),dt. 20-7-1978. 7. Ins. by G.S.R. 390 (E),dt. 18.5.2015.
2. Subs. by G.S.R. 376 (E),dt. 3-5-2010. Earlier Ins. by G.S.R. 198 (E), dt. 7-3-2003.
3. Rule 155B renumbered as sub-rule (1) by G.S.R. 376 (E),dt. 3-5-2010.
4. Ins. by G.S.R. 376 (E),dt. 3-5-2010.
5. Subs. by G.S.R 79 (E), dt. 14-2-2005.
6. Subs. by G.S.R. 376 (E),dt. 3-5-2010.
Drugs and Cosmetics Rules 1945
180
(ID) Notwithstanding the period for renewal of licence provided in rules 156 and
156 A, the licensee of the Ayurvedic, Siddha or UnaniTibb drug, which is not in
conformity with sub-rules (1B) and (1C), shall seek renewal of the licence with
appropriate name of the drug within a period of one year from the date of commencement
of Drugs and Cosmetics (4
th
Amendment) Rules, 2015:
Provided that this rule shall not be applicable to any batch of Ayurvedic,
Siddha or UnaniTibb drugs manufactured prior to the date of commencement of the Drugs
and Cosmetics (4
th
Amendment) Rules, 2015.
(IE) Whoever contravenes the provisions of rules (IB) to (ID) shall be punishable
under section 33-I of the Act.]
(2) The manufacture of Ayurvedic (including Siddha) or Unani drugs shall be
conducted under the direction and supervision of competent technical staff consisting at
least of one person, who is a whole time employee and who possesses the following
qualifications, namely:–
(a) A degree in Ayurveda or Ayurvedic Pharmacy, Siddha or Unani system of
medicine, as the case may be, conferred by a University, a State Government or Statutory
Faculties, Councils and Boards of Indian Systems of Medicines recognized by the Central
Government or a State Government for this purpose, or
(b) a diploma in Ayurveda, Siddha or Unani system of medicine granted by a State
Government for this purpose, or
(c) a graduate in Pharmacy or Pharmaceutical Chemistry or Chemistry or Botany
of
a University recognized by the Central Government with experience of at least two years
in the manufacture of drugs pertaining to the Ayurvedic or Siddha or Unani systems of
medicines, or
(d) a Vaid or Hakim registered in a State Register of Practitioners of indigenous
systems of medicines having experience of at least four years in the manufacture of
Ayurvedic or Siddha or Unani drugs, or
(e) a qualification as Pharmacist in Ayurvedic (including Siddha) or Unani systems
of medicines, possessing experience of not less than eight years in the manufacture of
Ayurvedic or Siddha or Unani drugs as may be recognized by the Central Government.
(3) The competent technical staff to direct and supervise the manufacture of
Ayurvedic drugs shall have qualifications in Ayurveda and the competent technical staff
to direct and supervise the manufacture of Siddha drugs and Unani drugs shall have
qualification in Siddha or Unani, as the case may be.
Drugs and Cosmetics Rules 1945
181
3
[157A. Maintaining of records of raw material used by licensed manufacturing unit
of Ayurveda, Siddha and Unani drugs in the preceding financial year.- Each licensed
manufacturing unit of Ayurveda or Siddha or Unani drugs shall keep a record of raw
material used by each licensed manufacturing unit of Ayurveda, Siddha or Unani drugs as
the case may be in the proforma given in Schedule TA in respect of all raw materials
utilized by that unit in the manufacture of Ayurveda or Siddha or Unani drugs in the
preceding financial year, and shall submit the same by the 30th day of June of the
succeeding financial year to the State Drug Licensing Authority of Ayurveda, Siddha and
Unani drugs and to the National Medicinal Plants Board or any agency nominated by the
National Medicinal Plant Board for this purpose.]
158. Conditions of licence.—A licence in Form 25D shall be subject to the conditions
stated therein and to the following further conditions, namely:–
(a) The licensee shall maintain proper records of the details of manufacture and of
the tests, if any, carried out by him, or by any other person on his behalf, of the raw
materials and finished products.
(b) The licensee shall allow an Inspector appointed under the Act to enter any
premises where the manufacture of a substance in respect of which the licence is issued is
carried on, to inspect the premises, to take samples of the raw material as well as finished
the products, and to inspect the records maintained under these rules.
1
[(c) The licensee shall maintain an Inspection Book in Form 35 to enable an
Inspector to record his impressions and the defects noticed.]
2
[158-A. Condition of loan licence.—A licence in Form 25E shall be subject to the
conditions stated therein and to the following conditions, namely:—
(a) The licence in Form 25E shall be deemed to be cancelled or suspended, if the
licence owned by the licensee in Form 25D whose manufacturing facilities have
been availed of by the licensee is cancelled or suspended, as the case may be, under
these rules.
(b) The licensee shall comply with the provisions of the Act and of the rules and
with such further requirements, if any, as may be specified in any rules subsequently
made under Chapter IV-A of the Act, provided that where such further requirements
are specified in the rules; these would come into force four months after publication in
the Official Gazette.
(c) The licensee shall maintain proper records of the details of manufacture
and of the tests, if any, carried out by him, or any other person on his behalf, of the
raw materials and finished products.
(d) The licensee shall allow an Inspector appointed under the Act to inspect all
registers and records maintained under these rules and shall supply to the Inspector
such information as he may require for the purpose of ascertaining whether the
provisions of the Act and the rules have been observed.
1
[(e) The licensee shall maintain an Inspection Book in form 35 to enable an
Inspector to record his impressions and the defects noticed.]
1. Ins. by G.S.R. 331 (E),dt. 8.5.1984.
2. Ins. by G.S.R. 376 (E), dt. 20.7.1978.
3. Ins. by G.S.R. 512 (E),dt. 9.7.2008.
Drugs and Cosmetics Rules 1945
182
1
[158(B) Guidelines for issue of license with respect to Ayurveda, Siddha or
Unani drugs.-
I. (A). Ayurveda, Siddha Unani Medicines under section 3(a):- Ayurveda, Siddha or
Unani drugs includes all medicines intended for internal or external use for or in the
diagnosis, treatment, mitigation or prevention of disease or disorder in human beings or
animals, and manufactured exclusively in accordance with the formulae described in the
authoritative books of Ayurvedic, Siddha and Unani Tibb system of medicine, as specified
in the First Schedule;
(B). Patent or Proprietary medicine under section 3(h);
(i) In relation to Ayurvedic, Siddha and Unani Tibb system of medicine of all
formulations containing only such ingredients mentioned in the formulae described in the
authoritative books of Ayurveda, Siddha or Unani Tibb system of medicines specified in
the First Schedule, but does not include a medicine which is administered by parenteral
route and also a formulation included in the authoritative books as specified in clause (a);
(ii) Balya/Poshak/Muqawi/Unavuporutkal/positive health Promoter formulations
having ingredients mentioned in books of First Schedule of the Drugs and Cosmetics Act
and recommended for promotional and preventive health.
(iii) Saundarya Prasadak (Husane afza)/Azhagh-sadhan formulation having ingredients
mentionedin Books of First Schedule of the Drugs and Cosmetics Act and recommended
for oral, skin, hair and body care.
(iv) Aushadh Ghana (Medicinal plant extracts - dry/wet) extract obtained from plant
mentioned in books of First Schedule of the Act including Aqueous or hydro-alcohol.
II.(A) For issue of licence to the medicine with respect to Ayurvedic, Siddha and
Unani, the conditions relating to safety study and the experience or evidence of
effectiveness shall be such as specified in columns (5) and (6) of The Table given below:-
Serial
number
Category
Ingredient
(S)
Indication
(s)
Safety
study
Experience/Evidence of
Effectiveness
1
2
3
4
5
6
Published
Literature
Proof of
Effectiveness
1
(A)
Ayurveda,
siddha and
Unani drugs,
given in 158
B as referred
in 3(a)
As per
text
As per
text
Not
Required
Required
Not Required
2
(B) Any
change in
dosage form
of Ayurveda,
siddha and
Unani drugs,
as described
in section 3
(a) of the
Drugs and
Cosmetics
As per
text
As per
text
Not
Required
Required
Not Required
Drugs and Cosmetics Rules 1945
183
Act, 1940
3
(C)
Ayurveda,
siddha and
Unani drugs,
referred in
3(a) to be
used for new
indication
As per
text
New
Not
Required
If Required
Required
II.B For issue of license with respect to Patent or Proprietary medicine. The condition
relating to Safety studies and experience or evidence of effectiveness shall be specified as
follows:-
Serial
number
Category
Ingredient
(S)
Indication
(s)
Safety
study
Experience/Evidence
of Effectiveness
1
2
3
4
5
6
Published
Literature
Proof of
Effectiveness
1
Patent
orPropri
etary
medicine
As per
text
Textual
Rationale
Not
Required
Of
Ingredients
Pilot study as
per relevant
protocol for
Ayurveda,
siddha and
Unani drugs
2
Ayurveda,
siddha and
Unani
drugswith
any of the
ingredients
of Schedule
E(1) of the
Drugs and
Cosmetics
Act, 1940
As per
text
Existing
Required
Required
Required
III. For issue of license with respect to Balya and Poshak medicines the person who
applied for license is required to submit the following:
(i) Photo-copy of the textual reference of ingredients used in the formulation as
mentioned in the book of 1st schedule;
(ii) Conduct safety studies in case the product contains of any of the ingredients as
specified in the Schedule E (1), as per the guidelines for evaluation of Ayurveda Siddha
and Unani Drugs formulations;
(iii) For textual indications the safety and effectiveness study is not required.
IV. For issue of license with respect to Saundarya Prasadak (Husane afza/Azhagu
Sodhan) the person who applied for license is required to:-
(i) Submit photo-copy of the textual reference of ingredients used in the formulation
as mentioned in the book of 1st schedule;
1. Ins. by G.S.R. 663 (E),dt. 10.10.2010.
Drugs and Cosmetics Rules 1945
184
(ii) Conduct safety studies, in case the formulation contains of any of the ingredients
as specified in the Schedule E (1), as per the guidelines for evaluation of Ayurveda,
Siddha and Unani formulation;
(iii) For textual indications the safety and effectiveness study is not required.
V. For issue of license with respect to medicine Aushadh Ghana extract of medicinal
plant (dry or wet).
Serial
number
Category
Ingredien
t (S)
Indication (s)
Safety study
Experience/Evidence of
Effectiveness
1
2
3
4
5
6
Published
Literature
Proof of
Effectiveness
1
(A)
Aqueous
As per
text
As per text
Not Required
Not
Required
Not Required
2
(Al).
Aqueous
As per
text
New
Indication**
Not Required
Not
Required
Required
3
(B) Hydro-
Alcohol
As per
text
As per text
Not Required
If
Required
Not Required
4
(B1)
Hydro-
Alcohol
As
specified
New
Indication**
Required
If
Required
Required
5
Other
than
Hydro/
HydroAlc
ohol
As
specified
As specified
Required
Acute,
Chronic,
mutagenicity
and
teratogenicit
y
If
Required
Required
* The standard protocol will also include concept of Anupan, Prakriti & Tridosh etc.
published by Central
Research Councils Ayurveda, Siddha, Unani and other Government/Research Bodies.
** New indication means which is other than mentioned in 1st schedule books of
Drugs & Cosmetics Act 1940.]
1
[158C. Form of Free Sale Certificate and Non-Conviction Certificate. – The State
Drug Controller or Licensing Authority shall, on request by the Ayurveda, Siddha and
Unani Drugs manufacturer, issue, within 15 days; from the date of application, Free Sale
Certificate in Form 26 E2-I for original License holder or in Form 26 E2-II for loan license
and Non Conviction Certifacate for both original and loan license holder in Form 26 E3 or
in the format as specified by the importing country or tenderer respectively, after
fulfilment of all requisite formalities as required in the respective formats.]
1. Ins. by G.S.R. 153 (E),dt. 5.3.2014.
Drugs and Cosmetics Rules 1945
185
159. Cancellation and suspension of licences— (1) The Licensing Authority may, after giving an
opportunity to show cause within a period which shall not be less than fifteen days from the date of
receipt of such notice, why such an order should not be passed, by an order in writing stating the
reasons therefor, cancel a licence issued under this Part or suspend it for such period as he thinks
fit, either wholly or in respect of some of the drugs to which it relates, if in his opinion, the
licensee has failed to comply with any of the conditions of the licence or with any provisions of the
Act and the rules made thereunder.
(2) A licensee whose licence has been suspended or cancelled may appeal to the State
Government within a period of three months from the date of receipt of the order which shall,
after considering the appeal, decide the same.
160. Identification of raw materials.— Raw materials used in the preparation of
Ayurvedic (including Siddha) or Unani drugs shall be identified and tested, wherever tests are
available for their genuineness, and records of such tests as are carried out for the purpose and
the methods thereof shall be maintained.
1
[PART
XVI (A)
APPROVAL OF INSTITUTIONS FOR CARRYING OUT TESTS ON
AYURVEDIC,
SIDDHA AND UNANI DRUGS AND RAW MATERIALS USED IN
THEIR
MANUFACTURE ON BEHALF OF LICENSEES FOR MANUFACTURE FOR SALE
OF
AYURVEDIC, SIDDHA AND UNANI
DRUGS
160-A. Application for grant of approval for testing Ayurvedic, Siddha and Unani
drugs.- Application for grant or renewal of approval for carrying out tests for identity, purity,
quality and strength of Ayurvedic, Siddha and Unani drugs or the raw materials used in the
manufacture thereof on behalf of licensees for manufacture for sale of the said Ayurvedic,
Siddha and Unani drugs, shall be made in Form 47 to the Licensing Authority appointed by
the State Government for the purposes of Part XVI, XVII or XVIII of these rules, as the case
may be, and referred to as the ‗approving authority‘ under this Part and shall be accompanied
by an inspection fee of six thousand rupees in respect of the drugs specified in the books
prescribed in First Schedule to the Act.
1. Subs. by G.S.R.73 (E), dt. 31-01-2003 and earlier Ins. by G.S.R. 701(E), dt. 27-9-2001.
Drugs and Cosmetics Rules 1945
186
Provided that the applicant shall furnish to the approving authority such additional
information as may be required by it in connection with the application in Form 47:
Provided further that if the applicant applies for renewal of approval after its expiry but
within six months of such expiry, the inspection fee payable shall be six thousand rupees plus
an additional inspection fee at the rate of one thousand rupees per month in the case of testing
of Ayurvedic, Siddha and Unani drugs specified in First Schedule to the Act.
Explanation. - For the purpose of this Part, the words ―Ayurvedic, Siddha and Unani
drugs‖ shall also mean and include the raw materials used in the manufacture of Ayurvedic,
Siddha and Unani drugs, as the case may be.
160B. Form in which approval to be granted for carrying out tests on Ayurvedic,
Siddha and Unani drugs on behalf of licensees for manufacture of Ayurvedic, Siddha
and Unani drugs and conditions for grant or renewal of such approval.-- (1) Approval for
carrying out such tests of identity, purity, quality and strength of Ayurvedic, Siddha and
Unani drugs as may be required under the provisions of these rules, on behalf of licensee for
manufacture of Ayurvedic, Siddha and Unani drugs shall be granted in Form 48.
(2) Before approval in Form 48 is granted or renewed, the following conditions shall be
complied with by the applicants, namely: -
(i) The premises where the tests are carried out shall be well lighted and properly
ventilated except where the nature of tests of any Ayurvedic, Siddha and Unani drug
warrants otherwise. Wherever necessary, the premises shall be air-conditioned so as to
maintain the accuracy and functioning of laboratory instruments or to enable the
performance of special tests such as sterility tests and microbiological tests.
(ii) (a) The applicant shall provide adequate space having regard to the nature and
number of samples of drugs proposed to be tested:
Provided that the approving authority shall determine from time to time whether
the space provided continues to be adequate:
Provided further that separate section shall be provided for (i) Chemistry, (ii)
Pharmacognosy, (iii) Ayurveda, Siddha and Unani, (iv) Microbiology, (v) Sample
Room, (vi) Office-cum-Record Room, with proper partitions and minimum required
area is 800 sq. ft.
1
[(b) The applicant shall provide a list of persons who may be employed with
him as experts, such as Chemist, Botanist and expert in Ayurveda/Siddha/Unani or
Pharmacist who shall possess a degree in Chemistry, Botany,
Ayurveda/Siddha/Unani/Bachelor in Pharmacy from a recognized University or
equivalent, with experience for 2 years for carrying out tests or analysis as per the
Ayurvedic, Siddha and Unani Pharmacopoeias].
The applicant shall provide adequate equipment essential for carrying out tests
for identity, purity, quality and strength of Ayurvedic, Siddha and Unani drugs as per
pharmacopoeial standards or other available standards.
1. Subs. by G.S.R. 674 (E), dt. 10-11-2005.
Drugs and Cosmetics Rules 1945
187
List of equipment recommended is given below:
Chemistry Section
1. Alcohol determination apparatus complete set.
2. volatile oil determination apparatus.
3. Boiling point determination apparatus.
4. Melting point determination apparatus.
5. Refractometer.
6. Polarimeter.
7. Viscometer (Ostwalds, Redwood Viscometer).
8. Tablet disintegration apparatus.
9. Moisture determination apparatus (IC filtrator).
10. U.V.Spectro-photometer.
11. Muffle furnace.
12. Electronic Balance.
13. Hot air oven(s) different range of temperature/vacuum oven.
14. Refrigerator.
15. Glass distillation apparatus/plant.
16. Water supply demineralised exchange equipment/distillation equipment.
17. Air conditioner.
18. LPG Gas cylinder with burners.
19. Water bath (temperature controlled).
20. Heating mantle(4) or as required.
21. TLC apparatus with all accessories.
22. Sieves 10 to 120 with sieve shaker.
23. Centrifuge machine.
24. Dehumidifier.
25. pH meter.
26. G.L.C. with F.I. detector.
27. Silica crucible.
28. Tablet friability tester.
29. Tablet dissolution tester.
30. Other related equipment, reagents, glasswares etc.
Pharmacognosy
Section
1. Microscope binocular.
2. Dissecting Microscope.
3. Microtome.
4. Chemical balance.
5. Microslide cabinet.
6. Aluminium slide trays.
7. Hot air oven.
8. Occular Micrometer.
9. Stage Micrometer.
10. Camera Lucida Prism type and mirror type.
11. Hot plates.
12. Refrigerator.
13. LPG Cylinder with burners.
14. Other related equipments, reagents, glasswares etc.
Note: Instuments like HPLC, HPTLC, Atomic Absorption spectrophotometer could be
arranged by tie up with other laboratories.
Drugs and Cosmetics Rules 1945
188
Microbiology
section
1. Laminar air flow bench (L.A.F.)
2. B.O.D. Incubator.
3. Plain Incubator.
4. Serological water bath.
5. Oven.
6. Autoclave/sterilizer.
7. Microscope (high power).
8. Colony counter.
9. Other related equipment and reagents.
(3). The applicant shall provide and maintain suitable equipment having regard to the
nature and number of samples of Ayurvedic, Siddha and Unani drugs intended to be tested
which shall be adequate in the opinion of the approving authority.
(4) The testing of Ayurvedic, Siddha and Unani drugs, as the case may be, for identity,
purity, quality and strength shall be carried out under the active direction of one of the experts
stated in clause (b) of sub-rule (2) who shall be the person-in-charge of testing and shall be
held responsible for the reports of test issued by the applicant.
(5) The testing of Ayurvedic, Siddha and Unani drugs, as the case may be, for identity,
purity, quality and strength shall be carried out by persons whose qualifications and
experience of testing are adequate as stated in clause (b) of sub-rule (2).
(6) The applicant shall provide books of standards recognized under the provisions of the
Act and the rules made thereunder and such books of reference as may be required in
connection with the testing or analysis of the products for the testing of which approval is
applied for.
(7) The applicant shall provide list of standard Ayurvedic, Siddha and Unani drugs
(Reference samples) recognized under the provisions of the Act and rules made thereunder
and such reference samples kept in the laboratory may be required in connection with the
testing or analysis of the products of which approval is applied for.
160C. Duration of approval. - An approval granted in Form 48 or renewed in Form 49
unless sooner suspended or withdrawn, shall be valid for a period of three years from the date
on which it is granted or renewed:
Provided that if an application for the renewal of an approval in Form 40 is made before
its expiry or if the application is made within six months of its expiry after the payment of the
additional inspection fee, the approval shall continue to be in force until orders to the contrary
are passed on the application and approval shall be deemed to have expired if the application
for renewal is not made within six months of expiry.
160D. Conditions of approval.–An approval in Form 48 shall be subject to the following
conditions, namely: -
I. The Institution granted approval under this Part (hereinafter referred to as the approved
laboratory) shall provide and maintain adequate staff and adequate premises and equipment as
specified in rule 160-B.
II. The approved laboratory shall provide proper facilities for storage so as to preserve
the properties of the samples to be tested by it.
Drugs and Cosmetics Rules 1945
189
III. The approved laboratory shall maintain records of tests for identity, purity, quality
and strength carried out on all samples of Ayurvedic, Siddha and Unani drugs and the results
thereof together with the protocols of tests showing the readings and calculation in such form
as to be available for inspection and such records shall be retained in the case of substances
for which date of expiry is assigned; for a period of two years from such date of expiry and in
the case of other substances, for a period of three years.
IV. The approved laboratory shall allow the Inspector appointed under this Act to enter
with or without prior notice the premises where testing is carried out and to inspect the
premises and the equipment used for test and the testing procedures employed. The laboratory
shall allow the Inspectors to inspect the registers and records maintained under these rules and
shall supply to such Inspectors such information as they may require for the purpose of
ascertaining whether the provisions of the Act and rules made thereunder have been observed.
V. The approved laboratory shall from time to time report to the approving authority any
changes in the person-in-charge of testing of Ayurvedic, Siddha and Unani drugs or the expert
staff responsible for testing, as the case may be, and any material alterations in the premises
or changes in the equipment used for the purposes of testing which have been made since the
date of last inspection made on behalf of the approving authority before the grant or renewal
of approval.
VI. The approved laboratory shall furnish reports of the results of tests or analysis in
Form 50.
VII. In case any sample of Ayurvedic, Siddha and Unani drug is found on test to be not
of standard quality, the approved laboratory shall furnish to the approving authority and the
licensing authority of the State where the manufacturer and/or sender of the Ayurvedic,
Siddha and Unani drugs is located, a copy of the test report of the sample with the protocols
of tests applied.
VIII. The approved laboratory shall comply with the provisions of the Act and rules
made thereunder and with such further requirements, if any, as may be specified in the rules
made from time to time under Chapter IV-A of the Act of which the approving authority has
given the approved laboratory not less than four months‘ notice.
IX. The approved laboratory shall maintain an inspection book to enable the Inspector to
record his impression or defects noticed.
160-E. Inspection before grant of approval.— Before an approval in Form 48 is granted,
the approving authority shall cause the laboratory at which the testing of Ayurvedic, Siddha
and Unani drugs, as the case may be, is proposed to be carried out to be inspected jointly by
the Inspectors appointed or designated by the Central Government and State Government for
this purpose, who shall examine the premises and the equipment intended to be used for
testing of drugs and verify into the professional qualifications of the expert staff who are or
may be employed by the laboratory.
160F. Report of inspection.— The Inspectors appointed by the Central Government as
stated in Rule 160-E shall forward to the approving authority a detailed report of the results of
the inspection.
160G. Procedure of approving authority. - (1) If the approving authority after such
further enquiry, if any, as it may consider necessary, is satisfied that the requirements of the
rules made under the Act have been complied with and that the conditions of the approval and
the rules made under the Act have been observed, it shall grant approval in Form 48.
Drugs and Cosmetics Rules 1945
190
(2) If the approving authority is not satisfied, it shall reject the application and shall
inform the applicant of the reasons for such rejection and of the conditions which shall be
satisfied before approval could be granted.
160H. Application after rejection. - If within a period of six months from the rejection of
an application for approval, the applicant informs the approving authority that the conditions
laid down have been satisfied and deposits inspection fee of two thousand rupees, the
approving authority may, if, after causing a further inspection to be made and after being
satisfied that the conditions for grant of approval have been complied with, grant the approval
in Form 48.
160-I. Renewal. - On an application being made for renewal, the approving authority
shall, after causing an inspection to be made and if satisfied that the conditions of the
approval and the rules made under the Act have been complied with, shall issue a certificate
of renewal in Form 49.
160J. Withdrawal and suspension of approvals. - (1) The approving authority may, after
giving the approved laboratory an opportunity to show cause why such an order should not be
passed, by an order in writing stating the reasons therefor, withdraw an approval granted
under this Part or suspend it for such period as it thinks fit either wholly or in respect of
testing of some of the categories of Ayurvedic, Siddha and Unani drugs to which it relates, if
in his opinion the approved laboratory had failed to comply with any of the conditions of the
approval or with any provision of the Act or the rules made thereunder.
(2) Any approved laboratory, whose approval has been suspended or withdrawn, may,
within three months of the date of the order of suspension or withdrawal, appeal to the State
Government which shall dispose of the appeal in consultation with a panel of competent
persons appointed by the Department of Indian Systems of Medicine & Homoeopathy,
Government of India in this behalf and notified in the Official Gazette.]
1
[PART
XVII
2
[LABELLING, PACKING AND LIMIT OF ALCOHOL IN]
AYURVEDIC
(INCLUDING SIDDHA) OR UNANI
DRUGS
161.
2
[Labelling, packing and limit of alcohol.]—(1) There shall be conspicuously
displayed on the label of the container or package of an Ayurvedic (including Siddha) or
Unani drug, the true list of all the ingredients
3
[with the botanical names of plant based
ingredients along with plant part(s) and form of ingredients, in which, these are] used in the
manufacture of the preparation together with quantity of each of the ingredients incorporated
therein and a reference to the method of preparation thereof as detailed in the standard text
and Adikarana, as are prescribed in the authoritative books specified in the First Schedule to
the Act
3
[and in respect of Patent or Proprietary Ayurveda, Siddha or Unani drugs, the true list
of all ingredients with the botanical names of plant based ingredients along with part(s) and
form of ingredients, in which, these are used in the formulation, with their quantity]:
Provided that if the list of ingredients contained in the medicine is large and cannot be
accommodated on the label, the same may be printed separately and enclosed with packing
and reference be made to this effect on the label.
(2) The container of a medicine for internal use made up ready for the treatment of human
ailments shall, if it is made up from a substance specified in Schedule E (1), be labelled
conspicuously with the words ‗Caution: To be taken under medical supervision‘ both in
English and Hindi language.
1. Ins. by notification F.1-23/6, dt. 2.2.1970. 3. Ins. by G.S.R. 844(E), dt. 26.11.2012
2. Subs. by G.S.R. 904(E), dt. 2.11.1992.
Drugs and Cosmetics Rules 1945
191
(3) Subject to the other provisions of these rules, the following particulars shall be either
printed or written in indelible ink and shall appear in a conspicuous manner on the label of the
innermost container of any Ayurvedic (including Siddha) or Unani drug
2
[Patent or
Proprietary Ayurveda, Siddha or Unani drugs] and on any other covering in which the
container is packed', namely−
(i) The name of the drug.
3
[For Ayurveda, Siddha or Unani drugs] this purpose the
name shall be the same as mentioned in the authoritative books included in the First
Schedule of the Act.
(ii) A correct statement of the net content in terms of weight, measure or number as
the case may be. The weight and volume shall be expressed in metric system.
(iii) The name and address of the manufacturer.
(iv) The number of the licence under which the drug is manufactured, the figure
representing the manufacturing licence number being preceded by the words
‗Manufacturing Licence Number‘ or ‗Mfg. Lic. No.‘ or ‗M.L.‘.
(v) A distinctive batch number, that is to say, the number by reference to which
details of manufacture of the particular batch from which the substance in the container
is taken are recorded and are available for inspection, the figure representing the batch
number being preceded by the words ―Batch No.‖ or ―Batch‖ or ―Lot Number‖ or ―Lot
No.‖ or ―Lot‖ or any distinguishing prefix.
(vi) The date of manufacture. For this purpose the date of manufacture shall be the
date of completion of the final products, or the date of bottling or packing for issue.
(vii) The words ―Ayurvedic medicine‖ or ―Siddha medicine‖ or ―Unani medicine‖ as
the case may be.
(viii) The words ―FOR EXTERNAL USE ONLY‖ if the medicine is for external
application.
(ix) Every drug intended for distribution to the medical profession, as a free sample
shall, while complying with the labelling provisions under clauses (i) to (viii), further
bear on the label of the container the words ―Physicians sample. Not to be sold‖ which
shall be over-printed.
1
[(x)(a) Preparation (Asavas) with high content of alcohol as base
Name of the drug Maximum size of packing
(i) Karpur Asava 15 ml
(ii) Ahiphenasava 15 ml
(iii) Margamadasava 15 ml
(ix)(b) Preparations containing self-generated alcohol
Name of the drug Maximum content of alcohol
(Ethyl alcohol v/v)
Maximum
size of
packing
(i) Mritsanjivani Sura
16 per cent
30 ml.
(ii)
Mahadrakshasava
16 per cent
120 m
l
.]
1. Subs. by G.S.R. 904 (E), dt. 2-11-1992.
2. Ins. by G.S.R. 844(E), dt. 26.11.2012.
3. Subs. by G.S.R. 844(E), dt. 26.11.2012.
Drugs and Cosmetics Rules 1945
192
(4) Nothing in these rules shall be deemed to require the labelling of any transparent
cover or of any wrapper case or other covering used solely for the purpose of packing,
transport or delivery.
1
[161A. Exemption in labeling and packing, provisions for export of Ayurvedic
(including Siddha) and Unani drugs.- (1) Labels and packages or containers of Ayurvedic,
Siddha and Unani drugs for export may be adopted to meet the specific requirements of the
law of the country to which the said drug is to be exported, but the following particulars shall
appear in conspicuous position on the container in which drug is packed and on every other
covering in which that container is packed, namely :
(a) Name of the Ayurvedic, Siddha and Unani drug (Single or compound
formulations;
(b) the name, address of the manufacturer and the number of licence under which
the drug has been manufactured;
(c) batch or lot number;
(d) date of manufacture, along with the date for ―Best for use before‖;
(e) main ingredients, if required by the importing country;
(f) for export:
Provided that where Ayurvedic, Siddha and Unani Single or compound drug not
classified under the First Schedule or Schedule E-(I), is required by the consignee to be not
labeled with the name and address of the manufacturer, the labels on packages or containers
shall bear a code number as approved by the Licensing Authority mentioned in rule 152.
(2) the provisions of Rule 161 shall not apply to a medicine made up ―ready for
treatment‖, whether after, or without, alteration, which is supplied on the prescription of a
registered medical practitioner if the medicine is labeled with the following particulars,
namely:–
(a) the name and address of the suppliers;
(b) the words ―For External Use Only‖, if the medicine is for external application.]
2
[161B. 1. The date of expiry of Ayurveda, Siddha and Unani medicines shall be
conspicuously displayed on the label of container or package of an Ayurvedic, Siddhas and
Unani medicines, and after the said date of expiry, these medicines shall not be in circulation.
2. The Shelf-life i.e. for Ayurveda, Siddha and Unani medicines shall be as follows:-
(i) Shelf life or date of expiry for Ayurvedic medicines.
Sl. No.
Name of the Group of Ayurvedic Medicine
Shelf life and date ofexpiry
with effect fromthe date of
manufacture
1.
Churna, Kwatha Churna
2 years
2.
Gutika (Vati-Gutti, Pills, Tablets except Gutika
with Rasa)
3 years
3.
(i) Gutika Tablet containing Kasth aushadhi
(ii) Gutika,Tablet containing Kasth aushadi
and Rasa, Uprasa, Metallic Bhasmas, and
Guggulu.
3 years
5 years
4.
Rasaushadhies
No expiry date
1
5.
Asava Arista
No expiry date
1
6.
Avaleha
3 years
7.
Guggulu
5 years
8.
Mandura - Lauha
10 years
1. Ins. by G.S.R. 787 (E), dt. 17-10-2000.
2. Ins. by G.S.R. 764 (E), dt. 15-10-2009.
Drugs and Cosmetics Rules 1945
193
9.
Ghrita
2 years
10.
Taila
3 years
11.
Arka
1 year
12.
Dravaka, Lavana, Ksara
5 years
13.
Lepa Churna
3 years
14.
Dant Manjan Powder
2 years
15.
Dant Manjan Paste
2 years
16.
Lepa Guti
3 years
17.
Lepa Malahar (Ointment)/Liniment/Gels/ lotions
/creams
3 years
18.
Varti
2 years (one time use)
19.
Ghana Vati
3 years
20.
Kupipakva Rasayan
No expiry date
1
21.
Parpati
No expiry date
1
22.
Sveta parpati
2 years
23.
Pisti and Bhasma
No expiry date
1
24.
Svarna, Rajata, Lauha, Mandura, Abhraka
bhasma,Godanti, ShankhaBhasma, etc.
No expiry date
1
25.
Naga Bhasma, Vanga Bhasma, Tamra Bhasma
2
5 years
2
26.
Capsules made of soft gelatin (depending upon
thecontent material) for Kashtha aushadhi
3 years
27.
Capsules of hard gelatin (depending upon the
content material) -containing Kasth aushdhi with
Rasa, Bhasma,Parad-Gandhak
5 years
2
28.
Syrup/liquid oral
3 years
29.
(Kama/Nasa Bindu) Ear/Nasal drops
Eye drops
2 years
1 year
30.
Khand/Granule/Pak
3 years
31.
Dhoopans-Inhalers
2 years
32.
Pravahi Kwatha (with preservatives)
3 years
Note 1. Item at Sr. No.4, 5, 19, 20, 22, 23 have very long shelf life and they became more
efficacious with the passage of time and period of ten years shall be mandatory for keeping the
records of such items.
Note 2. Bhasmas at Sr. No. 23, start solidifying after five years and they need one or two
‗Puta‘again before using in the dosage form.
(ii) Shelf life or date of expiry for Siddha Medicines
Sl. No.
Name of the Group of Medicine
Shelf life and date ofexpiry with effect
from the date of manufacture
1.
Karpam
No expiry date*
2.
Cunnam
5 years
3.
Kalanku
No expiry date*
4.
Kattu
No expiry date*
5.
Parpam
No expiry date*
6.
Centuram
No expiry date*
7.
Karuppu
No expiry date*
8.
Patankam
5 years
9.
Kulampu
5 years
10.
Meluku
5 years
11.
Tinir
2 years
12.
Tiravakam
2 years
13.
Mattirai
3 years
Drugs and Cosmetics Rules 1945
194
14.
Tailam
3 years
15.
Ilakam
3 years
16.
Iracayanaam
3 years
17.
Ney
2 years
18.
Manappaku
3 years
19.
Venney
3 years
20.
Vatakam
3 years
21.
Curanam
2 years
22.
Pura Maruntukal
5 years
Note. * Items at Sr. No.1, 3, 4, 5, 6, 22 have very long shelf life and they became more
efficacious with the passage of time and period of ten years shall be mandatory for keeping the
records of such items.
(iii) Shelf life or date of expiry for Unani System of Medicines
Sl. No.
Name of the Group of Medicine
Shelf life and date ofexpiry with effect
from the date of manufacture
1.
Habb (Pills)
3 years
2.
Qurs (Tablets)
3 years
3.
Majoon/Dawa
3 years
4.
Khamira
3 years
5.
Itrifal
3 years
6.
Tiryaq
3 years
7.
Laooq
2 years
8.
Laboob
2 years
9.
Halwa
2 years
10.
Mufarreh/Yaqooti
2 years
11.
Burood/Surma/Kohal
3 years
12.
Kushta
5 years
13.
Raughaniyat
3 years
14.
Marham/Zimad/Qairooti
3 years
15.
Ayarij/Sufoof
2 years
16.
Safoof (Namak wala/containing salt)
1 year
17.
Sharbat/Sikanjabeen
3 years
18.
Jawarish
3 years
19.
Capsule
3 years
20.
Arq
1 year
21
Qutoor
1 year
22.
Nabeez
5 years
23.
Murabba
1 year
24.
Tila
2 years]
1
[PART
XVIII
GOVERNMENT ANALYSTS AND INSPECTORS
FOR AYURVEDIC (INCLUDING SIDDHA) OR UNANI DRUGS
162. Duties of Inspectors specially authorised to inspect the manufacture of Ayurvedic
(including Siddha) or Unani drugs—Subject to the instructions of the controlling authority, it
shall be the duty of an Inspector authorised to inspect the manufacture of Ayurvedic
(including Siddha) or Unani drugs–
1. Ins. by notification F.1-23/6, dt. 2-2-1970.
Drugs and Cosmetics Rules 1945
195
(i) to inspect not less than twice a year, all premises licensed for manufacture of
Ayurvedic (including Siddha) or Unani drugs within the area allotted to him and to satisfy
himself that the conditions of the licence and the provisions of the Act and the rules made
thereunder are being observed;
(ii) to send forthwith to the controlling authority after each inspection a detailed
report indicating whether or not the conditions of the licence and the provisions of the Act
and the rules made thereunder are being observed;
(iii) to take samples of the drugs manufactured on the premises and send them for test
or analysis in accordance with these rules;
(iv) to institute prosecutions in respect of violation of the Act and the Rules made
thereunder.
1
[162A. Qualifications of the State Drug Licensing Authority for Licensing
of Ayurvdeda , Siddha and Unani drugs− (a) The Ayurvedic/ Siddha/ Unani qualifications
as per Schedule II of the Indian Medicine Central Council Act, 1970 (84 of 1970)/ B Pharma
(Ayurveda) of a recognized University.
(b) At least 5 years experience in the Ayurveda/ Siddha/ Unani drug manufacturing or
testing of Ayurvedic, Siddha and Unani drugs or enforcement of provisions of Chapter IVA
of the Drugs and Cosmetics Act,1940 and Rules made thereunder or teaching/ research on
clinical practice of Ayurveda/ Siddha/ Unani System.]
163. Procedure for despatch of sample to Government Analyst and its receipt by the
Government Analyst—(1) Sample for test or analysis shall be sent to the Government Analyst
by registered post or by hand in a sealed package, enclosed together with a memorandum in
Form 18-A in an outer cover addressed to the Government Analyst.
(2) The package as well as the outer cover shall be marked with a distinguishing number.
(3) A copy of the memorandum and a specimen impression of the seal used to seal the
package shall be sent by registered post or by hand to the Government Analyst.
(4) On receipt of the package from an Inspector, the Government Analyst or an Officer
authorised by him in writing in this behalf shall open the package and shall also record the
conditions of the seals on the package.
(5) After the test or analysis has been completed, one copy of the results of the test or
analysis shall be supplied forthwith to the sender in Form 13-A. A copy of the result in
Form 13A shall also be sent simultaneously to the Controlling Authority and to the Drugs
Controller, India.
2
[PHARMACOPOEIAL LABORATORY FOR INDIAN MEDICINES TO FUNCTION
AS CENTRAL DRUGS LABORATORY FOR THE PURPOSE OF TESTING OR
ANALYSIS OF AYURVEDA, SIDDHA AND UNANI DRUGS
163.A Functions - The Pharmacopoeial Laboratory for Indian Medicine at Ghaziabad shall
function as a Central Drugs Laboratory for the purpose of testing or analysis of Ayurveda,
Siddha and Unani Drugs.
Its functions shall be:-
(1) to develop Pharmacopoeial standards and draft monographs and amendments
alongwith standardized methods for the Ayurvedic, Siddha, Unani drugs;
(2) to act as Central Appellate Drug Laboratory for testing of Ayurveda, Siddha and
Unani drugs,
(3) to analyse or test such samples of Ayurvedic, Siddha, Unani drugs as may be sent
to it under sub-section (2) of section 11, or under sub-section (4) or section 25, of the Act;
(4) to maintain reference museum and herbarium for the drugs used in Ayurveda,
Siddha and Unani (ASU) system.
(5) to run a training centre for quality control methods in the Ayurveda, Siddha or
Unani systems of medicines;
(6) to carry out such other duties as may be entrusted to it by the Government of India.
1. Ins. by G.S.R. 76 (E), dt. 3.2.2003.
2. Ins. by G.S.R. 352 (E), dt. 1.6.2006.
Drugs and Cosmetics Rules 1945
196
163B. The functions of the Central Drug Laboratory in respect of Ayurvedic, Siddha and Unani
drugs shall be carried out at the Pharmacopoeial Laboratory for Ayurvedic, Siddha and Unani
medicine, Ghaziabad, (Uttar Pradesh) and the functions of the Director in respect of the said drugs
shall be exercised by the Director of the said laboratory.
163C. Despatch of samples for test or analysis - (1) Samples for testing or analysis of Ayurveda,
Siddha and Unani drugs under Sub-section (2) of Section 11 or sub-section (1) of section 25 and
section 33-H of the Act shall be sent by registered post in a sealed packet, enclosed with a
memorandum in Form 1 A, specified in Schedule A, in an outer cover addressed to the Director,
Pharmacopoeial Laboratory for Indian Medicine.
(2) The packet as well as the outer cover, shall be marked with a distinguished number.
(3) A copy of the memorandum in Form 1A and a specimen impression of the seal used to seal the
packet shall be sent separately by registered post to the Director, Pharmacopoeial Laboratory for
Indian Medicine.
163D. Recording of condition of seals - On receipt of the packet, it shall be opened by an officer
authorized in writing on that behalf by the Director, Pharmacopoeial laboratory for Indian
Medicine, who shall record the condition of the seal on the packet.
163E. Report of result of test or analysis - After test or analysis, the result of the test or analysis,
together with full protocols of the tests applied, shall be supplied forthwith to the sender in Form
2A of as specified in the said schedule.
163F. Fees - The fees for test and analysis shall be as specified in Schedule B-1
163G. Signature on certificates - Certificates issued under these rules by the Pharmacopoeial
Laboratory for Indian Medicine, shall be signed by the Director or by an officer authorized by the
Central Government to sign such certificates.
164. Method of test or analysis to be employed in relation to Ayurvedic (including
Siddha) or Unani drugs.—The method of test or analysis to be employed in relation to an
Ayurvedic (including Siddha) or Unani drug shall be such as may be specified in the
Ayurvedic (including Siddha) or Unani Pharmacopoeia, or if no such pharmacopoeias are
available or if no tests are specified in such pharmacopoeias, such tests as the Government
Analyst may employ, such tests being scientifically established to determine whether the drug
contains the ingredients as stated on the label.
165. Qualifications of Government Analyst. —A person who is appointed a Government
Analyst under section 33 F of the Act shall be a person possessing the qualifications
prescribed in rule 44 or a degree in Ayurveda, Siddha or Unani System, as the case may be,
conferred by a University, a State Government or Statutory Faculties, Councils and Boards of
Indian Systems of Medicine recognized by the Central or State Government, as the case may
be, for this purpose and has had not less than three years‘ post graduate experience in the
analysis of drugs in a laboratory under the control of (i) a Government Analyst appointed
under the Act, or (ii) a Chemical Examiner to Government, or (iii) the Head of an institution
specially approved for the purpose by the appointing authority.
166. Duties of Government Analyst– (1) The Government Analyst shall analyze or test or
cause to be analyzed or tested such samples of Ayurvedic (including Siddha) or Unani drugs
as may be sent to him by Inspectors or any other persons or authority authorised by the
Central Government or State Government under the provisions of Chapter IV A of the Act
and shall furnish reports of the results of test or analysis in accordance with these rules.
Drugs and Cosmetics Rules 1945
197
(2) A Government Analyst appointed under section 33F shall from time to time forward
to the Government reports giving the result of analytical work and research with a view to
their publications at the discretion of the Government.]
1
[167. Qualifications of Inspector.–A person who is appointed an Inspector under section
33G shall be a person who—
(a) has the qualifications laid down under rule 49 and shall have undergone
practical training in the manufacture of Ayurvedic (including Siddha) or Unani drug, as
the case may be; or
(b) has a degree in Ayurvedic or Siddha or Unani System or a degree in Ayurveda
Pharmacy, as the case may be, conferred by a University or State Government or a
Statutory Faculty, Council or Board of Indian Systems of Medicine recognized by the
Central Government or the State Government for this purpose; or
(c) has a diploma in Ayurveda, Siddha or Unani Systems, as the case may be, granted
by a State Government or an Institution recognized by the Central Government or a State
Government for this purpose.
2
[PART
XIX
STANDARDS OF AYURVEDIC, SIDDHA AND UNANI
DRUGS
168. Standards to be complied with in manufacture for sale or for distribution of
Ayurvedic, Siddha and Unani Drugs.-
Class of Drugs Standards to be complied
with
1.
3
[* * *] drugs included in
Ayurvedic Pharmacopoeia.
2. Asavas and Arishtas
The standards for identity, purity and strength as
given in the editions of Ayurvedic
Pharmacopoeia of India for the time being in
force.
The upper limit of alcohol as self generated
alcohol should not exceed 12% v/v excepting
those that are otherwise notified by the Central
Government from time to time.]
1. Amended by G.S.R. 376 (E), dt. 20.7.1978.
2. Ins. by G.S.R. 519(E), dt. 26.6.1995.
3.The word ―Single‖ omitted by G.S.R. 422(E), dt. 11.6.2002.
Drugs and Cosmetics Rules 1945
198
1
[169. Permitted Excipients.- Permitted Excipients along with their standards i.e. additives,
preservatives, antioxidants, flavouring agents, chelating agents etc. permitted in the Indian
Pharmacopoeia (IP), Prevention of Food Adulteration Act, 1954 and Bureau of Indian Standard
Act, 1986 are permitted for use in Ayurveda, Siddha and Unani drugs with the following
conditions, namely:-
1. The above excipients shall be used in the permissible limits as prescribed in the Indian
Pharmacopoeia/ Prevention of Food Adulteration Act, 1954/ Food Product Order/ Bureau of
Indian Standard Act, 1986 and they shall comply with the respective quality specifications,
not exceeding any specified limits of usage therein, and except Hydrogenated vegetable oil.
2. Only Natural coloring agents as permitted under rule 26 of Prevention of Food Adulteration
Rules, 1955 will be used for Ayurveda, Siddha and Unani drugs and additionally, colors
permitted under Rule 127 of the Drugs and Cosmetics Rules, 1945 shall be used for
Proprietary Ayurveda, Siddha and Unani drugs as defined in subclause (i) of clause (h) of
section 3 of Drugs and Cosmetics Act, 1940, not exceeding any specified limits of usage
therein.
3. Preservatives and Coloring agents shall be mentioned on the label for the information of the
consumer as required under rule 161 of the Drugs and Cosmetics Rules, 1945.
4. Additives used in various processes and in formulating dosage forms shall be mentioned
clearly with quantities used, in the application for licenses and the record for the same shall
be maintained by the manufacturers.
5. Manufacturers shall be responsible to ensure rationality, safety and quantity used of various
excipients in the formulation.
6. If any excipients or additive or preservative etc. referred in Indian Pharmacopoeia/
Prevention of Food Adulteration Act, 1954/ Food Product Order/ Bureau of Indian Standard
Act, 1986 is deleted at a particular point of time, this will also be deleted simultaneously for
the use in Ayurveda, Siddha and Unani drugs.
7. Following artificial sweeteners as per maximum limit indicated below may be used in
various dosage forms of Ayurveda, Siddha, Unani Proprietary Medicines:-
Artificial sweeteners may be used only in proprietary ASU products and the label of such
products should carry a statutory warning stating the name and quantity of the artificial sweetener
used.
The recommended Acceptable Daily Intake (ADI) of these sweeteners as laid down by US
FDA is as follows:
Sr. No. Sucralose Aspartame Saccharin Acesulfame K
1 5 mg/kg body 40 mg/kg body 5 mg/kg body 15 mg/kg body weight weight
weight weight
One third of the above ADI would be permissible for use in Ayurveda, Siddha, Unani Patent
and Proprietary Drugs.
8. Any previous notification issued by the Department of AYUSH regarding use of excipients
/ additives or preservatives in Ayurveda, Siddha and Unani medicines stands superseded.]
1. Subs. by G.S.R. 755 (E), dt. 23.10.2008. Earlier ins. by G.S.R. 285 (E), dt. 11.5.2005.
Drugs and Cosmetics Rules 1945
199
SCHEDULE A
FORM
1
(See rule
4)
Memorandum to the Central Drugs
Laboratory
Serial
Number
..................................
To the Director, Central Drugs
L
a
boratory
......................................................
From......................................
I send herewith, under the provisions of section 25 (4) of the Drugs and Cosmetics
Act,
1940, sample(s) of a drug purporting to be ....................for test or analysis and request that a
report of the result of the test or analysis may be supplied to this Court.
(2) The distinguishing number on the packet
is
............................................
(3) Particulars of offence
alleged
...................................................................
(4) Matter on which opinion is required .......................................
(5) A fee of Rs
.................
has been deposited in Court.
Date
....................
…….............
Magistra
te
1
[FORM
1
(See rule 163C
)
Memorandum to the Pharmacopoeial
Laboratory for Indian Medicine (PLIM)
From ..................................
(Full name, Designation and Postal address of the sender)
Serial No......................................
To the Director,
Pharmacopoeial Laboratory for Indian Medicine,
I send herewith, under the provisions of section 11(2)/section 25(4) and section 33H
of the Drugs and Cosmetics
Act,
1940, sample(s) of a drug purporting to be ....................for
test or analysis and request that a report of the result of the test or analysis may be
supplied to this Court.
(2) The distinguishing number on the packet
is
............................................
(3) Particulars of offence alleged ...................................................................
(4) Matter on which opinion is required .......................................
(5) A fee of Rs
.................
has been deposited in Court.
Date
.................... ……….
….............
Magistra
te/Authorized Signatory]
1. Ins. by G.S.R. 352(E) , dt. 1.6.2006.
Drugs and Cosmetics Rules 1945
200
FORM
2
(See rule
6)
Certificate of test or analysis by the Central Drugs
Laboratory
Certified that the sample bearing
numb
e
r
.......................................
………………..
purporting to be a
s
a
mp
le of.
..................................................
received
on
.................... with
memorandum No
................................................................
dated.................................... from
...............................................
h
as
b
een te
s
te
d
/ a
n
al
ys
ed a
n
d t
h
at t
h
e
r
e
su
lt of
s
u
ch t e
s
t /
analysis is as stated below.
2. The condition of the seals on the packet on receipt was as follows: —
*3. In the opinion of the undersigned the sample is of standard quality is not of
standard quality as
defined
in the Drugs and Cosmetics Act, 1940 and Rules thereunder for
the reasons given below:–
Director
Date………………
Central Drugs Laboratory or other authorised officer
Details of results of test or analysis with protocols of test applied
Director
Date
..................Central Drugs Laboratory or other authorised officer
* If opinion is required on any other matter, the paragraph should be suitably amended.
1
[FORM
2A
(See rule 163E
)
Certificate of test or analysis from the Pharmacopoeial
Laboratory for Indian Medicine or Governmen Analyst
Certified that the sample bearing
numb
e
r
.......................................
………………..
purporting to be a
s
a
mp
le of.
..................................................
received
on
.................... with
memorandum No
................................................................
dated.................................... from
...............................................
h
as
b
een te
s
te
d
/ a
n
al
ys
ed a
n
d t
h
at t
h
e
r
e
su
lt of
s
u
ch t e
s
t /
analysis is as stated below.
2. The condition of the seals on the packet on receipt was as follows: —
*3. In the opinion of the undersigned the sample is of standard quality as
defined
in the
Drugs and Cosmetics Act, 1940 and Rules thereunder for the reasons given below.
Or
In the opinion of the undersigned the sample is not of standard quality as
defined
in the
Drugs and Cosmetics Act, 1940 and Rules thereunder for the reasons given below.
―Note: *delete whichever is not applicable.‖
(Signature of the Analyst Person-in-Charge of testing)
Date…………….
Place…………….
Name & Designation and Seal…………….
Name and Address of the laboratory ……………]
1. Ins. by G.S.R. 352(E) , dt. 1.6.2006.
Drugs and Cosmetics Rules 1945
201
1
FORMS 3-7
(
Omitted
)
2
[FORM
8
(See rule
24)
Application for licence to import drugs (excluding those specified in Schedule X) to the
Drugs
and Cosmetics Rules,
1945
I/We* ......................................................... (full address with telephone number, fax
number and e-mail address) hereby apply for a licence to import drugs specified below
manufactured by M/s
...........................................
(full address with telephone no, fax and
e- mail no.).
2. Names of the drugs to be imported:
(1)
(2)
(3)
3. I/We* ..................................................... enclose herewith an undertaking in Form
9
dated …………signed by the manufacturer as required by rule 24 of the Drugs and
Cosmetics
Rules, 1945.
4. I/We* ................................................... enclose herewith a copy of Registration
Certificate concerning the drugs to be imported in India, issued under Form 41 of the rules,
vide Registration Certificate No .....................dated .................. issued through M/s.
.............................
(name and full
address)
................................valid up
to
................................
5
I/W
e
*
.................................................... hold a valid wholesale licence for sale or
distribution of drugs or valid licence to manufacture drugs, under the provisions of the Act and
rules made thereunder. A copy of the said licence is enclosed.
6. A fee of ..................has been credited to Government under the Head of Account "0210-
Medical and Public Health, 04-Public Health, 104-Fees and Fines" under the Drugs and
Cosmetics Rules, 1945 - Central vide Challan No .........................
dated
................(attached in
original)
Place: ......
Date: ...........
*Delete whichever is not applicable.]
Signature
.......................
Name..............................
Designation
...................
Seal/Stamp of Manufacturer's agent in India.
1. Forms 3 to 7 omitted by Notfn. No. F. 1-16/57-D, dt. 15-6-1957.
2. Subs. by G.S.R. 604(E) , dt. 24.8.2001.
Drugs and Cosmetics Rules 1945
202
1
[FORM
8A
(See rule
24)
Application for licence to import drugs specified in Schedule X to the Drugs and
Cosmetics
Rules,
1945
I/We*
...............................
(full address with telephone number, fax number and e-mail
address) hereby apply for a licence to import drugs specified below manufactured
by
M/s ....................................... (full address with telephone no, fax and e-mail no.).
2. Name of the drugs to be imported:
(1)
(2)
(3)
3. I/We*
........................................
enclose herewith an undertaking in Form 9
dated……………si
gn
ed
b
y t
h
e
m
a
nuf
act
ur
er a s
r
e
qu
i
r
ed
b
y
ru
le
2
4
o
f t
h
e
Drug
s a
n
d
Cosmetics Rules, 1945.
4. I/We*
...........................................
enclose herewith a copy of Registration Certificate
concerning the drugs to be imported in India, issued under Form 41 of the rules, vide
Registration Certificate No dated issued through M/s.
................................................
(name and full address)
............................
……………
valid upto………………………………
5. I/We* ............................. hold a valid wholesale licence for sale or distribution of drug or
licence to manufacture drugs, under the provisions of the Act and rules made thereunder.
A copy of the said licence is enclosed.
6. A fee of
..........................
has been credited to Government under the Head of Account
"0210 - Medical and Public Health, 04- Public Health, 104- Fees and Fines" under the
Drugs and Cosmetics Rules 1945 - Central vide Challan
No
....................... dated .................
(attached in original).
Place: ......
Date: ...........
*Delete whichever is not applicable.
Signature .................................
Nam
e
.....................................
Designation .............................
Seal/Stamp of Manufacturer's agent in
India.]
1. Subs. by G.S.R. 604(E), dt.24.8.2001.
Drugs and Cosmetics Rules 1945
203
FORM
9
(See rule
24)
Form of undertaking to accompany an application for an import licence
Whereas .............................. of............................. intends to apply for a licence under
the
Drugs and Cosmetics Rules, 1945, for the import into India, of the drugs specified below
manufactured by us, we……………………………of…………………………..hereby give
this undertaking that for the duration of the said licence—
(1) the said applicant shall be our agent for the import of drugs into India;
(2) we shall comply with the conditions imposed on a licence by
1
[rules 74 and 78] of
the Drugs and Cosmetics Rules, 1945;
(3)we declare that we are carrying on the manufacture of the drugs mentioned in
this undertaking at the premises specified below, and we shall from time to time report any
change of premises on which manufacture will be carried on and in cases where
manufacture is carried on in more than one factory any change in the distribution of
functions between the factories;
(4) we shall comply with the provisions of Part IX of the Drugs and Cosmetics Rules,
1945;
(5) every drug manufactured by us for import under licence into India shall as
regards strength, quality and purity conform with the provisions of Chapter III of the Drugs
and Cosmetics Act, 1940, and the Drugs and Cosmetics Rules, 1945;
(6) we shall comply with such further requirements, if any, as may be specified by
Rules, by the Central Government under the Act and of which the licensing authority has
given to the licensee not less than four months' notice.
Names of drugs and classes of drugs
Particulars of premises where manufacture is carried on.
Date.......................
2
[Signature, Name, Designation Seal/Stamp
of manufacturer or on behalf of the manufacturer.]
1. Subs. by. G.S.R. 462(E), dt. 22.6.1982.
2. Subs. by G.S.R. 604(E), dt. 24.8.2001
Drugs and Cosmetics Rules 1945
204
.
1
[FORM
10
(See rules 23 and
27)
Licence to import drugs (excluding those specified in Schedule X) to the Drugs
and
Cosmetic Rules,
1945
Licence
Numb
e
r
..............
Dat
e
...
…………..
1. ........................................................................................
(Name and full address of the
i
mpor
te
r)
i
s
hereby licensed to import into India during the period for which the licence is in
force, the drugs specified below, manufactured by
M
/
s
..................................................
(name and full address) and any other drugs manufactured by the said manufacturer as may
from time to time be endorsed on this licence.
2. This licence shall be in force from ........................... to ............. unless it is sooner
suspended or cancelled under the said rules.
3. Names of drugs to be imported.
Place : ……….
Date : ………. Licensing Authority
Seal/S
t
amp
Conditions of
Licence.
1. A photocopy of licence shall be displayed in a prominent place in a part of the
premises, and the original licence shall be produced, whenever required.
2. Each batch of drug imported into India shall be accompanied with a detailed batch
test report and a batch release certificate, duly signed and authenticated by the
manufacturer with date of testing, date of release and the date of forwarding such
reports. The imported batch of each drug shall be subjected to examination and
testing as the licensing authority deems fit prior to its marketing.
3. The licensee shall be responsible for the business activities of the manufacturer
in
India along with the registration holder and his authorised agent.
4. The licensee shall inform the licensing authority forthwith in writing in the event
of
any change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be deemed
to be valid for a maximum period of three months from the date on which the change
takes place unless, in the meantime, a fresh licence has been taken from the licensing
authority in the name of the firm with the changed constitution.]
1. Subs. by G.S.R. 604(E) ,dt. 24.8.2001.
Drugs and Cosmetics Rules 1945
205
1
[FORM
10A
(See rules 23 and
27)
Licence to import drugs specified in Schedule X to the Drugs and Cosmetics Rules,
1945
Licence
Number
............................. Date…………………….
...............................................................................................................(Name
and full address of
the importer) is hereby licensed to import into India during the period for which the licence is
in force, the drugs specified below, manufactured by M/s ...................................... (name and
full address) and any other drugs manufactured by the said manufacturer as may from time to
time be endorsed on this licence.
2. This licence shall be in force
from
............................. to
..........................
unless it is
sooner suspended or cancelled under the said rules.
3. Names of drugs to be imported.
Place:......................
Date: .....................
*Delete whichever is not applicable.
Licensing Authority
Seal/Stamp.
Conditions of
Licen
ce
1. A photocopy of licence shall be displayed in a prominent place in a part of the
premises, and the original licence shall be produced, whenever required.
2. Each batch of drug imported into India shall be accompanied with a detailed batch
test report and a batch release certificate, duly signed and authenticated by the
manufacturer with date of testing, date of release and the date of forwarding such
reports. The imported batch of each drug shall be subjected to examination and
testing as the licensing authority deems fit prior to its marketing.
3. The licensee shall be responsible for the business activities of the manufacturer
in
India along with the registration holder and his authorised agent.
4. The licensee shall inform the licensing authority forthwith in writing in the event of
any change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be deemed
to be valid for a maximum period of three months from the date on which the change
takes place unless, in the meantime, a fresh licence has been taken from the licensing
authority in the name of the firm with the changed constitution.]
1. Subs. by G.S.R. 604(E), dt. 24.8.2001.
Drugs and Cosmetics Rules 1945
206
FORM
11
(See rule
33)
Licence to import drugs for the purposes of examination, test or
analysis
1
………………of
.......................... is hereby licensed to import
from
................................
the
drugs specified below for the purposes of examination, test or analysis at
...............................or in such other places as the licensing authority may from time to time
authorise.
2. This licence is subject to the conditions prescribed in the Rules under the Drugs a
nd
Cosmetics Act, 1940.
3. This licence shall, unless previously suspended or revoked, be in force for a period of
one year from the date specified below:–
Name of drugs
Quantities which may be imported
Date............................. Licensing
Au
t
hor
ity
Seal/Stamp
1
[FORM
1
1
A
(See rule
33A)
Licence to import drugs by a Government Hospital or Autonomous Medical Institution for
t
h
e treatment of
patients
Licence No ……………. Date……………….
Dr.
...........................................................
……………………………………………Designation
…………………………………………………………………………………………………..of
…………………………………………………………………………………………………….
(Name of College/Hospital/Autonomous
Institution)
is hereby licenced to import from M/s ..............................(name and full address) the drugs
specified below for the purpose of treatment of patients for the disease (name of the disease)
.................... at ............................. or in such other places as the licensing authority may from
time to time authorise.
2. This licence shall, unless previously suspended or revoked, be in force for a period of
one year from the date of issue specified above.
3. Names of drugs to be imported:
Name of drugs
Quantities which may be imported
Place : ............
Date :.............
Conditions of Licence
Licensing Authority
Seal / Stamp
1. The licence shall be displayed in the Office of the Medical Superintendent of
Government Hospital / Head of Institution of Autonomous Medical Institution.
2. The licensee shall store the drugs imported under this licence under proper
storage conditions.
3. The drugs imported under this licence shall be exclusively used for the treatment
of patients, and a record shall be maintained in this regard, by a registered pharmacist
giving the full name(s) and address(es) of the patients, diagnosis, dosage schedule, total
quantity of drugs imported and issued, and shall be countersigned by the Medical
Superintendent of the Government Hospital or Head of the Autonomous Medical
Institution which shall be produced, on demand by an Inspector appointed under the Act.]
___________________________________________________________________________
1. Subs. by G.S.R.. 604(E), dt. 24.8.2001.
Drugs and Cosmetics Rules 1945
207
FORM
12
(See rule
34)
Application for licence to import drugs for purpose of examination, test or
analysis
I,… …………………………………resident of ………………………………. by
occupation………………. hereby apply for a licence to import the drugs specified below for
the purposes of examination, test or analysis at
..............................
from ..........................and
I undertake to comply with the conditions applicable to the licence.
1
[A fee of
rupees
...................... has been credited to Government under the head of
Account ―0210-Medical and Public Health, 04-Public Health, 104-Fees and Fines‖ under the
Drugs and Cosmetics Rules, 1945—Central vide Challan No…….dated………(attached in
original).]
Name of drugs
Quantities which may be imported
Place……..
Date……… Licensing Authority
1. Subs. by G.S.R. .604(E), dt. 24.8.2001.
1
[FORM
12A
(See rule 36, Second
Proviso)
Application for the issue of a permit to import small quantities of drugs for personal
use
I,
.........................................
resident of ..............................................................by
occupation.................................................
hereby apply for a permit to import the drugs
specified below for personal use from ....................................................................
I attach a prescription from a registered medical practitioner in regard to the need for the
said drugs.
Name of drugs
Quantities which may be imported
Date............................... Signature...........................
1. Added by Notifn No. F.1-36/54-DS, dt: 3.3.1955.
Drugs and Cosmetics Rules 1945
208
1
[FORM
12AA
(See rule
34A)
Application for licence to import small quantities of new drugs by a Government Hospital
or
Autonomous Medical Institution for the treatment of
patients.
I,
..................
…………… (name and designation)
...............................
……………..
of ………………………………… (name of the Hospital/Autonomous Medical Institution)
hereby apply for a licence to import small quantities of new drugs specified below for the
purpose of treatment of patients for the disease ..................................................... (name of the
disease)…… … ………… at……………………………….(name and place of the
hosp
ital
)
and I undertake to comply with the conditions applicable to the licence and other provisions
of the Drugs and Cosmetics Act, 1940 and the rules made thereunder, from time to time.
1. A fee of rupees ............. has been credited to Government under the Head of
Account "0210-Medical and Public Health, 04- Medical and Public Health, 104- Fees
and Fines" under the Drugs and Cosmetics Rules, 1945 - Central vide Challan
No……………..dated
...................... (attached in original).
2. Name of new drugs to be imported:
Name of drugs
Quantities which may be imported
Place: ……….. Signature……………………..
Date: ……….. Name…………………………
Seal/Stamp………………….
Cert
ific
at
e
Certified that the drugs specified above for import are urgently required for the
treatment of patients suffering from and that the said drug(s) is/are not available in India.
Place………….. Signature
...............
……..
Date ................. Medical Superintendent of the Government Hospital / Head of
Autonomous Medical
Inst
it
ution
Seal /
Stamp.]
1. Subs. by. G.S.R. 604(E), dt. 24.8.2001.
Drugs and Cosmetics Rules 1945
209
1
[FORM
12B
(See rule 36, Second
Proviso)
Permit for the import of small quantities of drugs for personal
us
e
…………………………of
...............................................
is hereby permitted to
import
from.........................................
the drugs specified below for personal use.
2. This permit is subject to the conditions prescribed in the Rules under the Drugs and
Cosmetics Act, 1940.
3. This permit shall, unless previously suspended or revoked, be in force for a period of
six months from date specified below.
Name of drugs
Quantities which may be imported
Date…………….. Licensing Authority]
FORM
13
(See rule
46)
Certificate of test or analysis by Government Analyst under section 25 (1) of the Drugs
and
Cosmetics Act,
1940
1. Name of Inspector from whom received ................................
2. Serial No. and date of Inspector's memorandum............................
3. Number of sample ...................................................
4. Date of receipt ....................................
5. Name of drugs purporting to be contained in the sample ..........................
6. Condition of seals on the
2
[packet or on portion of sample or container] ..........................
7. Result of test or analysis with protocols of test or analysis
applied
.............................
In the opinion of the undersigned the sample referred to
abov
e (is of standard/is not of standard) quality as defined in the Drugs and
Cosmetics Act, 1940 and Rules thereunder for the reasons given below.
for the reasons given below:-
Date................... Government Analyst.
1. Subs. by. G.S.R. 753(E), dt. 4.11.1999.
2. Subs. by G.S.R. 59(E), dt. 7.2.1995.
Drugs and Cosmetics Rules 1945
210
1
[FORM
13A
[See rule 163
(5)]
Certificates of tests or analysis by Government Analyst under section 33H of the Drugs
and
Cosmetics Act,
1940
1. Names of Inspector from whom received ...................................................
2. Serial No. and date of Inspector's
memor
a
ndum
...........................................
3. Number of sample.........................................................................................
4. Date of receipt .................................................................
5. Names of ingredients purporting to have been used in the preparation of the sample…..
6. Condition of seals on the
packag
e ......................................................................
7. Results of test or analysis ……………………………………………………..
2
[In the opinion of the undersigned the sample referred to above is of standard/is not of standard
quality as defined in the Drugs and Cosmetics Act, 1940 and the rules made thereunder for the
reasons given below]
Date................... Government Analyst..]
FORM
14A
(See rule
47)
Application from a purchaser for test or analysis of a drug under Section 26 of the Drugs
and
Cosmetics Act,
1940
1. Full name and address of the
applicant
....................................................................
2. Occupation................................................................
3. Name of drug purporting to be contained in the
samp
le ..........................................
4. Name and full address of the pharmacy or concern where the drug was
purchased…………….
5. Date on which purchased..............................................................................
6. Reasons why the drug is being submitted for test or analysis………………………….
3
[7. A fee of rupees
............................................................
vide Schedule B of the Drugs and
Cosmetics Rules, 1945, has been credited to Government under the head of account "080—
Medical—Miscellan e
ou
s—Fees
und
er
th
e
Drug
s and
Co
smetics
Ru
les,
194
5—
Central/State"—vide treasury receipt attached.]
I hereby declare that the drug being submitted for test was purchased by or for me. I
further declare that the sample of the drug being sent for test or analysis is exactly as it was
purchased and has not been tampered with in any way to reduce its potency.
Date..............................
Signed....
…….
1. Added by Notfn. No. F 1-23/67-D (S.O. 642), dt. 2.2.1970.
2. Ins. By G.S.R. 376(E), dt: 3..5.2010.
3. Added by Notfn. No. F. 1-3/51-D.S., dt. 15-10-1954
Drugs and Cosmetics Rules 1945
211
FORM
14-B
(See rule
47)
Certificate of test or analysis by Government Analyst under Section 26 of the Drugs
and
Cosmetics Act,
1940
1. Name of person from whom sample
rec
e
ived
.............................................
2. Date of receipt ..........................................................................................
3. Name of drug purporting to be contained in the
samp
le .....................................
4. Opinion of the Government Analyst—The sample referred to above is/is not of
standard quality as defined in the Drugs and Cosmetics Act, 1940 and Rules thereunder.
Date................... Government Analyst………….
1
[FORM
15
(See rules 54 and
145C)
Order under section 22 (1)(c) of the Drugs and Cosmetics Act, 1940 requiring a person not
to
dispose of stock in his
possession
Whereas, I have reasons to believe that the stocks of drugs/cosmetics in your
possession, detailed below contravene the provisions of section 18 of the Drugs and Cosmetics
Act, 1940;
Now, therefore, I hereby require you under clause (c) of sub-section (1) of section 22 of
the said Act not to dispose of the said stock for a period
of
..................
days from the date of this
order.
Date..................... Inspector……………
Details of stock of drugs/ cosmetics
Date........................... Inspector...................]
2
[FORM
16
(See rules 55 and
145-B)
Receipt for stock of drugs or cosmetics for record, register, document or material object
s
ei
z
e
d
under section 22 (1) (c) or (cc) of the Drugs and Cosmetics Act,
1940.
The stock of drugs or cosmetics for records, registers, documents or material objects
detailed below has / have this day been seized by me under the provisions of clause (c) or
clause (cc) of sub-section (1) of section 22 of the Drugs and Cosmetics Act. 1940 (23 of 1940)
from the premises of
............................................
situated at............................................
Date.........................
Inspector.
.......................
Details of drugs, cosmetics, records, registers, documents or material objects
seized.
Date...........................
Inspector.
..........................]
1. Subs. by G.S.R. 1594, dt. 28.10.1976.
2. Subs. by. G.S.R. 926 , dt. 24-6-1977.
Drugs and Cosmetics Rules 1945
212
1
[FORM
17
(See rules 56 and
145A)
Intimation to person from whom sample is taken
I have this day taken from the premises of ………………………….situated
at............................................ samples of the drugs / cosmetics specified below for the purpose of
test or analysis.
Date.........................
Inspector.
.......................
Details of samples
taken
Date.........................
Inspector.
................]
2
[FORM
17A
(See rules 56A and
145AA)
Receipt for samples of drugs or cosmetics taken where fair price tendered thereof under
sub-
section (I) of Section 23 of the Drugs and Cosmetics Act, 1940 is
refused
To
...................................
Whereas I, this............... day of .........
3
[20]
...........,
have taken from the premises
of…….. situated at................................ samples of drugs/cosmetics as specified below:-
Details of Samples…………………………
And whereas I had offered to pay you
rup
ee
s
...................... as the fair price of the
samples of drugs/cosmetics taken:
And whereas, you have refused to accept the fair price tendered thereof.
Now, therefore, I give you the receipt as the fair price tendered for the samples of the
drugs/cosmetics taken by me.
Date: ..................... Inspector ….. …..]
______________________________________________________________________________________________________________________
1. Subs. by S.O. 2139, dt. 5.6.1972.
2. Ins. by G.S.R. 292(E) , dt. 29.5.1997.
3. Subs. by G.S.R. 592(E) , dt. 13.8.2008.
Drugs and Cosmetics Rules 1945
213
FORM
18
(See Rule
57)
Memorandum to Government
Ana
l
yst
Serial No. of
M
e
mor
a
ndum
...................................................................................
From:
To
The Government Analyst
…………………………
…………………………
The portion of sample / container described below is sent herewith for test or analysis
under the provisions of clause (i) of sub-section (4) of Section 23 of the Drugs and Cosmetics
Act, 1940.
The portion of sample/container has been marked by me with the following mark.
Details of portion of sample or container with
1
[name of drug/cosmetic] which it
purports to contain—
Date.....................
Inspector.
....................
2
[FORM
18A
(See Rule 163 (1)
)
Memorandum to Government
Ana
l
yst
Serial No……..
From
To
The Government Analyst
…………………………
…………………………
The portion of sample / container described below is sent herewith for test or analysis
under the provisions of Section 33H of the Drugs and Cosmetics Act, 1940.
The portion of sample / container has been marked by me with the following mark.
Details of portion of sample or container with name of ingredients from which it is
claimed to be made.
Date.........................
Inspector.
.........................
1. Subs. by G.S.R. 370(E), dt. 7.4.1994.
2. Added by Notfn. No. F 1-23/67-D, dt. 2-2-1970.
Drugs and Cosmetics Rules 1945
214
1
[FORM
19
[See rule 59
(2)]
Application for grant or renewal of a
2
[licence to sell, stock or exhibit or offer for sale,
or
distribute] of drugs other than those specified in
Schedule
1 . I /
W
e
*
...................................hereby apply for licence to sell by wholsesale/retail
drugs
specified in Schedules C and C(1) excluding those specified in Schedule X *and/or drugs
other than those specified in Schedules C, C(1) and X to the Drugs and Cosmetics Rules, 1945
*and also to operate a pharmacy on the premises situated at........................................................
2. ** The sale and dispensing of drugs will be made under the personal supervision of the
registered pharmacists namely:-
(Name)
..............................................
(Qualification)…………………………………………
(Name)
................................................(Qualification)……………………………………………
3. Categories of drugs to be
sold
....................................................................................
4.
***
Particulars of special storage accommodation .................................................................
5. A fee of
rup
ee
s
.........................................
has been credited to the Government account under
the head of account ......................................
Date........................................ Signature
.........................
]
* Delete whichever is not applicable.
**
To be deleted if drugs will be sold only by wholesale.
***
Required only if products requiring special storage are to be sold.
1. Subs. by G.S.R. 462(E), dt. 22.6.1982.
2. Subs. by G.S.R. 788(E), dt. 10.10.1985.
FORM
19A
[See rule 59
(2)]
Application for the grant or renewal of a restricted
1
[licence to sell, stock or exhibit or offer
for
sale, or distribute] drugs by retail by
2
[***] dealers who do not engage t
h
e
services of a registered
pharmacist
1. I/We
.............................................
of.
..................................................hereby
apply for a licence to sell by retail
(i)
3
[Drugs other than those specified in Schedule C,
C1
and X] on the premises situated
at……/
2
[***]
or (ii)
4
[Drugs specified in Schedule C(1)] on the premises situated at …………………/
4
[Drugs specified in Schedule C(1)] as vendor in the
area……………………
2. Sales shall be restricted to such drugs as can be sold without the supervision of a
registered pharmacist under the Drugs and Cosmetics Rules.
3. Names or classes of drugs proposed to be
sold
...................................................
*4. Particulars of the storage accommodation for the storage of
5
[Schedule C(1)] on the
premises referred to above.
**5. The drugs for sale will be purchased from the following dealers and such other
dealers as may be endorsed on the licence by the Licensing Authority from time to time.
Name of the
dealers........................................Licence
No....................................
Drugs and Cosmetics Rules 1945
215
6. A fee of rupees
2
[***]/#twenty has been credited to Government under the head of
account................................................................................
Date............................... Signature ........................
*Delete whichever is not required.
**Applies only to an itinerant vendor.
#
Rupees five for itinerant vendors and applicant from a village or town having a population of 5000
or less, and rupees twenty for other restricted licence.
1. Subs. by G.S.R. 788(E) ,dt. 10.10.1985.
2. Omitted by. G. S. R. 231(E) , dt. 4.6.1996.
3. Subs. by G.S.R. 462(E), dt. 22.6.1982.
4. Subs. by.G.S.R. 487(E) , dt. 2.7.1984.
1
[FORM
19AA
(See rule
62C)
Application for grant or renewal of a
2
[licence to sell, stock or exhibit or offer for sale
by
wholesale, or distribute] drugs from a motor ve
hic
le
I
/
W
e * of hereby
apply for
2
[licence to sell, stock or exhibit or offer for sale by wholesale, or distribute]
drugs specified in Schedules C and C (1) and /or drugs other than those specified in Schedules C
and C (1) from the vehicle bearing registration no._ assigned under the Motor
Vehicles Act, 1939.
2.
Categories
of
drugs
to
be
sold
/
d
i
stributed
3. A fee of rupees has been credited to Government under
the
head
of
acc
ount
*4.Particulars of the storage accommodation for the storage of drugs specified in
Schedules C and C (1) on the vehicle referred to above.
Date
Signature
*Delete if not required.
1. Ins. by. G.S.R. 42 (E), dt. 25.1.1979.
2. Subs. by.G.S.R. 788(E), dt. 10.10.1985.
FORM
19B
(See rule
67A)
Application for
1
[licence to sell, stock or exhibit or offer for sale, or
distr
i
bute
]
Homoeopathic
medicin
e
s
1 . I / We*
.......................
of.................................
hereby apply for a licence to sell by
*wholesale/*retail Homoeopathic medicines on the premises situated at .......................................
**2. The sale and dispensing of Homoeopathic medicines shall be made under the
personal supervision of the following competent person in -charge.
Name
..........................
3
. A
f
ee
o
f
rup
e e s ................has been credited to Government under the head of
account.......................................................
Date......................... Signature ......................
*Delete whichever is not required.
** To be deleted if Homoeopathic medicines will be sold by wholesale.
1. Subs. By G.S.R. 788(E), dt.10.10.1985.
Drugs and Cosmetics Rules 1945
216
1
[FORM
19C
[See rule
59(2)]
Application for grant or renewal of a
2
[licence to sell, stock, exhibit or offer for sale,
or
distribute] of drugs specified in Schedule
.
1. I/We* ........................................ of................................hereby apply for a licence to
sell by *wholesale/*retail drugs specified in Schedule X to the Drugs and Cosmetics Rules,
1945. We operate a pharmacy on the premises, situated at ......................
2. ** The sale and dispensing of drugs will be made under the personal supervision of
the registered pharmacists mentioned below:-
(Name)
...............................................
(Qualification)
(Name) ................................................(Qualification)
3. Name of drugs to be sold.
4. *** Particulars of storage accommodation.
5. A fee of rupees
..........................................
has been credited to Government account
under the head of
accoun
t ....................................
D
ate ................ Signature ...........................
* Delete whichever is not applicable.
** To be deleted if drugs will be sold only by wholesale.
***Required only if products requiring special storage are to be sold.]
___________________________________________________________________________
1. Subs. by G.S.R. 462(E), dt. 22.6.1982.
2. Subs. by G.S.R. 788(E), dt. 10.10.1985.
FORM
20
[See rule
61(1)]
1
[Licence to sell, stock or exhibit or offer for sale, or distribute] drugs by retail other than
those
specified in
2
[Schedules C, C(1) and
X
]
1.
................................................
is hereby
1
[licensed to sell, stock or exhibit or offer for
sale, or distribute] by retail drugs other than those specified in
2
[Schedules C, C (1) and
X]
of the Drugs and Cosmetics Rules 1945, *and to operate a pharmacy on the premises
situ
at
ed
at
..........................
subject to the conditions specified below and to provisions of the Drugs and
Cosmetics Act, 1940 and the Rules thereunder.
2 The licence shall be in force
from
........................................
t
o
...........................
3. Name (s) of qualified person (s) in charge ....................................................
4. Categories of drugs..................................................
Name of the dealer…………………….Licence No…………………….
Date.................................... Licensing Authority
.......
……….
* Delete whichever is applicable
Conditions of
Licence
1. This licence shall be displayed in a prominent place in a part of the premises open to
the public.
2. The licensee shall comply with the provisions of the Drugs and Cosmetics Act, 1940 and
the Rules thereunder for the time being in force.
3. The licensee shall report to the Licensing Authority any change in the qualified staff
in charge within one month of such change.
Drugs and Cosmetics Rules 1945
217
4. No drug shall be sold unless such drug is purchased under cash or credit memo from
a duly licensed dealer or a duly licensed manufacturer.
5. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be
deemed to be valid for a maximum period of three months from the date on which
the change takes place unless, in the meantime, a fresh licence has been taken from
the Licensing Authority in the name of the firm with the changed constitution.
_
1. Subs. by G.S.R. 788(E), dt. 10.10.1985
2. Subs. by.G.S.R. 462(E), dt. 22.6.1982
FORM
20A
[See rule 61
(1)]
Restricted
1
[Licence to sell, stock or exhibit or offer for sale, or distribute] drugs by retail
other
than those specified in
2
[Schedules C, C (1) and X] for
3
[***] dealers who do not
engage t
h
e services of a registered
pharmacist
1. ......................................is hereby
1
[licensed to sell, stock or exhibit or offer for sale, or
Distribute] on the premises situated at
3
[***] .......................the following drugs being drugs
other than those specified in
2
[Schedules C, C (1) and X] of the Drugs and Cosmetics Rules,
1945, subject to the conditions specified below and to the provisions of the Drugs
and
Cosmetics Act, 1940 and the Rules made thereunder.
2. The licence shall be in force
from
........................................
t
o
..........................
3 The licensee can deal only in such drugs as can be sold without the supervision of
qualified person under the Drugs and Cosmetics Rules, 1945.
4
[***]
Name of the dealer ........................................
Licence
No
............................
Date.........................
Licensing Authority
Conditions of
Licence
1. This licence shall be displayed in a prominent place in a part of the premises open to
the public
. 3
[***].
2. The licensee shall comply with the provisions of the Drugs and Cosmetics
Act,
1940 and the Rules thereunder for the time being in force.
3. No drug shall be sold unless such drug is purchased under a cash or credit memo
from a duly licensed dealer or a duly licensed manufacturer.
4. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any change in
the constitution of the firm takes place, the current licence shall be deemed to be
valid for a maximum period of three months from the date on which the change
takes place unless, in the meantime, a fresh licence
h
as been taken from the
Licensing Authority in the name of the firm with the changed constitution.
1. Subs. by.G.S.R. 788(E), dt. 10.10.1985
2. Subs. by G.S.R. 462(E), dt. 22.6.1982.
3. Omitted by G.S.R. 231 (E) , dt. 4.6.1996
4 Sl. No. 4 omitted by G.S.R. 504(E) dt. 18.7.2002.
Drugs and Cosmetics Rules 1945
218
FORM
20B
[See rule 61
(1)]
1
[Licence to sell, stock or exhibit or offer for sale, or distribute] by wholesale, drugs other
than
those specified in
2
[Schedules C, C(I) and
X
]
1
...............................................
is hereby
1
[licensed to sell, stock or exhibit or offer for
sale, or distribute] by wholesale drugs other than those specified in
2
[Schedules C, C(1) and X]
on the premises situated at ............... subject to the conditions specified below and to the
provisions of the Drugs and Cosmetics Act, 1940, and the Rules thereunder.
2. The licence shall be in force
from
................................to
...............................
Date............................... Licence No………………
Licensing Authority.
Conditions of
Licence
1. This licence shall be displayed in a prominent place in part of the premises open to
the public.
2. The licensee shall comply with the provisions of the Drugs and Cosmetics
Act,
1940 and the Rules thereunder for the time being in force.
3
[3 (i) No drug shall be sold unless such drug is purchased under a cash or credit
memo from a duly licensed dealer or a duly licensed manufacturer.
(ii) No sale of any drug shall be made to a person not holding the requisite
1
[licence
to sell, stock or exhibit for sale, or distribute] the drug. Provided that this condition
shall not apply to the sale of any drug to—
(a) an officer or authority purchasing on behalf of Government, or
(b) a hospital, medical, educational or research institution or a registered medical
practitioner for the purpose of supply to his patients, or
4
[(c) a manufacturer of beverages, confectionery biscuits and other
non-medicinal products, where such drugs are required for processing these
products.]
5
[***]
5. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any change
in the constitution of the firm takes place, the current licence shall be deemed to be
valid for a maximum period of three months from the date on which the change takes
place unless, in the meantime, a fresh licence has been taken from the Licensing
Authority in the name of the firm with the changed constitution.
1. Subs. by.G.S.R. 788(E), dt. 10.10.1985.
2. Subs. by G.S.R. 462(E) , dt. 22.6.1982.
3. Subs. by Notfn. No. F. 1/63/61-D, dt. 17.7.1963.
4.Ins. by S.O.23, dt:23.12.1969.
5.Clause 4 ommited by S.O. 289, dt:20.12.1992. Earlier clause 4 added by Notfn. F. No. 1-113/69-D, dt. 23.12.1969.
1
[FORM
20BB
(See rule
62-D)
2
[Licence to sell, stock or exhibit or offer for sale by wholesale, or distribute] drugs other
than
those
specified in Schedule C and Schedule C (1) to the Drugs and Cosmetics Rules, 1945
from
a motor
veh
icle
1 . ………… i s h e r e b y
2
[l i c e n s e d to sell, stock or exhibit or offer for sale by
wholesale, or distribute] drugs other than those specified in Schedule C and Schedule
C(1) from the vehicle bearing registration no.____________________ assigned under
under Motor Vehicles Act, 1939, subject to the conditions specified below and to the
Drugs and Cosmetics Rules 1945
219
provisions of the Drugs and Cosmetics Act, 1940 and the Rules made thereunder.
2.
Th
e lic
en
ce
sh
all
b
e
in
forc
e
from
t
o
3. Categories of
drugs
.......................................................
Date:……….. Licence No……………..
Licensing
Authority.
Conditions of
Licence
1. This licence shall be displayed in a prominent place on the vehicle.
2. The licensee shall comply with the provisions of the Drugs and Cosmetics Act, 1940
and the Rules made thereunder for the time being in force.
3 (i) No drugs shall be sold by wholesale or distributed unless such drug is purchased
und
e
r
a cash or credit memo from a duly licensed dealer or a duly licensed manufacturer.
(ii) No sale by wholesale or distribution of any drug shall be made to a person not
holding the requisite
2
[licensed to sell, stock or exhibit or offer for sale by wholesale, or
distribute] the drug:
Provided that this condition shall not apply to the sale of any drug to—
( a) an officer or authority purchasing on behalf of the Government,
or
( b) a hospital, medical, educational or research institution or a registered
medical practitioner for the purpose of supply to his patients, or
(c) a manufacturer of beverages, confectionery, biscuits and other non-medical
products, where such drugs are required for processing these products.
4. The licensee shall inform the Licensing Authority in writing in the event of change in the
constitution of the firm operating under the licence. Where any change in the constitution
of the firm takes place, the current licence shall be deemed to be valid for a maximum
period of three months from the date on which the change takes place unless, in the
meantime, a fresh licence has been taken from the Licensing Authority in the name of the
firm with the changed constitution.
5. The licensee shall inform the Licensing Authority in writing in the event of any change in
ownership of the vehicle specified in this licence within seven days of such change.
_
1. Added by Notfn. No. X. 11013/7/76-D&MS (G.S.R. 42(E)), dt. 25.1.1979.
2. Subs. by G.S.R .788(E), dt.10.10.1985
1
[FORM
20-C
(See rule
67-C)
2
[Licence to sell, stock or exhibit or offer for sale, or distribute]
Homoeopathic
medicines by
retail
1. ……………………is hereby
2
[l i c e n s e d to sell, stock or exhibit or offer for sale
by wholesale, or distribute]by retail Homoeopathic medicines on the
premises situated at ......................subject to the conditions specified below and to the
provisions of the Drugs and Cosmetics Act, 1940 and the Rules made thereunder.
2. The licence shall be in force
from
...............................
to .......................
3. Name of the competent person in-charge.
Date.................................. Licensing Authority
Conditions of
Licence
1. The licence shall be displayed in a prominent place in a part of the premises open to
the public.
2. The licensee shall comply with the provisions applicable to
homo
e
op
at
h
ic
Drugs and Cosmetics Rules 1945
220
medicines under the Drugs and Cosmetics Act, 1940 and the Rules made thereunder
for the time being in force.
3. The licensee shall report to the Licensing Authority any change in the competent
staff within one month of such change.
3
[4. This licence authorises the sale of Homoeopathic medicines made from one earlier potency
up to a quantity of 30 ml at a time.]
4
[5. Where any change in the constitution of the firm takes place, a licensee shall inform the
Licensing Authority in writing about the same and the current licence shall be valid only
for a period of three months from the date on which the change takes place unless, in
the meantime, name of the firm with the changed constitution.]
1. Added by Notfn. No. F. 1-35/64-D (G.S.R. 1185), dt. 18.8.1964.
2
.
Subs. by.G.S.R. 788(E), dt. 10.10.1985.
3. Added by.Notfn. No. F. 1-59/68-D (S.O. 4816), dt. 19.11.1969.
4. Added. G.S.R. 665, dt. 28-5-1977.
1
[FORM
20D
(See rule
67C)
2
[Licence to sell, stock or exhibit or offer for sale, or distribute] Homoeopathic medicines
by
wholesale
1.
..........................................
is hereby
2
[licensed to sell, stock or exhibit or offer for
sale, or distribute] by wholesale Homoeopathic medicines on the premises situated
at..........................................................subject to the conditions specified below and to the
provisions of the Drugs and Cosmetics Act,. 1940 and the Rules made thereunder.
2. The licence shall be in force
from
.............................................to……………………..
Date............................. Licensing Authority.
Conditions of
Licence
1. This licence shall be displayed in a prominent place on the premises.
2. The licensee shall comply with the provisions as applicable to Homoeopathic
medicines under the Drugs and Cosmetics Act, 1940 and the Rules made thereunder
for the time being in force.
3. No sale of any drug shall be made to a person not holding the requisite
2
[l i c e n s e d to
sell, stock or exhibit or offer for sale, or distribute] the drug. Provided that this conditions
hall not apply to the sale of any drug to (a) an authority purchasing on behalf of
Government, or (b) a hospital, medical, educational or research institute or a
Homoeopathic medical practitioner for the purpose of supply to his patients.
3
[4 The licensee shall inform the Licensing Authority in writing in the event of any change in
the constitution of the firm operating under the licence and the current licence shall be valid
only for a period of three months from the date on which the change takes place unless, in
the meantime, a fresh licence has been taken from the Licensing Authority in the name of the
firm with the changed constitution.]
_
1. Added by Notfn. No. F.1-35/64-D, dt. 18.8.1964.
2. Subs. by.G.S.R. 788(E), dt. 10.10.1985.
3. Added by G.S.R. 665, date 28.5.1977.
Drugs and Cosmetics Rules 1945
221
1
[FORM
20E
(See rule 67
EE)
Certificate of renewal of
2
[Licence to sell, stock or exhibit or offer for sale, or
distribute
]
Homoeopathic
medicines
1. Number of licence and date of issue
..................................................………….
Certified that licence no ..... in Form 20C / 20D granted on the
..................... to.................
for sale of Homoeopathic medicines at the premises situated at ...................has been renewed
for a period
from
......... to
.............................
2. Name of competent persons in-charge.
Date........................... Licensing Authority.
1. Added by Notfn. No. F. 1-14/67-D, dt. 3.2.1969.
2. Subs. by G.S.R. 788 (E), dt. 10.10.1985
1
[FORM
20F
[See rule
61(3)]
Licence to sell, stock or exhibit for sale or distribute by retail drugs specified in Schedule
X
1. ………..is hereby licensed to sell, stock or exhibit for sale or distribute by retail
drugs specified in Schedule X to the Drugs and Cosmetics Rules, 1945 on the premises
situated at………………………………………………………..
2. Names of drugs.
3. This licence shall be in force from............
…………….to........
……………
4. Name(s) of registered pharmacist in-charge.
5. The licence is subject to the conditions stated below and the provisions of the
Drugs and Cosmetics Act, 1940 and the Rules made thereunder.
Date:..........................
Licence No………..
Licensing Authority……..
Conditions of Licence
1. This licence shall be displayed in a prominent place in a part of the premises open to the
public.
2. The licensee shall report to the licensing authority any change in the qualified staff
in charge within one month of such change.
3. No drug shall be stocked or sold unless such drug has been purchased under cash/credit
memo from a duly licensed dealer or a duly licensed manufacturer.
4. The licensee shall inform the licensing authority in writing in the event of any change
in the constitution of the firm operating under the licence. Where any change in the
constitution of the firm takes place, the current licence shall be deemed to be valid for a
maximum period of three months from the date on which the change takes place unless
in the meantime, a fresh licence has been taken from the licensing authority in the name
of the firm with the changed constitution.
.
1. Ins. by G.S. R. 462(E) , dt. 22.6.1982 corrected vide corrigendum G.S.R. 373(E) , dt. 2.5.1983.
Drugs and Cosmetics Rules 1945
222
1
[FORM
20G
[See rule
61(3)]
2
[Licence to sell, stock or exhibit or offer for sale, or distribute] by
wholesale
drugs specified in Schedule
X
1. ………………….is hereby
2
[licensed to sell, stock or exhibit or offer for sale, or
distribute] by wholesale drugs specified in Schedule X to the Drugs and Cosmetics Rules,
1945 on the premises situated at……………………………………………………..
2. Names of drugs……………………………………
3. This licence shall be in force
from................. to
.............................
4. The licence is subject to the conditions stated below and the provisions of the
Drugs and Cosmetics Act, 1940 and the Rules made thereunder.
Date:..........................
Licence No………..
Licensing Authority……..
Conditions of license
1. This licence shall be displayed in a prominent place in a part of the premises open to
the public.
2. The licensee shall comply with the provisions of the Drugs and Cosmetics Act, 1940
and the rules made thereunder.
3. No drug shall be stocked or sold unless such drug has been purchased under a cash or
credit memo from a duly licensed dealer or a duly licensed manufacturer.
4. The licensee shall forward to the licensing authority copies of the invoices of sales
made to the retail dealers.
5. No sale of any drug by wholesale shall be made to a person not possessing the requisite
2
[licence to sell, stock or exhibit or offer for sale, or distribute] drugs specified in Schedule
X :
Provided that this condition shall not apply to the sale of any drug to -
(a) an officer or authority purchasing on behalf of Government;
(b) a hospital, medical, educational or research institution, nursing home, Registered
Medical Practitioner for the purpose of supply to its/his patients or manufacturer
holding a licence in Form 25-E or 28-B to manufacture the drugs containing drugs
included in Schedule X.
3
[The licensee shall inform the licensing authority in writing in the event of any change in
the constitution of the firm operating under the licence, where any change in the constitution
of the firm takes place, the current licence shall be deemed to be valid for a maximum period of
three months from the date on which the change takes place unless in the meantime, a fresh
licence has been taken from the licensing authority in the name of the firm with the changed
constitution.]]
________________________________________________________________________
1. Ins. by. G..S. R. 462(E) , dt. 22.6.1982.
2. Ins. by. G.S..R. 788(E) , dt. 10.10.1985.
3. Ins. by 370(E), dt. 7.4.1994.
Drugs and Cosmetics Rules 1945
223
FORM
21
[See rule 61
(2)]
1
[Licence to sell, stock or exhibit or offer for sale,or distribute] by retail drugs specified
in
Schedules C and C (1)
2
[excluding those specified in Schedule
X
]
3
[
1........................................................ is hereby
1
[licensed to sell, stock or exhibit or
offer for sale, or distribute] by retail the following categories of drugs specified in Schedules
C and C (1)
2
[excluding those specified in Schedule X] to the Drugs and Cosmetics Rules,
19454 and to operate a pharmacy on the premises situated at ..................... subject to the
conditions specified below and to the provisions of the Drugs and Cosmetics Act, 1940 and
the Rules thereunder.]
2. The licence shall be in force from ....................to .......................
3. Name(s) of registered pharmacists in charge ...................................
3
[4. Categories of drugs .......................................................................]
Date........................................
Licence
No .......................
Licensing Authority
*Delete if not applicable.
Conditions of License
1. This licence shall be displayed in a prominent place in a part of the premises open
to the public.
2. The licensee shall report to the Licensing Authority any change in the qualified
staff in charge within one month of such change.
4
[***]
4. If the licensee wants to sell, stock or exhibit for sale, or distribute, during the
currency of the licence, additional categories of drugs listed in Schedules C and C(I)
2
[excluding those specified in Schedule X] but not included in this licence, he should
apply to the Licensing Authority for the necessary permission. This licence will be
deemed to extend to the categories of drugs in respect of which such permission is
given. This permission shall be endorsed on the licence by the Licensing Authority.
5
[5. No drug shall be sold unless such drug is purchased under a cash or credit memo
from a duly licensed dealer or a duly licensed manufacturer.]
6. The licensee shall inform the Licensing Authority in writing in the event of any change in
the constitution of the firm operating under the licence. Where any change in the
constitution of the firm takes place, the current licence shall be deemed to be valid for a
maximum period of three months from the date on which the change takes place, unless in
the meantime, a fresh licence has been taken from the Licensing Authority in the name of
the firm with the changed constitution.
__________________________________________________________________________
1. Subs. by G.S.R.788(E), dt. 10.10.1985.
2. Subs. by G.S.R. 462(E), dt. 22.6.1982
3. Amended by. S.O. 2139 ,dt. 12-8-1972.
4. Omitted by. G.S.R. 17(E) , dt. 7.1.1986.
5. Inerted. by Notfn. No. F. 1-63/61, dt. 17.7.1963
Drugs and Cosmetics Rules 1945
224
FORM
21A
[See rule 61
(2)]
1
[Licence to sell, stock or exhibit or offer for sale, or distribute] by retail drugs specified
in
2
[Schedule C (1)]
3
[excluding those specified in Schedule X]
4
[***] for dealers who do not
e
ngage
the services of a registered
pharmacist
1. ……………………is hereby
1
[licensed to sell, stock or exhibit or offer for sale, or
distribute] by retail on the premises situated at
4
[***] the following drugs being drugs specified
in
2
[Schedule C (1)]
3
[excluding those specified in Schedule X] to the Drugs and Cosmetics
Rules, 1945, subject to the conditions specified below and to the provisions of the Drugs and
Cosmetics Act, 1940 and the Rules thereunder.
2. The licence will be in force from………………………………….. .
3. Particulars of
2
[Schedule C (1)]
3
[excluding those specified in Schedule X] drugs to be
sold.
5
[***]
Name of dealer(s)……………….
Licence No………..
Date
.............................
Licensing Authority
Conditions of
Licence.
1. This licence shall be displayed in a prominent and conspicuous place in a part of the
premises open to the public
6
[***]
7
[***]
3. The licensee shall deal only in such drugs as can be sold without the supervision
of
a "qualified person" as defined in the Explanation to sub-rule (15) of rule 65 of the Drugs
and Cosmetics Rules, 1945.
4. No drug shall be sold unless such drug is purchased under cash or credit memo
from duly licensed manufacturer.
5. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be
deemed to be valid for a maximum period of three months from the date on which
the change takes place unless, in the meantime, a fresh licence has been taken from
the Licensing Authority in the name of the firm with the changed constitution.
_________________________________________________________________________
1 Subs. by G.S.R.788(E), dt. 10.10.1985.
2 Ins. By S.O. 1458, dt:27.4.1965.
3. Ins. by G.S.R. 462(E), dt. 22.6.1982.
4. Amended. by G.S.R 487(E), dt. 2.7.1984.
5. Item 4 omitted G.S.R. 504(E), dt. 18.7.2002
6. Certain words omitted by G.S.R. 231 (E), dt. 4.6.1996
7. Condition No. 2 omitted by G.S.R. 17 (E), dt:7.1.1986.
Drugs and Cosmetics Rules 1945
225
FORM
21B
[See rule
61(2)]
1
[Licence to sell, stock or exhibit or offer for sale, or distribute] by wholesale drugs specified
in
Schedules C and C (1)
2
[excluding those specified in Schedule
X
1. …………………is hereby
1
[licensed to sell, stock or exhibit or offer for sale, or
distribute] by wholesale on the premises situated at the following categories of drugs specified
in Schedule. C and C (1)
2
[excluding those specified in Schedule X] to the Drugs and
Cosmetics Rules, 1945.
Categories of
drugs
2. This licence shall be in force
from
.................................
to……………………….
3
[2A. The sale shall be made under the personal supervision of a competent person.
(Name of the competent person)].
3. This licence is subject to the conditions stated below and to the provisions of the
Drugs and Cosmetics Act, 1940 and the rules thereunder.
Licence No ...……..
Date............................ Licensing Authority.
Conditions of
Licence
1. This licence shall be displayed in a prominent place in a part of the premises open
to the public.
4
[2.***]
3. If the licensee wants to sell, stock or exhibit for sale or distribute during the
currency of the licence additional categories of drugs listed in Schedules C and C (1)
2
[excluding those specified in Schedule X] but not included in this licence, he
should apply to the Licensing Authority for the necessary permission. This licence
will be deemed to extend to the categories of drugs in respect of which such
permission is given. This permission shall be endorsed on the licence by the
Licensing Authority.
5
[4. (i) No drug shall be sold unless such drug is purchased under a cash or credit memo
from a duly licensed dealer or a duly licensed manufacturer.
(ii) No sale of any drug shall be made for purposes of resale to a person not holding the
requisite licence to sell, stock or exhibit for sale or distribute the drug:
Provided that this condition shall not apply to the sale of any drug to —
(a) an officer or authority purchasing on behalf of Government, or
(b) a hospital, medical, educational or research institute or a registered medical
practitioner for the purpose of supply to his patients, or
6
[(c) a manufacturer of hydrogenated vegetable oils, beverages, confectionary and other
non-medicinal products, where such drugs are required for processing these products.]
7
[5.***]
8
[6. The licensee shall inform the Licensing Authority in writing in the event of any change
in the constitution of the firm operating under the licence. Where any change in the
constitution of the firm takes place, the current licence shall be deemed to be valid for
a maximum period of three months from the date on which the change takes place
unless, in the meantime, a fresh licence has been taken from Licensing Authority in the
name of the firm with the changed constitution.
________________________________________________________
1. Subs. by. G.S.R.788(E), dt. 10.10.1985.
2. Subs. by.G.S.R.462(E), dt. 22.6.1982
3. Ins. by.G.S.R. 681(E), dt. 6.6.1988.
4. Condition no. 2 omitted by.G.S.R. 17(E), dt. 7.1.1986
5 Added by. Notfn. No. F. 1-63/61 -D, dt. 17.7.1963.
6.Added by Notfn. No. F. 1-113/69-D, dt. 23.12.1969.
7. Condition 5 omitted by S.O. 289, dt 20.12.1973 (w.e.f. 3.2.1973)
8. Ins. By S.O. 1458, dt:27.4.1965.
Drugs and Cosmetics Rules 1945
226
1
[FORM
21BB
[See Rule
62D]
Licence to sell by wholesale or to distribute drugs specified in Schedule C and Schedule C (1)
to
the Drugs and Cosmetics Rules, 1945 from a motor vehicle.
1. ............................... is hereby licensed to sell by wholesale, or to distribute drugs
specified in Schedule C and Schedule C(1) from the vehicle bearing registration no.
.....................................
assigned under Motor Vehicles Act, 1939, subject to the conditions
specified below and to the provisions of the Drugs and Cosmetics Act, 1940 and the Rules
made thereunder.
2. The licence shall be in force
from
............................
t
o
.......................
3. Categories of drugs ....................................................................
Date .................... Licence No……………
Licensing Authority………..
Conditions of licence
1. This licence shall be displayed in a prominent place on the vehicle.
2. No drugs to which this licence applies shall be sold by wholesale or distributed unless
the precautions as are published by the Licensing Authority from time to time in the
Official Gazette have been observed throughout the period during which it has been in the
possession of the licensee.
3. If the licensee wants to sell by wholesale or distribute during the currency of the
licence, additional categories of drugs listed in Schedules C and C (1) not included
in this licence, he shall apply to the Licensing Authority for necessary permission.
This licence shall be deemed to extend to the categories of drugs in respect of
which such permission is given. This shall be endorsed on the licence by the
Licensing Authority.
4. (i) No drugs shall be sold by wholesale or distributed unless such drug is purchased
under a cash or credit memo from a duly licensed manufacturer.
(ii) No sale for wholesale or distribution of any drug shall be made for the purpose of resale
to a person, not holding the requisite licence to sell, stock or exhibit for sale or distribute
the drug:
Provided that this condition shall not apply to the sale of any drug to—
(a) an officer or authority purchasing on behalf of the Government, or
(b) a hospital, medical, educational or research institution or a registered medical
practitioner for the purpose of supply to his patients, or
(c) a manufactures of hydrogenated vegetable oils, beverages, confectionery and
other non-medical products, where such drugs are required for processing their
products.
5. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be
deemed to be valid for a maximum period of three months from the date on
which the change takes place unless, in the meantime, a fresh licence has been
taken from
the Licensing Authority in the name of the firm with the changed constitution.
6. The licensee shall inform the Licensing Authority in writing in the event of any
change in the ownership of the vehicle specified in this licence within seven days of
such change.]
1. Added by Notfn. No. 11013/7/76DSMS (G.S.R. 42(E), dt. 25.1.1979.
Drugs and Cosmetics Rules 1945
227
FORM
21C
(See rule
63A)
Certificate of renewal of
1
[licence to sell, stock or exhibit or offer for
sa
le, or distribute]
drugs
Number of licence and date of
issue………………………………………………………………
1. Certified that licence
No
......................... in
2
[Form 20, 20A, 20B, 20F, 20G,
21,
21A or 21B], granted on the.....................to
................
for sale of the following drugs at t
h
e
premises situated at................... has been renewed for a period
from
............................to
............
2. Categories or particulars of
drugs
....................................................
3. Name (s) of registered pharmacist(s) in-charge............................
Date..................................... Licensing
Au
t
hor
ity
.
1. Subs. by G.S.R. 788(E),dt. 10.10.1985.
2. Subs. by .S.R. 462(E),dt. 22.6.1982.
1
[FORM
21CC
(See rule
63B)
Certificate of renewal of
2
[licence to sell, stock or exhibit or offer for sale by wholesale,
or
distribute] drugs from a motor vehicle
Number of licence and date of issue……………………………………………………………..
1. Certified that licence no……………….in Form 20-BB or Form 21-BB granted on
the
…………………………….to…………………………………………..for
sale by wholesale
or
distribution of the following drugs from the vehicle bearing registration
No………………………………. assigned under the Motor Vehicles Act, 1939 has been
renewed for a period
from……………………………..to
…………………………………………
2. Categories of the
drugs:
……………………….
……………………….
Date…………….. Licensing Authority.
____________________________________________________________________________
1. Subs. by G.S.R. 788(E), dt.10.10.1985.
2. Added by Notfn. No. 11013/7/76DSMS (G.S.R. 42(E), dt. 25.1.1979.
FORM
22
(See rule
67)
(Omitted by S.O. 289, dt.
20.12.1972)
FORM
23
(See rule
67)
(Omitted by S.O. 289, dt.
20.12.1972)
FORM
24
(See rule
69)
Application for the grant of or renewal of a
1
[licence to manufacture for sale or for
distr
i
bution]
of drugs other than those specified in
2
[Schedules C and C (1) and
X]
Drugs and Cosmetics Rules 1945
228
1 . I / We
................................................of.
....................................... hereby apply for the
grant / renewal of a licence to manufacture on the premises situated at .......................... the
following drugs being drugs other than those specified in
2
[Schedules C and C (1) and X] of
th
e
Drugs and Cosmetics Rules, 1945.
2. Names of drugs categorized according to Schedule M.
3. Names, qualifications and experience of technical staff employed for manufacture
and testing.
4. A fee of rupees ...................................................... has been credited to Government
under the head of account .......................................................................
Date.................................... Signature ....................
Note: The application should be accompanied by a plan of the premises.
1.
1. Subs. by. G.S.R. 788(E), dt. 10.10.1985.
2. Subs. by G.S.R. 462(E), dt. 22.6.1982.
FORM
24A
(See rule
69A)
Application for grant or renewal of a loan
1
[licence to manufacture for sale or for distribution]
of
drugs other than those specified in
2
[Schedules C and C (I) and
X
]
1 . I /We*.........................................................of
#
............................................hereby apply
for the grant/renewal of a loan licence to manufacture on the premises situated
at
...................................................................
C/o
§
................................................ the under-
mentioned drugs, other than those specified in
2
[Schedules C and C(1) and X] to the
Drugs and Cosmetics Rules, 1945.
Names of drugs (each substance to be separately specified).
2. The names, qualifications and experience of the expert staff actually connected with the
manufacture and testing of the specified products in manufacturing premises.
3. I/We enclose–
(a) A t
ru
e c
o
p
y of a let t e r
fr
om
m
e
/u
s to the
m
a
nufac
t
u
r
i
n
g c
o
nce
r
n
wh
os
e
manufacturing capacity is intended to be utilized by me/us.
(b) A true copy of a letter from the manufacturing concern that they agree to lend the
services of their expert staff, equipment and premises for the manufacture of each item
required by me/us and that they will analyse every batch of finished product and
maintain the registers of raw materials, finished products and reports of analysis
separately in this behalf.
(c) Specimens of labels, cartons of the products proposed to be manufactured.
4. A fee of rupees........................................................................has been credited t
o
Government under the head of account ....................................................................
Date......................................................
Signature
................………….
*
Enter here the name of the proprietor, partners of Managing Director as the case may be.
#
Enter here the name of the applicant firm and the address of the principal place of business.
§
Enter here the name and address of the manufacturing concern where the manufacture will be
actually carried out and also the Licence number under which the latter operates.
1. Subs. by G.S.R. 788(E), dt. 10.10.1985.
2. Subs. by G.S.R. 462(E), dt. 22.6.1982.
Drugs and Cosmetics Rules 1945
229
1
[FORM
24B
(See rule
69A)
Application for grant or renewal of licence to repack for sale or distribution of drugs,
being
drugs other than those specified in Schedules C and C (1)
2
[excluding those
specified
in
Schedule
X
]
1
.
1
/ We ………………of……………………….hereby apply for grant/renewal of a
licence to repack the following drugs at the premises situated at…………...
2. Names of the drugs to be
rep
ac
ked
.......................................................................
….
3. Name, qualification and experience of competent
s
ta
ff
............................................
4. A fee of rupees
…………
……………
h
as been
cr
edit ed to
Gover
n
m
e nt under the
h
e a d
o
f account
.........................................
………………………………………….
Date.......................................... Signature of applicant.
NOTE :—The application shall be accompanied by a plan of the premises.
_________________________________________________________________________
1. Ins. By S.O. 1196, dt:6.5.1960.
2. Subs. by G.S.R. 462(E), dt. 22.6.1982.
1
[FORM
24C
(See rule
85B)
Application for the grant or renewal of a
2
[licence to manufacture for sale or for
distribution
of] Homoeopathic medicines or a licence to manufacture potentised
preparations from
ba
ck potencies by licensees holding licence in Form
20C
3
[
1
. I /
W
e * ....................................... of ........................................ holder of licence
no
.......................................................
in Form 20-C hereby apply for the grant/renewal of
licence to manufacture the undermentioned Homoeopathic mother tinctures/potentised
preparations on the premises situated
at…………………………
………………………………….
Name of the Homoeopathic preparations
..................................................
………………….
….
(
E
a
c h i t e m t o
b
e separately specified)].
2. Names, qualifications and experience of technical staff employed for manufacture and
testing of Homoeopathic medicines.
3. A fee of rupees
.........................................
has been credited to Government under head
of account ...............................................................................................................
Date..................................... Signature...............................
Note 1. Delete whichever portion is not applicable.
2. The application should be accompanied by a plan of the premises.
_______________________________________________________________________
1. Amended by Notfn. No. F. 1-598-D, dt. 19.11.1969
2. Subs. by. G.S.R.788(E) dt. 10.10.1985.
3. Subs. by. G.S.R. 13(E) dt. 7.1.1983.
Drugs and Cosmetics Rules 1945
230
1
[FORM
24D
(See rule
153)
Application for the grant / renewal of a licence to manufacture for sale of Ayurvedic/
Siddha
or Unani
drugs
1
.
I
/
W
e
...........................................
of.....................................................hereby
apply for the
grant / renewal of a licence to manufacture Ayurvedic (including Siddha) or Unani drugs on
the premises situated at
..........................................................
…………………………….
2. Names of drugs to be manufactured (with details)
3. Names, qualifications and experience of technical staff employed for manufacture and
testing of Ayurvedic (including Siddha) or Unani drugs .............................................
4. A fee of rupees
...............................
has been credited to the Government under the head
of account
....................................
and the relevant Treasury Challan is enclosed herewith.
Date............................................
Signature
......................................
(applicant)
Note—The application should be accompanied by a Plan of the premises.]
1. Added by Notfn. No. 1-23/67-D,dt. 2.2.1970.
1
[FORM
24E
(See rule
154A)
Application for grant or renewal of a loan licence to manufacture for
sa
le
Ayurvedic (including Siddha) or Unani
Drugs
1. I / We
*
...........................................................................of
**
................................
hereby
apply for the grant / renewal of a loan licence to manufacture Ayurvedic (including Siddha) or
Unani Drugs on the premises situated at...................…………………………………………..
C
/
o
***
............................................................................…………………………………………
2. Names of drugs to be manufactured (with details).
3. The names, qualifications and experience of technical staff actually connected with
the manufacture and testing of Ayurvedic (including Siddha) or Unani drugs in
the manufacturing premises.
4. I / We* enclose,
(a) A true copy of a letter from me/us to the manufacturing concern whose
manufacturing capacity is intended to be utilized by me / us.
(b) A true copy of a letter from the manufacturing concern that they agree to
lend the services of their competent technical staff, equipment and premises
for the manufacture of each item required by me/us and that they shall
maintain the registers of raw materials and finished products separately in
this behalf.
(c) Specimen of labels, cartons of the drugs proposed to be
m
a
nufactured.
5. A fee of Rs
......................................................
has been credited to Government
under
t
h
e
h
e ad
o
f a c c
o
un
t
....................................
and the relevant Treasury Challan is enclosed
herewith.
Date ...................................... Signature
......................
………]
(applicant)
Drugs and Cosmetics Rules 1945
231
*
Enter here the name of the proprietor, partners or Managing Director as the case may be.
**
Enter here the name of the applicant firm and the address of the principal place of
business.
***
Enter here the name and address of the manufacturing concern where the manufacture will
be actually carried out and also the licence number under which the letter operates.
______________________________________________________________________
1. Added by G.S.R. 376 (E), dt. 20.7.1978.
1
[FORM
24F
(See rule
69)
Application for the grant or renewal of a
2
[licence to manufacture for sale or for distribution of]
drugs specified in Schedule X and not specified in Schedules C and C(1)
1.
I
/
W
e ...................... of ....................................hereby apply for the grant/renewal
of licence to manufacture on premises situated at ............................ the undermentioned drugs,
specified in Schedule X to the Drugs and Cosmetics Rules, 1945.
2. Names of drugs.
3. Names, qualifications and experience of technical staff employed for
manufacture and testing.
4. A fee of rupees...... has been credited to Government account under the head of
account....................................................
Signature
................
……….
Date:..........
Designation ..............
……….]
1. Subs. by .G.S.R. 462(E) ,dt. 22.6.1982.
2. Subs. by G.S.R. 788(E) dt. 10.10.1985.
Drugs and Cosmetics Rules 1945
232
FORM
25
(See rule
70)
1
[Licence to manufacture for sale or for distribution of] drugs other than those specified
in
2
[Schedules C and C(1) and
X
]
Number of Licence and date of
issue
................................................................
1
........................................................................
is hereby licensed to manufacture the
following categories of drugs being drugs other than those specified in
2
[Schedules C
and C (1) and X] to the Drugs and Cosmetics Rules, 1945, on the premises situated
at
.................................................................................
under the direction and supervision of the
following
3
[competent technical staff]:
(a)
3
[Competent technical staff]. (Names)……………………………………………
(b) Names of Drugs (each item to be separately specified)..................................….
2. The licence authorises the sale by way of wholesale dealing and storage for sale by the
licensee of the drugs manufactured under the licence, subject to the conditions applicable to
licence for sale.
3. The licence shall be in force
from................................................
t
o
...................
4. The licence is subject to the conditions stated below and to such other conditions as may
be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Da
te .....................................
*Delete whichever is not applicable.
Signature ............
Designation
..........
4
[*Licensing Authority/
*Central Licence Appoving Authority.]
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced at the request of an Inspector appointed under the
Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to
the Licensing Authority.
3. If the licensee wants to manufacture for sale additional items of drugs not included
above he should apply to the Licensing Authority for the necessary endorsement as
provided in Rule 69(5). This licence will be deemed to extend to the categories so
endorsed.
4. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any change
in the constitution of the firm takes place, the current licence shall be deemed
to be valid for a maximum period of three months from the date on which the
change takes place unless, in the meantime, a fresh licence has been taken from the
Licensing Authority in the name of the firm with the changed constitution.
_
1. Subs. by. G.S.R. 788(E) ,dt. 10.10.1985
2. Subs. by G.S.R. 462(E), dt. 22.6.1982.
3. Subs. by G.S.R. 231(E), dt. 4.6..1996.
4 Subs. by G.S.R. 923(E), dt. 14.12.1992.
Drugs and Cosmetics Rules 1945
233
FORM
25A
(See rule
70A)
Loan
1
[licence to manufacture for sale or for distribution of] drugs other than those
specified
In
2
[Schedules C and C (1) and
X
]
1. Number of licence and date of issue ............................................................
2.....................................................
of
.................................
is hereby granted a loan
licence to manufacture the following drugs other than those specified in
2
[Schedules C and C(1)
and X] t o t
h
e Drugs and Cosmetics Rules, 1945, on the premises situated at C/o under the
direction and supervision of the following
3
[competent technical staff]:
(a)
3
[competent technical staff] (Names):…………………….
(c) Names of
drugs
..................................
3. The licence authorises the sale by way of wholesale dealing and storage for sale by
the licensee of the drugs manufactured under the licence subject to the conditions applicable to
licences for sale.
4. The licence is subject to the conditions stated below and to such other conditions
as
may be specified in the Rules for the time being in force under the Drugs and Cosmetics
Act,
1940.
Date............................... Signature ………….
Designation
..
…..
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced at the request of an Inspector appointed under the
Drugs and Cosmetics Act, 1940.
2. Any change in the
3
[competent technical staff] named in the licence shall be forthwith
reported to the Licensing Authority.
3. If the licensee wants to undertake during the currency of the licence the
manufacture for of sale additional drugs he should apply to the Licensing Authority
for the necessary endorsement to the licence as provided in Rule 69-A. This licence
will be deemed to extend to the drugs so endorsed.
4. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be
deemed to be valid for a maximum period of three months from the date on which
the change takes place unless, in the meantime, a fresh licence has been taken from
the Licensing Authority in the name of the firm with the changed constitution.
1. Subs. by G.S.R. 788(E) , dt.10.10.1985.
2. Subs. by G.S.R. 462(E), dt. 22.6.1982.
3. Subs. by. G.S.R. 231(E) ,dt. 4.6.1996.
1
[ FORM
25B
(See rule
70)
Licence to repack for sale or distribution of drugs being drugs other than those specified i
n
Schedules C and C (1)
2
[excluding those specified in Schedule
X]
Number of licence and date of issue.
1. ……..
...................................
of .....................................is hereby granted a licence t
o
repack the following drugs for sale or distribution on the premises
s
it
u
ate
d
at
.................................
under the supervision of the following competent staff.
Drugs and Cosmetics Rules 1945
234
(a) Names of drugs to be repacked.
(b) Names of competent staff.
2. The licence shall be in force
from
......................................... to
............................
3. The licence authorises the sale by way of wholesale dealing by the licensee and
storage for sale by the licensee of the drugs repacked under the licence subject to conditions
applicable to licences for sale.
4. The licence is subject to the conditions stated below and to such other conditions as
may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act,
1940.
Date......................................
Signature
...
…………..
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced at the request of an Inspector appointed under the
Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to
the Licensing Authority.
3. If the licensee wants to repack for sale or distribution additional items he should
apply to the Licensing Authority for the necessary endorsement to this licence.
This licence will be deemed to extend to only those items so endorsed.
4. The drugs repacked under this licence shall bear on their label, apart from other
particulars required by these Rules, the name and address of the licensee and the
number of the licence under which the drug is repacked preceded by the words
"Rpg. Lic. No.".
5. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be
deemed to be valid for a maximum period of three months from the date on which
the change takes place unless, in the meantime, a fresh licence has been taken from
the Licensing Authority in the name of the firm with the changed constitution.
1. Added by Notfn. No. F. 1-22/59-D, dt. 9-4-1960.
2. Subs. by G.S.R. 462(E), dt. 22.6.1992.
1
[FORM
25C
(See rule
85D)
2
[Licence to manufacture for sale or for distribution of] Homoeopathic
medicines
Number of Licence and date of issue .....................................................................
3
[*1. ……….……….
of....................
who holds a licence in Form 20-C is hereby
licensed to manufacture undermentioned Homoeopathic Mother Tinctures/ potentised and other
preparations on the premises situated at
....
under the direction and supervision of the following
technical staff:
Names of the Homoeopathic preparations.
(Each item to be separately specified).
Names of the Technical
Staff....................................................
]
2. The licence shall be in force from
............................................ to
...................
3. The licence is subject to the conditions stated below and to such other conditions as
may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act,
1940.
Drugs and Cosmetics Rules 1945
235
Date......................................
S
i
gnature…….
Designation….
Conditions of
Licence
1. This licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced at the request of an Inspector appointed under the
Drugs and Cosmetics Act, 1940.
2. Any change in the expert staff named in the licence shall be forthwith reported to
the Licensing Authority.
4
[3. The licensee shall inform the Licensing Authority in writing in the event of any change in
the constitution of the firm operating under the licence. Where any change in the
constitution of the firm takes place, the current licence shall be deemed to be valid for a
maximum period of three months from the date on which the change takes place unless, in
the meantime, a fresh licence has been taken from the Licensing Authority in the name of
the firm with the changed constitution.]
*Delete the words ―who holds a licence in Form 20C‖ in case this is not applicable.
1. Added by Notfn No. F.1-36/64-D, dt:18.8.1964
2. Subs. by.. G.S.R.788(E) , dt. 10.10.1985.
3. Subs. by. G.S.R. 13(E) , dt. 7.1.1983.
4. Added by S.O. 903, dt. 28.2.1976.
1
[FORM
25D
(See rule
154)
Licence to manufacture for sale of Ayurvedic (including Siddha) or Unani drugs
No. of Licence……………………………………………………………
1. ….
.....................................
is / are hereby licensed to manufacture the following
Ayurvedic (including Siddha) or Unani drugs on the premises situated
at..................................................................................................
under the direction and
supervision of the following technical staff: —
(a) Technical staff (Names).
(b) Names of drugs (each item to be separately specified).
2. The licence shall be in force
from ..............................................
to
...................
3. The licence is subject to the conditions stated below and to such other conditions as may
be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date of issue: …………….
S
i
gna
t
ur
e
...............
Designation
............
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced at the request of an Inspector appointed under the
Drugs and Cosmetics Act, 1940.
2. Any change in the Technical staff named in the licence shall be forthwith reported
to the Licensing Authority.
3. This licence shall be deemed to extend to such additional items as the licensee may
intimate to the Licensing Authority from time to time, and as may be endorsed by
the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be
Drugs and Cosmetics Rules 1945
236
deemed to be valid for a maximum period of three months from the date on which
the change takes place unless, in the meantime, a fresh licence has been taken from
the Licensing Authority in the name of the firm with the changed constitution.]
1. Added by Notfn. No. 1-23/67 –D (S.O. 642), dt. 2-2-1970.
1
[FORM
25E
(See rule
154A)
Loan Licence to manufacture for sale Ayurvedic (including Siddha) or Unani
Drugs
1. Number of
Licence…………………………………………………………………….
2
..........................................................
of.
...........................................
is hereby granted a
loan licence to manufacture for sale Ayurvedic (including Siddha) or Unani drugs, on the
premises situated at
....................................................
C/o.....................................................under
the direction and supervision of the following expert technical staff:
(a) Technical staff (Names)……………………………….
(b) Names of drugs (each item to be separately specified)
3. The licence shall be in force
from ....................................
t
o…………………………………
4. The licence is subject to the conditions stated below and to such other conditions as may
be specified in the Rules for the time being in force under the Drugs and Cosmetics Act, 1940.
Date of Issue.................................................
Conditions of Licence
Signature ....................
Designation .................
1. This licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced on the request of an Inspector appointed under the
Drugs and Cosmetics Act, 1940.
2. Any change in the technical staff named in the licence shall be forthwith reported to
the Licensing Authority.
3. This licence shall be deemed to extend to such additional items as the licensee may
intimate to the Licensing Authority from time to time, and as may be endorsed by
the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any
change in the constitution of the firm takes place, the current licence shall be
deemed to be valid for a maximum period of three months from the date on which
the change takes place unless, in the meantime, a fresh licence has been taken from
the Licensing Authority in the name of the firm with the changed constitution.
______________________________________________________________________
1. Added by G.S.R. 376 (E), dt. 20.7.1978
1
[FORM
25F
(See rule
70)
2
[Licence to manufacture for sale or for distribution of] drugs specified in Schedule X and
no
t specified in Schedules C and
C(I)
1.
...................................................
of
.......................is hereby licensed to manufacture at
the premises situated at……………………………the following drugs specified in Schedule X to
the Drugs and Cosmetics Rules, 1945.
Drugs and Cosmetics Rules 1945
237
2. Names of drugs.
3. Names of approved
3
[competent technical staff]
4. The licence authorises the sale by way of wholesale dealing and storage for sale
by the licensee of the drugs manufactured under the licence subject to the
conditions applicable to licence for sale.
5. The licence shall be in force ................... to....................................
6. The licence is subject to conditions stated below and to other conditions as may
be specified in the rules for the time being in force under the Drugs and Cosmetics Act,
1940.
Date of issue..................... Signature .............................
Licence No ..................... Designation .........................
4
[*Licensing Authority/Central Licence Approving
Authority.]
*Delete whichever portion is not required.
Conditions of
Licence
1. The licence and any certificate of renewal in force shall be kept on the licensed premises
and shall be produced at the request of an Inspector appointed under the Drugs and Cosmetics
Act, 1940.
2. If the licensee wishes to undertake during the currency of the licence the manufacture
of any drug specified in Schedule X not included above, he should apply to the Licensing
Authority for the necessary endorsement of this licence. This licence shall be deemed to
extend to only those items so endorsed.
3. Any change in the
3
[competent technical staff] shall be forthwith reported to the
Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any change in
the constitution of the firm operating under the licence. Where any change in the
constitution of the firm takes place, the current licence shall be deemed to be valid for a
maximum period of three months from the date on which the change takes place unless, in the
meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm
with the changed constitution.
5. The licensee shall furnish to the Licensing Authority copies of the invoices of
sales made to dealers.
6. The licensee shall not manufacture drugs covered by this licence for use as
'Physician's Samples'.]
________________________________________________________________________________________
1. Subs. by G.S.R. 462(E) dt. 22.6.1982.
2. Subs. by G.S.R.788(E) dt. 10.10.1985.
3. Subs. by G.S.R.231(E) dt. 4.6.1996.
4. Subs. by G.S.R. 923(E) dt. 14.2.1992.
1
[FORM
26
(See rules 73 and
83)
Certificate of renewal of licence to manufacture for sale of drugs other than those specified
in
Schedule
X
1. Certified that licence No
........................................................................
granted on
the.................. to
.......................
for the manufacture of the following categories of drugs being
*drugs other than those specified in Schedules C, C (1) and X/*drugs specified by Schedules C
and C (1) excluding those specified in Schedule X to the Drugs and Cosmetics Rules,
1945, at the premises situated at
........................................................
has been renewed
from.......................
to.....................
2. Name(s) of approved
2
[competent technical staff] ...............
Drugs and Cosmetics Rules 1945
238
3
[3 Names of the drugs (each item to be separately specified) .......................
Signature
.............................
Date........
D
e
s
i
gna
ti
on
...................
4
[Licensing Authority/
*Central Licence Approving
Authority.]
*Delete whichever portion is not required.]
1. Subs. by G.S.R. 462(E) dt. 22.6.1982.
2. Subs. by G.S.R.231(E) dt. 4.6.1996
3. Ins. By G.S.R. 370(E) dt. 7.4.1994.
4. Subs. by G.S.R. 923(E), dt. 14.12.1992.
1
[FORM
26A
(See rules 73A and
83A)
Certificate of renewal of loan licence to manufacture for sale of drugs other than
thos
e specified in Schedule
X
1. Certified that a loan licence
No
............................................................granted on
the.............................................. to...........................................
for the manufacture of the
*drugs other than those specified in Schedules C, C (1) and X the undermentioned drugs
being drugs specified in Schedules C and C (1) excluding those specified in Schedule X, to
the Drugs and Cosmetics Rules, 1945, at the premises situated
at..............................
C/o .........................has been renewed from
.........................
to...................
2. Names of the drugs (each substance to be separately specified).
3. Names of the approved
2
[competent technical staff]
Da
te .............................
Signature………..
Designation………]
* Delete whichever is not applicable.
1.Ins. by G.S.R. 462(E), dt. 22.6.1982.
2. Subs. by G.S.R.231(E) dt. 4.6.1996.
1
[FORM
26B
(See rule
73B)
Certificate of renewal of licence to repack for sale or distribution of drugs being drugs
other
than
those specified in Schedules C and C (1)
2
[excluding those specified in Schedule
X
]
1. Certified that licence No
...................................................
granted on
the.......................
to......................................for the repacking of the following drugs at the premises situated
at .........................................has been renewed
from
.....................
to...........................................................Names of drugs to be
r
e
p
ac
k
e
d
....................................
2. Names of competent staff. .................................................
Date : ..... Signature………
Designation……….
Drugs and Cosmetics Rules 1945
239
* Delete whichever is not applicable.]
3
[*Licensing Authority.
*Central licence Approving Authority.]
1 Added by Notfn. No. F.1-22/5 9-D, dt. 9.4.1964.
2 Subs. by G.S.R. 462(E) dt. 22.6.1982.
3. Ins. by G.S.R. 923(E) dt. 14.12.1992
FORM
26C
(See rule
85G)
Certificate of renewal of licence to manufacture for sale of Homoeopathic
med
i
cin
e
s
1. Certified that licence No
........................
granted on the……………………….
to………… for the manufacture for sale of the Homoeopathic mother tinctures/potentised
preparation at the premises situated at
...............
has been renewed for a period
from the
......................................................................
to ......................................
……
2. Name of the technical
staff .................................................................. ……
1
[3. Names of the drugs (each item to be separately
specified)
............................
]
Date………………..
Signature
.......………..
Designation .. ………
1. Ins. by G.S.R. 370(E) dt. 7.4.1994.
1
[FORM 26D
(See rule 155)
Certificate of renewal of licence to manufacture for sale of Ayurvedic / Siddha or Unani
drugs
1. Certified that licence No
...................................................
granted on
the………………to Shri/ Messers
........................................................................
for the
manufacture of Ayurvedic/Siddha/Unani drugs at the premises situated
at………………….has
been renewed
from………………………….to
....................................
2. Names of technical staff ................................................................
2
[3. Names of drugs (each item to be separately specified).]]
Date ………..
S
i
gnature………..
Designation………..
____
1. Ins. by F. No.1 -23/67-D, dt. 2-2-1970.
2. Ins. by G.S.R 376 (E), dt. 20.7.1978
1
[FORM
26E
(See rule
155A)
Certificate of renewal of loan licence to manufacture for sale
of
Ayurvedic / Siddha or Unani
Drugs
1. Certified that loan Licence No ....................................granted on
the……………………………………to………………………………………………...………
for the
m
a
n
ufacture ofAyurvedic/ Siddha or Unani drugs at the premises situated
at.............................................................. C/o ...........................................
has been renewed
from..............................................................to .....................................................
…………….
Drugs and Cosmetics Rules 1945
240
2 Names of technical staff.
Da
te:
…………
Signature............
Designation………..
1. Added by G.S.R. 376(E), dt. 20.7.1978.
1
[FORM
26E-I
(See rule
157B)
Certificate of Good Manufacturing Practices (GMP) to manufacture
of
Ayurveda, Siddha or Unani
drugs
Certified that manufacturing unit licensee, namely ...................... situated at ................
State .................. Licence
No
........................... comply with the requirements of Good
Manufacturing Practices of Ayurveda-Siddha-Unani drugs as laid down in Schedule T of the
Drugs and Cosmetics Rules, 1945.
This certificate is valid for a
2
[period of five years and the Good Manufactruing Practices
(GMP) is valid for the various dosage forms or Rasaushadhis, as follows:]
Date :....... Signature………..
Place : ..
..
Designation……
Licensing Authority for Ayurveda/ Siddha/ Unani Drugs.]
_________________________________________________________________________________________________________________
1.subs. by G.S.R.198(E), dt. 7.3.2003. Earlier Ins. by G.S.R. 561(E), dt. 23.6.2000.
2.Subs. by G.S.R. 376(E), dt. 3.5.2010
1
[FORM
26E2-I
(See rule
158C)
State Drug Controller or Licensing Authority for Ayurveda, Siddha and Unani Medicines
Name of the State or Union territory……..
Free Sale Certificate
It is certified that M/s. …….(Name of the company)……..situated at ………. (Address)
...................... is holding valid Ayurvedic/Siddha/Unani Drug Manufacturing License
Number............... valid till ……and certificate of Good Manufacturing Practices for the
State or Union territory of ……The manufacturer has applied for renewal of license on
..................(to be mentioned, if application for renewal of license has not been rejected).
It is also certified that the manufacturing plant siuated at
………..(Address)……..in which the Ayurvedic or Unani or Sidhha products are
manufactured, conforms to the requirement of Good Manufacturing Practices and is
subjected to inspection as per rules.
The firm has been permitted under License Number………..to manufacture and
market the following products (attach list of products, if multiple) freely for sale in India
under the provisions of the Drugs and Cosemtics Atc, 1940 and the rules thereunder.
(i)…………
(ii)…………
(iii)………..
Date :....... (Seal of issuing Officer) … … … … … … … …
Drugs and Cosmetics Rules 1945
241
( Signature and Name)
State Drug Controller/Licensing Authority
Address………………………………………
Name of State or Union territory…………]
_________________________________________________________________________________________________________________
1.Ins. by G.S.R. 153 (E), dt. 5.3.2014.
1
[FORM
26E2-II
(See rule
158C)
State Drug Controller or Licensing Authority for Ayurveda, Siddha and Unani Medicines
Name of the State or Union territory……..
Free Sale Certificate
It is certified that M/s. …….(Name of the company)……..situated at ………. (Address)
...................... is holding valid Ayurvedic/Siddha/Unani Drug Manufacturing Loan
License Number............... valid till ……and the valid certificate of Good Manufacturing
Practices for the State or Union territory of ……The manufacturer has applied for renewal
of loan license on ..................(to be mentioned, if application for renewal of license has
not been rejected).
It is also certified that the manufacturing plant siuated at
………..(Address)……..in which the Ayurvedic or Unani or Sidhha products are
manufactured, conforms to the requirement of Good Manufacturing Practices and is
subjected toinspection as per rules.
The firm has been permitted under Loan License Number………..to manufacture
and market the following products (attach list of products, if multiple) freely for sale in
India under the provisions of the Drugs and Cosemtics Atc, 1940 (23 of 1940) and the
rules thereunder.
(i)…………
(ii)…………
(iii)………..
Date :....... (Seal of issuing Officer) … … … … … … .
( Signature and Name)
State Drug Controller/Licensing Authority
Address………………………………………
Name of State or Union territory…………
]
_________________________________________________________________________________________________________________
1.Ins. by G.S.R. 153 (E), dt. 5.3.2014.
1
[FORM
26 E3
(See rule
158C)
State Drug Controller or Licensing Authority for Ayurveda, Siddha and Unani Medicines
Name of the State or Union territory……..
Non-Conviction Certificate
It is certified that M/s. …….(Name of the company)……..situated at ………. (Registered
Address) ...................... is holding valid Ayurvedic/Siddha/Unani Drug Manufacturing
License Number............... in Form 25D/25E valid till ……and certificate of Good
Drugs and Cosmetics Rules 1945
242
Manufacturing Practices/valid Good Manufacturing Practices certificate of principal or
original manufacturer for the State or Union territory of ……The manufacturer has
applied for renewal of license on ..................(date to be mentioned, if application for
renewal of license has not been rejected).
As per the records of the State Drug Controller or Licensing Authority, as it may
be, and affidavit (Annexure I) given by the company, the firm has not been conicted under
the Drugs and Cosmetics Act, 1940 (23 of 1940) and the rules thereunder in the State or
Union territory of …….., during the last three years of the issuing of this certificate.
This certificate shall be valid only for six months from the date of issue.
Date :....... (Seal of issuing Officer) … … … … … … … … … … … … .
( Signature and Name)
State Drug Controller/Licensing Authority for
Ayurveda, Siddha and Unani Medicines.
Address………………………………………
Name of State or Union territory…………]
1
[ANNEXURE-1
(Proforma of Affidavit to be submitted on stamp paper of Rs. 50 attested by
Magistrate not below the rank of first class)
I, …………S/O………….age…….working as ……….of………..(Name and address of
the company)……from ……to……do hereby solemnly affirm and declare as under:
1. That I, in the capacity of Authorized Signnatory of ……(name and address of the
company)….,am duly competent to depose and verify the present affidavit.
2. That I apply for Non-conviction Certificate on behalf of M/s. …………..
3. Thar I declare that I am aware of the details of my organization asnd day to day
activities from….to….
4. That I hereby undertake that the Non-Conviction Certificate, if issued, will be
utilized for the bona fide purpose only.
5. I declare that the aforesaid firm is not convicted under the Drugs and Cosmetics Act,
1940 and rules thereunder during the last three years.
6. That it is my true statement.
……………………….
Signatature of Deponent
Verification
Verified at………….(Palce and State)……….….today on this………..…..day
of…..(month)….(Year)…..that the contents of the above affidavit are true to my
knowledge and belief and no part of it is false and nothing has been concealed
therefrom.
……………………….
Signature of Deponent]
Witness with Address
1.
2.
_________________________________________________________________________________________________________________
1.Ins. by G.S.R. 153 (E), dt. 5.3.2014.
Drugs and Cosmetics Rules 1945
243
1
[FORM
26F
(See rules 73 and
83)
Certificate of renewal of licence to manufacture for sale of drugs specified in Schedule
X
1. Certified that licence No
................................
granted on the
................
to
..............
for the
m
a
nu
facture
o
f drugs
sp
ec ified in
S
c
hed
u
le X to t
h
e
Dru
g
s
an
d Cosmetics
Rules, 1945, at the premises situated at………………………….. has been renewed
from…………………………………….
to…………………………
2. Names of drugs (each substance to be separately specified).
3. Names of the approved
2
[competent technical staff].
Date:………
Date of issue……
Signature………….
Designation……….
3
[*Licensing Authority/Central Licence Approving Authority]
*Delete whichever is not applicable.
1. Ins. by. G.S.R. 462(E) ,dt. 22.6.1982.
2. Subs. by G.S.R. 231(E), dt. 4.6.1996.
3. Subs. by G.S.R. 923(E), dt. 14.12.1992.
1
[FORM
26G
(See rules 122F
)
Certificate of renewal of licence to operate a Blood Bank for processing of
whole human blood and/or* for preparation for sale or distribution of its
components
1. Certified that Licence
No
....................... . granted on …………….. to
M/s……………….
..........................................
for the operation of a Blood Bank for processing of whole human
blood and*/or for preparation of its components at the premises
s
it
u
ate
d
at...........................................
is hereby renewed with effect from……….. to
..................
2. Name(s) of items :
1.
2.
3.
3. Name(s) of competent Technical Staff:
1.
2.
3.
Dated………….
Signature………….
Designation……….
[*Licensing Authority/Central Licence Approving Authority]
* Delete whichever is not applicable.
1. Subs. by G.S.R 245(E) dt. 5.4.1999.
Drugs and Cosmetics Rules 1945
244
1
[FORM
26H
(See rules 68A, 76, 77,
78)
Certificate of renewal of licence to manufacture for sale of
2
[Large
Volum
e
Parenterals/Sera and Vaccines/recombinant DNA (r-DNA)derived drugs] specified in
Schedules C and
C(I)
excluding those specified in Schedule
X
1. Certified that licence
No...............................
granted on the .................. to ............
for
the manufacture of following
2
[Large Volume Parenterals/Sera and Vaccines/recombinant
DNA (r-DNA) derived drugs] at the premises situated at
.................................
has been renewed
from........to………
2. Name(s) of drug(s)
........................................
……………………………………….
(each item to be separately specified).
3. Name(s) of competent technical staff:
(a) responsible for manufacturing (b) responsible for
testing
1.
1.
2.
2.
3.
3.
4.
4.
Date:………
Signature………….
Designation……….
[*Licensing Authority/Central Licence Approving Authority]
* Delete whichever is not applicable.
1. Ins. by G.S.R. 119(E), dt. 11.3.1996.
2. Subs. By G.S.R. 26 (E), dt: 19.1.2006.
1
[FORM
26-I
(See rules
122-I)
Certificate of renewal of licence for manufacture of blood
produc
t.
1. Certified that licence no
.....................
granted on the .................. to M/s. ........... for
the manufacture of blood products at the premises situated at .............................is hereby
renewed with effect
from
.........
……… to…………………
2.
Name(s) of item (s):
1.
2.
3.
3.
Name(s) of competent technical staff:
(a) responsible for manufacturing
(b) responsible for testing
1.
1.
2.
2.
3.
3.
4.
4.
Drugs and Cosmetics Rules 1945
245
Date:………
Signature………….
Designation……….
[*Licensing Authority/Central Licence Approving Authority]
_
* Delete whichever is not applicable.
1. Ins. by G.S.R 245(E), dt. 5.4.1999.
1
[FORM
26-J
(See rules
122G, 122H, 122I, 122P)
Certificate of renewal of licence for collection, processing, testing, storage, banking and
release of umblical cord blood stem cells.
Certified that licence no
.....................
granted on the .................. to M/s. ........... for
collection, processing, testing, storage, banking and release of umblical cord blood stem cells at
the premises situated at .............................is hereby renewed with effect
from
.........
…………..…
to…………………
1. Name(s) of competent technical staff:
1……………..
2……………..
3……………..
Date:………
Signature………….
Designation……….
[*Licensing Authority/Central Licence Approving Authority]
* Delete whichever is not applicable.
1. Ins. by G.S.R 899(E), dt. 27.12.2011.
1
[FORM
26J
(See rules 83A and 83AA
)
Certificate of renewal of loan licence to manufacture for sale of Large
Volum
e
Parenterals/Sera and Vaccines/recombinant DNA (r-DNA) derived drugs specified in
Schedules C and
C(I)
excluding those specified in Schedule
X
Certified that licence no ..................... granted on the .................. to M/s. ........... for the
manufacture of following Large Volume Parenterals/Sera and Vaccines/recombinant DNA (r-
DNA) derived drugs at the premises situated at .............................has been renewed from
.........…………..… to…………………
2. Name(s) of drug (s)……………(Each item to be separately specified)
3. Name(s) of competent technical staff:
(a) responsible for manufacturing
(b) responsible for testing
1.
1.
2.
2.
3.
3.
4.
4.
Date:………
Signature………….
Designation……….
[*Licensing Authority/Central Licence Approving Authority]
* Delete whichever is not applicable.
1. Ins. by G.S.R 574(E), dt.17.6.2012.
Drugs and Cosmetics Rules 1945
246
FORM
27
Application for grant or renewal of a
1
[licence to manufacture for sale or for distribution]
of
drugs specified in Schedules C and C (1)
2
[excluding
those
specified in
3
[Part XB and] Schedule
X]
1
.
I
/ We
........................................................
hereby apply for the grant / renewal of a
licence to manufacture on the premises situated at the undermentioned drugs, being
drugs specified in Schedules C and C (1)
2
[excluding those specified in
3
[Part XB and] Schedule
X] to the Drugs and Cosmetics Rules, 1945.
Names of drugs……..………(each item to be separately specified).
2. The names, qualifications and experience of the expert staff responsible for the
manufacture and testing of the above mentioned drugs.
(a) Name (s) of staff responsible for test
....................................
(b)
Name (s) of staff responsible for manufacture..........................
3. The premises and plan are ready for inspection/ will be ready for inspection on…..
4. A fee of
rupees ....................................................
and an inspection fee of rupees
………………has been credited to Government under the head of acc
oun
t
…………….
Date
......................................... Signature………
Designation…...
Note-The application shall be accompanied by a plan of premises.
_
1. Ins. by. G.S.R. 788(E), dt. 10.10.1985. 3. Ins. by G.S.R. 28(E), dt. 22.1.1993.
2. Subs. by G.S.R. 462(E), dt. 22.6.1982.
FORM
27A
(See rule
75A)
Application for grant or renewal of a loan
1
[licence to manufacture for sale or for
distribut
i
on
of] drugs specified in Schedules C and C(1)
2
[excluding those specified i
n
Part XB and Schedule
X]
1. I /
W
e
*
.....................................of
#
....................................................
…..hereby apply
for the grant/ renewal of Loan Licence to manufacture on the premises situated
at
C/o
$
……………………………………….
the undermentioned drugs, being drugs specified
in Schedules C and C (1)
2
[excluding those specified in Part XB and Schedule X] to the Drugs
and Cosmetics Rules.
Names of drugs (each substance to be separately specified).
2. The names, qualifications and experience of the expert staff actually connected with
the manufacture and testing of the specified products in the manufacturing premises.
(a) Name (s) of expert staff responsible for
manufactur
e
..................................
(b) Name (s) of the expert staff responsible for testing ...........................................
3. I /We
enclose:
(a) A true copy of a letter from me / us to manufacturing concern whose
manufacturing capacity is intended to be utilized by me / us.
(b) A true copy of a letter from the manufacturing concern that they agree to
lend the services of their competent technical staff, equipment and premises
for the manufacture of each item required by me / us and that they shall
Drugs and Cosmetics Rules 1945
247
will analyse every batch of finished product and maintain the registers of raw
materials, finished products and reports of analysis separately on this behalf.
(c) Specimens of labels, cartons of the drugs proposed to be
m
a
nufactured.
4. A fee of Rs
........................................................
has been credited to Government under
the head of acc
ount
..........................................................
…………………………………….
Date
....................................... Signature
..................
……
Designation………………..
* Enter here name of the proprietor, partners or Managing Director, as the case may be.
# Enter here name of the applicant firm and the address of the principal place of business.
$ Enter here the name and address of the manufacturing concern where the manufacture will be
actually carried out and also the licence number under which the latter operates.
1. Subs. by G.S.R. 788(E) ,dt. 10.10.1985.
2. Ins. By G.S.R. 462(E), dt: 22.6.1982.
1
[FORM
27B
Application for grant or renewal of a
2
[licence to manufacture for sale or for distribution
o
f
]
drugs specified in Schedules C, C(I) and
X
1.
I/We
...................
of ........................... hereby apply for the grant/renewal of a licence
to manufacture on the premises situated at…………………………… the undermentioned
drugs, specified in Schedules C, C(I) and X to the Drugs and Cosmetics Rules, 1945.
2. Names of drugs.
3. The names, qualifications and experience of the expert staff responsible for
the manufacture and testing of the abovementioned drugs.
(a) Name(s) of staff responsible for testing:
(b) Name(s) of staff responsible for manufacture:
4. The premises and plant* are ready for inspection/will be ready for inspection on
.....
5. A fee of rupees
..........................................
and an inspection fee of
rup
ee
s
.........
has
been credited to the Government under the head of a
ccount
......................................................
Date.................. Signature……………
Note: The application shall be accompanied by a plan of the premises.]
* Delete whichever is not applicable.
1. Subs. by G.S.R. 462(E) dt. 22.6.1982.
2. Subs. by G.S.R. 788(E) ,dt. 10.10.1985.
Drugs and Cosmetics Rules 1945
248
1
[FORM
27C
(See rule
122-F)
Application for grant/renewal* of licence for the operation of a Blood Bank for processing
of
whole blood and/or* preparation of Blood
Components
1. I/We,
................................
of M/s
.....................................................
hereby apply for the
grant of licence/renewal of licence number
................................................
dated………….to
operate a Blood Bank, for processing of whole blood and/or* for preparation of its components
on the premises situated at …………………………………………………..
2. Name(s) of the item
(s)
1.
2.
3.
3. The name(s), qualification and experience of competent Technical Staff are as under:
(a) Name(s) of Medical Officer.
(b) Name(s) of Technical Supervisor
(c) Name(s) of Registered Nurse.
(d) Name(s) of Blood Bank Technician.
4. The premises and plant are ready for inspection/will be ready for inspection on..... ….
5. A licence fee of rupees
....................
and an inspection fee of
rup
ee
s
..................
has been
credited to the Government under the Head of Account
..........................
(receipt enclosed)
Signature
.... …………………
Date
d.
........... Name and Designation………
* Delete whichever is not applicable.
Notes
:
1. The application shall be accompanied by a plan of the premises, list of machinery and
equipment for collection, processing, storage and testing of whole blood and its
components, memorandum of association/constitution of the firm, copies of certificate
relating to educational qualifications and experience of the competent technical staff and
documents relating to ownership or tenancy of the premises.
2. A copy of the application together with the relevant enclosures shall also be sent to
the Central Licence Approving Authority and to the Zonal/Sub-Zonal Officers
concerned of the Central Drugs Standard Control Organization].
_______________________________________________________________________
1. Subs. by G.S.R. 245(E), dt. 5.4.1999.
1
[FORM
27D
(See rule
75)
Application for grant or renewal of a licence to manufacture for
sale
or for distribution of
2
[Large Volume Parenterals/Sera and
Va
ccine
s/recombinant DNA (r-DNA) derived drugs]
excluding those specified in Schedule
X
1.
I/We ............................
of ..................................hereby apply for grant/renewal of a
licence to manufacture for sale or distribution on the premises situated at……………..…the
undermentioned
2
[Large Volume Parenterals/Sera and Vaccines/recombinant DNA (r-DNA)
derived drugs], specified in Schedules C
and
C(1) to the Drugs and Cosmetics Rules, 1945.
2. Name(s) of drug(s)
.........................................
(each item to be separately specified).
Drugs and Cosmetics Rules 1945
249
3. The name(s), qualifications and experience of the competent technical staff responsible
for the manufacture of the above mentioned drugs.
(a) Name(s) of staff responsible for testing ...................
(b) Name(s) of staff responsible for
manufacturing
.............
4. The premises and plant are ready for inspection/will be ready for inspection
on………………………
5. A fee of
rup
ee
s
.............................. and an inspection fee of rupees .............has been
credited to the Government under the Head of Account......................
Date: ............
S
i
gna
t
ur
e ..............................
Designation.........................
Notes:
1. The application is to be accompanied by a plan of the premises, list of machinery and
equipment to be employed for manufacture and testing, memorandum of
association/constitution of the firm, copies of qualification and experience of
competent technical staff and documents relating to ownership or tenancy of the premises.
2. A copy of the application together with the relevant enclosures shall also be sent
each to the Central Licence Approving Authority and concerned Zonal/Sub-Zonal
Officers of Central Drugs Standard Control Organization].
_
1. Ins. by. G.S.R.119(E), dt. 11-3-1996.
2. Subs. By G.S.R.26 (E) dt: 19.1.2006.
1
[FORM
27DA
(See rule
75A)
Application for grant or renewal of a loan licence to manufacture for
sale
or for distribution of
Large Volume Parenterals/Sera and
Va
ccine
s/recombinant DNA (r-DNA) derived drugs
excluding those specified in Schedule
X
1.
I/We* ............................
of #..................................hereby apply for grant/renewal of a
loan licence to manufacture on the premises situated at c/o @……………..…the
undermentioned drugs being Large Volume Parenterals/Sera and Vaccines/recombinant DNA
(r-DNA) derived drugs specified in Schedules C,
C(1) excluding those specified in Schedule X
to the Drugs and Cosmetics Rules, 1945.
2. Name(s) of drug(s)
..................................
(each item to be separately specified).
3. The name(s), qualifications and experience of the competent technical staff responsible
for the manufacture of the above mentioned drugs.
(a) Name(s) of competent technical staff responsible for testing ...................
(b) Name(s) of competent technical staff responsible for
manufacturing
.............
4. I /We
enclose:
(a) A true copy of a letter from me / us to manufacturing concern whose
manufacturing capacity is intended to be utilized by me / us.
(b) A true copy of a letter from the manufacturing concern that they agree to
lend the services of their competent technical staff, equipment and premises
for the manufacture of each item required by me / us and that they shall
will analyse every batch of finished product and maintain the registers of raw
materials, finished products and reports of analysis separately on this behalf.
(c) Specimens of labels, cartons of the drugs proposed to be
m
a
nufactured.
5. A fee of
rup
ee
s
..............................has been credited to the Government under the Head of
Account......................]
Drugs and Cosmetics Rules 1945
250
Date: ............
S
i
gna
t
ur
e ..............................
Designation.........................
* Enter here name of the proprietor, prtners or managing director, as may be.
# Enter here nam of the applicant firm and the address of the principal place of business.
@ Enter here the name and address of the manufacturing concern where the manufacture
will be actually carried out and also the license number under which the latter operates.
_
1. Ins. by. G.S.R. 574 (E), dt.07-7-2012.
1
[FORM
27E
(See rule
122F)
Application for grant/renewal* of licence to manufacture blood products for
sale or distribution
1. I/We ........................ of M/s
....................................................
hereby apply for
the grant of licence/renewal of licence number
................................................
dated………..
to manufacture Blood products on the premises situated at .......................... ……………….
2. Name(s) of the item(s)
1.
2.
3.
4.
3. The name(s), qualification and experience of competent Technical Staff are as
under:
(a) responsible for manufacturing (b) responsible for te
s
ti
ng
1. 1.
2. 2.
3. 3.
4. The premises and plant are ready for inspection/will be ready for inspection on.......
5. A licence fee of rupees ………… ..... ……………….and an inspection fee of
rup
ee
s
.............................................................................
has been credited to the Government under
th
e
Head of
Account..................................................
(receipt enclosed)
Signature
.... ………….
Date
d.
........... Name and
Designation........
….
* Delete whichever is not applicable.
Notes:
1. The application shall be accompanied by a plan of the premises, list of machinery and
equ i
pm
ent for
m
a
nu
fact ure of
bl
o
od
pr
od
u
c ts,
m
e
mora
nd
um
o
f
association/constitution of the firm, copies of certificate relating to educational
qualifications and experience of the competent technical staff and documents relating to
ownership or tenancy of the said premises.
2. A copy of the application together with the relevant enclosures shall also be sent to
the Central Licence Approving Authority and to the Zonal/Sub-Zonal Officers
concerned of the Central Drugs Standard Control Organization].
1. Ins. by G.S.R. 245(E), dt. 5-4-1999.
Drugs and Cosmetics Rules 1945
251
1
[FORM
27F
(See rule
122F)
Application for grant/renewal* of licence for collection, processing, testing,
storage, banking and release of umblical cord blood stem cells
1. I/We ........................ of M/s
....................................................
hereby apply for
the grant of licence/renewal* of licence number
................................................
dated………..
for collection, processing, testing, storage, banking and release of umblical cord blood stem
cells on the premises situated at .......................... ……………….
2. Name(s), qualification and experinec of competent technical staff are as under:
1. Medical Director
2.Laboratory In-charge
3.Technical Supervisor
4.Cord Blood Bank Technician (s)
3. The premises and plant are ready for inspection/will be ready for inspection on.......
4. A licence fee of rupees ………… ..... ……………….and an inspection fee of
rup
ee
s
............
has been credited to the Government under
th
e Head of
Account..................................................
(receipt enclosed)
Signature
.... ………….
Date
d.
........... Name and
Designation........
….
* Delete whichever is not applicable.
Notes:
1. The application shall be accompanied by a plan of the premises, list of machinery and
equ i
pm
ent for
m
a
nu
fact ure of
bl
o
od
pr
od
u
c ts,
m
e
mora
nd
um
o
f
association/constitution of the firm, copies of certificate relating to educational
qualifications and experience of the competent technical staff and documents relating to
ownership or tenancy of the said premises.
2. A copy of the application together with the relevant enclosures shall also be sent to
the Central Licence Approving Authority and to the Zonal/Sub-Zonal Officers
concerned of the Central Drugs Standard Control Organization].
1. Ins. by G.S.R. 899(E), dt. 27-12-2011.
FORM
28
(See rule
76)
1
[Licence to manufacture for sale or for distribution of] drugs specified i
n
Schedules C and C (1)
2
[excluding those specified in Schedule X]
Number of Licence and date of issue .................................................................
1. ………………………………. is hereby licensed to manufacture at the premises
situated at the following drugs, being drugs specified in Schedules C and C (1)
2
[excluding
those specified in Schedule X] to the Drugs and Cosmetics Rules, 1945.
Names of drugs .........................................................
2. Names of approved
3
[competent technical staff].
3. The licence authorises the sale by way of wholesale dealing and storage for sale by
the licensee of the drugs manufactured under the licence subject to the conditions applicable to
licences for sale.
4. The licence will be in force from
.........................................to
.......................
Drugs and Cosmetics Rules 1945
252
5. The licence is subject to the conditions stated below and to such other conditions as
may be specified in the Rules for the time being in force under the Drugs and Cosmetics
Act,1940.
Date:………
Signature………….
Designation……….
4
[*Licensing Authority/Central Licence Approving Authority]
*Delete whichever is not applicable
Conditions of
Licence
1 This licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced at the request of an Inspector appointed under the Drugs and
Cosmetics Act, 1940.
2 If the licensee wants to undertake during the currency of the licence the manufacture
any drug specified in Schedules C and C (1)
2
[excluding those specified in Schedule X] not
included above, he should apply to the Licensing Authority for the necessary endorsement as
provided in rule 75(3). This licence will be deemed to extend to the items so endorsed.
3 Any change in the
3
[competent technical staff] shall be forthwith reported to the
Licensing
Au
t
hor
it
y.
4 The licensee shall inform the Licensing Authority in writing in the event of any change in
the constitution of the firm operating under the licence. Where any change in the
constitution of the firm takes place, the current licence shall be deemed to be valid for a
maximum period of three months from the date on which the change takes place unless,
in the meantime, a fresh licence has been taken from the Licensing Authority in the name
of the firm with the changed constitution.
1. Subs. by G.S.R. 788(E), dt. 10.10.1985.
2. Ins. by G.S.R. 462(E), dt. 22.6.1982.
3. Subs. by G.S.R. 231(E), dt. 4.6.1996
4. Subs. by G.S.R. 923(E), dt. 14.12.1992.
FORM
28A
(See rule
76-A)
Loan
1
[Licence to manufacture for sale or for distribution of] drugs specified in Schedules
C
and C (1)
2
[excluding those specified in Schedule
X
]
1. Number of licence and date of issue ............................................................
2. …………………………………….
of............................................
……………..is
hereby granted a loan licence to manufacture on the premises situated at ……………...
C
/
o
............................................................................
the following drugs being drugs specified in
Schedules C and C (1)
2
[excluding those specified in Schedule X] to the Drugs and Cosmetics
Rules, 1945.
Names of Drugs ......................................................
3. Names of
3
[competent technical
staff]
................................................
4
[3A. The licence shall be in force
from ............................................
to....................
4. The licence authorises the sale by way of wholesale dealing by the licensee and
storage for sale by the licensee of the drugs manufactured under the licence subject to the
conditions applicable to licence for sale.
5 The licence is subject to the conditions stated below and to such other conditions as
may be specified in the Rules for the time being in force under the Drugs and Cosmetics Act,
1940.
Drugs and Cosmetics Rules 1945
253
Date of issue: ……….
Signature…………
Designation
................
Conditions of Licence
1. This licence and any certificate of renewal in force shall be kept
on the approved premises and shall be produced at the request of
an Inspector appointed under the Drugs and Cosmetics Act, 1940.
2. If the licensee wishes to undertake during the currency of the
licence to manufacture any drugs specified in Schedules C and C (1)
2
[excluding those specified in Schedule X] not included above, he should
apply to the Licensing Authority for the necessary endorsement to the
licence as provided in rule 75A. This licence will be deemed to extend to
the items so endorsed.
3. Any change in the
3
[competenet technical staff] shall be
forthwith reported to the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of
any change in the constitution of the firm operating under the licence.
Where any change in the constitution of the firm takes place, the
current licence shall be deemed to be valid for a maximum period of
three months from the date on which the change takes place unless, in the
meantime, a fresh licence has been taken from the Licensing Authority in
the name of the firm with the changed constitution.
1. Subs. by G.S.R 788(E), dt. 10-10-1985.
2. Ins. by G.S.R. 462(E), dt. 22.6.1982.
3. Subs. by G.S.R.231(E) dt. 4.6.1996.
4. Added by Notfn. F. No. 1-10/62-D, dated 10.4.1964.
1
[FORM
28B
(See rule
76)
2
[Licence to manufacture for sale or for distribution of] drugs specified
in
Schedules C, C(I) and
X
No of Licence…………………………………………………………………………
1. .............................................................. is hereby licensed to manufacture
at the premises situated at
..................................................
the following drugs specified
in Schedules C, C(I) and X to the Drugs and Cosmetics Rules, 1945.
Name of
drugs………………………………………………
2. Names of
3
[competent technical staff]
3. The licence authorises the sale by way of wholesale dealing and storage for
sale by the licensee of the drugs manufactured under the licence subject to the
conditions applicable to licence for sale.
4. The licence will be in force...................to ....................................
5. The licence is subject to conditions stated below and to other conditions as
may be specified in the rules for the time being in force under the Drugs and
Cosmetics Act, 1940.
Date:………
Signature………….
Designation……….
4
[*Licensing Authority/Central Licence Approving Authority]
*Delete whichever is not applicable
Drugs and Cosmetics Rules 1945
254
Conditions of
Licence
1. The licence and any certificate of renewal in force shall be kept on the approved
premises and shall be produced at the request of an Inspector appointed under the Drugs
and Cosmetics Act, 1940.
2. If the licensee wishes to undertake during the currency of the licence
the manufacture of any drug specified in Schedule X not included above, he should
apply to the Licensing Authority for the necessary endorsement as provided in Rule
75(4). This licence will be deemed to be applicable to the items so endorsed.
3. Any change in the
1
[competent technical staff] shall be forthwith reported to
the Licensing Authority.
4. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under licence. Where any change in
the constitution of the firm takes place, the current licence shall be deemed to be
valid for a maximum period of three months from the date on which the change takes
place unless, in the meantime, a fresh licence has been taken from the Licensing
Authority in the name of the firm
with the changed
constitution.
5. The licensee shall furnish to the Licensing Authority copies of the invoices
of sales made to dealers.
6. The licensee shall not manufacture drugs specified in Schedule X covered by
this licence for use as ―Physicians Samples‖.]
__________________________________________________________________
1. Subs. by G.S.R. 462(E) dt. 22.6.1982.
2. Subs. by G.S.R.788(E) dt. 10.10.1985.
3. Subs. by G.S.R.231(E) dt. 4.6.1996.
4. Subs. by G.S.R. 923(E) dt. 14.12.1992.
1
[FORM
28C
(See rule
122-G)
Licence to operate a Blood Bank for collection, storage and processing of whole
human
blood
and/or* its components for sale or
dis
t
ribu
t
ion
l. Number of licence................ date of issue
...........................
at the premises
situated at
…………………………………………………………………………………….
2.
M
/
s
..........................................
is hereby licensed to collect, store, process and
distribute whole blood and/or its components.
3. Name(s) of the item(s) :
1.
2.
4. Name(s) of the Competent Technical Staff:
1.
2.
3.
5. The licence authorises licensee to collect, store, distribute and
processing of whole blood and/or blood components subject to the conditions
applicable to this licence.
6. The licence shall be in force from ................ …………….to..…………..
7. The licence shall be subject to the conditions stated below and to such
other conditions as may be specified from time to time in the Rules made
under Drugs and Cosmetics Act, 1940.
Dated: ……
Drugs and Cosmetics Rules 1945
255
Signature………………………
Name and
Des
i
gna
t
ion
.............
*Licensing
Authority/
*Central Licence Approving
Authority
* Delete whichever is not applicable
Conditions of Licence
1. The licensee shall neither collect blood from any professional donor
or paid donor nor shall he prepare blood components from the blood
collected from such a donor.
2. The licence and any certificate of renewal in force shall be displayed
on the approved premises and the original shall be produced at the
request of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
3. Any change in the technical staff shall be forthwith reported to the
Licensing
Authority and/or Central Licence Approving Authority.
4. The licensee shall inform the Licensing Authority and/or Central
Licence approving Authority in writing in the event of any change in the
constitution of the firm operating under the licence. Where any change in
the constitution of the firm takes places, the current licence shall be
deemed to be valid for maximum
period of three months from the date on which the change has taken
place unless, in the meantime, a fresh licence has been taken from the
Licensing Authority and/or Central Licence Approving Authority in the
name of the firm with the changed constitution.]
1.Ins. by G.S.R. 245(E), dt.
5.4.1999.
1
[FORM
28D
(See Rules
76)
Licence to manufacture for saleor for distribution of
2
[Large Volume
Parenterals/Sera
and
Vaccines/recombinant DNA (r-DNA) derived drugs] specified in
Schedules C and C(I) excluding those specified in Schedule
X
Number of
licence ...............................................
and date of
issue……………………….
1.
.................................
is hereby licensed to manufacture at the premises
situated
at.................................................
the following
2
[Large Volume
Parenterals/Sera and Vaccines/recombinant DNA (r-DNA) derived drugs] specified in
Schedules C and C(1) excluding those specified in Schedule X to the Drugs and
Cosmetics Rules, 1945.
2. Name(s) of drug(s).......................(each item to be separately specified).
3. Name(s) of competent technical staff:
(a) responsible for manufacturing (b) responsible for testing
1. 1.
2. 2.
4. The licence authorises the sale by way of wholesale dealing and storage
for sale
Drugs and Cosmetics Rules 1945
256
by the licensee of the drugs manufactured under the licence, subject to the conditions
applicable to licence for sale.
5. The licence shall be in force
from......................................................
t
o
......................
6. The licence shall be subject to the conditions stated below and to
such other
conditions as shall be specified in the rules for the time being in force under the
Drugs and
Cosmetics
Act, 1940.
Date: ……..
Signature………
Designation…...
*Licensing Authority/*Central Licence Approving Authority
* Delete whichever is not applicable
Conditions of
Licence
1. The licence and any certificate of renewal in force shall be kept on the
approved premises and shall be produced at the request of an Inspector
appointed under the Drugs and Cosmetics Act, 1940.
2. If the licensee wishes to undertake during the currency of the licence
to manufacture of any drug specified in Schedule C and/or C(I) excluding those
specified in Schedule X not included above, he should apply to the Licensing
Authority and or Central Licence Approving Authority for the necessary endorsement
as provided in the rules. This licence shall be deemed to extend to the items so
endorsed.
3. Any change in the competent technical staff named in the licence shall be
forthwith reported to the Licensing Authority and/or Central Licence Approving
Authority.
4. The licensee shall inform the licensing authority and/or Central Licence
Approving Authority in writing in the event of any change in the constitution of
the firm operating under the licence. Where any change in the constitution of the firm
takes place, the current licnece shall be deemed to be valid for a maximum period of
three months from the date on which the change takes place unless, in the meantime, a
fresh licence has been applied
along with
prescribed fee and necessary documents to the
Licensing Authority and/or Central Licence Approving Authority in the name of the
firm with the changed constitution.]
____________________________________________________________________
1. Ins. by G.S.R. 119(E), dt: 11.3.1996.
2. Subs. By G.S.R. 26(E), dt: 19.1.2006.
1
[FORM
28DA
(See Rules
76A, 78A, 83AA)
Loan licence to manufacture for sale or for distribution of Large Volume
Parenterals/Sera
and
Vaccines/recombinant DNA (r-DNA) derived drugs excluding
those specified in Schedule
X
Number of
licence ...............................................
and date of
issue……………………….
1.
................................. of …………………..
is hereby granted a loan license to
manufacture on the premises situated
at....................c/o.............................
the
following drugs being
2
[Large Volume Parenterals/Sera and Vaccines/recombinant
Drugs and Cosmetics Rules 1945
257
DNA (r-DNA) derived drugs] specified in Schedules C and C(1) excluding those
specified in Schedule X to the Drugs and Cosmetics Rules, 1945.
2. Name(s) of drug(s).......................(each item to be separately specified).
3. Name(s) of competent technical staff:
(a) responsible for manufacturing (b) responsible for testing
1. 1.
2. 2.
4. The licence authorises the sale by way of wholesale dealing and storage for
sale by the licensee of the drugs manufactured under the licence, subject to the
conditions applicable to licence for sale.
5. The licence shall be in force
from......................................................
t
o
......................
6. The licence shall be subject to the conditions stated below and to
such other conditions as shall be specified in the rules for the time being in
force under the Drugs and Cosmetics Act, 1940.
Date: ……..
Signature………
Designation…...
*Licensing Authority/*Central Licence Approving Authority
* Delete whichever is not applicable
Conditions of
Licence
1. The licence and any certificate of renewal in force shall be kept on the
approved premises and shall be produced at the request of an Inspector
appointed under the Drugs and Cosmetics Act, 1940.
2. If the licensee wishes to undertake during the currency of the licence
to manufacture of any drug specified in Schedule C and/or C(I) excluding those
specified in Schedule X not included above, he should apply to the Licensing
Authority and or Central Licence Approving Authority for the necessary endorsement
as provided in the rules. This licence shall be deemed to extend to the items so
endorsed.
3. Any change in the competent technical staff named in the licence shall be
forthwith reported to the Licensing Authority and/or Central Licence Approving
Authority.
4. The licensee shall inform the licensing authority and/or Central Licence
Approving Authority in writing in the event of any change in the constitution of
the firm operating under the licence. Where any change in the constitution of the firm
takes place, the current licnece shall be deemed to be valid for a maximum period of
three months from the date on which the change takes place unless, in the meantime, a
fresh licence has been applied
along with
prescribed fee and necessary documents to the
Licensing Authority and/or Central Licence Approving Authority in the name of the
firm with the changed constitution.]
____________________________________________________________________
1. Ins. by G.S.R. 574(E), dt: 17.7.2012.
1
[FORM
28E
(See rule 122
G)
Licence to manufacture and store blood products for sale or
dis
t
ribu
ti
on.
l. Number of licence ............ date of issue
................................
at the premises
situated at…………………………………....................................................................
Drugs and Cosmetics Rules 1945
258
2.
M
/
s
........................................
is hereby licensed to manufacture, store, sell or
distribute the following blood products:-
3.
Name(s) of the item(s) :
1.
2.
3.
4.
Name(s) of the competent technical staff:
(a) responsible for manufacturing
(b) responsible for testing
1.
1.
2.
2.
3.
3.
5. The licence authorises licensee to manufacture, store, sell or distribute
the blood products, subject to the conditions applicable to this licence.
6. The licence shall be in force
from
................ to........................
7. The licence shall be subject to the conditions stated below and to such
other conditions as may be specified from time to time in the rules made under
Drugs and Cosmetics Act, 1940.
Dated.: ........
S
i
gnatur
e
..........
………………..
Name and
Designation
..
……….
*Licensing Authority/ *Central Licence Approving
Authority
* Delete whichever is not applicable
Conditions of License
1. The licensee shall not manufacture blood products from the blood drawn
from any professional donor or paid donor.
2. The licence and any certificate of renewal in force shall be displayed on
the approved premises and shall be produced at the request
of an Inspector appointed under the Drugs and Cosmetics Act, 1940.
3. Any change in the technical staff shall be forthwith reported to the
Licensing Authority and/or Central Licence Approving Authority.
4. The licensee shall inform the Licensing Authority and/or Central
Licence Approving Authority in writing any change in the constitution
of the firm operating under the licence. In the event of any change
in the constitution of the firm, the licence shall be deemed to be
valid for a period of three months from the date on which the change
takes place unless, in the meantime, a fresh licence has been taken
from the Licensing Authority and/or Central Licence
Ap
provin
g
Auth
ority in the name of the firm with the c
h
anged constitution.]
_
1. Ins. by G.S.R. 245(E), dt. 5.4.1999.
1
[FORM
28F
(See rules 122
F to 122-I, 122K, 122P)
Licence To Collect, Process, Test, Store, Banking And Release Of Umbilical
Cord Blood Stem Cells
.
Drugs and Cosmetics Rules 1945
259
l. Number of licence ............ date of issue
................................
at the premises
situated at…………………………………....................................................................
2.
M
/
s
........................................
is hereby licensed to collect, process, test, store,
banking and release of umbilical cord blood stem cells.
3.
Name(s) of competent technical staff :
1.
2.
3.
4.
4. The licence authorises licensee to collect, process, test, store, banking and
release of umbilical cord blood stem cells.
5. The licence shall be in force
from
................ to........................
6. The licence shall be subject to the conditions stated below and to such
other conditions as may be specified from time to time in the rules made under
Drugs and Cosmetics Act, 1940.
Dated.: ........
S
i
gnatur
e
..........
………………..
Name and
Designation
..
……….
*Licensing Authority/ *Central Licence Approving
Authority
* Delete whichever is not applicable
Conditions of License
1. Umbilical cord blood specific for an individual will be collected after signing an
agreement with the parent(s), whose child‘s umbilical cord blood is to be collected,
and the cord blood bank.
2. Umbilical cord blood shall be collected from hospitals, nursing homes, birthing
centres and from any other place where a consenting mother delivers, under the
supervision of the qualified Registered Medical Practitioner responsible for the
delivery.
3. The licence and any certificate of renewal in force shall be displayed on the approved
premises and the original shall be produced at the request of an inspector appointed under
the Drugs and Cosmetics Act, 1940.
4.Any change in the technical staff shall be forthwith reported to the
Licensing Authority and/or Central Licence Approving Authority.
5. The licensee shall inform the Licensing Authority and/or Central
Licence Approving Authority in writing any change in the constitution
of the firm operating under the licence. In the event of any change
in the constitution of the firm, the licence shall be deemed to be
valid for a period of three months from the date on which the change
takes place unless, in the meantime, a fresh licence has been taken
from the Licensing Authority and/or Central Licence
Ap
provin
g
Auth
ority in the name of the firm with the c
h
anged constitution.]
_
1. Ins. by G.S.R. 889(E), dt. 27.12.2011.
FORM
29
(See rule
89)
Licence to manufacture drugs for purposes of examination, test or
analysis
Drugs and Cosmetics Rules 1945
260
1.
…......................of…………………
is hereby licensed to
manufacture the drugs specified below for purposes of examination, test or
analysis at………………………………
2. This licence is subject to the conditions prescribed in Part VIII of the
Drugs and Cosmetics Rules, 1945.
3. This licence shall be in force for one year from date specified below.
Names of
drugs
Date : ……… Licensing
Authority………………
FORM
30
(See rule
90)
Application for licence to manufacture drugs for purposes of examination, test
or
analysis
1.
…………………………………….of
..............
…………………by
occupation
..................... hereby apply for licence to manufacture the drugs specified below for
purposes of examination, test or analysis at and I undertake to comply with the
conditions applicable to the licence.
Names of
Drugs
Date.........................................
Signature…………………..
1
[FORM
31
(See rule
139)
Application for grant or renewal of a
2
[licence to manufacture cosmetics for sale or f
or
Distribution]
1
.
1
/
We.........................................
of.
........................ hereby apply for grant
/renewal of a licence to manufacture on the premises situated at.......... the following
cosmetics :-
2. Names of Cosmetics ......................................................................
3. Names, qualifications and experience of technical staff employed for
manufacture and te
sting
..........................................................
………
4. A fee of rupees ...........................................has been credited to
Government under the head of account........................................................
Date...................................... Signature…………..
Note: The application should be accompanied by a plan of the premises.
1. Added by Notfn No.F.1-36/64-D (G.S.R.1183), dt:17.8.1964.
2. Subs. by G..S.R .788 (E), dt. 10.10.1985.
1
[FORM
31A
(See
rule138A)
Application for grant or renewal of loan
2
[licence to manufacture cosmetics for sale or
for distribution]
Drugs and Cosmetics Rules 1945
261
1. I /
W
e
...............................................of.
.............................hereby apply
for gra
n
t/
r
enewal of a loan licence to
m
a nufacture c
o
smetics for sale on
the
premises
s i t
u
at e d
at………………………….C/o
..............……………….the
following
cosmetics
:—
2. Names of Cosmetics..............................................................
3. The names, qualifications and experience of the expert shall actually connected
with the manufacture and testing of the specified products in the manufacturing
premises.
4. I /We enclose−
(a) A true copy of a letter from me / us to the manufacturing concern
whose manufacturing capacity is intended to be utilized by me / us.
(b) A true copy of a letter from the *manufacturing concern that they agree to
lend the services of their competent technical staff, equipment and premises for
the manufacture of each item required by me / us and that they will analyse every
batch of and maintain the registers of raw materials , finished products and
reports of analysis separately in this behalf.
(c) specimen of labels, cartons of the products proposed to be manufactured.
5. A fee of
rup
ee
s
.........................................................
has been credited to
Government under the head of account..........................................................
Date…………. Signature…………
*Enter here the name and address of the manufacturing concern where the manufacture
will be actually carried out and also their licence number.
1. Ins. by G.S.R. 444, dt. 28-4-1973.
2. Subs. by G.S.R. 788(E), dt. 10.10.1985.
1
[FORM
32
(See
rule140)
2
[Licence to manufacture cosmetics for sale or for distribution]
Number of Licence and date of issue
1 ...…………………is hereby licensed to manufacture on the premises
situated at
...........................................
the following cosmetics under the supervision of the
following technical staff:-
(a) Names of cosmetics.
(b) Names of technical staff
2. The licence shall remain in force from…………..to…………(both days inclusives)
3. The licence is subject to the conditions stated below and to such other conditions
as may be specified in the Drugs and Cosmetics Rules, 1945.
Date.......................................... Signature ..............
Designation ............
Conditions of
Licence
1. This licence and any certificate of renewal in force shall be kept on the
approved
premises and shall be produced at the request of an Inspector
appointed under the Drugs and Cosmetics Act, 1940.
Drugs and Cosmetics Rules 1945
262
2. Any change in the technical staff shall be forthwith
reported to the Licensing Authority.
3. If the licensee wants to manufacture for sale of additional items he should
apply to the Licensing Authority for the necessary endorsement to the licence
as provided in rule 138 (3). This licence shall be deemed to extend to the cosmetics so
endorsed.
3
[4. The licensee shall inform the Licensing Authority in writing in the event of any
change in the constitution of the firm operating under the licence. Where any change
in the constitution of the firm takes place, the current licence shall be deemed to be
valid for a maximum period of three months from the date on which the change takes
place unless, in the meantime, a fresh licence has been taken from the Licensing
Authority in the name of the firm with the changed constitution.]
1. Added by Notfn No.F.1-36/64-D, dt:17.8.1964.
2. Subs. by G.S.R. 788 (E), dt. 10.10.1985.
3. Added by S.O. 903, dt. 10-2-1976.
1
[FORM
32A
(See rule
139B)
Loan
2
[licence to manufacture cosmetics for sale or for
dis
t
ribution
]
1. Number of Licence and date of issue…………………………
2 .
................................................of. .............................................
is hereby granted
a loan licence to manufacture the following cosmetics on the premises situated
at
..............................................................C
/
o............................................
under the
direction and personal supervision of the following technical staff:
(a) Names of technical staff.
(b) Names of cosmetics.
3. The licence shall remain in force from
...........................
to ..................
4. The licence is subject to the conditions stated below and to such other
conditions as are specified in the rules for the time being in force under the Drugs and
Cosmetics Act, 1940.
Date.................................... Signature ..................
D
e
s
i
gna
ti
on
..............
Conditions of
Licence
1. This licence and any certificate of renewal in force shall be kept on the
approved premises and shall be produced at the request of an Inspector
appointed under the Drugs and Cosmetics Act, 1940.
2. Any change in the technical staff shall be forthwith reported to the
Licensing Authority.
3. If the licensee wants to manufacture for sale additional items he should apply to
the Licensing Authority for the necessary endorsement to the licence as
provided in rule 138A(5).This licence shall be deemed to extend to
the cosmetics so endorsed.]
____________________________________________________________________
1. Ins. by G.S.R. 444, dt. 28-4-1973.
2. Ins. by G.S.R. 788 (E), dt. 10.10.1985.
1
[FORM
33
(See rule
141)
Certificate of renewal of licence to manufacture cosmetics for
sal
e
Drugs and Cosmetics Rules 1945
263
1. Certified that licence No………………….granted on the……………………….
t
o………………………f
or t
h
e
m
a
nu
factu
re
fo
r sale
o
f the
fo
ll
owin
g cosmetics
at the premises situated at……………………has been renewed
from……………and shall expire on……………………………
2. Names of cosmetics.
3. Names of technical staff
Date…………….. Signature……………..
Designation……………]
_____________________________________________________________________________________
1. Ins. by G.S.R. 1183, dt. 17.8.1964.
1
[FORM
33A
(See rule
141-A)
Certificate of renewal of loan licence to manufacture cosmetic for
sale
1. Certified that loan licence No………….granted on the ………………..
. to……………………for the manufacture for sale of the following
cosmetics at the premises situated at C/o………………………………………has
been renewed
from…………………………………to
.......................................................
2. Names of cosmetics.
3. Names of technical staff.
Date……… Signature………..
Designation………]
1. Added by G.S.R. 444, dt. 28-4-1973.
1
[FORM
34
(See rules 131 and
150)
Certificate of test or analysis of cosmetic by the Central Drugs Laboratory
or
the
Government Analyst
1. Name of the officer or Inspector from whom received ........................................
2. Serial number and date of the Officer's / Inspector's memorandum ..................
3. Number of
samp
le ....................................................
4. Date of
receip
t ........................................................
5. Name of the Cosmetic purporting to be contained in the sample………….
6. Condition of seals on the
2
[packet or on portion of sample or container]
7. Results of test or analysis :— The sample of cosmetics—
(a) contains a prescribed colour only/does not contain a prescribed colour.
(b) does not contain harmful ingredients/ contains harmful ingredients
(c) conforms/does not conform to claims m,ade on the label as to the nature and quality
of the cosmetics.
3
[(d) contains not more than …………….parts per million of Lead and ………..parts
per million of Arsenic……………../contains more than ………………parts per
million of Lead and ………parts per million of Arsenic.]
Date……
Director…………………..
Central Drugs Laboratoy/Government Analyst]
Drugs and Cosmetics Rules 1945
264
1. Added by Notfn No.F.1-36/64-D (G.S.R 1183), dt:17.8.1964.
2. Subs. by G.S.R. 59(E), dt. 7.2.1995.
3. Subs. by G.S.R. 510(E), dt. 26.7.1982.
1
[FORM
35
2
[See Rules 65, 67-G, 74, 74A, 74B, 78, 78A, 85H, 122P, 142, 142-B,
150E, 158 and
158A]
Form in which the Inspection Book shall be
ma
i
n
t
a
i
ned
(A) The cover of the Inspection Book shall contain the following particulars, namely :—
1. The name and address of the licensee..........................................................
2. Licence number and the date upto which the licence is valid
.............................
(B)
(i) The pages of the Inspection Book shall be serially numbered and duly
stamped by the Licensing Authority. The pages, other than the first and the last
pages, shall have the following particulars:--
Name and designation of the Inspector who inspects the premises of the licensee:−
Date of Inspection........................
Observations of the
Inspector
.................
Signature of the
Insp
ect
or
(ii) The first and last pages of the Inspection Book shall be endorsed by the Licensing
Authority with the following words, namely:—
Inspection Book maintained by M/s………………………………………………
situated at ………… for licence number ………… in Form ……….. under the
Drugs and Cosmetics Rules, 1945.
Seal and Signature of the Licensing Authority.
Notes:-
(i) Printed copy of the Inspection Book may be obtained by the licensee from the
Licensing Authority on payment.
(ii) The Inspection Book shall be maintained at the premises of the licensee.
(iii) The observations made by the Drug Inspector shall be in triplicate. The
original copy shall be retained in the Inspection Book to be maintained in the
premises of the licensee. The duplicate copy shall be sent to the Licensing
Authority. The triplicate copy shall be taken as record by the Inspector.
1. Added by Notfn. No.F.1-14/68-D (G.S.R. 3869), dt. 26.10.1968.
2. Subs. by G.S.R. 592(E), dt: 13.8.2008.
1
[FORM
36
(See rule
150B)
Application for grant or renewal of approval for carrying out tests on drugs/
cosmetics or
raw
materials used in the manufacture thereof on behalf of licensees
for manufacture for sale
of
drugs /c
osme
tics
(1)
*I/We………………………………….of………………………….hereby
apply
for the grant or renewal of approval for carrying out tests of identity, purity,
quality and strength on the following categories of drugs / items of cosmetics or
Drugs and Cosmetics Rules 1945
265
raw materials used in the manufacture thereof on behalf of licensees for manufacture
for sale of drugs / cosmetics.
(2) *Categories of drugs, items of cosmetics:
(a) Drugs other than those specified in Schedules C and C (1) and also
excluding Homoeopathic Drugs:-
1. Crude vegetable drugs.
2. Mechanical contraceptives.
3. Surgical dressings.
4. Drugs requiring the use of ultravoilet /
Infra Red. or Chromatography.
5. Disinfectants.
6. Other drugs.
(b) Drugs specified in Schedules C and C (1):—
1. Sera, Vaccines, Antigens, Toxins, Antitoxins,
Toxoids, Bacteriophages and similar
Immunological Products.
2. Antibiotics.
3. Vitamins
4. Parenteral preparations.
5. Sterilized surgical ligature / suture.
6. Drugs requiring the use of animals for their test.
7. Drugs requiring microbiological tests.
8. Drugs requiring the use of Ultravoilet/ Infra Red/ Spectrophotomete
or
Chromatography.
9. Other drugs.
(c) Homoeopathic drugs.
(d) Cosmetics.
(3) Name, qualifications and experience of expert staff employed for testing
and the person-in-charge of testing.
(4) List of testing equipments
provided.
(5) *I/We enclose a plan of the testing premises showing the location and area
of the different sections thereof.
(6) An inspection fee of rupees ........................................................has been
credited to Government under the Head of Account...................................................
Date.......................... Signature………]
* Delete whichever is not applicable
1. Ins. by Notfn. No .X. 11014/7/76-D&MS (G.S.R 1172), dt. 23-8-1977.
1
[FORM
37
(See rule
150C)
Approval for carrying out tests on drugs / cosmetics and raw materials used in their
manu
f
a
ct
ur
e on behalf of licensees for manufacture for sale of drugs /c
osme
tics
Number of approval and date of issue:…………………………
Drugs and Cosmetics Rules 1945
266
(1) Approval is hereby granted t
o
...............................................................
…….for
carrying out tests for identity, purity, quality and strength on the following categories
of drugs/items of cosm etic s a
n
d the
ra
w
m
a terials
use
d in the
m
a
nufac
ture
thereof on the
pre
m
ise
s situat
ed
..........................................................................
Categories of drugs / items of cosmetics
…………………………..
…………………………..
…………………………..
(2) Names of
2
[competent technical staff] employed for testing and the
person-in- charge of testing.
(3) The approval shall be in force
from
.........................................
to........................
(4) The approval is subject to the conditions stated below and such other
conditions as may be specified in the rules for the time being in force under the Act.
Date.....................................
Signature
...................................
Designation
................................
Conditions of
Approval
(1) This approval and any certificate of renewal in Form 38 shall be kept in the
approved premises and shall be produced at the request of the Inspectors appointed
under the Act.
(2) If the approved institution wishes to undertake during the currency of the
approval the testing of any other category of drugs or items of cosmetics it should
apply to the approving authority for necessary endorsement as provided in rule
150-B.This approval will be deemed to extend to the item so endorsed.
(3) Any change in the analytical staff or in the person-in-charge of the testing
shall be forthwith reported to the approving authority.
3
[(4) The approved institution shall inform the approving authority in writing in the
event of any change of the constitution of the institution operating under this Form.
Where any change in the constitution of the institution takes place, the current approval
shall be deemed to be valid
for
a maximum period of three months from the date on
which the change takes place unless in the meantime, a fresh approval has been taken
from the approving authority in the name of the institution with the changed
constitution.]
1.Ins. by G.S.R.1172, dt:23.8.1977.
2. Subs. by. G.S.R. 231(E), dt. 4.6.1996.
3. Ins. by G.S.R. 681 (E), dt. 5-12-1980.
1
[FORM
38
(See rule
150J)
Certificate of renewal of approval for carrying out tests on drugs / cosmetics and raw
mater
i
als
used in the manufacture thereof on behalf of licensees for manufacture for
sale of drugs /
cosmetics
(1) Certified that approval number
..................................
granted on the
..............................................................................................
for carrying out tests of
identity, purity, quality and strength on the following categories of drugs/ items
of cosmetics and the raw materials used in the manufacture thereof at the premises
situated at…………………………has been renewed from…………….to ...................
Categories of drugs/items of cosmetics
………………………..
……………………………
Drugs and Cosmetics Rules 1945
267
(2) Names of
2
[competent technical staff] and person-in-charge of testing.
Date
............................... Signature.......……….
Designation…………..
________________________________________________________________________
1. Ins. By G.S.R. 1172, dt:23.8.1977.
2.Subs. by. G.S.R.231(E) ,dt. 4.6.1996.
1
[FORM 39
[See
rule150E(f)]
Report of test or analysis by approved institution
(1) Name of manufacturer from whom sample received together
with his manufacturing licence number under the Act and under the rules
made thereunder.
(2) Reference number and date of the letter from the manufacturer under
which the sample was forwarded.
(3) Date of receipt of the sample.
(4) Name of drug / cosmetics / raw material purporting to be contained in the
sample.
(5) Details of raw material/final product in bulk/final product (in finished
pack)* as obtained from the manufacturer:
(a) Original manufacturer's name in the case of raw materials
and drugs repacked.
(b) Batch number.
2
[(c) Batch size as represented by sample.]
(d) Date of manufacture, if any.
(e) Date of expiry, if any.
(6) Results of test or analysis with protocols of test or analysis applied.
In the opinion of the undersigned, the sample referred to above is *of
standard quality/is not of standard quality as defined in the Act and the rules made
thereunder for the reasons given below.
Date.................................. ......................................................
Signature of Person-in-charge of
testing
Note:- Final product includes repacked material.
*Delete whichever is not applicable
1. Ins. By G.S.R. 1172, dt:23.8.1977.
2. Subs. by. G.S.R. 681(E), dt. 6.6.1988.
1
[Forms 40 to
43
(Pertaining to Ayurveda, Siddha and Unani drugs replaced by Forms Nos
.47 to 50.)
[1. Ins. by G.S.R. 701(E), dt. 27.9.2001
]
1
[FORM
40
(See rule
24-A)
Application for issue of Registration Certificate for import of drugs into India under
the
Drugs
and Cosmetics Rules
1945
Drugs and Cosmetics Rules 1945
268
I
/
W
e
*
……………………………… (Name and full address) hereby apply for the
grant of Regi
stration
Certificate for the manufacturer, M/s……….……. (full address with
telephone, fax and E-mail address of the foreign manufacturer) for his premises, and
manufactured drugs meant for import into India.
1. Names of drugs for registration.
2
[***]
2. I/We enclose herewith the information and undertakings specified in Schedule
D (1) and Schedule D(II) duly signed by the manufacturer for
grant of Registration Certificate for the premises stated below.
3. A fee of_______________for registration of premises, the particulars
of
w
hich are
g
i
v
en
b
el
o
w,
o
f the
m
a
n
u
f
act
u
rer
h
as
b
een c
r
e
d
ited to t
h
e
Government under the Head of Account "0210-Medical and Public Health, 04-Public
Health, 104-Fees and Fines‖ under the Drugs and Cosmetics Rules, 1945-Central vide
Challan No.________
dated__________________(attached
in original).
4. A fee of__________________for registration of the drugs for
import as specified at Serial No. 2 above has been credited to the Government
under the Head of Account "0210-Medical and Public Health, 04-Public Health,
104-Fees and Fines" under the Drugs and Cosmetics Rules, 1945-Central vide
Challan No._______, dated___________. (attached in original).
5. Particulars of premises to be registered where manufacture is
carried on: Address
(es)………………..
Telephone
No………………..
Fax……………………………
E-mail……………………….
I/We* undertake to comply with all terms and conditions required to
obtain Registration Certificate and to keep it valid during its validity period.
Place:
Date:
Signature
Name
Designation ____________________
Seal/Stamp of manufacturer or his authorised Agent
in India.
(Note: In case the applicant is an authorised agent of the manufacturer in India, the Power of
Attorney is to be enclosed).
*Delete whichever is not applicable.
__________________________________________________________________
1. Ins. by G.S.R. 604(E) dt. 24-8-2001 (w.e.f. 1-1-2003).
2. Figures 1,2,3 omitted by G.S.R. 35(E), dt. 20.1.2005.
1
[FORM 41
(See
rule
27
A)
Regist
ration
Certificate
Registration Certificate to be issued for import of drugs into India under Drugs
and
Cosmetics Rules,
1945
Registration Certificate No…………. Date……
Drugs and Cosmetics Rules 1945
269
M/s ___________________________________ (Name and full address of registered
office) having factory premises at……..(full address) has been registered under
rule 27-A as a manufacturer and is hereby issued this Registration Certificate.
2. Name (s) of drugs which may be imported under this Registration Certificate:
2
[***]
3. This Registration Certificate shall be in force from
__________ to_unless it is sooner suspended or cancelled under the rules.
4. This Registration Certificate is issued through the office of the manufacturer
or his authorised agent in India M/s (name and full address)________ who
will be responsib le for t
h
e business activities of t
h
e manufacturer, in India in all
respects.
5. This Registration Certificate is subject to the conditions, stated below
and to such other conditions as may be specified in the Act and the
rules, from time to time.
Place……….
Date………….
Licensing Authority
Seal/Stamp
Conditions of the Registration Certificate.
1. The Registration Certificate shall be displayed at a prominent place by the
authorised agent.
2. No drug shall be registered unless it has a free sale approval in the country of
origin, and/or in other major countries.
3. The manufacturer or his authorised agent in India shall comply with the
conditions of the import licence issued under the Drugs and
Cosmetics Rules, 1945.
4. The manufacturer or his authorised agent in India shall inform the licensing
authority forthwith in the event of any administrative action taken due to adverse
reaction, viz. market withdrawal, regulatory restrictions, or cancellation of
authorization, and/or not of standard quality report of any drug pertaining
to this Registration Certificate declared by the Regulatory Authority of the
country of origin or by any Regulatory Authority of any other country, where the drug
is marketed/sold or distributed.
The dispatch and marketing of the drug in such cases shall be stopped
immediately, and the licensing authority shall be informed immediately. Further
action in respect of such stopped marketing of drug shall be followed as per the
direction of the licensing authority. In such cases, action equivalent to that taken with
reference to the concerned drug in the country of origin or in the country of marketing
shall be followed in India also, in consultation with the licensing authority. The
licensing authority may, however, direct any further modification to this course of
action, including the withdrawal of the drug from Indian market within 48 hours
time period.
5. The manufacturer or his authorised agent in India shall inform the licensing
authority within 30 days in writing in the event of any change in manufacturing process,
or in packaging, or in labelling or in testing, or in documentation of any of the
drugs pertaining to this Registration Certificate.
In such cases, where there shall be any major change/modification in
manufacturing, or in processing or in testing, or in documentation as the case may be,
at the discretion of the licensing authority, the manufacturer or his authorised agent in
Drugs and Cosmetics Rules 1945
270
India shall obtain necessary approval within 30 days by submitting a separate
application along with the registration fee, as specified in clause (ii) of sub-rule (3) of
rule 24-A.
6. The manufacturer or his authorised agent in India shall inform the
licensing authority immediately in writing in the event of any change in the
constitution of the firm and / or address of the registered office / factory premises
operating under this Registration Certificate. Where any such change in the
constitution of the firm and/or address takes place, the current Registration Certificate
shall be deemed to be valid for a maximum period of three months from the date
on which the change has taken place unless, in the meantime, a fresh
Registration Certificate has been taken from the licensing authority in the
name of the firm with the changed constitution of the firm and/or
changed address of the registered office or factory premises.]
1. Ins. by G.S.R. No.604(E), dt. 24-8-2001 (w.e.f. 1-1-2003)
2. Figures 1,2,3 omitted by G.S.R. 32, dt. 20.1.2005.
1
[FORM
42
(See rule 129
A)
Application for issue of Registration Certificate for import of cosmetics into India
under the
Drugs
and Cosmetics Rules,
1945
I
/
W
e
*
……………………………… (Name and full address) hereby apply for the
grant of Regi
stration
Certificate for the manufacturer, M/s……….……. (full address with
telephone, fax and E-mail address of the foreign manufacturer) for his premises, and
manufactured cosmetics meant for import into India.
1. Name of cosmetics along with their brand name and pack size(s) and variants for
registration.
(1) ……………… (4)………………..
(2)………………. (5)………………..
(3)………………. (6)………………...
2. I/We* enclose herewith the information and undertakings specified in
Schedule D (III) duly signed by the manufacturer for grant of Registration Certificate
for the premises stated below.
3. A fee of_______________for registration of cosmetics for import
as specified at serial no. 2 above has
b
een c
r
e
d
ited to t
h
e C e n t r a l
Government under the Head of Account "0210-Medical and Public Health, 04-Public
Health, 104-Fees and Fines‖ under the Drugs and Cosmetics Rules, 1945-Central vide
Challan No.________
dated__________________(attached
in original).
4. Particulars of premises to be registered where manufacture is carried on:
Address
(es)………………..
Telephone
No………………..
Fax………………..
E-mail……………………….
I/We* undertake to comply with all terms and conditions required to
obtain Registration Certificate and to keep it valid during its validity period.
Place:…….
Date:……..
Signature……………..
Name…………………
Designation………….
Seal/Stamp of manufacturer or his authorised Agent in India.
Drugs and Cosmetics Rules 1945
271
(Note: In case the applicant is an authorised agent of the manufacturer in India, the Power of
Attorney is to be enclosed).
*Delete whichever is not applicable.
__________________________________________________________________
1. Ins. by G.S.R. 4 26 (E) dt. 19-5-2010, read with corrigendum G.S.R263(E) dt:30.3.2011, corrigendum G.S.R.
733(E) dt:29.9.2011, corrigendum G.S.R.270(E) dt:30.3.2012 and corrigendum G.S.R. 733(E) dt:29.9.2012.
1
[FORM 43
(See
rule
129C)
Regist
ration
Certificate
Registration Certificate to be issued for import of cosmetics into India under
Drugs
and
Cosmetics Rules,
1945
Registration Certificate No…………. Date……………..…
M/s ___________________________________ (Name and full address of registered
office)…………….having factory premises at … … … … . . ( full address) has been
registered under rule 1 2 9 A as a manufacturer and is hereby issued this
Registration Certificate.
2. Name (s) of cosmetics, along with thrir brand names and pack size(s) and variants
which may be imported under this Registration Certificate:
(1)……………………
(2)……………………
(3)……………………
3. This Registration Certificate shall be in force from ……
to…………..unless it is sooner suspended or cancelled under the rules.
4. This Registration Certificate is issued through the office of the manufacturer or
his authorised agent or importer in India or by the subsidiary in India authorized by
the manufacturer, namely.-M/s (name and full address)________ who shall be
responsib le for t
h
e business activities of t
h
e manufacturer, in India in all
respects.
5. This Registration Certificate is subject to the conditions, stated below
and to such other conditions as may be specified in the Drugs and
Cosmetics Act, 1940 and the rules made thereunder, from time to time in this regard..
Place……….
Date………….
Licensing Authority
Seal/Stamp
Conditions of the Registration Certificate.
1. The Registration Certificate shall be produced by the authorised
importer/distributor/agent as and when required by the licensing authority/regulatory
authority.
2. The manufacturer or his authorised importer/distributor/agent in India shall
inform the licensing authority forthwith in the event of any administrative action
taken namely, market withdrawal, regulatory restrictions, or cancellation of
authorization, and/or not of standard quality report of any cosmetic
pertaining to this Registration Certificate declared by the Regulatory
Authority of the country of origin or by any Regulatory Authority of any
other country, where the cosmetic is marketed/sold or distributed.
The dispatch and marketing of the cosmetic in such cases shall be stopped
immediately, and the licensing authority shall be informed immediately. Further
action in respect of such stopped marketing of drug shall be followed as per the
Drugs and Cosmetics Rules 1945
272
direction of the licensing authority. In such cases, action equivalent to that taken with
reference to the concerned cosmetic in the country of origin or in the country of
marketing shall be followed in India also, in consultation with the licensing authority.
The licensing authority may, however, direct any further modification to this
course of action, including the withdrawal of the cosmetic from Indian market
within 48 hours time period.
3. The manufacturer or his authorised agent/importer/distributor or subsidiary in
India shall inform the licensing authority within 30 days in writing in the event of
additional variants/additional cosmetic category/additional manufacturing location or
any change in labeling or in testing, or in documentation of any of the
c o s m e t i c pertaining to this Registration Certificate.
In such cases, where there shall be additional variants/additional cosmetic
category/additional manufacturing location, as the case may be, at the discretion of the
licensing authority, the manufacturer or his authorised
agent/importer/distributor/subsidary in India shall apply for necessary approval within
30 days by submitting a separate application along with the registration fee.
4. The manufacturer or his authorised agent in India shall inform the
licensing authority immediately in writing in the event of any change in the
constitution of the firm and / or address of the registered office / factory premises
operating under this Registration Certificate. Where any such change in the
constitution of the firm and/or address takes place, the current Registration Certificate
shall be deemed to be valid for a maximum period of three months from the date
on which the change has taken place unless, in the meantime, a fresh
Registration Certificate has been taken from the licensing authority in the
name of the firm with the changed constitution of the firm and/or
changed address of the registered office or factory premises.]
1. Ins. by G.S.R. 4 26 (E) dt. 19-5-2010, read with corrigendum G.S.R263(E) dt:30.3.2011, corrigendum G.S.R.
733(E) dt:29.9.2011, corrigendum G.S.R.270(E) dt:30.3.2012 and corrigendum G.S.R. 733(E) dt:29..2012.
1
[FORM
44
(See rules 122A, 122B, 122D and 122
DA)
Application for grant of permission to import or manufacture a New Drug or to
und
e
r
t
a
ke clinical
trial.
I/We*…………………………………………
of
M
/
s.
........................
…………..
(address) hereby apply for grant of permission for import of and/or clinical trial or
for approval to manufacture a new drug or fixed dose combination or subsequent
permission for already approved new drug. The necessary information / data is given
below :
1. Particulars of new drug :
(1) Name of the drug.
(2) Dosage form.
(3) Composition of the formulation :
(4) Test specification.
(i) active ingredients.
(ii) inactive ingredients.
(5) Pharmacological classification of the drug.
(6) Indications for which proposed to be used.
(7) Manufacturer of the raw material (bulk drug substances).
(8) Patent status of the drug.
2. Data submitted along with the application (as per Schedule Y with indexing
and page numbers:)
A. Permission to market a new drug :
Drugs and Cosmetics Rules 1945
273
(1) Chemical and Pharmaceutical information.
(2) Animal Pharmacology.
(3) Animal Toxicology.
(4) Human / Clinical Pharmacology (Phase I).
(5) Exploratory Clinical Trials (Phase II).
(6) Confirmatory Clinical Trials (Phase III) (including published review
articles)
(7) Bio-availability, dissolution and stability study data.
(8) Regulatory status in other countries.
(9) Marketing information :
(a) Proposed product monograph.
(b) Drafts of labels and cartons.
(10) Application for test licence.
2
[(11) New Chemical Entity and Global Clinical Trial-
(a) Assessment of risk versus benefit to the patients
(b) Innovation vis-à-vis existing therapeutic option
(c) Unmet medical need in the country.]
B. Subsequent approval / permission for manufacture of already approved new
drug :
(a) Formulation:
(1) Bio-availability / bio-equivalence protocol.
(2) Name of the investigator/center.
(3) Source of raw material (bulk drug substances) and stability study data.
(b) Raw material (bulk drug substances):
(1) Manufacturing method.
(2) Quality control parameters and/or analytical specification, stability report.
(3) Animal toxicity data.
C. Approval / Permission for fixed dose combination:
(1) Therapeutic Justification.
(authentic literature in
3
[pre-reviewed journals]/text
books)
(2) Data on
pharmacokinetics/pharmacodynamics
combination.
(3) Any other data generated by the applicant on the safety and
efficacy of the combination.
D. Subsequent Approval or approval for new indication - new dosage form:
(1) Number and date of Approval / permission already granted.
(2) Therapeutic justification for new claim / modified dosage form
(3) Data generated on safety, efficacy and quality parameters.
A total fee of rupees
............................................
(in
words)
............................. has been
credited to the Government under the Head of
Account...............................
(Photocopy of
receipt is enclosed).
Dated : .....
Signature…….
Designat
i
on…………….
Note: *Delete whichever is not applicable.
_
1. Forms 44 to 46 A ins. by No.G.S.R. 900 (E), dt. 12.12.2001.
2. Ins. By G.S.R. 826 (E), dt. 30.10.2015.
3. Subs by G.S.R. 26(E), dt. 19.1.2006.
Drugs and Cosmetics Rules 1945
274
1
[FORM
45
(See rules 122 A, 122 D and 122
DA)
Permission to import Finished Formulation of a New Drug
Number of the permission and date of
issue……………………………………………..
M/s
.....................................................................
of……………………………………….
(address) is hereby permitted to import the following new drug formulation under rule
122 A /122 D/122 DA of the Drugs and Cosmetics Rules, 1945.
(1) Name of the New Drug :
(2) Dosage form :
(3) Composition :
(4) Indications :
Dated:...............
Signature............................
Name and designation of Licensing Authority
Conditions for Grant of Approval /
Permission.
(1) The formulation shall conform to the specifications approved by the
Licensing Authority.
(2) The proper name of the drug shall be printed or written in indelible ink
and shall appear in a more conspicuous manner than the trade name, if any, which
shall be shown immediately after or under the proper name on the label of the
innermost container of the drug or every other covering in which the container is
packed.
(3) The label of the innermost container of the drug and every other covering in
which the container is packed shall bear a conspicuous red vertical line on the
left side running throughout the body of the label which shall not be less than 1
mm in width and without disturbing the other conditions printed on the label to
depict it as prescription drug.
(4) The label on the immediate container of the drug as well as the packing in which
the container is enclosed should contain the following warning:
"WARNING : To be sold by retail on the prescription of a .............................. Only."
2
[(5) Post marketing surveillance study shall be conducted during initial period
of two years of marketing of the new drug formulation, after getting the protocol
and the names of the investigator duly approved by the Licensing Authority.]
(6) All reported adverse reactions related to the drug shall be intimated to the
Drugs Controller, India and Licensing Authority and regulatory action resulting from
their review should be complied with.
(7) No claims except those mentioned above shall be made for the drug without the
prior approval of the Licensing Authority.
(8) Specimen of the carton, labels, package insert that will be adopted for
marketing the drug in the country shall be got approved from the Licensing Authority
before the drugs is marketed.
(9) Each consignment of imported drug shall be accompanied by a test/analysis
report.
_
1. Ins. by No.G.S.R. 900 (E), dt. 12.12.2001.
2. Subs by G.S.R. 101(E), dt. 18.2.2011.
Drugs and Cosmetics Rules 1945
275
1
[FORM
45A
(See rules 122A and 122
DA)
Permission to import raw material (new bulk drug
substance)
Number of the permission and date of issue…………………………………………….
M/s ...................................................................................of……………………(address)
is hereby permitted to import the following raw material (new bulk drug substances)
under rule 122 A / 122DA of the Drugs and Cosmetics Rules, 1945, namely :-
Name of the raw material (new bulk drug substances):
(1) ............................................
(2) .............................................
(3) ............................................
Dated ..................
Signature
..............
Name and Designation of the Licensing Authority……………
Conditions for Grant of Approval /
P
e
rmission
(1) The raw material (new bulk drug substance) shall conform to the test
specifications as approved by the Licensing Authority.
(2) For manufacture of raw material (new bulk drug substance) or its
formulation in the country, separate approval under rule 122-B shall be obtained
from the Licensing Authority.
(3) The permission to import shall not be used to convey or imply that the raw
material
(new bulk drug) is categorized as "life saving or essential drug."]
_
1. Ins. By G.S.R. 900 (E), dt. 12.12.2001.
1
[FORM
46
(See rules 122 B, 122 D and 122
DA)
Permission / Approval for manufacture of new drug f
ormula
ti
on
Number of permission and date of issue
....................... ……………………………….
M/s
of ............................................ (address) is hereby granted Permission/Approval to
manufacture following new drug formulation under rule 122B/122D/122DA of the
Drugs and Cosmetics Rules, 1945, namely :-
(1) Name of the formulation:
(2) Dosage form:
(3) Composition:
(4) Indications:
Dated ……………. Signature ......
Name and designation of Licensing Athority……….
Conditions for Grant of Approval / Permission.
(1) The formulation shall conform to the specifications approved by the
Licensing Authority.
(2) The proper name of the drug shall be printed or written in indelible ink and
shall appear in a more conspicuous manner than the trade name, if any, which shall
be shown immediately after or under the proper name on the label of he
innermost container of the drug or every other covering in which the container is
packed.
Drugs and Cosmetics Rules 1945
276
(3) The label of the innermost container of the drug and every other covering
in which the container is packed shall bear a conspicuous red vertical line on the left
side running throughout the body of the label which shall not be less than 1 mm in
width and without disturbing the other conditions printed on the label to depict it
as prescription drug.
(4) The label on the immediate container of the drug as well as the packing in
which the container is enclosed should contain the following warning:
"WARNING : To be sold by retail on the prescription of a
...........................
only."
2
[(5) Post marketing surveillance study shall be conducted during initial
period of two years of marketing of the new drug formulation, after getting the
protocol and the names of the investigator duly approved by the Licensing Authority.]
(6) All reported adverse reactions related to the drug shall be intimated to the
Drugs Controller, India and Licensing Authority and regulatory action resulting from
their review should be complied with.
(7) No claims except those mentioned above shall be made for the drug without
the prior approval of the Licensing Authority.
(8) Specimen of the carton, labels, package insert that will be adopted for
marketing the drug in the country shall be got approved from the Licensing Authority
before the drug is marketed.
_
1. Ins. by G.S.R. 900 (E), dt. 12.12.2001.
2. Subs by G.S.R.101(E), dt. 18.2.2011.
1
[FORM
46A
(See rules 122 B and 122
DA)
Permission/ Approval for manufacture of raw material
(new bulk drug substance
)
Name of the permission/ approval and date of i
ssu
e ..................................
M/s
............................................
of...........................................
(address) is hereby
granted Permission/Approval to manufacture the following raw material (new
bulk drug substance) under rule 122B / 122DA of the Drugs and Cosmetics Rules,
1945.
Name of the raw material (new bulk drug
subs
tance
):
(1)
..................................................................
(2)
................................................................
(3) ….
..............................................................
Dated
..............
Signature
..........................
Name and designation of Licensing Authority.
Conditions for Grant of Permission
/Appro
v
al
(1) The raw material (new bulk drug substance) shall conform to the
specifications approved by the Licensing Authority.
(2) The raw material (new bulk drug substance) can be sold to only those
manufacturers who have permission, in writing, from Licensing Authority, either to use
the drug for development purpose/clinical trial-bio-equivalence study or to manufacture
the formulation.
(3) For manufacture of the formulation in the country, separate approval under
rule 122B shall be obtained from the Licensing Authority.]
1. Ins. by No.G.S.R. 900 (E), dt. 12.12.2001.
Drugs and Cosmetics Rules 1945
277
1
[FORM
47
(See rule 160
A)
Application for grant or renewal of approval for carrying out tests on Ayurvedic,
Siddha
and
Unani drugs or raw materials used in the manufacture thereof on
behalf of licensees f
or
manufacture for sale of Ayurvedic, Siddha and Unani
drugs
1. *I/We................................................ of
....................................
hereby apply
for the grant/renewal of approval for carrying out tests of identity, purity, quality and
strength on the following categories of Ayurvedic, Siddha and Unani drugs or raw
materials used in the manufacture thereof on behalf of licensee for manufacture for
sale of Ayurvedic, Siddha and Unani drugs.
2. *Categories of Ayurvedic, Siddha and Unani drugs other than those specified in the
First Schedule to this Act for which testing will be carried out:
AYURVEDA AND SIDDHA
UNANI
1.
Asava and Arista
1.
Nabeez, Khal (Sirka)
2.
Arka-Tinir
2.
Majoon and its sub-categories
Itrifal, Jawarish, Khameera,
Laooq, Halwar
3.
Avaleha and Paka-Ilakam
3.
Sufoof, Zuroor, Sunoon.
4.
Kavatha Curna-Kutinir Curanam
4.
Namak, Khar
5.
Guggulu
5.
Raughan
6.
Ghrita-Ney
6.
Zimad
7
Churna-Curanam
7.
Habb (Pill)
8.
Taila-Tailam
8.
Shiyaf
9.
Dravaka-Tiravakam
9.
Qutoor (drops)
10.
Lavana-Uppu
10.
Kohal (Surma), Kajal
11.
Kshara-Saram
11.
Satt, Usara
12.
Lepa-Pacai
12.
Kushta
13.
Vati, Gutika-Kulikai
13.
Joshanda (Single drugs)
14.
Vartti
14.
Sharbat Sikanjabeen
15.
Netrabindu (Aschyotan)
15.
Sayyal, Arq (Distillates)
16.
Anjana-Kanmai
16.
Qurs (Tablet)
17.
Sattva-Sattu
17.
Marham, Qairooti
18.
Kupipakva Rasayana-Kuppi Centuram
18.
Humool, Furzaja
19.
Parpati
19.
Bakhoor
20.
Pishti
20.
Nabati Advia
21.
Bhasma-Parpam
21.
Maadni Advia
22.
Mandura-Atai kutinir
22.
Asjad Advia
23.
Rasay oga-C entur
am 23. Haiwani Advia
24. Lauha 24. Jauhar
25. Ghana Sattva 25. Natool
26. Kvath Pravahi- Kutinir 26. Nashooq, Naswar
27. Panak (Syrup)-Manappaku 27. Shamoom
Drugs and Cosmetics Rules 1945
278
28. Tablet-Mattirai 28. Saoot (Nasal drops)
29. Capsule 29. Mazoogh
30. Ointment- Kalimapu 30. Tila
31. Phalavarti 31. Lashooq
32. Dhoomravarti/Doopan 32. Gulqand
33. Kshar Sutra/Kshar Varti 33. Fateela
34. Single drugs: 34. Ghaza, Utban, Sasbhh
(a) Plant based
(b) Mineral based
(c) Metal based
(d) Animal based
(e) Synthetic
(f) Any other Ayurvedic, Siddha, Unani formulation
35. Pushp (Phool) 35. Capsule
36. Nasya 36. Huqna
37. Swarasa (Fresh juice) 37. Naurah
38. Karna Bindu (Ear drops) 38. Latookh
39. Any other dosage of Patent and 39. Vajoor (Throat paint)
Proprietary and Ayurvedic, Siddha,
Unani Drug
40. Mazmazah (Mouth washer)
(3) Names, qualifications and experience of experts employed for testing and
the person in-charge of testing.
(4) List of testing equipment provided.
(5) *I/We enclose a plan of the testing premises showing the location and area
of the different sections thereof.
(6) An inspection fee of rupees
..........................
has been credited to Government
under the head of
accoun
t .............................
Dated…………
Signature……….
Full address of the Applicant
*Delete which is not applicable.
1. Ins. by G.S.R. 701(E), dt. 27.9.2001 and subs. by G.S.R. 73(E), dt. 31.1.2003.
1
[FORM
48
(See Rule 160
B)
Approval for carrying out tests or analysis on Ayurvedic, Siddha and Unani drugs or
raw
materials used in the manufacture thereof on behalf of licensees for manufacture
for sale of Ayurvedic, Siddha and Unani
drugs
Number of approval and date of issue…………………
1. Approval is hereby granted to .........................................................for carrying
out tests in identity, purity, quality and strength on the following categories of
Ayurvedic, Siddha or Unani drugs and the raw materials used in the manufacture
thereof on the premises situated at ..............................................................
Drugs and Cosmetics Rules 1945
279
Categories of Ayurvedic, Siddha and Unani drugs.
……………………………………………
……………………………………………
……………………………………………
2. Name of experts employed for testing and the person-in-charge of te
sting
………………………………(experts)
and……………………… (person in-charge).
3. The approval shall be in force
from
......................... t
o.....................................
4. The approval is subject to the conditions stated below and such other
conditions as may be specified in the rules for the time being in force under the Act.
Date ............................ Signature .....................
Place
........................... Designation ....................
Seal of State Licensing Authority
Conditions of
appro
v
al
(1) This approval and any certificate of renewal in Form 49 shall be displayed
in the approved
prem
i ses and
s
h
all be produced at the request of the
Inspectors appointed under the Act.
(2) If the applicant wishes to undertake during the currency of the approval the
testing of any other category of Ayurvedic, Siddha or Unani drugs it should apply to
the approving authority for necessary endorsement as provided in Rule 160A. This
approval will be deemed to extend to the items so endorsed.
(3) Any change in the experts or in the person in-charge of the testing
shall be forthwith reported to the approving authority.
(4) The applicant shall inform the approving authority in writing in the event of
any change of the constitution of the laboratory operating under this Form. Where any
change in the constitution of the laboratory takes place, the current approval shall be
deemed to be valid for a maximum period of three months from the date on which the
change takes place unless in the meantime, a fresh approval has been taken from the
approving authority in the name of the laboratory with the changed constitution.]
_
1.Ins. by G.S.R. No.702(E) dt. 27-9-2001 and subs.by.G.S.R.73(E), dt.31.01.2003.
1
[Form
49
(See rule 160-
I)
Certificate of renewal for carrying out tests or analysis on Ayurvedic, Siddha or
Unani drugs or raw materials used in the manufacture thereof on behalf of licensees
for
manufacture for sale of Ayurvedic, Siddha or Unani
drugs
1. Certified that approval number
........................... g
r
a
n
t ed
o
n t
h
e
...........
day
o
f
...................................................................................... 20
…. for carrying
ou
t
tests of identity, purity, quality and strength on the following categories
of
Ayurvedic, Siddha or Unani, drugs and the raw materials used in the
m
a
nuf
act
ur
e
thereof at the premises situated at ............................... has been renewed from
……….
t
o................
(date).
Catagories of Ayurvedic, Siddha or Unani drugs:
……………………………………………….
2. Name of experts and the person-in-charge of testing……………………..
(experts)
and………………….(person
in charge)
Drugs and Cosmetics Rules 1945
280
Date: ....................
Signature
...........................
Place : .................
Designation
.........
Seal of State Licensing Authority ]
1. Ins. by G.S.R. No.701(E) dt. 27-9-2001 and subs. by G.S.R.73(E) dt. 31.01.2003.
1
[FORM
50
[See rule 160
D(f)]
Report of test or analysis by approved Laboratory
(1) Name of manufacturer from whom sample received together with his
manufacturing licence number under the Act or the rules made
thereunder.
…………………………………………………………………………………………
(2) Reference number and date of the letter from the manufacturer under which the
same was forwarded.
…………………………………………………………………………………………
(3) Date of receipt of the sample
……………………………………………………………………………………………
(4) Name of Ayurvedic, Siddha and Unani drug of raw material purporting to be
contained in the sample.
……………………………………………………………………………………………
(5) Details of raw material of final product (in bulk finished pack)* as obtained
from the manufacturer:
(a) Original manufacturer's name in the case of raw materials and drugs
repacked…… …………………………….
(b) Batch
number…………………………………
(c) Batch size as represented by sample……………..
(d)
Dat
e of manufacture, if any .......…………………
(e) Date of expiry, if any………………………………….
(6) Results of test or analysis with protocols of test or analysis applied or as
per Ayurvedic, Siddha or Unani Pharmacopoeial standards.
(7) Other specific tests for identity, purity, quality and strength of Patent
and Proprietary drugs.
In the opinion of the undersigned, the sample referred to above is of standard
*quality/is not of standard quality as defined in the Act or the rules made thereunder for
the reasons given below
……………………………………………………………………………………………
Date…….
Place…..
(Signature of the person-in-charge of testing)
(F. No……………………………..)
Name and Designation and Seal…………
Name and Address of the Laboratory……
License No……………..
Note: Final product includes repacked material.
*Delete whichever is not applicable.
1. Ins. by G.S.R. 701(E) dt. 27-9-2001 and subs. by G.S.R.73(E) dt. 31.1.2003
Drugs and Cosmetics Rules 1945
281
1
[SCHEDULE B
(See rules 7 and
48)
Fees for test or analysis by the Central Drugs Laboratories or State Drugs
Laboratories
:
1. I. Fees for test and assay of Drugs requiring use of animals
Adrenocorticotrophic hormone assay
Rupees
1000
Gonadotrophic hormone for LH activity
1000
FSH Activity
1000
Posterior pituitary extract or its synthetic substitute for
400
oxytocin activity
Vasopressor activity
400
Insulin and insulin in combination for hypoglycaemic activity
2000
Hyaluronidase
500
Glucagon
2000
Heparin for anticoagulant activity
600
Protamine sulphate
300
Depressor or Histamine like substane
300
Pyrogen test
500
Antigenecity or foreign protein test
300
Abnormal or undue toxicity or safety test
200
Determination of Lethal doses, LD
10
or
LD
50
in mice
800
Skin sensitivity/eye irrigation
250
Implantation test
2000
2.
Microbiological tests and assays -
Bioassay of Antibiotic
400
Microbiological assay of vitamins
300
Phenol coefficient
300
Preservatives – Microbial challenge test
2000
Sterility test – Parenteral preparations
100
Surgical dressings
200
Syringes and needles
300
Transfusion and infusion sets or assemblies
400
Other sterile devices
1. Subs. by G.S.R. No.478(E), dt. 7-8-1998.
Drugs and Cosmetics Rules 1945
282
3. Identification tests -
(a)
Chemical Methods
50
(b)
Microscopical
50
(c)
IR Spectroscopy
150
(d)
(e)
UV Spectroscopy
Chromotography
100
(i)
Paper
100
(ii)
Thin layer
150
(iii)
Column
100
(iv)
GLC
250
(v)
HPLC
500
(vi)
Gel Filtration
300
(f)
Electrophoresis
(i) Paper and Cellulose acetate
200
(ii) Polyacrylamide Gel, starch gel, agar gel
300 each
4.
Physical tests –
(a)
(b)
Optical rotation, specific gravity, refractive index,
weight per ml, fluorescence.
Viscocity
75 each
100
(c)
(d)
(e)
pH, Solubility, loss on drying, net content, ash, sulphated ash
etc.
Absorbancy, wt/unit area (surgical), foreign matter, extractive
value, thread count etc.
Uniformity of weight
(i) Tablets
20 each
30 each
15
(i) Capsules
20
(f)
(g)
Acid value, iodine value, peroxide value,
Soponification value, acetyl value.
Disintegration tests –
100 each
(i) Ordinary tablets
20
(ii) Capsule
30
(iii) Sugar Coated tablets
50
(iv) Enteric coated tablets
100
(h)
Dissolution test
250
(i)
(j)
(k)
Uniformity of content.
Wt. per unit area (powder), particle size, count, methoxy
value.
Limit test for impurities
500
200 each
100 each
(l)
Related substances
(i) T LC method
(A) Without reference standard
150
(B) With reference standard
250
Drugs and Cosmetics Rules 1945
283
(ii) Gas Liquid Chromatography
(A) Without reference standard
(B) With reference standard
(iii)High pressure Liquid Chromatography
(A)Without reference
standards
(B)With
reference standards
250
350
100
500
500
(m) Water (Karl Fisher) 200
(5) Assays -
(a) General chemical methods 100 for each
ingredient
(b) Non-aqueous/instrumental 200 for each
ingredient
(c) Chromatography
(i) TLC
250
(ii) Column
200
(iii) GLC
350
(iv) HPLC
500
(v) Gel filtration
400
(d) Nitrogen determination
200
(e) Medicinal gases
400
(6)
Polymorph test -
300
(Content of polymorph A in chloramphenicol palmitate)
Surgical sutures (Depending on number of tests to be carried)
200-500
Other miscellaneous tests
100-500
II
Fees for Sera and Vaccine –
Sterility test
100
Abnormal toxicity test
400
Specific toxicity test
800
Inactivation test (Rabies)
200
Potency testing of rabies vaccine
2025
Potency testing of pertussis fraction of DPT vaccine
2025
Potency testing of tetanus fraction of DPT/DT/TT vaccine
2500
Potency testing of diphtheria Fraction of DPT/DTE vaccine.
2700
Testing of antisera for the specific titre
1000
Potency testing measles/Mumps/Rubella vaccine
760 each
Testing of Oral Polio Vaccine (OPV) –
Potency
4550
Identity
1000
Stability
800
Potency testing of Japanese Encephalitis Vaccine
3900
Potency testing of Snake
400
Venom serum
for each venom
Identity testing for vaccines/sera
Cell culture (Other than OPV)
400
Other than cell culture
100
Drugs and Cosmetics Rules 1945
284
Estimation of volume/pH/total solids/No. of
organisms/Physical checking.
Estimation of total proteins/aluminium
50 each
content/phenol/formaldehyde/thiomersal/moisture. 200 each
Pyrogen testing 500
Stability test for vaccines other than Oral Polio Vaccine 4550
III Cosmetics
400 – 1500
(The exact amount of the fee shall be determined by the
Director of Laboratory or the Government Analyst, as the case
may be).
IV Rubber Condoms
IV Homoeopathic medicines:
1. Identification test for raw material of botanical origin (other
than assay of constituents).
2. Identification test for raw material of chemical origin (other
than assay)
1000
125
100
3. Limit test for drugs of chemical origin 150
4. Assay of total alkaloids or of drugs of chemical origin 100
5. Identification test for drugs of animal origins or
microbiological.
6. Fees for testing of Mother tincture, lower potencies upto
3x
or
equivalent.
7. U.V. or I.R. or H.P.C.L. defect determination
Determination of Biochemic drug through atomic absorbance
spectrophotometer.
100
100
75
75
Note :-
1. For tests not listed in the Schedule, charges will be determined by the Director or
the Government Analyst of the laboratory / institute as the case may be.
2. For the tests relating to Ayurvedic, Unani and Siddha medicines, charges will be
determined by the Adviser (Indigenous System of Medicine), Director or Government
Analyst of the Laboratory / Institute, as the cased may be.]
1. Subs by G.S.R. 478 (E), dt:7.8.1998.
Drugs and Cosmetics Rules 1945
285
1
[SCHEDULE B(1)
(See rules 163F
)
FEES FOR THE TEST OR ANALYSIS BY THE PHARMACOPOEIAL LABORATORY FOR
INDIAN MEDICINE (PLIM) OR THE GOVERNMENT ANALYST
Type of testing/analysis
Cost of testing or
analysis in Rupees
(1)
(2)
1.
Test for sterlity
250.00
2.
Abnormal toxicity or undue toxicity or safety test
750.00
3.
Determination of lethal does LD 50 to 10 on mice
2500.00
4.
Chemical test for each ingredient
500.00
5.
Disinfectants
1000.00
6.
Any other test requiring animal experimentation
500.00
7.
Microbiological assay
750.00
8.
Microscopic examination of single drugs
250.00
9.
Microscopic examination of raw material of compound
drug
500.00
10.
Chemical identification as per Pharmacopoeia
250.00
11.
Disintegration of tablets and capsules
(a) ordinary
(b) sugar coated
(c) enteric coated
100.00
200.00
400.00
12.
Psysiochemical Assays
300.00
13.
Test other than assay (limit tests for impurities, ash
content, total solids, acid value, saponification value,
loss on drying etc.) for each test.
100.00
14.
Optical rotation
250.00
15.
Refractive index
250.00
16.
Arsenic testing
250.00
17.
Paper chromatography
250.00
18.
Thin layer chromatography
300.00
19.
Column chromatography
2500.00
20.
Gas liquid chromatography
1000.00
21.
HPTLC restricted to single drugs qualitative
1000.00
22.
Atomical absorption spectrophotometry for Hg, Pb, As,
Cd
500.00
23.
Cosmetics/ tails/ creams
500.00
24.
Identification test for raw material of plant origin (other
than assay of constitutents)
125.00
25.
Identification test for raw material of chemical origin
(other than assay)
100.00
26.
Limit test for drug of chemical origin
150.00
27.
Other miscellaneous tests
1000.00
Drugs and Cosmetics Rules 1945
286
Note: Sample testing charges will be determined / revised by the Director or Government Analyst of the
Pharmacopoeial laboratory for Indian Medicine, as the case may be, in consultation with the Department of
Ayurveda, Yoga, Unani, Siddha and Homoeopathy, Ministry of Health and Family Welfare.
1
[SCHEDULE C
(See rules 23, 61 and 76 and Part
X)
Biological and Special
Products
1. Sera.
2. Solution of serum proteins intended for injection.
2
[3. Vaccines for parenteral injections.
4. Toxins.
5. Antigen.
6. Antitoxins.
7. Neo-arsphenamine and analogous substances used for the specific treatment of infective
diseases.
8. Insulin.
9. Pituitary (Posterior Lobe) Extract.
10. Adrenaline and Solutions of Salts of Adrenaline.
3
[11. Antibiotics and preparations thereof in a form to be administered parenterally.]
4
[12 Any other preparation which is meant for parenteral administration as such or after being
made up with a solvent or medium or any other sterile product and which-
(a) requires to be stored in a refrigerator; or
(b) does not require to be stored in a refrigerator.]
13. Sterilized surgical ligature and sterilized surgical suture.
2
[14. Bacteriophages.
5
[15 Ophthalmic preparations.]
6
[16 Sterile Disposable Devices for single use only.]
1. Amended by Notfn. No. F. 1-30/47-A, dt. 5-1-1950
2. Amended by Notfn. No. F. 1-8/60-D, dt. 31-8-1960
3. Subs. by No. G.S.R. 487(E) ,dt. 2.7.1984.
4. Amended by Notfn. No. F. 1-14/68-D, dt. 26-10-1968
5. Ins. by Notfn. No. G.S.R. 1242(E) ,dt. 17.9.1979
6. Ins. by Notfn. No. G.S.R. 109(E) ,dt. 22.2.1994.
Drugs and Cosmetics Rules 1945
287
1
[SCHEDULE C (1)
(See Rule 23, 61 and
76)
Other Special
Products
1 Drugs belonging to the Digitalis group and preparations containing drugs belonging to the
Digitals group not in a form to be administered parenterally.
2 Ergot and preparations containing Ergot not in a form to be administered parenterally.
3 Adrenaline and preparations containing Adrenaline not in a form to be administered
parenterally.
4 Fish Liver Oil and preparations containing Fish Liver Oil.
5 Vitamins and preparations containing any vitamins not in a form to be administered
parenterally.
6 Liver extract and preparations containing liver extract not in a form to be administered
parenterally.
7 Hormones and preparations containing Hormones not in a form to be administered
parenterally.
8 Vaccine not in a form to be administered parenterally.
2
[9. Antibiotics and preparations thereof not in a form to be administered parenterally.]
3
[10. In-vitro Blood Grouping Sera.
11. In-vitro Diagnostic Devices for HIV, HbsAg and HCV.]
1. Amended by. Notfn. No. F. 1-22/59-D, dt. 9-4-1960
2. Subs. by.G.S.R.487(E) ,dt. 2-7-1984.
3. Ins. By G.S.R. 601(E), dt. 27.8.2002.
Drugs and Cosmetics Rules 1945
288
SCHEDULE D
[See Rule
43]
Class of drugs
Extent and conditions of exemption
1.
Substances not intended for
All provisions of Chapter III of the Act and rules
medicinal use
thereunder subject to the condition that if the
substance is imported in bulk, the importer shall
certify that the substance is imported for non-
medicinal uses, and if imported otherwise than in
bulk, each container shall bear a label indicating
that the substance is not intended for medicinal
use or is of commercial quality.
1
[Further,
permission from licensing authority as defined in
clause (b) of rule 21 has to be obtained for import
of the substance for non-medicinal use without
registration and import license.]
2
[***]
3
[***]
4
[5.
(i)
The following substances, which are
used both as articles of food as well
as drugs:-
All condensed or powdered milk
whether pure, skimmed or malted,
fortified with vitamins and minerals.
All provisions of Chapter III of the Act
and rules thereunder.
(ii)
Farex, Oats, Lactose and all other
similar cereal preparations whether
fortified with vitamins or otherwise
excepting those for parenteral
use.
(iii)
(iv)
Virol, Bovril, Chicken essence and
all other similar predigested foods.
Ginger, Pepper, Cumin, Cinnamon
and all other similar spices and
condiments unless they are
specifically labelled as
conforming to the standards in the
5
[Indian Pharmacopoeia or the
official pharmacopoeias and the
official compendia of the drug
standards prescribed under the
Act and rules made thereunder].
1. Ins. By G.S.R 724 (E), dt:7-11-2013.
2. Serial no 2, 3, omitted by Notfn. No. F-1-6/62-D (S.O.2889), dt: 2-7-1969.
3. Serial no 4, omitted by G.S.R.604 (E) ,dt. 24-8-2001
4. Amended by Notfn. F. 1-53/55-D, dt. 7.1.1957.
5.Amended by G.S.R. 19, dt: 15-12-1977.
Drugs and Cosmetics Rules 1945
289
Class of drugs Extent and conditions of exemption
1
[6.
2
[7.
Drugs and cosmetics
imported for
manufacture and export
by units situated in
―Special Economic
Zones‖ as notified by the
Government of India
from time to time.
Custom Made Devices
The provisions of Chapter III of the Act and rules
thereunder which required them to be covered by an
import licence, import registration and import through
notified port of entry, subject to the conditions that these
drugs and cosmetics shall not be diverted for sale in the
country:
Provided that such imported drugs and cosmetics
may be permitted to the domestic area if they meet the
requirements of standard procedure for import and
registration as required under Chapter III of the Act and
rules thereunder.
All provisions of Chapter III of the Act and the rules
made thereunder, subject to the condition that the device is
specifically made in accordance with a duly qualified
medical practitioner‘s written prescription under his
responsibility, in accordance with specific design
characteristics and is intended for the sole use of a
particular patient and the label should bear the word
―custom made device.‖ Explanation.––Mass produced
devices which only need adoption to meet the specific
requirements of the medical practitioner or any other
professional user shall not be considered to be custom
made devices.]
1. Ins. by G.S.R. 528(E), dt. 8.7.2003.
2. Ins. By G.S.R 690 (E) dated 25-09-2014.
Drugs and Cosmetics Rules 1945
290
1
[SCHEDULE D(I)
(See rule 21 (d) and rule 24
A)
Information and undertaking required to be submitted by the manufacturer or his
authorized
agent with the Application Form for a Registration Certificate. The format shall be
properly
filled in for each application in Form 40. The detailed information, secret in nature, may
be
furnished on a Computer
Floppy.
1. Particulars of the manufacturer and manufacturing premises
1.1 Name and address of the manufacturing premises (Telephone No.,
Fax No., E-mail address) to be registered.
1.2 Name(s) and address(es) of the Proprietor /Partners / Directors.
1.3 Name and address of the authorized Agent in India, responsible for
the business of the manufacturer.
1.4 A brief profile of the manufacturer‘s business activity, in domestic as well as
global market.
1.5 A copy of Plant Master File (duly notarised)
1.6 A copy of Plant Registration / approval Certificate issued by the Ministry of
Health/National Regulatory Authority of the foreign country concerned (duly
notarised)
1.7 A brief profile of the manufacturer‘s research activity.
2. Particulars of the manufactured drugs to be registered under Registration
Certificate.
2.1 Names of drugs (Bulk/Formulation/Special product) to be registered meant for
import into and use in India.
2.2 A copy of the approved list showing the bulk drugs/formulations/special
products mentioned in 2.1 above are permitted for manufacturing / marketing
in the country of origin (duly notarized).
2.3
2
[A copy of Good Manufacturing Practice (GMP) certificate as per WHO –
GMP guidelines or Certificate of Pharmaceutical Products (CPP) or written
confirmation for active substances exported to European Union which is
equivalent to GMP certificate issued as per WHO – GMP guidelines, by the
National Regulatory Authority of the country of origin or a copy of the
certificate equivalent to GMP certificate as per WHO GMP guidelines issued
by National Regulator of United States of America or Japan or Australia or
Canada or the European Union for the purpose of marketing of the drugs in
their country, in relation to bulk drugs or formulations or special product
meant for import into India.]
2.4 The domestic prices of the drugs to be registered in India, in the currency of the
country of origin.
2.5 The name(s) of the drug(s) which are original research products of the
manufacturer.
1. Ins. by G.S.R. No.604(E) , dt. 24-8-2001 (w.e.f. 1-1-2003).
2. Subs. by G.S.R. No. 897(E) , dt. 21-9-2016.
Drugs and Cosmetics Rules 1945
291
3. Undertaking to declare that:
-
3.1. We shall comply with all the conditions imposed on the Registration Certificate,
read with rules 74 and 78 of the Drugs and Cosmetics rules, 1945.
3.2 We declare that we are carrying on the manufacture of the drugs mentioned in
this Schedule, at the premises specified above, and we shall from time to time
report any change of premises on which manufacture will be carried on and in
cases where manufacture is carried on in more than one factory any change in
the distribution of functions between the factories.
3.3 We shall comply with the provisions of Part IX of the Drugs and Cosmetics
Rules,
1945.
3.4 Every drug manufactured by us for import under the Registration Certificate
into India shall be as regard strength, quality and purity conforms with the
provisions of Chapter III of Drugs and Cosmetics Act, 1940 and Part IV of the
Drugs and Cosmetics Rules 1945, and their amendments from time to time.
3.5 We shall from time to time report for any change or manufacturing process, or
in packaging, or in labelling, or in testing, or in documentation of any of the
drugs, pertaining to the Registration Certificate, to be granted to us. Where any
change in respect of any of the drugs under the Registration Certificate has
taken place, in respect of any of the above matters, we shall inform the same to
the licensing authority in writing within 30 days from the date of such changes.
In such cases, where there will be any major change/modification in
manufacturing or in processing or in testing, or in documentation, as the case
may be, at the discretion of the licensing authority, we shall obtain necessary
approval within 30 days by submitting a separate application, alongwith the
registration fee as specified in clause (ii) of sub rule (3) of rule 24-A.
3.6 We shall from time to time report for any administrative action taken due to
adverse reaction, viz. market withdrawal regulatory restriction, or cancellation
of authorization and/or ―not of standard quality report‖ of any drug pertaining
to the Registration Certificate declared by any Regulatory Authority of any
country where the drug is marketed/sold or distributed. The despatch and
marketing of the drug in such cases, shall be stopped immediately and the
licensing authority shall be informed immediately. Further action in respect of
stop marketing of drug shall be taken as per the directions of the licensing
authority. In such cases, action equivalent to that taken with reference to the
concerned drug(s) in the country of origin or in the country of marketing will be
followed in India also, in consultation with the licensing authority. The
licensing authority may direct any further modification to this course of action,
including the withdrawal of the drug from Indian market within 48 hours time
period.
3.7 We shall comply with such further requirements, if any, as may be specified, by
the Government of India, under the Act and the rules made there under.
3.8 We shall allow the licensing authority and/or any person authorized by him in
that behalf to enter and inspect the manufacturing premises and to examine the
process/procedure and documents in respect of any drug manufactured by us for
which the application for Registration Certificate has been made.
Drugs and Cosmetics Rules 1945
292
3.9 We shall allow the licensing authority or any person authorized by him in that
behalf to take samples of the drugs concerned for test, analysis or examination,
if considered necessary by the licensing authority.
Place:
Date:
Signature of the manufacturer
1
[or his authorized
agent]
Seal /
Stamp
1. Ins. by G.S.R. 35(E), dt. 20.1.2005.
Drugs and Cosmetics Rules 1945
293
SCHEDULE D(II)
[See rule 21 (d) and rule 24
A]
Information required to be submitted by the manufacturer or his authorized agent with
the
Application Form for the registration of a bulk drug/formulation/special product for its
import
into
India.
The format shall be properly filled in and the detailed information, secret in
nature,
may be furnished
on a Computer
Floppy
1. GENERAL
1.1. Name of the drug/formulation/special product, a brief description and the
therapeutic class to which it belongs.
1.2 Regulatory status of the drug. Free Sale Certificate and/or Certificate of Pharmaceutical
Products (CPP) issued by the Regulatory Authority of the country of origin. Free sale
approval issued by the Regulatory Authorities of other major countries.
1.3 Drugs Master File (DMF) for the drug to be registered (duly notarised).
1.4
1
[GMP certificate as per WHO-GMP format, or Certificate of Pharmaceutical Products
(CPP), or written confirmation for active substances exported to the European Union
which is equivalent to GMP certificate issued as per WHO – GMP guidelines, by the
National Regulatory Authority of the country of origin or a duly notarised copy of the
certificate equivalent to GMP certificate as per WHO-GMP guidelines issued by
United States of America or Japan or Australia or Canada or the European Union for
the purpose of marketing of the drug in their country.]
1.5 List of countries where marketing authorization or import permission for the said drug is
granted with date (respective authorisation shall be enclosed).
1.6 List of countries where marketing authorisation or import permission for the said drug is
cancelled/withdrawn with date.
1.7 List of countries where marketing authorisation or import permission for the said drug is
pending since (date).
1.8 Domestic price of the drug in the currency followed in the country of origin.
1.9 List of countries where the said drug is patented.
2. CHEMICAL AND PHARMACEUTICAL INFORMATION OF DRUGS.
2.1 Chemical name.
Code name or number, if any.
Non-proprietary or generic name, if any.
Structure.
Physico-chemical properties.
2.2 Dosage form and its composition.
Qualitative and Quantitative composition in terms of the active substances(s) and
excipient(s). List of active substance(s) separately from the constituent(s) of excipients.
2.3 Specifications of active and inactive ingredient (s) including pharmacopoeial references.
2.4 Source of active ingredient(s), name and address.
2.5
Tests for identification of the active ingredient(s),
Method of its assays and tests for impurity profile with reference standards for the
impurities (Protocol to be submitted alongwith reference standards for the impurities /
relative substances).
2.6 Outline method and flow chart of manufacture of the bulk drug or finished formulation
or special product.
2.7 Detailed test protocol for the drug with pharmacopoeial reference or in- house
specification as approved by the registration authority, in the country of origin.
Drugs and Cosmetics Rules 1945
294
2.8 Stability data including accelerated
stability and real time stability analysis.
1. Subs. by G.S.R. 897 (E), dt. 21.9.2016.
2.9 Documentation on pack size.
2.10 Numerical expression on EAN bar code on the labels and cartons,
2.11 Safety documents on containers and closures.
2.12 Documentation on storage conditions.
2.13 Three samples of medicinal product/drug and outlet packing are to be submitted with
batch certificates. Additional samples as well as reference substances with batch
certificates including date of manufacture, shelf life, and storage conditions of reference
substance may be required both during registration procedure and during validity of
registration decision.
2.14 Batch test reports/certificate of five consecutive production batches in details of the
medicinal product are to be submitted for every site of manufacturing premises.
2.15 Manner of labelling as per rule 96 of the Drugs and Cosmetics Rules 1945.
2.16 Package insert.
2.17 Details of safety handling procedure of the drug.
2.18 Details of PMS study report for marketing period not exceeding five years.
.
3. BIOLOGICAL AND
BIOPHARMACEUTICAL
INFORMATION OF
DRUGS
3.1 Biological control tests applied on the starting material, if applicable.
3.2 Biological control tests applied on the intermediate products, if applicable.
3.3 Biological control tests applied on the finished medical products, if applicable.
3.4 Stability of the finished products in terms of biological potency of the drug, if
applicable.
3.5 Sterility tests, if applicable, specification and protocol therein.
3.6 Pyrogen tests, if applicable, specification and protocol therein.
3.7 Acute and sub-acute toxicity tests, if applicable specification and protocol therein.
3.8 Bio-availability studies and bio-equivalence data, if applicable.
3.9 Data relating to the environmental risk assessment for r-DNA products.
3.10 Other information relevant under the section.
4. PHARMACOLOGICAL AND TOXICOLOGICAL INFORMATION OF DRUGS.
Executive summary of the product is to be submitted mentioning the specific and general
pharmacological actions of the drug and pharmacokinetic studies on absorption, metabolism,
distribution and excretion. A separate note is to be given on acute and sub-acute toxicity studies
and long term toxicity studies. Specific studies on reproductive toxicity, local toxicity and
carcinogenic activity of the drug is to be elaborated, as far as possible.
5 CLINICAL DOCUMENTATION
A new drug as defined under rule 122-E of the Drugs and Cosmetics Rules, 1945 is
required to be permitted separately by the licensing authority under rule 122-A of the said rules
prior to its registration. Such a new drug requires a brief summary and clinical documentation,
alongwith permission under 122-A of the said rules for its Registration Certificate.
6. LABELLING AND PACKAGING INFORMATION OF DRUGS.
6.1 Labels should conform as per the specifications under the Drugs and Cosmetics
Drugs and Cosmetics Rules 1945
295
Rules 1945.
6.2 Package insert should be in English and shall indicate the following therapeutic
indications: -
Posology and method of administration.
Contra-indications.
Special warnings and special precautions for use, if any.
Interaction with other medicaments and other forms of interaction.
Pregnancy and lactation, if contra-indicated.
Effects on ability to drive and use machines, if contra-indicated.
Undesirable effects/side effects.
Antidote for overdosing.
6.3 Package insert should indicate the following pharmaceutical information: -
List of excipients.
Incompatibilities.
Shelf life in the medical product as packaged for sale.
Shelf life after dilution or reconstitution according to direction.
Shelf life after first opening the container.
Special precautions for storage.
Nature and specification of the container.
Instructions for use/handling.
7 SPECIFIC INFORMATION REQUIRED FOR THE SPECIAL PRODUCTS (to be
supplied, separately in Annexures, as ‗A‘, ‗B‘ and ‗C‘)
The information submitted above is true to the best of my knowledge and belief.
Place:
Date :
Signature of the manufacturer
1
[or his authorized agent]
Seal/Stamp
NB: 1. Any change in the process of manufacture, method of testing, labelling, packaging,
designing of the sale pack, medical literature and documentation is to be intimated to the
licensing authority forthwith and permission to be obtained from him within 30 days
time period.
2. Information relating to Serial No.4 and Serial No.5 are not applicable for drugs
figuring in Indian Pharmacopoeia and also for the drugs figuring in United States of
Pharmacopoeia, European Pharmacopoeia, and British Pharmacopoeia provided such
drugs have already been approved for marketing in India for the applicant under
rules 122A, 122B, 122C or 122D of the Drugs and Cosmetics Rules 1945.
1.Ins. by G.S.R. 35(E), dt. 20.1.2005.
Drugs and Cosmetics Rules 1945
296
ANNEXURE A
(See Schedule D-II, item
No.7)
INFORMATION TO BE SUBMITTED IN SCHEDULE D-II
SPECIFIC INFORMATION REQUIRED FOR THE BLOOD PRODUCTS
A product dossier showing the:
1. Details of source Plasma, its viral screening, storage and transport from Collection Centres to
Fractionation Centre. Regulatory status of Collection Centres.
2. Details of Fractionation Centre, Regulatory Status, Method of Fractionation and
Control
Processes.
3. Details of viral inactivation process for enveloped and non-enveloped virus(es) and viral
validation studies to assess the viral load of the product. Testing of viral screening at
any stage
is
to be highlighted with the details of the kits used with their respective sensitivity and specificity.
4. Bulk filtration prior to pharmaceutical packing giving the full details of Micro-filtration or
nanofiltration followed.
5. Complete details of pharmaceutical processing and utilization.
6. Test protocol of the product showing the specifications and pharmacopoeial method
followed for various testing parameters.
Specific batch test report for at least 3 batches showing the specifications of each testing
parameter.
7. Pack size and labelling.
8. Product insert.
9 Specimen Batch Release Certificate issued by the National Regulatory Authority of the
country of origin.
Specific processings like safe handling, material control, area control, pasteurization,
stability studies, storage at quarantine stage and finished stage and packaging should be
highlighted in the product dossier.
The information submitted above is true to the best of my knowledge and belief.
Place:
Date:
Signature of the
manufacturer
Seal /
Stamp
NB: 1. Any change in the process of manufacture, method of testing, labelling, packaging,
designing of the sale pack, medical literature and documentation is to be intimated to the
licensing authority forthwith and permission to be obtained from him within 30 days time
period.
Drugs and Cosmetics Rules 1945
297
ANNEXURE-B
(See Schedule D-II, item
No.7)
INFORMATION TO BE SUBMITTED IN SCHEDULE D-II
SPECIFIC
INFORMATION REQUIRED FOR THE DIAGNOSTIC
KITS
A Product dossier showing the :
1. The details of source antigen or antibody as the case may be and characterization of the
same. Process control of coating of antigen or antibody on the base material like
Nitrocellulose paper, strips or cards or ELISA wells etc.
Detailed composition of the kit and manufacturing flow chart process of the kit showing
the specific flow diagram of individual components or source of the individual
components.
2. Test protocol of the kit showing the specifications and method of testing. In house
evaluation report of sensitivity, specificity and stability studies carried out by the
manufacturer.
3. The report of evaluation in details conducted by the National Control Authority of country
of origin.
Specimen batch test report for at least consecutive 3 batches showing specification of
each testing parameter.
4. The detailed test report of all the components used/packed in the finished kit.
5. Pack size and labelling.
6. Product insert.
Specific evaluation report, if done by any laboratory in India, showing the sensitivity and
specificity of the kit.
Specific processing like safe handling, material control, area control, process control,
stability studies, storage at quarantine stage and finished stage, packaging should be
highlighted in the product dossier.
The information submitted above is true to the best of my knowledge and belief.
Place:
Date:
Signature of the
manufacturer
Seal /
S
t
amp
NB: 1.Any change in the process of manufacture, method of testing, labelling, packaging,
designing of the sale pack, medical literature and documentation is to be intimated to the
licensing authority forthwith and permission to be obtained from him within
30 days time
period.
Drugs and Cosmetics Rules 1945
298
ANNEXURE-C
(See Schedule D-II, item
No.7)
INFORMATION TO BE SUBMITTED IN SCHEDULE
D-II
SPECIFIC INFORMATION REQUIRED FOR
VACCINES
A Product dossier showing the:
1. History, source, date of receipt, storage, identity and characterization of the seed strain.
2. Detailed flow chart of manufacturing process showing all the details of in-process control
on toxicity, potency study and stability data of the final bulk and the final finished
product including the storage temperature.
3. Complete details of chemical and pharmaceutical data for the product.
Composition and dosage form – method of manufacture with detailed flow chart – control
of starting material – control tests on intermediate and finished products – certificate of
analysis of finished products – validation of critical manufacturing steps.
4. Test protocol of the vaccines showing the specification and method of testing
including pharmacopoeial specification.
5. Specimen batch test report for at least consecutive three batches showing the
specification of each testing parameter.
6. The detailed test reports of all the components used / packed in the finished vaccine.
7. Pack-size and labelling.
8. Product insert
9. Specimen batch release certificates issued by the National Regulatory Authority of the
country of origin.
10. Summary of pre-clinical and clinical data including :
(a) Prescribing information.
(b) Pharmacological and toxicological data pertaining to tests on animals
Characterisation of immuno response and safety study in human use, in
specific conditions.
Specific information on source of seed strain, its characterization, inactivation, etc. and
processings like safe handling, material control, area control, process control, stability studies,
storage at quarantine stage and finished state, packaging should be highlighted in the product
dossier.
Specimen production and quality control protocols for at least three consecutive lots
showing the specifications for each quality control parameter including pharmacopoeial
requirement shall be submitted for study.
The information submitted above is true to the best of my knowledge and belief.
Place:
Date:
Signature of the
manufacturer
Seal /
Stamp
Drugs and Cosmetics Rules 1945
299
NB: 1. Any change in the process of manufacture, method of testing, labelling, packaging,
designing of the sale pack, medical literature and documentation is to be intimated to the
licensing authority forthwith and permission to be obtained from him within 30 days time
period.
2. All vaccines shall be new drugs unless certified otherwise by the liencesing authority
approved under rule 21 of the Drugs and Cosmetic Rules, 1945. A copy of approval
of the vaccine issued by the said licensing authority is to be enclosed, prior to issue of
Registration Certificate of the said vaccines.
1
[SCHEDULE D (III)
(See rule 129 A)
INFORMATION AND UNDERTAKING REQUIRED TO BE SUBMITiED BY THE
MANUFACTURER OR HIS AUTHORISED IMPORTER/DISTRIBUTOR/AGENT WITH THE
APPLICATION FORM FOR A REGISTRATION CERTIFICATE.
(The format shall be properly filled in for each application in form 42)
1. PARTICULARS OF THE MANUFACTURER AND MANUFACTURING PREMISES.-
(a) Name and address of the manufacturer and manufacturing premises to be registered along with
telephone numbers, Fax numbers and e-mail address.
(b) Name(s) and address of the Partners/Directors.
(c) Name and address of the authorised importer/distributor/agent in India, responsible for the business
of the manufacturer.
(d) A brief profile of the manufacturer ‘s business activity, in domestic as well as global market.
2. PARTICULARS OF THE COSMETICS TO B E RE G IST E RED UNDER
REGISTRATION CERTIFICATE.-
(a) Names of cosmetics along with their brands name, category, pack sizes and variants to be
registered and meant for import into and use in India.
(b) Particulars of the manufacturing licenses/registration/marketing authorizations (if any) under which
the cosmetics are being manufactured in the country of origin along with the copy of the licenses/
marketing authorization/registration issued by the Regulatory Authority of that country.
(c) List of countries where marketing authorization or import permission for the said cosmetic has
been granted.
3. CHEMICAL INFORMATION OF COSMETICS.-
(a) Name(s) of ingredients in the nomenclature of standard references, along with percentages
contained in the cosmetic.
(b) Specification and testing method for testing of the cosmetic(s).
(c) Manner of labelling as per Drugs and Cosmetics Rules, 1945.
(d) Package insert (if any).
4. UNDERTAKINGTO DECLARETHAT.-
(a) We shall comply with all the conditions imposed on the Registration Certificate for the import of
cosmetics as required under the provisions of Drugs and Cosmetics rules, 1945.
(b) We declare that we are carrying on the manufacture of the cosmetics mentioned in this Schedule, at
the premises specified above, and we shall from time to time report any change of premises on
which manufacture will be carried on and in cases where manufacture is carried on in more than
one factory any change in the distribution of functions between the factories.
(c) We shall comply with the provisions of Part XIII of the Drugs and Cosmetics Rules, 1945.
(d) Every cosmetic manufactured by us for import under the Registration Certificate into India shall
conform to the specifications given in the Drugs & Cosmetics Rules, 1945 as amended from time
to time.
(e) We shall inform to the licensing authority, within 30 days in the event of any change in variants or
in category or in manufacturing location or in labelling or in documentation of any of the cosmetic
pertaining to the certificate to be granted to us.
1. Ins. By G.S.R. 426 (E) dated 19-05-2010, read with corrigendum G.S.R. 263(E) dated 30-05-2011, corrigendum G.S.R. dated
29-09-2011, corrigendum G.S.R. 270(E) dated 30-03-2012 and corrigendum G.S.R. 733(E), dated 29-09-2012.
Drugs and Cosmetics Rules 1945
300
(f) We shall from time to time report for any administrative action taken due to adverse reaction, viz.
market withdrawals/regulatory restriction, or cancellation of authorisation and/or ―not of standard
quality report‖ of any cosmetic pertaining to the Registration Certificate declared by any
Regulatory Authority of any country where the cosmetic is marketed/sold or distributed. The
despatch and marketing of the cosmetic in such cases, shall be stopped and the licensing authority
shall be informed immediately.
(g) We shall comply with such further requirements, if any, as may be specified, by the Government of
India, under the Act and the Rules, made thereunder.
(h) We shall allow the licensing authority or any person authorised by him in that behalf to take
samples of the cosmetics for testing if considered necessary by the licensing authority.
The information submitted above is true to the best of my/our knowledge and belief.
Place:
Date:
Signature of the manufacturer or his authorized agent
Seal/Stamp.
1
[***]
2
[SCHEDULE E(1)
[See rule 161 (2)]
List of poisonous substances under the Ayurvedic (including Siddha)
and Unani Systems of Medicine
A. AYURVEDIC SYSTEM
I
Drugs of vegetable origin
1
Ahipena (Except seeds)
Papaver somniferum Linn.
2
Arka
Calotropis procera (Ait.) R.Br. ex.
3
Bhallataka
Semecarpus anacardium Linn. F.
4
Bhanga (Except seeds)
Cannabis sativa Linn. (Except seeds)
5
Danti
Baliospermum montanum Mull. Arg.
6
Dhattura
Datura metal Linn..
7
Gunja (seed)
Abrus precatorium Linn. (seed)
8
Jaipala (seed)
Croton tiglium Linn.
9
Karaveera
Rerium indicum Mill.
10
Langali
Gloriosa superba Linn.
11
Parasika Yavani
Hyoscyamus niger Linn.
12
Vatsanabha
Vishamushti
Acontium chasmanthum Stapf ex Holm.
Strychnox nuxvomica Linn.
13
Shringivisha
Acontium chasmanthum Stapf ex Holm.
II
Drugs of Animal Origin.
14
Sarpa Visha
Snake poison.
III
15
Drugs of Mineral Origin
Gauripashana
Arsenic.
16
Hartala
Arseno sulphide.
17
Manahashila
Arseno sulphide.
18
Parada
Mercury.
19
Rasa Karpura
Hydrargyri subchloridum.
20
Tuttha
Copper sulphate.
21
Hingula
Cinnabar.
1 ―Schedule E‖ omitted No.G.S.R. 462(E),dt 22-6-1982.
2. Subs. By G.S.R. 683(E) dated 19-08-2010.
Drugs and Cosmetics Rules 1945
301
B. SIDDHA SYSTEM
1.
Abini
Papaver somniferum Linn.
2.
Alari
Nerium indicum Mill.
3.
Attru thummatti
Citrullus colocynthis (L.) Schrad
4.
Umathai
Datura stramonium Linn.
5.
Etti
Stychnos nux vomica Linn.
6.
Ganja (except seed)
Cannabis sativa Linn.
7.
Kalappaki Kizahangu
Glorisa superba Linn.
8.
Kodikkalli (exempted for external use)
Euphorbia tirucalli Linn.
9.
Kattu Thumatti
Cucumis trigonus Roxb.
10
Kunri (except root)
Arbus precatorius Linn.
11.
Cheramkottai
Semecarpus anacardium Linn f.
12.
Thillai
Exoecoria agallocha Linn.
13.
Nabi
Aconitum ferox Wall.
14.
Nervalam
Croton tiglium Linn.
15.
Pugaielai
Nicotiana tabacum Linn.
16.
Mancevikkalli
Euphorbia species
C. UNANI SYSTEM
I Drugs of vegetable origin
1. Afiyun (except seed)
Papaver somniferum Linn.
2. Bazrul-banj Hyoscyamus niger Linn.
3. Bish Aconitum chasmanthum Strapfex Holmes.
4. Bhang Cannabis sativa Linn.
5. Charas Canabis sativa Linn.
6. Dhatura seeds Datura metal Linn (seeds).
7. Kuchla Strychnos nuxvomica Linn.
8. Shokran Conium maculatum Linn.
II Drugs of Animal origin
9. Sanp (head) Snake (head).
10. Telni makkhi Mylabris cichori Linn.
Mylabaris pustulata Thund.
Mylabris macilenta .
III
Drugs of Mineral origin
1. Darchikna
Hydrargryi perchloridum.
2. Hira
Diamond.
3. Ras Kapoor
Hydrargryi Subchloridum (calomel).
4. Shingruf
Hydrargryi bisulphuratum.
5. Zangar
Cupri subacetas.
6. Sammul-Far
(Abyaz, Asfar, Aswad and Ahmar)
(white, yellow, black and red, Arsenic).
Copper Sulphate.
7. Tootiya
Copper Sulphate
8. Para
Hydrargyrum.
9. Hartal
Arsenic trisulphide (yellow).]
Drugs and Cosmetics Rules 1945
302
SCHEDULE F
(See rule 78 and Part X)
1
[***]
2
[PART XII
B
REQUIREMENTS FOR THE FUNCTIONING AND OPERATION OF A
BLOOD
BANK AND / OR FOR PREPARATION OF BLOOD
COMPONENTS.
I. BLOOD BANKS / BLOOD
COMPONENTS
A. GENERAL
1. Location and Surroundings : The blood bank shall be located at a place which
shall be away from open sewage, drain, public lavatory or similar unhygienic
surroundings.
2. Building : The building (s) used for operation of a blood bank and/or
preparation of blood components shall be constructed in such a manner so as to
permit the operation of the blood bank and preparation of blood components
under hygienic conditions and shall avoid the entry of insects, rodents and flies.
It shall be well lighted, ventilated and screened (mesh), wherever necessary.
The walls and floors of the rooms, where collection of blood or preparation of
blood components or blood products is carried out shall be smooth, washable
and capable of being kept clean. Drains shall be of adequate size and where
connected directly to a sewer, shall be equipped with traps to prevent back
siphonage.
3. Health, clothing and sanitation of staff: The employees shall be free from
contagious or infectious diseases. They shall be provided with clean overalls,
head-gears, foot-wears and gloves, wherever required. There shall be adequate,
clean and convenient hand washing and toilet facilities.
B. ACCOMMODATION FOR A BLOOD BANK.
A blood bank shall have an area of 100 square meters for its operations and an
additional area of 50 square meters for preparation of blood components. It shall be
consisting of a room each for –
(1) registration and medical examination with adequate furniture and facilities for
registration and selection of donors;
(2) blood collection (air-conditioned);
1. Part I to Part XIIA omitted by G.S.R. 663 (E), dated 03-07-1992 corrected vide corrigendum G.S.R.
27(E) dated 22-01-1993.
2. Part XIIB and Part XIIC, were sub. By G.S.R. 245 (E) dated 05-04-1999, previously Part XIIB and XIIC,
were substituted for Part XIIB by G.S.R. 28(E) dated 22-01-1992 and before that Part XIIB was added by
notification number F 1-17/67-D, 24-06-1967.
Drugs and Cosmetics Rules 1945
303
(3) blood component preparation. (This shall be air-conditioned to maintain
temperature between 20 degree centigrade to 25 degree centigrade);
(4) laboratory for blood group serology (air-conditioned);
(5) laboratory for blood transmissible diseases like Hepatitis, Syphilis, Malaria,
HIV-antibodies (air-conditioned);
(6) sterilization-cum-washing;
(7) refreshment-cum-rest room (air-conditioned);
(8) store-cum-records.
NOTES :
(1) The above requirements as to accommodation and area may be relaxed, in
respect of testing laboratories and sterilization-cum-washing room, for reasons to be
recorded in writing by the Licensing Authority and/or the Central Licence Approving
Authority, in respect of blood banks operating in hospitals, provided the hospital
concerned has a pathological laboratory and a sterilization-cum-washing room common
with other departments in the said hospital.
(2) Refreshments to the donor after phlebotomy shall be served so that he is kept
under observation in the blood bank.
C PERSONNEL
staff:-
Every blood bank shall have following categories of whole time competent technical
(a) Medical Officer, possessing the qualifications specified in condition (i) of rule 122-G.
(b) Blood Bank Technician(s) possessing –
(i) Degree in Medical Laboratory Technology (M.L.T) with six months‘
experience in the testing of blood and/or its components; or
(ii) Diploma in Medical Laboratory Technology (M.L.T) with one year‘s
experience in the testing of blood and / or its components, the degree or diploma being
from a University / Institution recognized by the Central Government or State
Government.
(c) Registered Nurse(s);
(d) Technical supervisor (where blood components are manufactured), possessing-
(i) Degree in Medical Laboratory Technology (M.L.T) with six months‘
experience in the preparation of blood components; or
(ii) Diploma in Medical Laboratory Technology (M.L.T) with one year‘s
experience in the preparation of blood components,
the degree or diploma being from a University / Institution recognized by the Central
Government or State Government.
Drugs and Cosmetics Rules 1945
304
NOTES :
(1) The requirements of qualification and experience in respect of Technical Supervisor
and Blood Bank Technician shall apply in the cases of persons who are approved by
the Licensing Authority and/or Central Licence Approving Authority after the
commencement of the Drugs and Cosmetics (Amendment) Rules, 1999*.
(2) As regards, the number of whole time competent technical personnel, the blood bank
shall comply with the requirements laid down in the Directorate General of Health
Services Manual.
(3) It shall be the responsibility of the licensee to ensure through maintenance of records
and other latest techniques used in blood banking system that the personnel involved
in blood banking activities for collection, storage, testing and distribution are
adequately trained in the current Good Manufacturing Practices/Standard Operating
Procedures for the tasks undertaken by each personnel. The personnel shall be made
aware of the principles of Good Manufacturing Practices / Standard Operating
Procedures that affect them and receive initial and continuing training relevant to their
needs.
D. MAINTENANCE
The premises shall be maintained in a clean and proper manner to ensure adequate cleaning
and maintenance of proper operations. The facilities shall include:-
(1) Privacy and thorough examination of individuals to determine their suitability as
donors.
(2) Collection of blood from donors with minimal risk of contamination of exposure to
activities and equipment unrelated to blood collection.
(3) Storage of blood or blood components pending completion of tests.
(4) Provision for quarantine, storage of blood and blood components in a designated
location, pending repetition of those tests that initially give questionable serological
results.
(5) Provision for quarantine, storage, handling and disposal of products and reagents not
suitable for use.
(6) Storage of finished products prior to distribution or issue.
(7) Proper collection, processing, compatibility testing, storage and distribution of blood
and blood components to prevent contamination.
(8) Adequate and proper performance of all procedures relating to plasmapheresis,
plateletpheresis and leucapheresis.
(9) Proper conduct of all packaging, labelling and other finishing operations.
(10) Provision for safe and sanitary disposal of –
(i) Blood and/or blood components not suitable for use, distribution or sale.
(ii) Trash and items used during the collection, processing and compatibility
testing of blood and / or blood components.
*Note : 2
nd
Amendment Rules, 1999 (w.e.f. 5-4-1999)
Drugs and Cosmetics Rules 1945
305
E. EQUIPMENT
Equipment used in the collection, processing, testing, storage and sale/distribution of
blood and its components shall be maintained in a clean and proper manner and so
placed as to facilitate cleaning and maintenance. The equipment shall be observed,
standardized and calibrated on a regularly scheduled basis as described in the
Standard Operating Procedures Manual and shall operate in the manner for which it
was designed so as to ensure compliance with the official requirements (the
equipments) as stated below for blood and its components.
Equipment that shall be observed, standardized and calibrated with at least the following
frequencies:
EQUIPMENT PERFORMANCE FREQUENCY FREQUENCY
OF
CALIBRATION
1. Temperature
Recorder
Compare against
thermometer
Daily As often as
necessary
2 Refrigerated centrifuge Observe speed
and
temperature
Each day
of use
As often as
necessary
3 Hematocrit centrifuge – – Standardise
before initial
use, after repair
or adjustments
and annually.
4,
General lab.
Centrifuge
–
–
Tachometer,
every 6 months.
5.
Automated
typing
Blood
Observe controls for
correct results
Each day
of use
–
6. Haemoglobinometer Standardize against
cyanamethemoglob
ulin standard
−ditto−
–
7.
Refractiometer or
Urinometer
Standardize against
distilled water
− ditto −
–
8.
Blood container
weighing device
Standardize against
container of known
− ditto –
As often as
necessary
weight.
9
Water Bath
Observe temperature
− ditto −
−ditto−
10 Rh view box
(wherever
necessary)
–ditto–
− ditto − − ditto−
Drugs and Cosmetics Rules 1945
306
11
Autoclave
Observe temperature
Each day
of use
As often as
necessary
12
Serologic rotators
Observe controls for
correct results
-- ditto--
Speed as often
as necessary.
13
Laboratory
thermometers
–
–
Before initial
use
14 Electronic thermometers – Monthly –
15 Blood agitator Observe weight of the
first container of blood
filled for correct results
Each day of use Standardize with
container of
known mass or
value before
initial use, and
after repairs or
adjustments.
F. SUPPLIES AND REAGENTS:
All supplies and reagents used in the collection, processing, compatibility, testing, storage
and distribution of blood and blood components shall be stored at proper temperature in a
safe and hygienic place, in a proper manner and in particular:–
(a) all supplies coming in contact with blood and blood components intended for
transfusion shall be sterile, pyrogen-free, and shall not interact with the product in
such a manner as to have an adverse effect upon the safety, purity, potency or
effectiveness of the product.
(b) supplies and reagents that do not bear an expiry date shall be stored in a manner that
the oldest is used first.
(c) supplies and reagents shall be used in a manner consistent with instructions provided
by the manufacturer.
(d) all final containers and closures for blood and blood components not intended for
transfusion shall be clean and free of surface solids and other contaminants.
(e) each blood collecting container and its satellite container(s), if any, shall be
examined visually for damage or evidence of contamination prior to its use and
immediately after filling. Such examination shall include inspection for breakage of
seals, when indicated, and abnormal discoloration. Where any defect is observed,
the container shall not be used or, if detected after filling, shall be properly
discarded.
(f) representative samples of each lot of the following reagents and/or solutions shall be
tested regularly on a scheduled basis by methods described in the Standard
Operating Procedures Manual to determine their capacity to perform as required,
Drugs and Cosmetics Rules 1945
307
Reagents and solutions Frequency of testing alongwith controls
Anti-human serum
Blood grouping serums
Each day of use
Each day of use
Lectin Each day of use
Antibody screening and reverse
grouping cells
Each day of use
Hepatitis test reagents Each run
Syphilis serology reagents Each run
Enzymes Each day of use
HIV I and II reagents Each
run
Norm
al saline (LISS and PBS) Each day of use
Bovine Albumin
Each day of use.
G. GOOD MANUFACTURING PRACTICES (GMPs) /STANDARD OPERATING
PROCEDURES (SOPs):
Written Standard Operating Procedures shall be maintained and shall include all steps
to be followed in the collection, processing, compatibility testing, storage and sale or
distribution of blood and/or preparation of blood components for homologous transfusion,
autologous transfusion and further manufacturing purposes. Such procedures shall be
available to the personnel for use in the concerned areas. The Standard Operating Procedures
shall inter alia include:
1. (a) criteria used to determine donor suitability.
(b)
(c)
methods of performing donor qualifying tests and measurements including minimum
and maximum values for a test or procedure, when a factor in determining
acceptability;
solutions and methods used to prepare the site of phlebotomy so as to give maximum
assurance of a sterile container of blood;
(d) method of accurately relating the product (s) to the donor;
(e) blood collection procedure, including in-process precautions taken to measure
accurately the quality of blood drawn from the donor;
(f) methods of component preparation, including any time restrictions for specific steps
in processing;
(g) all tests and repeat tests performed on blood and blood components during
processing;
(h) pre-transfusion testing, wherever applicable, including precautions to be taken to
identify accurately the recipient blood components during processing;
Drugs and Cosmetics Rules 1945
308
(i) procedures of managing adverse reactions in donor and recipient reactions:
(j) storage temperatures and methods of controlling storage temperatures for blood and
its components and reagents;
(k) length of expiry dates, if any assigned for all final products;
(l) criteria for determining whether returned blood is suitable for re-issue;
(m) procedures used for relating a unit of blood or blood component from the donor to
its final disposal;
(n) quality control procedures for supplies and reagents employed in blood
collection, processing and re-transfusion testing;
(o) schedules and procedures for equipment maintenance and calibration;
(p) labelling procedures to safeguard its mix-ups, receipt, issue, rejected and in-hand;
(q) procedures of plasmapheresis, plateletphersis and leucapheresis if performed, including
precautions to be taken to ensure re-infusion of donor‘s own cells;
(r) procedures for preparing recovered (salvaged) plasma if performed, including details of
separation, pooling, labelling, storage and distribution;
(s) all records pertinent to the lot or unit maintained pursuant to these regulations shall be
reviewed before the release or distribution of a lot or unit of final product. The review or
portions of the review may be performed at appropriate periods during or after blood
collection, processing, testing and storage. A thorough investigation, including the
conclusions and follow-up, of any unexplained discrepancy or the failure of a lot or unit
to meet any of its specification shall be made and recorded.
(2) A licensee may utilise current Standard Operating Procedures, such as the Manuals of
the following organizations, so long as such specific procedures are consistent with, and
at least as stringent as, the requirements contained in this Part, namely :-
(i) Directorate General of Health Services Manual.
(ii) Other Organisations or individual blood bank‘s manuals, subject to the
approval of State Licensing Authority and Central Licence Approving Authority.
H. CRITERIA FOR BLOOD DONATION:
Conditions for donation of blood:
(1) General – No person shall donate blood and no blood bank shall draw
blood from a person, more than once in three months. The donor shall be in good
health, mentally alert and physically fit and shall not be inmates of jail, persons having
multiple sex partners and drug-addicts. The donors shall fulfil the following
requirements, namely: -
Drugs and Cosmetics Rules 1945
309
1
[(a) the donor shall be in the age group of 18 to 65 years;]
(b) the donor shall not be less than 45 kilograms;
( c) temperature and pulse of the donor shall be normal;
(d ) the systolic and diastolic blood pressure are within normal limits without
medication;
(e)
haemoglobin which shall not be less than 12.5 grams;
(f) the donor shall be free from acute respiratory diseases;
(g) the donor shall be free from any skin diseases at the site of
phlebotomy
;
(h)
the donor shall be free from any disease transmissible by blood transfusion,
insofar as can be determined by history and examination indicated above;
(i) the arms and forearms of the donor shall be free from skin punctures or scars
indicative of professional blood donors or addiction of self injected
narcotics.
(2) Additional qualifications of donor – No person shall donate blood, and no
blood bank shall draw blood from a donor, in the conditions mentioned in column (1)
of the Table given below before the expiry of the period of deferment mentioned in the
column (2) of the said Table.
Table: Deferment of blood donation
CONDITIONS PERIOD OF DEFERMENT
(1)
(2)_
(a)
(b)
(c)
(d)
(e)
(f)
(h)
Abortions
History of Blood transfusion
Surgery
Typhoid
History of Malaria and duly
treated
Tattoo
Breast feeding
6 months
6 months
12 months
12 months after recovery
2 months (endemic)
3 years (non endemic area)
6 months
12 months after delivery
(i)
(j)
Immunization (Cholera,
Typhoid, Diphtheria, Tetanus,
Plague, Gammaglobulin)
Rabies vaccination
15 days
1 year after vaccination
(k)
History of Hepatitis in
family or close contact
12 months
(l)
Immunoglobulin
12 months
(3) No person shall donate blood and no blood bank shall draw blood from a person,
suffering from any of the diseases mentioned below, namely:–
(a) Cancer
(b) Heart disease
1. Subs. By G.S.R 101 (E), dt:18-2-2011
Drugs and Cosmetics Rules 1945
310
(c) Abnormal bleeding tendencies
(d) Unexplained weight loss
(e) Diabetes-controlled on insulin
1
[(f) Hepatitis infection]
(g) Chronic nephritis
(h) Signs and symptoms, suggestive of AIDS
(i ) Liver diseases
(j) Tuberculosis
(k) Polycythemia Vera.
(l) Asthma
(m) Epilepsy
(n) Leprosy
(o) Schizophrenia
(p) Endocrine disorders
I. GENERAL EQUIPMENTS AND INSTRUMENTS.
1. For blood collection
room:
(i) Donor beds, chairs and tables: These shall be suitably and comfortably
cushioned and shall be of appropriate size.
(ii) Bedside table
(iii) Sphygmomanometer and stethoscope
(iv) Recovery beds for donors.
(v) Refrigerators, for storing separately tested and untested blood,
maintaining temperature between 2 to 6 degree centigrade with digital
dial thermometer, recording thermograph and alarm device, with
provision for continuous power supply.
(vi) Weighing devices for donor and blood containers.
2. For haemoglobin determination:
(i) Copper sulphate solution (specific gravity 1.053)
(ii) Sterile lancet and impregnated alcohol swabs.
(iii) Capillary tube (1.3 x 1.4 x 96 mm for Pasteur pipettes)
(iv) Rubber bulbs for capillary tubings.
(v) Sahli‘s haemoglobinometer / Colorimetric method.
3. For temperature and pulse
determination.
(i) Clinical thermometers
(ii) Watch (fitted with a second-hand) and a stop-watch.
4. For blood containers:
(a) Only disposable PVC blood bags shall be used (closed system) as per
specifications of IP/USP/BP.
(b) Anti-coagulants: The anti-coagulant solution shall be sterile, pyrogen-free
and of the following composition that will ensure satisfactory safety and
efficacy of the whole blood and/or for all the separate blood components.
(i) Citrate Phosphate Dextrose Adenine solution (CPDA) or Citrate
Phosphate
Dextrose Adenine – 1 (CPDA-1) – 14 ml solution shall be required
for
1. Subs. by G.S.R. No. 40(E), dated 29-01-2001.
Drugs and Cosmetics Rules 1945
311
100 ml of blood.
Note 1.- (i) In case of
single/double/triple/quadruple
blood collection bags used for
blood component preparations, CPDA blood collection bags may be used.
(ii) Acid Citrate Dextrose solution (A.C.D. with Formula-A) I.P. – 15 ml solution
shall be required for 100 ml of blood,
(iii) Additive solutions such as SAGM, ADSOL, NUTRICEL may be used for
storing and retaining Red Blood Corpuscles up to 42 days.
Note 2.- The licensee shall ensure that the anti-coagulant solutions are of a licensed
manufacturer and the blood bags in which the said solutions are contained
have
a certificate of analysis of the said manufacturer.
5. Emergency equipments/items:
(i) Oxygen cylinder with mask, gauge and pressure regulator.
(ii) 5 per cent Glucose or Normal Saline.
(iii) Disposable sterile syringes and needles of various sizes.
(iv) Disposable sterile I.V. infusion sets.
(v) Ampoules of Adrenaline, Noradrenaline, Mephentin, Betamethasone or
Dexamethasone, Metoclorpropamide injections.
(vi) Aspirin.
6. Accessories:
(i) Such as blankets, emesis basins, haemostats, set clamps, sponge forceps, gauze,
dressing jars, solution jars, waste cans.
(ii) Medium cotton balls, 1.25 cm adhesive tapes.
(iii) Denatured spirit, Tincture Iodine, green soap or liquid soap.
(iv) Paper napkins or towels.
(v) Autoclave with temperature and pressure indicator.
(vi) Incinerator
(vii) Stand-by generator
7. Laboratory equipment:
(i) Refrigerators, for storing diagnostic kits and reagents, maintaining a temperature
between 4 to 6 degree centigrade (plus/minus 2 degrees centigrade) with digital
dial thermometer having provision for continuous power supply.
(ii) Compound Microscope with low and high power objectives.
(iii) Centrifuge Table Model.
(iv) Water bath: having range between 37 degree centigrade to 56 degree centigrade.
(v) Rh viewing box in case of slide technique.
(vi) Incubator with thermostatic control.
(vii) Mechanical shakers for serological tests for Syphilis.
(viii) Hand-lens for observing tests conducted in tubes.
(ix) Serological graduated pipettes of various sizes.
(x) Pipettes (Pasteur).
(xi) Glass slides.
Drugs and Cosmetics Rules 1945
312
(xii) Test tubes of various sizes / micrometer plates (U or V type).
(xiii) Precipitating tubes 6mm x 50mm of different sizes and glass beakers of different
sizes.
(xiv) Test tube racks of different specifications.
(xv) Interval timer electric or spring wound.
(xvi) Equipment and materials for cleaning glass wares adequately.
(xvii) Insulated containers for transporting blood, between 2 degree centigrade to 10
degree centigrade temperatures, to wards and hospitals.
(xviii) Wash bottles.
(xix) Filter papers.
(xx) Dielectric tube sealer.
(xxi) Plain and EDTA vials.
(xxii) Chemical balance (wherever necessary).
(xxiii) ELISA reader with printer, washer and micropipettes.
J. SPECIAL REAGENTS :
(1) Standard blood grouping sera Anti A, Anti B and Anti D with known controls.
Rh typing sera shall be in double quantity and each of different brand or if
from the same supplier each supply shall be of different lot numbers.
(2) Reagents for serological tests for syphilis and positive sera for controls.
(3) Anti Human Globulin Serum (Coomb‘s serum).
(4) Bovine Albumin 22 percent Enzyme reagents for incomplete antibodies.
1
[(5) ELISA or RPHA test kits for Hepatitis and HIV I & II.
(6) Detergent and other agents for cleaning laboratory glass wares.
K. TESTING OF WHOLE BLOOD :
(1) It shall be responsibility of the licensee to ensure that the whole blood
collected, processed and supplied conforms to the standards laid down in
the Indian Pharmacopoeia and other tests published, if any,
by the Government.
(2) Freedom from HIV antibodies (AIDS) Tests. – Every licensee shall get
samples of every blood unit tested, before use, for freedom from HIV 1 and
HIV II antibodies either from laboratories specified for the purpose by the
Central Government or in his own laboratory. The results of such testing
shall be recorded on the label of the container.
(3) Each blood unit shall also be tested for freedom from
2
[(Hepatitis B
surface antigen and Hepatitis C Virus antibody)] VDRL and malarial
parasite and results of such testing shall be recorded on the label
of the container.
NOTES (a) Blood samples of donors in pilot tube and the blood samples of the
Recipient shall be preserved for 7 days after
issue.
(b) The blood intended for transfusion shall not be frozen at any stage.
(c) Blood containers shall not come directly in contact with ice at any stage.
1. Subs. By G.S.R. 733(E) dated 21-12-2005
2. Subs. by G.S.R. 40(E) dated 29-01-2001
Drugs and Cosmetics Rules 1945
313
L RECORDS :
The records which the licensee is required to maintain shall include inter alia the
following particulars, namely:
(1) Blood donor record: It shall indicate serial number, date of bleeding, name,
address and signature of donor with other particulars of age, weight,
haemoglobin, blood grouping, blood pressure, medical examination, bag
number and patient‘s detail for whom donated in case of replacement
donation, category of donation (voluntary / replacement) and deferral
records and signature of Medical Officer In-charge.
(2) Master records for blood and its components: It shall indicate bag serial
number, date of collection, date of expiry, quantity in ml. ABO/Rh Group,
results for testing of HIV I and HIV II antibodies, Malaria, V.D.R.L.
1
[(Hepatitis B surface antigen and Hepatitis C Virus antibody)] and
irregular antibodies (if any), name and address of the donor with
particulars, utilization issue number, components prepared or discarded
and signature of the Medical Officer in charge.
(3) Issue Register: It shall indicate serial number, date and time of issue bag
serial number, ABO/RH Group, total quantity in ml, name and address of
the recipient, group of recipient, unit/institution, details of cros-matching
report, indication for transfusion.
(4 ) Records of components supplied: Quantity supplied; compatibility report,
details of recipient and signature of issuing person.
(5) Records of ACD/CPD/CPD-A/SAGM bags giving details of manufacturer,
batch number, date of supply, and results of testing.
(6) Register for diagnostic kits and reagents used: name of the
kits/reagents, details of batch number, date of expiry and date of use.
(7) Blood bank must issue the cross matching report of the blood to the
patient together with the blood unit.
(8) Transfusion adverse reaction records.
(9) Records of purchase, use and stock in hand of disposable needles,
syringes, blood bags, shall be maintained.
NOTE : The above records shall be kept by the licensee for a period of five
years.
M. LABELS :
The labels on every bag containing blood and/or component shall contain the
following particulars, namely;
(1) The proper name of the product in a prominent place and in bold letters on the bag.
(2) Name and address of the blood bank
(3) Licence number
1 Subs. by G.S.R. 40(E), dt. 29.1.2001 (w.e.f. 1.6.2001).
Drugs and Cosmetics Rules 1945
314
(4) Serial number
(5) The date on which the blood is drawn and the date of expiry as prescribed under
Schedule P to these rules.
(6) A colored label shall be put on every bag containing blood. The following color
scheme for the said labels shall be used for different groups of blood:
Blood Group Colour of the label
O Blue
A Yellow
B Pink
AB
White
(7) The results of the tests for
1
[(Hepatitis B surface antigen and Hepatitis C Virus
antibody)] syphilis, freedom from HIV I and HIV II antibodies and malarial
parasite.
(8) The Rh. Group.
(9) Total volume of blood, the preparation of blood, nature and percentage of anti-
coagulant.
(10) Keep continuously temperature at 2 degree centigrade to 6 degree centigrade for
whole human blood and/or components as contained under III of Part XII B.
(11) Disposable transfusion sets with filter shall be used in administration
equipment.
(12) Appropriate compatible cross-matched blood without atypical antibody i
n
recipient shall be used.
(13) The contents of the bag shall not be used if there is any visible evidence of
deterioration like haemolysis, clotting or discoloration.
(14) The label shall indicate the appropriate donor classification like
―Voluntary
Donor‖ or ―Replacement Donor‖ in no less prominence than the proper name.
NOTES :
1. In the case of blood components, particulars of the blood from which such
components have been prepared shall be given against item numbers (5), (7), (8),
(9) and (14).
2. The blood and/or its components shall be distributed on the prescription of a
Registered Medical Practitioner.
II. BLOOD DONATION CAMPS.
A blood donation camp may be organized by –
1. Subs. by G.S.R 40(E), dt. 29.1.2001.
Drugs and Cosmetics Rules 1945
315
(a) a licensed designated Regional Blood Transfusion Centre ; or
(b) a licensed Government blood bank; or
(c) the Indian Red Cross society; or
NOTES:
(i) ― Designated Regional Blood Transfusion Centre‖ shall be a center approved
and designated by a Blood Transfusion Council constituted by a State Government
to collect, process and distribute blood and its components to cater to the needs of
the region and that center has also been licensed and approved by the
Licensing Authority and Central Licence Approving Authority for the purpose.
(ii) The designated Regional Blood Transfusion Centre, Government blood bank and
Indian Red Cross Society shall intimate within a period of seven days, the venue
where the blood camp was held and details of group wise blood units collected in
the said camp to the Licensing Authority and Central Licence Approving Authority.
For holding a blood donation camp, the following requirements shall
be fulfilled/complied with, namely: -
(A) Premises, personnel etc.
(a) Premises under the blood donation camp shall have sufficient area and
the location shall be hygienic so as to allow proper operation, maintenance
and cleaning.
(b) All information regarding the personnel working, equipment used and
facilities available at such a Camp shall be well documented and made
available for inspection, if required, and ensuring -
(i) Continuous and uninterrupted electrical supply for equipment used in the
Camp;
(ii) Adequate lighting for all the required activities;
(iii) Hand-washing facilities for staff;
(iv) Reliable communication system to the central office of the
Controller/ Organizer of the Camp;
(v) Furniture and equipment arranged within the available space;
(vi) Refreshment facilities for donors and staff;
(vii) Facilities for medical examination of the donors;
(viii) Proper disposal of waste.
(B) Personnel for Out-door Blood Donation Camp:
To collect blood from 50 to 70 donors in about 3 hours or from 100 to
200 donors in 5 hours, the following requirements shall be fulfilled / complied with:
(i) one Medical Officer and two nurses or phlebotomists for
managing 6-8 donor tables;
(ii) two medico social workers;
(iii) three blood bank technicians;
(iv) two attendants;
Drugs and Cosmetics Rules 1945
316
(v) vehicle having a capacity to seat 8-10 persons, with provision for
carriage of donation goods including facilities to conduct a blood
donation camp;
(C) Equipments :
1. BP apparatus.
2. Stethoscope.
3. Blood bags (single, double, triple, quadruple).
4. Donor questionnaire.
5. Weighing device for donors.
6. Weighing device for blood bags.
7. Artery forceps, scissors.
8. Stripper for blood tubing.
9. Bed sheets, blankets/mattress.
10. Lancets, swab stick/tooth picks.
11. Glass slides.
12. Portable Hb meter/copper sulphate.
13. Test tube (big) and 12x100mm (small).
14. Test tube stand.
15. Anti-A, Anti-B and Anti-AB, Antisera and Anti-D.
16. Test tube sealer film.
17. Medicated adhesive tape.
18. Plastic waste basket.
19. Donor cards and refreshment for donors.
20 Emergency medical kit.
21 Insulated blood bag containers with provisions for storing between 2
degree centigrade to 10 degree centigrade.
22. Dielectric sealer or portable tube sealer.
23. Needle destroyer (wherever necessary).
III. PROCESSING OF BLOOD COMPONENTS FROM WHOLE BLOOD BY A BLOOD
BANK
The Blood components shall be prepared by blood banks as a part of the
Blood Bank services. The conditions for grant or renewal of licence to prepare blood
components shall be as follows: -
A. ACCOMMODATION:
(1) Rooms with adequate area and other specification, for preparing blood
components depending on quantum of workload shall be as specified in item
B under the heading ―1. BLOOD BANKS/BLOOD COMPONENTS‘ of this
Part.
(2) Preparation of Blood components shall be carried out only under closed
system using single double, triple or quadruple plastic bags except for
preparation of Red Blood Cells Concentrates, where single bags may be used
with transfer bags.
B. EQUIPMENT :
Drugs and Cosmetics Rules 1945
317
(i) Air Conditioner;
(ii) Laminar air flow bench;
(iii) Suitable refrigerated centrifuge;
(iv) Plasma expresser;
(v) Clipper and clips and/or dielectric sealer;
(vi) Weighing device;
(vii) Dry rubber balancing material;
(viii) Artery forceps,
scissors;
(ix) Refrigerator maintaining a temperature between 2 degree
centigrade to 6 degree centigrade, a digital dial thermometer with
recording thermograph and alarm device, with provision for continuous
power supply;
(x) Platelet agitator with incubator (wherever necessary);
(xi) Deep freezers maintaining a temperature between minus 30 degree
centigrade to minus 40 degree centigrade and minus 75 degree
centigrade to minus 80 degree centigrade;
(xii) Refrigerated Water bath for Plasma Thawing;
(xiii) Insulated blood bag containers with provisions for storing at
appropriate temperature for transport purposes;
C. PERSONNEL:
The whole time competent technical staff meant for processing of Blood Components (that is
Medical Officer, Technical Supervisor, Blood Bank Technicians and Registered Nurse) shall be as
specified in item C, under the heading ― 1. BLOOD BANKS/BLOOD COMPONENTS‖ of this
Part.
D. TESTING FACILITIES:
General: Facilities for A, B, AB and O groups and Rh(D) grouping.
1
[(Hepatitis B surface antigen
and Hepatitis C Virus antibody)], VDRL, HIV I and HIV II antibodies and malarial parasites
shall be mandatory for every blood unit before it is used for the preparation of blood components.
The results of such testing shall be indicated on the label.
E. CATEGORIES OF BLOOD COMPONENTS:
(1) CONCENTRATED HUMAN RED BLOOD CORPUSCLES:
The product shall be known as ―Packed Red Blood Cells‖ that is Packed Red Blood Cells
remaining after separating plasma from human blood.
General Requirements:
(a) Storage: Immediately after processing, the Packed Red Blood Cells shall
be kept at a temperature maintained between 2 degree centigrade to 6
degree centigrade.
(b) Inspection: The component shall be inspected immediately after
separation of the plasma, during storage and again at the time of issue.
The product shall not be issued if there is any abnormality in color or
physical appearance or any indication of microbial contamination.
(c) Suitability of Donor: The source of blood for Packed Red Blood Cells shall
be obtained from a donor who meets the criteria for Blood Donation as
specified in item H under the heading ―I. BLOOD BANKS/BLOOD
COMPONENTS‖ of this Part.
1. Subs. by G.S.R. 40(E), dt. 29.1.2001.
Drugs and Cosmetics Rules 1945
318
(d) Testing of Whole Blood: Blood from which Packed Red Blood Cells are
prepared shall be tested as specified in item K relating to Testing Of Whole
Blood under the heading ―I. BLOOD BANKS/BLOOD COMPONENTS‖ of
this Part.
(e) Pilot samples: Pilot samples collected in integral tubing or in separate pilot
tubes shall meet the following specifications:
(i) One or more pilot samples of either the original blood or the
Packed Red Blood Cells being processed shall be preserved with
each unit of Packed Red Blood Cells which is issued.
(ii) Before they are filled, all pilot sample tubes shall be marked
or identified so as to relate them to the donor of that unit or Packed
Red Blood Cells.
(iii) Before the final container is filled or at the time the final
product is prepared, the pilot samples tubes accompanying a unit
of Packed Red Blood Cells, shall be attached in a tamper-proof
manner that shall conspicuously identify removal and re-
attachment.
(iv) All pilot sample tubes, accompanying a unit of packed red
blood cells, shall be filled immediately after the blood is
collected or at the time the final product is prepared, in each case,
by the person who performs the collection of preparation.
F. Processing:
(i) Separation: Packed Red Blood Cells shall be separated from
the whole blood, --
(a) if the whole blood is stored in ACD solution within 21 days, and
(b) if the whole blood is stored in CPDA-1 solution, within 35 days,
from the date of collection. Packed Red Blood Cells may be
prepared either by centrifugation done in a manner that shall not
tend to increase the temperature of the blood or by normal
undisturbed sedimentation method. A portion of the plasma,
sufficient to ensure optimal cell preservation, shall be left with the
packed Red Blood Cells.
(ii) Packed Red Blood Cells Frozen: Cryophylactic substance may
be added to the Packed Red Blood Cells for extended
manufacturer‘s storage not warmer than minus 65 degree
centigrade provided the manufacturer submits data to the
satisfaction of the Licensing Authority and Central Licence
Approving Authority, as adequately demonstrating through in-vivo
cells survival and other appropriate tests that the addition of the
substance, the material used and the processing methods results
in a final product meets the required standards of safety, purity
and potency for Packed Red Blood Cells, and that the frozen
Drugs and Cosmetics Rules 1945
319
product shall maintain those properties for the specified expiry
period.
(iii) Testing: Packed Red Blood Cells shall conform to the standards
as laid down in the Indian Pharmacopoeia.
(2) PLATELETS CONCENTRATES:
The product shall be known as ―Platelets Concentrates‖ that is platelets
collected from one unit of blood and re-suspended in an appropriate volume of original
plasma.
General Requirements:
(i) Source: The source material for platelets shall be platelet rich plasma or
buffy coat which may be obtained from the whole blood or by plateletpheresis.
(ii) Processing :
(a) Separation of buffy-coat or platelet-rich plasma and platelets and re-
suspension of the platelets shall be in a closed system by centrifugal
method with appropriate speed, force and time.
(b) Immediately after collection, the whole blood or plasma shall be held in
storage between 20 degree centigrade to 24 degree centigrade. When
it is to be transported from the venue of blood collection to the
processing laboratory, during such transport action, the temperature as
close as possible to a range between 20 degree centigrade to 24 degree
centigrade shall be ensured. The platelet concentrates shall be
separated within 6 hours after the time of collection of the unit of
whole blood or plasma.
(c) The time and speed of centrifugation shall be demonstrated to produce an
unclamped product, without visible haemolysis, that yields a count of not
less than 3.5 x 10
10
(3.5 x 10 raised to the power of 10) and 4.5 x 10
10
(4.5 x 10 raised to the power ten) i.e. platelets per unit from a unit of 350
ml and 450 ml blood respectively. One percent of total platelets
prepared shall be tested of which 75 per cent of the units shall conform to
the above said platelet count.
(d) The volume of original plasma used for re-suspension of the platelets
shall be determined by the maintenance of the pH of not less than 6
during the storage period. The pH shall be measured on a sample of
platelets which has been stored for the permissible maximum expiry
period at 20 degree centigrade to 24 degree centigrade.
(e) Final containers used for platelets shall be colorless and transparent to
permit visual inspection of the contents. The caps selected shall
maintain a hermetic seal to prevent contamination of the contents. The
container material shall not interact with the contents, under the
normal conditions of the storage and use, in such a manner as to have an
adverse effect upon the safety, purity, potency, or efficacy of the
product. At the time of filling, the final container shall be marked or
identified by number so as to relate it to the donor.
(iii) Storage: Immediately after re-suspension, platelets shall be
placed in storage not exceeding for a period of 5 days, between
20 degree centigrade to 24 degree centigrade, with continuous
gentle agitation of the platelet concentrates maintained throughout
such storage
Drugs and Cosmetics Rules 1945
320
(iv) Testing: The units prepared from different donors shall be tested at
the end of the storage period for –
(a) Platelet count;
(b) pH of not less than 6 measured at the storage temperature of
the unit;
(c) measurement of actual plasma volume;
(d) one percent of the total platelets prepared shall be tested
for sterility;
(e) the tests of functional viability of the platelets shall be done
by swirling movement before issue.
(f) if the results of the testing indicate that the product does not
meet the specified requirements, immediate corrective action
shall be taken and records maintained;
(v) Compatibility Test: Compatible transfusion for the purpose of
variable number of Red Blood Cells, A, B, AB and O grouping shall be
done if the platelets concentrate is contaminated with red blood cells.
(3) GRANULOCYTE CONCENTRATES:
(i) Storage: It shall be kept between 20 degree centigrade to 24
degree centigrade for a maximum period of 24 hours;
(ii) Unit of granulocytes shall not be less than 1 x 10
10
(i.e. 1 x 10 raised to
the power of 10) when prepared on cell separator;
(iii) Group specific tests/HLA test wherever required shall be carried out.
(4) FRESH FROZEN PLASMA:
Plasma frozen within 6 hours after blood collection and stored at a temperature
not warmer than minus 30 degree centigrade, shall be preserved for a period of
not more than one year.
(5) CRYOPRECIPITATE:
Concentrate of anti-hemophiliac factor shall be prepared by thawing of the fresh
plasma frozen stored at minus 30 degree centigrade.
(a)
Storage:
Cryoprecipitate shall be preserved at a temperature not higher than minus 30
degree centigrade and may be preserved for a period of not more than one
year from the date of collection.
(b) Activity:
Anti-hemophiliac factor activity in the final product shall be not less than 80
units per bag. One percent of the total cryoprecipitate prepared shall be tested
of which seventy five percent of the unit shall conform to the said
specification.
F PLASMAPHERESIS, PLATELETPHERESIS, LEUCAPHERESIS, USING A
CELL SEPARATOR.
An area of 10 square meters shall be provided for apheresis in the blood bank.
The blood banks specifically permitted to undertake the said apheresis on the donor
shall observe the criteria as specified in item H relating to Criteria for blood donation ―I.
Blood Banks/Blood Components‖ of this Part. The written consent of the donor shall be taken
and the donor must be explained, the hazards of apheresis. The Medical Officer shall certify
that the donor is fit for apheresis and it shall be carried out by a trained person under
supervision of the Medical Officer.
Drugs and Cosmetics Rules 1945
321
(A) PLASMAPHERESIS,
PLATELETPHERESIS
AND LEUCAPHERESIS:
The donors subjected to plasmapheresis, plateletpheresis and leucapheresis shall, in
addition to the criteria specified in item H relating to the CRITERIA FOR BLOOD
DONATION, under the heading ―I. BLOOD BANKS/BLOOD COMPONENTS‖ of this Part
being observed, be also subjected to protein estimation on post-pheresis/first sitting whose
results shall be taken as reference for subsequent/sitting. It shall also be necessary that the
total plasma obtained from such donor and periodicity of Plasmapheresis shall be according to
the standards described under validt. Standard Operating Procedures.
NOTE :
(i) At least 48 hours must elapse between successive apheresis and not more
than twice in a week.
(ii) Extracoporeal blood volume shall not exceed 15% of donor‘s estimated
blood volume.
(iii) Platelet pheresis shall not be carried out on donors who have taken
medication containing Asprin within 3 days prior to donation.
(iv) If during plateletpheresis or leucapheresis, RBCs cannot be re-transfused
then at least 12 weeks shall elapse before a second cytapheresis procedure
is conducted.
(B) MONITORING FOR APHERESIS:
Before starting apheresis procedure, hemoglobin or haematocrit shall be done. Platelet count,
WBC counts, differential count may be carried out. In repeated plasmapheresis, the serum
protein shall be 6 gm./ml.
(C) COLLECTION OF PLASMA:
The quantity of plasma separated from the blood of donor shall not exceed 500 ml. per sitting
and once in a fortnight or shall not exceed 1000 ml per month.
PART XII C
I. REQUIREMENTS FOR MANUFACTURE OF BLOOD PRODUCTS
The blood products shall be manufactured in a separate premises other than that
meant for blood bank. The requirements that are essential for grant or renewal of licence to
manufacture blood products such as Albumin, Plasma Protein Fraction, Immunoglobins and
Coagulation Factor Concentrates, shall be as follows, namely: -
A. GENERAL REQUIREMENTS:
1. Location and surroundings, buildings and water
supp
ly:
The requirements as regards location and surrounding, buildings and water
supply as contained in paragraphs 1.1.1, 1.1.2, 1.1.3 of Part 1 of Schedule M shall
apply mutatis mutandis to the manufacture of blood products.
2. Disposal of waste and infectious materials:
Drugs and Cosmetics Rules 1945
322
(i) The requirements as regards disposal of waste and infectious materials as
contained in paragraph 1.1.4 of Part 1 of Schedule M shall apply mutatis
mutandis to the manufacture of blood products.
(ii) Proper facility shall also be provided for potentially infectious materials,
particularly HIV I & HIV II
1
[(Hepatitis B surface antigen and Hepatitis C
Virus antibody)] through autoclaving, incineration or any other suitable
validt. methods.
3. Health, clothing and sanitation personnel:
(i) The requirement as contained in paragraph 3 of Part I
of
Schedule M shall be complied
with.
(ii) The personnel working in the manufacturing areas shall be
vaccinated against Hepatitis B virus and other infectious transmitting
diseases.
4. Requirements for manufacturing area for Blood
Products
:
(i) For the manufacture of blood products, separate enclosed areas specifically
designated for the purpose shall be provided. These areas be provided with air locks for
entry and shall be essentially dust free and ventilated with an air supply. Air supply for
manufacturing area shall be filtered through bacteria retaining filters (HEPA Filters) and
shall be at a pressure higher than in the adjacent areas.
The filters shall be checked for performance on installation and periodically
thereafter, and records thereof shall be maintained.
(ii) Interior surfaces (walls, floors and ceilings) shall be smooth and free from
cracks, they shall not shed matter and shall permit easy cleaning and disinfection. Drains
shall be excluded from aseptic areas.
1. Subs. by G.S.R. 40(E) dated 29-01-2001
Drugs and Cosmetics Rules 1945
323
Routine microbial counts of the manufacturing area shall be carried out during
manufacturing operations. The results of such counts shall be checked against well
documented in-house standards and records maintained.
Access to the manufacturing areas shall be restricted to a minimum number of
authorized personnel. Special procedures for entering and leaving the manufacturing
areas shall be prominently displayed.
(iii) Sinks shall be excluded from aseptic areas. Any sink installed in other clean
areas shall be of suitable material such as stainless steel, without an overflow, and be
supplied with water of potable quality. Adequate precautions shall be taken to avoid
contamination of the drainage system with dangerous effluents and airborne dissemination
of pathogenic micro-organisms.
(iv) Lighting, air-conditioning, ventilation shall be designed to maintain a
satisfactory temperature and relative humidity to minimize contamination and to take account
of the comfort of personnel working with protective clothing.
(v) Premises used for the manufacture of blood products shall be suitably designed and
constructed to facilitate good sanitation.
(vi) Premises shall be carefully maintained and it shall be ensured that repair and
maintenance operations do not present any hazard to the quality of products. Premises shall
be cleaned and, where applicable, disinfected according to detailed written validt.
procedures.
(vii) Adequate facilities and equipments shall be used for the manufacture of blood
products derived from blood plasma.
(viii) All containers of blood products, regardless of the stage of manufacture, shall be
identified by securely attached labels. Cross contamination shall be prevented by adoption
of the following measures, namely: –
(a) processing and filling shall be in segregated areas;
(b) manufacture of different products at the same time shall be
avoided;
(c) simultaneous filling of the different products shall be avoided;
(d) ensure transfer, containers/materials by means of airlocks, air
extraction, clothing change and careful washing and decontamination of
equipment;
(e) protecting containers/materials against the risk of contamination
caused by re-circulation of untreated air or by accidental re-entry of
extracted air;
(f) using containers that are sterilized or are of documented low
―bioburden‖,
(ix) Positive pressure area shall be dedicated to the processing area concerned; (x) Air-
handling units shall be dedicated to the processing area concerned;
(xi) Pipe work, valves and vent filters shall be properly designed to facilitate cleaning
and sterilization. Valves on fractionation/reacting vessels shall be completely steam
sterilisable. Air vent filters shall be hydrophobic and shall be validated for their designated
use.
5. Ancillary Areas :
(i) Rest and refreshment rooms shall be separated from other areas.
Drugs and Cosmetics Rules 1945
324
(ii) Facilities for changing and storing clothes and for washing and toilet
purposes shall be easily accessible and appropriate for the number of users.
Toilets shall not be connected directly with production or storage areas.
(iii) Maintenance workshops shall be separated from production areas.
Wherever parts and tools are stored in the production area, they shall be kept in
rooms or lockers reserved for that use.
(iv) Animal houses shall be well isolated from other areas with separate
entrance.
B. COLLECTION AND STORAGE OF PLASMA FOR FRACTIONATION
(a) Collection:
(1) Plasma shall be collected from the licensed Blood Banks through a
cold chain process and stored in frozen condition not warmer than minus
twenty degree centigrade.
(2) Individual plasma shall remain in quarantine till it is tested for
1
[( Hepatitis B and Hepatitis C Virus antibody)], HIV I and HIV II.
(3) A sample from pooled – lot plasma of about 10-12 units of different
donors shall be tested for
1
[(Hepatitis B and Heptitis C Virus antibody)] HIV I
and HIV II and if the same sample found negative, only then it shall be taken
up for fractionation.
(b) Storage Area :
(1) Storage areas shall be of sufficient space and capacity to allow orderly
storage of the various categories of materials, intermediates, bulk and finished
products, products in quarantine, released, rejected, returned, or recalled
products.
(2) Storage areas shall be designed or adopted to ensure good storage
conditioning. In particular, they shall be clean, dry and maintained within
temperature required for such storage and where special storage conditions are
required (e.g. temperature, humidity), these shall be provided, checked and
monitored.
(3) Receiving and dispatch bays shall protect materials and products from the
weather and shall be designed and equipped to allow containers of incoming
materials to be cleaned, if necessary, before storage.
(4) Where quarantine status is ensured by storage in separate areas, these
areas shall be clearly marked and their access restricted only to authorized
personnel.
(5) There shall be separate sampling area for raw materials. If sampling is
performed in the storage area, it shall be conducted in such a way so as to
prevent contamination or cross-contamination.
(6) Segregation shall be provided for the storage of rejected, recalled, or
returned materials or products.
(7) Adequate facility shall be provided for supply of ancillary material, such
as ethanol, water, salts and polyethylene glycol. Separate facilities shall be
provided for the recovery of organic solvents used in fractionation.
1. Subs. by G.S.R 40(E), dt. 29.1.2001 (w.e.f. 1.6.2001)
Drugs and Cosmetics Rules 1945
325
C. PERSONNEL :
(1) Manufacture :
The manufacture of blood products shall be conducted under the
active direction and personal supervision of competent technical staff,
consisting of at
least one person who shall be a whole time employee, with one year
practical experience in the manufacture of blood products / plasma
fractionation and possesses –-
(a) Post-graduate degree in Medicine–M.D.
(Microbiology/Pathology/
Bacteriology/Immunology/Biochemistry);
or
(b) Post-graduate degree in Science (Microbiology); or
(c) Post-graduate degree ib Pharmacy (Microbiology), from a
recognized University or Institution.
2. Testing :
The head of the testing unit shall be independent of the
manufacturing unit and testing shall be conducted under the active
direction and personal supervision of competent technical staff consisting
at least one person who shall be a whole time employee. The Head of the
testing unit shall have eighteen months practical experience in the testing of
drugs, especially the blood products and possesses –
(a) Post-graduate degree in Pharmacy or Science–
(Chemistry/ Microbiology/ Bio-chemistry); or
(b) Post-graduate degree in Medicine–
M.D(Microbiology/Pathology/ Biochemistry), from a recognized
University or Institution.
D. PRODUCTION CONTROL :
(1) The production area and the viral inactivation room shall be
centrally air- conditioned and fitted with HEPA filters having Grade C
(Class 10,000) environment as given in the Table below.
(2) The filling and sealing shall be carried out under aseptic
conditions in centrally air-conditioned areas fitted with HEPA Filters
Grade A or, as the case may be, Grade B (Class 100) environment given
in the said Table.
TABLE
AIR CLASSIFICATION SYSTEM FOR MANUFACTURE OF STERILE
PRODUCTS.
Grade
Maximum number of particles
permitted per m
3
0.5 – 5 micron Less than 5 micron
Maximum number of Viable
Micro-organism permitted per
m
3
Drugs and Cosmetics Rules 1945
326
A (Class 100)
(Laminar - Airflow
workstation)
3500
None
Less than 1
B (Class 100)
3500
None
Less than 5
C (Class 10,000)
3,50,000
2000
Less than 100
(3) The physical and chemical operations used for the manufacture of
plasma fractionation shall maintain high yield of safe and effective protein.
(4) The fractionation procedure used shall give a good yield of products
meeting the in-house quality requirements as approved by the Licensing
Authority and Central Licence Approving Authority reducing the risk of
microbiological contamination and protein denaturation to the minimum.
(5) The procedure adopted shall not affect the antibody activity and
biological half- life or biological characteristics of the products.
E. VIRAL INACTIVATION PROCESS :
The procedure used by the licensee to inactivate the pathogenic organisms such
as enveloped and non-enveloped virus, especially infectivity from HIV I &
HIV II,
1
[(Hepatitis B surface antigens and Hepatitis C Virus antibody)], the viral
inactivation and validation methods adopted by the licensee, shall be submitted for
approval to the Licensing Authority and Central Licence Approving Authority.
NOTES:
(1) No preservative (except stabilizer to prevent – protein denaturation such as
glycine, sodium chloride or sodium caprylate) shall be added to Albumin,
Plasma Protein Fraction, Intravenous Immunoglobulins or Coagulation
Factor Concentrates without the prior approval of Licensing Authority and
Central Licence Approving Authority.
(2) The licensee shall ensure that the said stabilizers do not have deleterial
effect on the final product in the quantity present so as not to cause any
untoward or adverse reaction in human beings.
F. QUALITY CONTROL:
Separate facilities shall be provided for Quality Control such as
Hematological, Bio-chemical, Physico-chemical, Microbiological, Pyrogens,
Instrumental and Safety testing. The Quality Control Department shall have
inter alia the following principal duties, namely :-
(1) To prepare detailed instructions for carrying out test and analysis.
(2) To approve or reject raw material, components, containers, closures, in-
process materials, packaging material, labelling and finished products.
(3) To release or reject batch of finished products which are ready for
distribution.
(4) To evaluate the adequacy of the conditions under which raw materials, semi-
finished products and finished products are stored.
1. Subs. by G.S.R 40(E), dt. 29.1.2001 (w.e.f. 1.6.2001)
Drugs and Cosmetics Rules 1945
327
(5) To evaluate the quality and stability of finished products and when necessary of
raw materials and semi-finished products.
(6) To review production records to ensure that no errors have occurred or if errors
have occurred that they have been fully investigated.
(7) To approve or reject all procedures, or specifications impacting on the identity,
strength, quality and purity of the product.
(8) To establish shelf-life and storage requirements on the basis of stability tests
related to storage conditions.
(9) To establish and when necessary revise, control procedures and specifications.
(10) To review complaints, recalls, returned or salvaged products and investigations
conducted there under for each product.
(11) To review Ma
ster Formula Records/Cards periodically.
G. TESTING OF BLOOD PRODUCTS:
The products manufactured shall conform to the standards specified in the
Indian Pharmacopoeia and where standards of any product is not specified in the
Pharmacopoeia, the standard for such product shall conform to the standard
specified in the United States Pharmacopoeia or the British Pharmacopoeia. The
final products shall be tested for freedom from HIV I and HIV II antibodies
1
[(Hepatitis B surface antigen and Hepatitis C Virus antibody)].
H. STORAGE OF FINISHED PRODUCT :
(i) The final products shall be stored between two degree centigrade to eight
degree centigrade, unless otherwise specified by the Central Licence Approving
Authority.
(ii) The shelf-life assigned to the products by the licensee shall be submitted
for approval to the Licensing Authority and Central Licence Approving Authority.
I. LABELLING :
The products manufactured shall be labelled as specified in the
Indian Pharmacopoeia, the British Pharmacopoeia or the United Stated Pharmacopoeia
which shall be in addition to any other requirement stated under Part IX or Part X
of these rules. The labels shall indicate the results of test for
1
[(Hepatitis B surface
antigen and Hepatitis C Virus antibody)] freedom from HIV I and HIV II antibodies.
J. RECORDS:
The licensee shall maintain records as per Schedule U and also comply with
Batch manufacturing records as specified in Paragraph 9 of Part -I of Schedule M and
any other requirement as may be directed by Licensing Authority and Central Licence
Approving Authority.
K. MASTER FORMULA RECORDS:
The licensee shall maintain Master Formula Records relating to all
manufacturing and quality control procedures for each product, which shall be
prepared and endorsed by the Competent Technical Staff, i.e. Head of the
manufacturing unit. The Master Formula Records shall contain: –
(i) the patent or proprietary name of the product along with the generic
name, if any, strength and the dosage form;
(ii) a description or identification of the final containers, packaging materials,
labels and closures to be used;
1. Subs. by G.S.R 40(E), dt. 29.1.2001(w.e.f. 1.6.2001)
Drugs and Cosmetics Rules 1945
328
(iii) the identity, quantity and quality of each raw material to be used irrespective
of whether or not it appears in the finished product. The permissible
overage that may be included in a formulated batch shall be indicated;
(iv) a description of all vessels and equipments and the sizes used in the process;
(v) manufacturing and control instructions along with parameters for critical
steps such as mixing, drying, blending, sieving and sterilizing the product;
(vi) the theoretical yield to be expected from the formulation at different
stages of manufacture and permissible yield limits;
(vii) detailed instructions on precautions to be taken in the manufacture and
storage of drugs and of semi finished products; and
(viii) the requirements in-process quality control tests and analysis to be carried
out during each stage of manufacture including the designation of
persons or departments responsible for the execution of such tests and
analysis.
II. REQUIREMENTS FOR MANUFACTURE OF BLOOD PRODUCTS FROM BULK
FINISHED PRODUCTS
Where the blood products, such as Albumin, Plasma Protein Fraction,
Immunoglobulins and Coagulation Factor Concentrates are manufactured through the
manufacturing activities of filling and sealing the blood products from bulk powder
or solution or both, the requirements as they apply to the manufacture of blood products
from whole blood shall apply mutatis mutandis to such manufacture of blood products,
unless other requirements have been approved by the Central Licence Approving
Authority.]
1
[PART XIID
REQUIREMENTS FOR COLLECTION, PROCESSING, TESTING, STORAGE,
BANKING AND RELEASE OF UMBILICAL CORD BLOOD DERIVED STEM CELLS
(A) GENERAL REQUIREMENTS
1. Location, Surroundings and Building: The building (s) for storage of Umbilical cord blood
shall be so situated and shall have such measures as to avoid risk of contamination from external
environment including open sewage, drain, public lavatory or any factory which produces
disagreeable or obnoxious odour or fumes, excessive soot, smoke, chemical or biological
emissions.
2. Buildings and premises: (1) The premises used for processing and storage shall be designed,
constructed and adapted and maintained to ensure that the above operations and other ancillary
functions are performed smoothly under hygienic conditions and in sterile areas wherever
required. They shall also conform to the conditions laid down in the Factories Act, 1948 (63 of
1948).
The premises shall be:
(a) Adequately provided with working space to allow orderly and logical placement of
equipment, material and movement of personnel so as to maintain safe operations and
prevent contamination;
(b) Designed / constructed / maintained to prevent entry of insects, pests, birds, vermins and
rodent. interior surfaces (walls, floors, ceilings and doors) shall be smooth and free from
cracks, and permit easy cleaning, painting and disinfection, and in aseptic areas the
surfaces shall be impervious, non-shedding, non-flaking and non-cracking;
(c) Flooring shall be unbroken and provided with a cove both at the junction between the
wall and the floor as well as the wall and the ceiling.
1. Inserted by G.S.R. 899(E) dated 27-12-2011
Drugs and Cosmetics Rules 1945
329
(d) Provided with light fitting and grills which shall flush with the walls and not hanging
from the ceiling to prevent contamination;
(e) If provided with fire escapes, these shall be suitably installed in the walls without any
gaps;
(f) Provided with the furniture in aseptic areas which is smooth, washable and made of
stainless steel or any other appropriate non shedding material other than wood;
(g) Provided with separate areas for processing and storage of products to prevent mix- ups,
product contaminations and cross contamination;
(h) Provided with defined environmental conditions for temperature, humidity, ventilation
and air filtration. Classifications shall be defined and, if appropriate, monitored.
(2) A periodical record of cleaning and renovating of the premises shall be maintained.
3. Disposal of waste and infectious materials:
(a) Waste materials awaiting disposal shall be stored safely;
(b) The disposal of sewage and effluents from the facility shall be in conformity with the
requirements of the Pollution Control Board;
(c) All bio-medical waste shall be dealt with in accordance with the provisions of the Bio-
medical Waste Management and Handling Rules, 1996.
4. Health, clothing and Sanitation of personnel:
(a) All personnel shall undergo medical examination prior to employment and shall be free
from infectious and contagious diseases and thereafter they should be medically
examined periodically at least once a year and for this purpose records shall be
maintained thereof:
(b) All personnel, prior to and during employment, shall be trained in practices which ensure
personal hygiene and a high level of personal hygiene shall be observed by all those
engaged in the collection, processing, banking of umbilical cord blood;
(c) All persons shall wear clean body coverings appropriate for their duties before entering
the Processing Zone and the Change Rooms with adequate facilities shall be provided
prior to entry into any specific zone;
(d) Smoking, eating, drinking is prohibited inside the Laboratory;
(e) All personnel working in the Laboratory shall be protected against virus infections.
5. Requirements for Processing, Testing and Storage Areas for Umbilical cord blood stem cells:
(a) Separate dedicated areas specifically designed for the purpose and the workload shall be
provided:
(b) There shall be separate areas for designated work purposes namely:-
(i) Cord blood Reception: cord blood reception area with space for transient storage of
units and physical examination shall have adequate facilities for registration, date
entry and generation of bar-coded labels. Air condition area of at lease 10.00 Sq.
meters shall be provided;
(ii) Cord blood processing area: The room shall be clean and have an air handling
System to provide a Class 10,000 environment. Entry to this area shall be through
air lock. The room will house Class 100 biological safety cabinets for Umbilical
cord blood processing. The temperature of the clean room shall be maintained 20
ºC to 25ºC and with a positive differential pressure of 10-15 pascals and Relative
humidity of 50-60% Minimum area shall be 10.00 Sq. meters for the activity;
(iii) Haematology and Serology Laboratory: The laboratory shall be equipped and
utilized for the purpose of independently testing of Umbilical Cord Blood for ABO
grouping and Rh Typing, Total Nucleated Cell Count, Progenitor cell count and
Drugs and Cosmetics Rules 1945
330
viability test. The room shall be air-conditioned and area of at least 10.00 Sq. meters
shall be provided.
(iv) Transfusion Transmissible Disease Screening Laboratory: The Laboratory shall be
equipped and utilized for screening tests on maternal blood for infectious diseases
viz. HIV I & II; Hepatitis B & C virus, syphilis, malaria, CMV and HTLV. The room
shall be air-conditioned and area of at least 10.00 Sq. meters shall be provided.
(v) Sterility Testing Laboratory: The laboratory shall be used for performing Sterility
tests on Umbilical Cord blood unit. The premises may be classified depending on the
testing method used. The room shall be air-conditioned with adequate and ancillary
area for media prepar ation, sterilization, incubation and decontamination. Area of
at least 10.00 Sq. meters shall be provided.
(vi) HLA Typing Laboratory: The Umbilical Cord blood unit shall have arrangements
for HLA typing and genetic disease testing. In-house testing can be done by
providing a well demarcated laboratory from the processing area for evaluation of
possible genetic disease and HLA typing. The area shall have Class 100,000
environment and air-conditioned and area of at least 10.00 Sq. meters shall be
provided.
(vii) Sterilization-cum-washing: Appropriate facility shall be provided within the
premises for proper washing and sterilization. This facility would be optional for
laboratories using entirely disposable items.
(viii) Records and Store Rooms: There shall be designed record room(s) and store
room(s) of at least 10.00 Sq. meters each. The access to record room shall be
permitted only to authorized person. The room will have adequate protective
facilities as the documents and records are to be preserved for long years.
(ix) Cryogenic Storage room: A minimum space of 20.00 sq. meters shall be provided by
the licensee. The cryogenic storage room shall have provision for temperature
monitoring of storage vessels, liquid nitrogen level in storage vessels and oxygen
meter. The service space between each liquid nitrogen storage vessel, supply
cylinders and connecting hose should be minimum 1.00 sq. Meters. Separate
storage space for other accessories required shall be provided. The room shall be air-
conditioned.
(x) General Storage area: General storage area shall be provided to store all the
consumables, under conditions deemed optimum for storage by manufacturers.
B. COLLECTION AND STORAGE OF PROCESSED UMBILICAL CORD BLOOD
COMPONENT
1. Collection:
(a) Umbilical Cord blood unit specific for an individual will be collected after signing an
agreement with the parents, whose child‘s Umbilical Cord blood is to be collected and
the cord blood bank. Private and Public Umbilical Cord blood banking to have different
agreements;
(b) Umbilical Cord blood shall be collected from hospitals, nursing homes, birthing centers
and from any other place where a consenting mother delivers, under the supervision of
the qualified Registered Medical Practitioner responsible for the delivery;
(c) The cord blood shall be collected aseptically in a disposable PVC bag, containing
adequate quantity of sterile, pyrogen free anti-coagulant and sealed effectively and such
PVC Bags shall be procured from licensed manufacturer;
(d) The Umbilical Cord blood would be collected from a premises operating in hygienic
condition to allow proper operation, maintenance and cleaning.
2. Transportation:
Drugs and Cosmetics Rules 1945
331
(a) Umbilical Cord blood shall be transported from the birthing center to the designated
laboratory under and as per procedure prescribed by the cord blood bank;
(b) The transportation procedure shall be validated to ensure optimum survival of the Stem
Cells;
(c) The transportation temperature should be between 18 to 28ºC;
(d) The time period between collection and processing shall not exceed 72 hours.
3. Storage:
(a) The Umbilical Cord blood shall be stored at room temperature between 20 to 25ºC in the
reception area prior to processing;
(b) Samples pending tests for specific transfusion transmittable infectious diseases shall be
stored in a segregated manner.
Note:- Temperature range between 4 to 37 degrees Celsius, for the whole time period of transit
may be allowed beyond the 18ºC to 28ºC in exceptional cases. The effects of deviation of transit
temperature from the optimum, on the product shall be adequately explained by the licensee in
the client education booklet.
C. PERSONNEL
Cord blood bank shall have following categories of whole time competent technical staff,
namely:-
1. Medical Director:- The operation of cord blood bank shall be conducted under the active
directions and supervision of a Medical Director who is a whole time employee and is
possessing a Post Graduate degree in medicine – MD [Pathology/Transfusion
Medicine/Microbiology] and has experience / training in cord blood processing and
Cryogenic Storage.
2. Laboratory In-charge: The laboratory in-charge shall have Post Graduate qualification in
Physiology or Botany or Zoology or Cell Biology or Microbiology or Biochemistry or Life
Sciences or Graduate in Pharmacy and one year working experience in pathological
laboratory licensed by the local health authority or any microbiology laboratory of a licensed
drug manufacturing / testing unit and or experience / training in cord blood processing and
cryogenic storage.
3. Technical Supervisor (cord blood processing):- The technical supervisor shall have a:
(a) Degree in Physiology or Botany or Zoology, Pharmacy or Cell Biology or Bio
Sciences or Microbiology or Biochemistry or Medical Laboratory Technology
(M.L.T.) with minimum of three years of experience in the preparation of blood
components and / or experience or training in cord blood processing and Cryogenic
Storage; or
(b) Diploma in Medical Laboratory Technology (M.L.T.) with five years experience in
the preparation of blood components and experience or training in cord blood
processing and Cryogenic Storage shall be essential.
4. Cord Blood Bank Technician(s):- The technicians employed shall have a:
(a) A degree in Physiology or Botany or Zoology or Pharmacy or Cell Biology or Bio
Science or Microbiology or Biochemistry or Medical Laboratory Technology
(M.L.T.) with six months experience and or training in cord blood processing and
cryogenic storage; or
(b) Diploma in Medical Laboratory Technology (MLT) with one year experience in the
testing of bloodand / or its components and / or experience or training in cord blood
processing and Cryogenic Storage.
D. AIR HANDLING SYSTEM
1. Air handling for sterile areas shall be different from those for other areas. The filter
configuration in the air handling system shall be suitably designed to achieve the grade of
Drugs and Cosmetics Rules 1945
332
air as given in the Table I. The environmental microbiological monitoring of clean areas
shall be in accordance to the recommended limits given in Table II.
2. The Processing area shall have HVAC system and fitted with HEPA Filters having Grade
C (Class 10,000) environment as given in Table I.
3. The entire processing shall be done conforming to Grade A (Class 100) Standard of air
quality.
TABLE I
AIR BORNE PARTICULATE CLASSIFICATIONS FOR MANUFACTURE OF STERILE
PRODUCTS
Grade
Maximum number of permitted particles per cubic meter equal to or above
At rest (b)
In Operation (a)
A
B(a)
C(a)
D(a)
0.5µm
3,500
3,500
3,50,000
35,00,000
5 µm
0
0
2000
20,000
0.5 µm
3,500
3,50,000
35,00,000
Not defined
5µm
0
2000
20,000
Not defined
Notes:-
(a) In order to reach the B, C and D air grades, the number of air changes shall be related to
the size of the room and the equipment and personnel present in the room. The air system
shall be provided with the appropriate filters such as HEPA for grades A, B and C. The
maximum permitted number of particles in the ―at rest‖ condition shall approximately
be as under:-
[Grade A and B corresponds with class 100 or M 3.5 or class 5]; Grade C with Class
10,000 or M 5.5 or ISO Class 7; Grade D with Class 1,00,000 or M 6.5 or ISO Class 8.
(b) The requirement and limit for the area shall depend on the nature of the operation carried
out.
TABLE II
RECOMMENDED LIMITS FOR MICROBIOLOGICAL MONITORING OF
CLEAN AREAS ―IN OPERATION‖
Notes:-
(a) These are average values.
(b) Individual settle plates may be exposed for not less than two hours in Grade B, C and
D areas and for not less than thirty minutes in Grade A area.
E. QUALITY CONTROL
1. Facilities shall be provided for Quality Control such as Haematological, Microbiological and
Instrumental testing.
Grade
Air samples
Cfu/m3
Settle Plates
(dia 90mm)
cfu/2hrs
Contact
plates (dia 55
mm) cfu per
plate
Glove points
(Five fingers)
cfu per glove
A
Less than
1
Less
than 1
Less
than 1
Less
than 1
B
10
5
5
5
C
100
50
25
-
D
500
100
50
-
Drugs and Cosmetics Rules 1945
333
2. Following duties shall be performed under the function of quality control:
(a) To prepare detailed instructions for carrying out such tests and analysis;
(b) To approve or reject raw materials and consumables, used in any step, on the basis of
approved specifications;
(c) Haematological tests like Total Nucleated Cell Counts, Mononuclear Cell Count,
Enumeration of the population of Stem Cells, Stem Cell viability shall be performed on
samples of processed Umbilical cord blood unit;
(d) Microbiological Tests shall be done on Maternal Blood samples for freedom from
Hepatitis B Surface Antigen, Hepatitis C Virus antibody, HIV I and II antibodies.
Syphilis, Malaria, CMV and HTLV. Bacterial and Fungal Culture shall be done on the
umbilical cord blood samples;
(e) Instruments which would be used to process test and store the UCB unit would be
validated before commissioning and calibrated from time to time to check their
conformity to specific standards according to an approved and valid protocol;
(f) The environmental monitoring of the clean rooms would be done at periodic intervals
according to an accepted and validated protocol;
(g) All tests mentioned above shall be done in house except tests under itme numbers (e), (f)
and test for enumeration of Stem Cell Population, HLA typing and Genetic Disease
Testing which may be outsourced to a competent third party approved by the licensing
authority.
F. SCREENING TESTS
1. The maternal blood sample shall be tested for
(a) Hepatitis B;
(b) Hepatitis C;
(c) HIV 1 & 2;
(d) Syphilis;
(e) Malaria;
(f) CMV;
(g) HTLV
2. The Umbilical Cord Blood shall be tested for
(a) Total Nucleated Cell count;
(b) Total Mononuclear Cell Count;
(c) Progenitor Cell (CD34+) enumeration;
(d) Cell Viability;
(e) ABO Group and Rh Type;
(f) Sterility as regards Bacterial and Fungal contamination status;
(g) HLA Matching (Only for allogenic Cord Blood Units).
G. STORAGE
1. The Umbilical cord blood shall be cryopreserved using a controlled rate freezing or
equivalent validated procedures. The frozen storage shall be at minus 196ºC and shall not
be warmer than minus 150ºC.
2. There will be no shelf life for this class of product.
H. REFERENCE SAMPLES
1. At least two reference samples shall be collected from cord blood unit product prior to
cryopreservation and stored at minus 196ºC and shall not be warmer than minus 150ºC.
2. At least one additional reference sample shall be stored at minus 76ºC or colder for the
purposes other than viability analysis.
I. LABELLING
1. Initial label placed during collection shall specify:
Drugs and Cosmetics Rules 1945
334
(a) Human Umbilical Cord Blood;
(b) Approximate Volume or weight of contents in the collection bag [UCB+
Anticoagulant];
(c) Mother ‘s name;
(d) Place of collection;
(e) Date and time of collection;
(f) Collected by;
(g) To be labeled in bold, ―ROOM TEMPERATURE ONLY– DO NOT REFRIGERATE,
DO NOT IRRADIATE‖;
(h) Manufacturing license number.
2. Label at completion of processing and before issue - Cryogenic Storage Label [Statutory
label] shall indicate the following:-
(a) Name of product:- Human Progenitor Cell [HPC] – Cord Blood;
(b) Volume or weight of contents;
(c) Percentage of Cryoprotectant [DMSO];
(d) Percentage of any other additive / preservant;
(e) Date of collection [birth] ………………………;
(f) Date of processing ……………………………..;
(g) Name of manufacturer………………………….;
(h) Manufacturing license number;
(i) Storage temperature – not less than, - 196ºC and shall not be warmer than minus 150ºC,
(j) Unique Traceability Number and / or BAR Code.
3. Issue label at the time of release of Cord Blood Unit shall indicate the following namely:-
(a) Name of manufacturer;
(b) License number;
(c) All details of the Cryogenic Storage Label;
(d) The results of Total Nucleated Cells, Progenitor Cell percentage {CD34+), Viability;
(e) Results of Transfusion Transmittable diseases testing on maternal blood;
(f) ABO Group and Rh Type;
(g) Date of processing;
(h) Result of HLA typing (allogenic);
(i) Statement ―properly identify intended Recipient and Product‖;
(j) A statement indicating that leukoreduction filters should not be used;
(k) Statement ―Do not irradiate‖
(l) Name and address of receiving hospital.
J. RECORDS OR DOCUMENTATION
1. The licensee shall maintain the following records
(a) Client / donor enrolment / agreement record;
(b) Collection of unit and transportation record;
(c) Master record of stored unit;
(d) HLA Matching record;
(e) Unit Release Register;
(f) Stock Register for Blood Collection Bag Cryoprotectant and Preservant, RBC
Sedimentation Enhancer;
(g) Stock Register for Diagnostic Kits, Reagents and other consumables;
(h) Record on feedback after use of cord blood / Adverse reaction record.
2. The following Standard Operating Procedures shall be maintained by the licensee, namely:-
(a) Umbilical Cord Blood collection;
(b) Transportation of the collected Umbilical cord Blood unit;
(c) Processing of Umbilical cord blood unit;
(d) Cryogenic storage of processed umbilical cord blood unit;
Drugs and Cosmetics Rules 1945
335
(e) Testing of maternal blood for transfusion transmittable infections;
(f) Testing of Umbilical cord blood for ABO Grouping and Rh Typing;
(g) Testing of Umbilical cord blood unit for Total Nucleated Cell Count, Mononuclear
Cell Count, Progenitor Cell (CD34+) enumeration, and viability;
(h) Testing of Umbilical cord blood stem cell unit for sterility;
(i) Disposal of bio medical waste;
(j) Dispensation of Umbilical cord blood unit;
(k) Preventive maintenance Protocol for all Instruments;
(l) Acceptance / Rejection procedure of consumables;
(m) Environment monitoring of classified areas;
(n) Any other standard operative procedure as per requirements.
K. CORD BLOOD RELEASE
1. There shall be designated area with adequate space for procedures and records related to cord
blood unit selection and release.
2. The cord blood bank shall obtain written or electronic request from the transplant physician
or designee for shipment of the cord blood unit.
3. Accompanying documentation at the time of issue from the cord blood bank shall include
indications, contra-indications, caution, instruction for handling and use of the cord blood
unit including short-term storage and preparation for transplantation.
4. Procedure for transportation of cryopreserved cord blood unit within the facility shall be
designed to protect the integrity of the unit and the health and safety of the personnel.
5. Cryopreserved cord blood unit stored at -150ºC or colder shall be transported in a liquid
nitrogen cooled dry shipper that contains adequate absorbed liquid nitrogen and has been
validated to maintain temperature below -150ºC for at least 48 hours beyond the expected
time of arrival at the receiving facility.
1
[PART
XIII]
GENERAL
1. For the purposes of this Schedule, any test or method of testing described in
the
2
[Indian Pharmacopoeia] shall be deemed to be a method approved by the Licensing
Authority.
2. The Licensing Authority shall publish in the Official Gazette from time to
time particulars of any test or method of testing approved by him.
1. Renumbered by Notification No. F-18-1/46, dt. 18-6-48
2. Subs. by G.S.R. 19, dated 15-12-1977
Drugs and Cosmetics Rules 1945
336
1
[SCHEDULE F(I)
PART 1
–
VACCINES
(A) PROVISIONS APPLICABLE TO THE PRODUCION OF BACTERIAL VACCINES:
1. Definition. –(1) This part of the Schedule applies to bacterial vaccines made from
any micro-organism pathogenic to man or other animal and to vaccines made from other
micro-organisms which have any antigenic value.
(2) For the purposes of this part of the Schedule, a bacterial vaccine means a sterile
suspension of a killed culture of the micro-organism from which the vaccine derives its name
or a sterile extract or derivative of a micro-organism, or a pure suspension of living micro-
organisms which have been previously made avirulent.
2. Staff of Establishment.–A competent expert in bacteriology with sufficient
experience in the manufacture and standardisation of biological products shall be in charge of
the establishment responsible for the production of bacterial vaccine and he shall be assisted
by a staff adequate for carrying out the tests required during the preparation and
standardisation of the vaccines.
3. Proper Name.–The proper name of any vaccine shall be the name of the micro-
organism from which it is made followed by the word ―Vaccine‖ unless this Schedule
otherwise provides or if there is no other special provision in this Schedule, some other name
as approved by the Licensing Authority. Provided that in the case of the undermentioned
preparations the proper name of the vaccine may be as follows: –
1. Anthrax Spore Vaccine (Living).
2. Blackquarter Vaccine.
3. Enterotoxaemia Vaccine.
4. Fowl Cholera Vaccine.
5. Haemorrhagic Septicaemia Adjuvant Vaccine.
6. Haemorrhagic Septicaemia Vaccine (Broth).
2
[7. Multi Component Clostridial Vaccine.
8. Hemorrhagic Septicaemia Vaccine – Alum Treated.]
4. Records.–Cultures used in the preparation of vaccine before being manipulated
into
a vaccine, should be thoroughly tested for identity by the generally accepted tests applicable
to the particular micro-organisms.
The permanent records which the licensee is required to keep shall include amongst
others, a record of the origin, properties and characteristics of the cultures.
5. Combined Vaccines.–Vaccines may be issued either singly or combined in any
proportion in the same container. In the case of combination of vaccines, a name for the
combined vaccine may be submitted by the licensee to the Licensing Authority, and if
approved, may be used as the proper name of the vaccine.
1. Added by Ministry of Health F.P., W.H and U.D. Notfn. No. F.1-6/62-D (SO. 2889), dt. 2-7-1969
2. Ins. by G.S.R. 659(E) ,dt. 31.8.1994.
Drugs and Cosmetics Rules 1945
337
6. Preparation– Bacterial vaccines, simple or polyvalent, are prepared from selected
cultures after careful examination for their identity, specificity, purity and antigencity. They
may be prepared in the following manner:.–
(a) Formal Cultures or Bacterins.– The selected pure culture strain or strain
are grown in a suitable fluid medium, at an optimum temperature, for an appropriate
period. The pure growth is then exposed to the action of solution of Formaldehyde I.P. in
suitable concentration and temperature. The product is finally filled in suitable sterilised
containers which are subsequently sealed.
(b) Vaccine of Bacterial Products or Bacterial Derivatives.–These vaccines
are prepared by growing the organisms on suitable media and then deriving specific
antigenic constituents of the bacteria by various special methods.
(c) Living Bacterial Vaccines.– They are prepared from non-pathogenic but
fully immunogenic strains of micro-organism. Strict aseptic precautions are taken
throughout the preparation against the introduction of microbial contaminants.
7. General Standards:.
(a )Description.– Bacterial vaccines are colourless to yellowish brown liquids
containing dead or viable bacteria in homogenous suspension.
(b) Identification.–All types of vaccines confer active immunity in the susceptible
animals which can be demonstrated by injecting suitable experimental animals with the
calculated doses of the product and subsequently determining the presence of the
protective antibodies in their serum and/or by challenging the vaccinated animals by
injecting virulent strain of the homologous organisms. The protected animals should
survive the challenge.
(c) Test for Sterility.–All bacterial vaccines shall be tested for sterility in
accordance with the provision of Rules 115 to 119 (both inclusive). If the vaccine
contains added bactericide or bacteriostatic, a quantity of medium sufficient to render
the growth inhibitor ineffective is added to the sample, or a suitable substance is added
to the sample, or a suitable substance is added in concentration sufficient to render the
growth inhibitor ineffective but not itself to inhibit the growth of micro-organism.
(d) Purity Tests for Living Bacterial Vaccine.–Petri dishes containing suitable
media are streaked with the final product and incubated at 37˚ C for 72 hours. The
vaccine passes the test if no growth of micro-organisms other than those from which the
vaccine was prepared is observed. Other tests include examination for motility of the
organisms, fermentation reactions and thermoagglutination test and dye-inhibitor tests
in case of bruceliza vaccine.
(e) Safety Test.– The safety of the vaccine shall be assessed by injecting it in
appropriate doses in suitable susceptible animals. No animal should show any
untoward, general or local reaction within seven days after inoculation.
(f). Potency Test.–Wherever applicable, susceptible experimental animals are
inoculated with the calculated doses of the final product. The animals are challenged
after the period of immunisation, with virulent infective dose of the homologous culture
along with the controls. The potency of the vaccine is assessed by the survival of the
vaccinated animals and the death of the controls.
8. Labelling:
(a) The label on the ampoule or the bottle shall indicate:.–
(i) Proper name.
(ii) Contents in millilitres or doses.
(iii) Potency, if any.
Drugs and Cosmetics Rules 1945
338
(iv) Batch number.
(v) Expiry date.
(b) The label on the outside container shall indicate:
(i) Proper name.
(ii) Contents in Millilitres or doses.
(iii) Batch number.
(iv) Date of manufacture.
(v) Manufacturing licence No.
(vi) Manufacturer‘s name and address.
(vii) ―For animal treatment only‖.
(viii) Storage conditions.
9. Storage.–-Bacterial vaccines shall be stored, protected from light at temperature
between 2˚C to 4˚C and shall not be frozen.
10. Date of manufacture.– The date of manufacture shall be, unless otherwise specified
in the individual monograph in this part, as defined in clause (b) of sub-rule (3) of rule 109.
Anthrax Spore Vaccine (Living)
1. Synonyms.–-Avirulent Anthrax Spore Vaccine or Bacillus Anthracis Vaccine
(Living).
2. Definition.–-The vaccine is a suspension of living spores of an uncapsulated
avirulent strain of B anthracis in 50 per cent glycerine saline.
3. Preparation.–-Avirulent B, anthracis of known antigenicity is grown on suitable
medium at pH 7.4 in Roux flasks. After 72 hours incubation at 37˚ C, the pure sporulated
culture growth which shows 70 to 80 per cent sporulation is washed with normal saline and
glycerinated to the extent of 50 per cent by weight of the culture washing and the whole
suspension is kept at room temperature for twenty-one days to allow for the stabilization of
the spores.
4. Standard:.
(a) Description.–- It is slightly opalescent or pale brown semi-viscous liquid.
(b) Identification.–-Uncapsulated B anthracis which is avirulent can be isolated
from the vaccine.
(c) Sterility test.–- Should comply with the test for sterility described in the general
monograph on ―Bacterial Vaccine‖.
(d) Purity Test.–- Complies with the ―Purity Tests for Living Bacterial Vaccine‖
described under the general monograph on ―Bacterial Vaccines‖.
(e) Safety Test.–-Four healthy adult guinea-pigs each weighing 300-450 g. not
previously treated with any material which will interfere with the test are inoculated
subcutaneously, two with 0.2 ml. each and two with 0.5 ml. each of the unglycerinated
suspension respectively. Four more guinea-pigs are injected with 1:5 dilution of the
glycerinated product in the same manner. No untoward reaction should be observed and
none of the animals should die of anthrax during the period of observation for seven days.
Drugs and Cosmetics Rules 1945
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(f) Safety and Potency Test in sheep and goat–Spore count of the glycerinated
suspension is made after twenty-one days from the date of glycerination. Three
plates for each of the three dilution 10
5
, 10
6
and 10
7
are made.
Eight sheep and eight goats each weighing not less than 18 kg. are injected
subcutaneously in the following manner:–
two sheep : Each subcutaneously with 10 ml. of the stock suspension
(for
safety).
two goats : Each subcutaneously with 5 ml. of the stock
suspension (for safety).
six sheep : Each subcutaneously with one million spores
suspended in 50 per cent glycerine saline solution.
six goats : Each subcutaneously with one million spores suspended in
50 per cent glycerine saline solution.
None of these animals should die of anthrax. Twenty one days after vaccination, the
animals are challenged with 100 lethal doses of virulent B. anthracis spores along with two
healthy sheep and two goats as controls.
All the controls should die of anthrax within 72 hours after challenge and at least 66 per
cent of the vaccinated animals should survive. The animals shall be observed for a minimum
of ten days from the date of challenge.
1
[(g) Viable Count.– The vaccine when plated on suitable media should show 10
million viable spores per cattle dose and 5 million spores per sheep dose.]
5. Labelling and Storage.– Should comply with the requirements for ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖.
2
[6. Expiry Date.– The date of expiry of the potency of the vaccine shall be not more
than two years from the date of manufacture if stored in 4
o
C and six months, if stored at room
temperature.]
Blackquarter
Vaccine
1. Synonym.–Blackleg vaccine or Quarter Evil Vaccine.
2. Definition.– Blackquarter Vaccine is a culture of Clostridium chauvoei grown in a
suitable anaerobic fluid medium and rendered sterile and toxic by the addition of Solution of
Formaldehyde I.P. in such a manner that it retains its immunising properties.
3. Preparation.–Cultures of Cl. Chauvoei are grown in a suitable anaerobic fluid
medium and killed by the addition of a suitable concentration of Solution of Formaldehyde
I.P. The final product shall be adjusted to pH.7.0.
4. Standards:.
(a) Description.–It is a yellowish brown liquid containing dead bacteria in
suspension.
(b) Identification.–It protects susceptible animals against infection with Cl.
Chauvoei.
(c) Sterility Test.–Should comply with the test for sterility described in the
general monograph on ―Bacterial Vaccine‖.
1. Subs. by. G.S.R 659 (E) ,dt.. 31-8-1994.
2. Ins. by. G.S.R 659 (E) ,dt.. 31-8-1994.
Drugs and Cosmetics Rules 1945
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(d) Safety and Potency Tests.–At least six adult healthy guinea-pigs each
weighing 300 g to 450 g are injected subcutaneously each with 3 ml. of the product
followed a week later by a second injection with the same dose. They should not
show any systemic reaction but may show only a minimum of local reaction.
Fourteen days after the second injection six of the vaccinated guinea-pigs are
challenged intramuscularly with 25 viable spores of Cl. Chauvoei equivalent to 5
c.h.d. along with 0.2 ml. of a 5 per cent solution of calcium chloride. Two controls
are used. The controls should die of the specific injection and at least 4 of the six
vaccinated animals should survive before the product is passed for issue.
5. Labelling and Storage.– Should comply with the requirements of ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖.
6. Expiry Date.–- The date of expiry of the potency of the vaccine shall not be more
than twenty-four months from the date of manufacture.
Brucella Abortus ( Strain 19 Vaccine)
(Living)
1. Synonym.–Contagious Abortion Vaccine, (Strain 19) (Living).
2. Definition.–Brucella Abortus (Strain 19) Vaccine (Living) is a suspension of a pure
smooth living culture of Br. Abortus of low virulence in normal saline solution.
3. Preparation.–Forty eight to seventy-two hour old growth of Br. Abortus (Strain 19)
on potato agar medium in Roux flasks washed with buffered normal saline solution pH 6.4
and the pure growth from the flasks are pooled together, 0.5 ml. of the pooled product is
mixed with 4.5 ml. of normal saline solution at pH 6.4 in graduated centrifuge tube and
centrifuge at 3000 r.p.m for one hour. The percentage of cell deposit is assessed by reading
the amount of cell deposit obtained.
The concentrated suspension is then diluted with buffer normal saline solution so that the
final product contains 0.72 per cent bacterial cell deposit.
4. Standard:
(a) Description.–It is an almost white turbid liquid containing live bacteria in
suspension.
(b) Identification.–It consists of Gram-negative bacilli capable of protecting
susceptible animals against Brucellosis.
(c) Sterility Test.–Should comply with the test for sterility described in the general
monograph on ―Bacterial Vaccine‖.
(d) Purity Test.–A smear of the finished products is examined microscopically
after staining by Gram‘s method for evidence of any contamination. When grown on
suitable media, Br. Abortus should be obtained in a pure state.
(e) Safety Test.–Two healthy guinea-pigs each weighing 300 g. to 450g. are
inoculated subcutaneously each with 1.0 ml. of the final product. The guinea-pigs
should not show excessive reaction of a toxic nature during the period of observation of
ten days.
(f) Potency Test.–Each of a group of four healthy guinea-pigs, drawn from a
uniform stock and each weighing 300 g. to 450 g. is injected intra-muscularly with 1 ml.
of the vaccine, and is challenged nine weeks after vaccination by the intramuscular
injection of 1 ml. of a suspension containing 5,000 fully virulent Br. Abortus organisms.
Each of a group of two unvaccinated guinea-pigs is similarly injected. After a further six
weeks, the guinea-pigs are killed and cultures are made from their spleens. More than
half of the vaccinated guinea-pigs contain no demonstrable Br. Abortus in the spleen; all
the controls are infected.
Drugs and Cosmetics Rules 1945
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(g) Viable Count.–The vaccine when plated on suitable media should show
between 14, 000 million and 18,000 million Br. Abortus organisms per ml. At least 80
per cent brucella organisms should be in the smooth phase.
4. Labelling and storage.– Should comply with the requirements of ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖. The liquid vaccine
shall be issued fresh as far as possible without allowing any period of storage after
manufacture.
5. Expiry Date–The date of expiry of the vaccine shall be not more than five weeks
from the date of manufacture.
Enterotoxaemia
Vaccine
1. Synonyms.–Clostridium Welchii, Type D, Formal Culture: Pulpy Kidney Vaccine.
2. Definition.–Enterotoxaemia Vaccine is a culture of a highly toxigenic strain of
Clostridium type D, group is an anaerobic medium rendered sterile and toxic by the addition
of Solution of Formaldehyde I.P in such a manner that it retains its immunising properties.
3. Preparation.– Selected toxigenic strain of Cl. Welchii type D, is grown in a liquid
medium under conditions which ensure maximum epsilon toxin production. The culture is
checked for purity and toxicity as tested in mice. Solution of Formaldehyde I.P. is added in
suitable concentration and the formolised culture is kept at 37˚ C till the production is sterile
and non-toxic.
4. Standard:
(a) Description- It is a yellowish brown liquid containing dead bacteria in
suspension.
(b) Identification- When injected into susceptible animals it stimulates the
production of epsilon antitoxin of Cl. Welchii, type D.
(c) Sterility Test- Complies with the test for sterility described in the general
monograph on ‗Bacterial Vaccines‘.
(d) Safety and Potency Tests- At least eight sheep each weighing not less than 18
kg. or twelve rabbits each weighing 1 kg. to 1.5 kg. are used for testing the safety and
potency of each brew of the vaccine. Two sheep receive subcutaneously 10 ml. each
and the other six sheep receive each 2.5 ml. of the product subcutaneously. The rabbits
are given subcutaneously a dose of 5 ml. each. The sheep and rabbits are observed for
five days. They should show only a minimum local reaction and no systemic reaction.
The sheep receiving 10 ml. are withdrawn from experiments after five days. Each of
the other six sheep is inoculated with a second dose of 2.5 ml. fourteen days after the
first injection. The rabbits are inoculated with 5 ml. as a second dose, after one month
of the first inoculation. Ten days after the second inoculation the sera of sheep or
rabbits are pooled separately. The pooled serum of each group of animal shall contain
in each ml. not less than two international units of Cl. Welchii epsilon antitoxin which
is determined by testing on mice as follows:
One ml. of the pooled serum is mixed with one ml. of the epsilon toxin of Cl.
Welchii type D, containing 300 mouse-minimum-lethal-doses (mouse m.l.d.) and kept at
room temperature for half an hour. At least two mice each weighing not less than 18 g.
are each given intravenously 0.2 ml. of the mixture. As control two mice each weighing
not less than 18 g. should each receive 0.2 ml. of the toxin containing 300 mouse m.l.d
per ml. diluted with equal volume of normal saline. The control mice should die within 1
to 2 hours while the mice receiving the mixture of serum and toxin should survive for at
Drugs and Cosmetics Rules 1945
342
least two days. Sera containing one International Unit of epsilon antitoxin per ml. will be
able to neutralise 150 mouse m.l.d. of epsilon toxin of Cl. Welchii, type D.
5. Labelling and Storage.–Should comply with the requirements regarding
―Labelling‖ and ―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖.
6. Expiry Date.–The expiry date of potency of the vaccine shall be not more than
twelve months from the date of manufacture.
Fowl Cholera Vaccine
(Polyvalent)
1. Synonym.–Pasteurella Septica Vaccine (Avian).
2. Definition.–Fowl Cholera Vaccine is a formolised pure broth culture of virulent
strains of Pasteurella Septica (Avian).
3. Preparation.–The strains are grown separately in nutrient broth for 48 hours at 37˚
C. The pure growth is killed by the addition of a Solution of Formaldehyde I.P in a suitable
concentration. The cultures are then mixed in equal proportions and the final vaccine is
bottled in suitable containers.
4. Standard-
(a) Description.–It is a light yellow liquid containing dead bacteria in
suspension.
(b) Identification.–It protects susceptible birds against P. aviseptica
infection.
(c) Sterility test.–Complies with the test for ―Sterility‖ described under the
general monograph on ―Bacterial Vaccines‖..
(d) Safety Test.–Two healthy young fowls each weighing not less than 400 g. or
twelve healthy mice are inoculated subcutaneously each with 1 ml. of the final product.
The birds should not show any untoward reaction during the period of observation for
seven days.
5. Labelling and Storage.–Should comply with the requirements of ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖.
6. Expiry Date.–The date of expiry of potency of the Vaccine shall be not more than
six months from the date of manufacture.
Hemorrhagic Septicaemia Adjuvant
Vaccine
1. Synonym.– Pasteurella Septica Adjuvant Vaccine.
2. Definition.–The vaccine is a homogenous suspension of formolised agar-washed
Pasteurella septica with liquid paraffin and lanolin.
3. Preparation.–Pure growth of a highly antigenic strain of P. Septica in phase 1 grown
on nutrient agar medium containing 0.5 per cent yeast extract is washed with 0.5 per cent
formol saline. The pooled suspension is diluted with normal saline to contain
approximately 2100 million P. Septica organisms per ml. The safety test of this adjusted
suspension is conducted on four white mice each weighing not less than 18 g. and observed
for three days before it is mixed with liquid paraffin and lanolin in suitable proportion.
The mixture is blended until a homogenous emulsion is obtained which is filled in
suitable containers.
4. Standard:
(a) Description− It is a white thick oily liquid containing dead bacteria in
suspension.
(b) Identification.–It protects susceptible animals against infection with P. Septica.
Drugs and Cosmetics Rules 1945
343
(c) Sterility Test.–It complies with the test for ―Sterility‖ described in the general
Monograph on ―Bacterial Vaccines‖.
(d) Safety Test.– Six white mice each weighing not less than 18 g. are inoculated
intraperitoneally each with 0.5 ml. of the vaccine. None of the mice should die of
pasteurellosis during the observation period for seven days.
(e) Potency Test.–Three susceptible calves in good condition between the ages of
nine months to three years are injected intramuscularly, each with 2 ml. of the vaccine, in
the case of animals weighing upto 140 kg. and 3 ml. for heavier ones.
Three weeks later these animals along with two healthy animals of the same type and
species are challenged subcutaneously with 18 hours old broth culture of P. Septica
equivalent to at least 50 million mouse minimum infective dose. Both the controls should die
of pasteurellosis and at least two out of the three protected animals should survive the
challenge dose for a period of seven days.
5. Labelling and storage- Should comply with the requirements for ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖.
6. Expiry Date- The date of expiry of potency of the vaccine shall be not more than
twelve months from the date of manufacture.
Haemorrhagic Septicaemia Vaccine
(Broth)
1. Synonym.–Pasteurella Septica Vaccine (Broth).
2. Definition.–Haemorrhagic Septicaemia Vaccine is formolised culture of a virulent
strain of Pasteurella septica in nutrient broth.
3. Preparation.–.Septica culture is grown in nutrient broth at 37˚C. The pure growth is
killed by the addition of a solution of Formaldehyde I.P. in a suitable concentration.
4. Standard:
(a) Description.–It is a pale yellow liquid containing dead bacteria in suspension.
(b) Identification.–It protects susceptible animals against infection with P.Septica.
(c) Sterility Test.–Complies with the test for ―Sterility‖ described under the general
monograph on ―Bacterial Vaccines‖.
(d) Safety Test.–Four healthy rabbits each weighing 1 kg. to 1.5 kg. are inoculated
subcutaneously each with 5 ml. of the product. There should be no untoward reaction
during the period of observation for seven days. Alternately two rabbits and six mice
may be employed. The dose for mice will be 0.5 ml.
5. Labelling and Storage.–Should comply with the requirements of ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖.
6. Expiry Date.–The date of expiry of potency of the vaccine shall be not more than
six months from the date of manufacture.
Salmonella Abortus Equi
Vaccine
1. Synonym.–Equine Abortion Vaccine.
2. Definition.– Equine Abortion Vaccine is a mixture of equal parts of pure formolised
cultures of smooth laboratory strains of Salmonella abortus equi.
3. Preparation.–The strains are grown separately on plain agar in Roux flasks, for 24-
28 hours at 37˚ C. The pure growth is washed with normal saline solution and the washings
are pooled together. The suspension is standardised to contain approximately 600 million
Sal.Abortus equi organisms per ml. using normal saline solution as diluent. The culture is
killed by the addition of sufficient quantity of solution of Formaldehyde I.P in a suitable
Drugs and Cosmetics Rules 1945
344
concentration and the product is kept at 37˚C for seven days. Potassium alum is added to
give
a
final concentration of 1 per cent
4. Standard:
(a) Description.–It is an opalescent liquid containing dead bacteria in suspension.
(b) Identification.–It protects susceptible animals against infection with Sal.
Abortus equi.
(c) Sterility Test.–Complies with the test for sterility described in the general
monograph on ―Bacterial Vaccines‖.
(d) Safety Test- Six white mice each weighing not less than 18 g. are inoculated
intraperitoneally each with 0.5 ml. of the product. None of the mice should die of
salmonellosis. The mice are observed for ninety-six hours.
5. Labelling and Storage- Should comply with the requirements for ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖.
6. Expiry Date- The date of expiry of potency of the vaccine shall be not more than six
months from the date of manufacture.
Streptococcus Equi
vaccine
1. Synonym.– Strangles Vaccine
2. Definition.– Streptococcus equi Vaccine is a phenolised culture of a number of
different isolates of Streptococcus equi in glucose serum broth.
3. Preparation.– Equal proportions of forty-eight hours old pure cultures of different
isolates of Str. Equi in serum glucose both are mixed together. The suspension is centrifuged
and the deposit is washed with normal saline solution after removing the supernatant. The
washed cells are suspended in normal saline and heated in a water bath 65˚C for two hours.
Phenol and normal saline are added to give a final concentration of 1200 million Str. Equi
organisms per ml. and 0.5 per cent of phenol in the vaccine.
4. Standard-
(a) Description.– It is a slightly opalescent liquid containing dead bacteria in
suspension.
(b) Identification.–It protects susceptible animals against infection with Str. Equi.
(c) Sterility Test.–Complies with the test for ―Sterility‖ described in the general
monograph on ―Bacterial Vaccines‖, the nutrient broth being replaced by glucose broth.
(e) Safety Test.–Two ponies and two rabbits (each weighing not less than 1 kg.)
are inoculated each with 10 ml. and 2 ml. respectively of the final product. The animals
should not show any untoward reaction during the period of observation of seven days.
5. Labelling and Storage.–Should comply with the requirements for ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines‖
6. Expiry Date.– The date of expiry of potency of the vaccine shall be not more than
six months from the date of manufacture.
Old Adjuvant Vaccine against Pasteurellosis in Sheep and
Goats.
1. Synonym- Pasteurella Septica Adjuvant Vaccine for ovines and Caprines.
2. Definition- The vaccine is a homogenous suspension of formolised agarwashed
Pasteurella septica of ovine origin with liquid paraffin and lanolin.
Drugs and Cosmetics Rules 1945
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3. Preparation− Pure growth of highly antigenic strains (R1, R2, R4) in phase I
grown separately on nutrient agar medium containing 0.5 per cent yeast extract is washed
with 0.5 per cent Normal saline. Equal quantities of the suspension of three strains diluted
with Normal saline to contain approximately 2100 million organisms per ml. is pooled
together. The safety test of this adjusted pooled suspension is conducted in for white mice
each weighing not less than 18 g. and observed for three days before it is mixed with liquid
paraffin and lanolin in suitable proportion.
The mixture is blended until a homogenous emulsion is obtained which is filled in
suitable containers.
4. Standards:
(a) Description- It is a white thick oily liquid containing dead bacteria in
suspension.
(b) Identification- It protects susceptible animals against infection with
P. Septica.
(c) Sterility Test- Complies with the test for sterility described in the general
monograph on ―Bacterial Vaccines‖.
(d) Safety Test- Six white mice each weighing not less than 18 g. are inoculated
intra-peritoneally each with 0.5 ml. of the vaccine. None of the mice should die of
Pasteurellosis druing the observation period of seven days.
The vaccine is also inoculated into six sheep and six goats in a dose of 3 ml. each
intramuscularly and are observed for a period of seven days. During this period none
should die of Pasteurellosis.
(e) Potency Test- Not being done at present.
5. Labelling and Storage- Should comply with the requirements for ―Labelling‖ and
―Storage‖ as laid down in the general monograph on ―Bacterial Vaccines.
6. Expiry Date- The expiry date of Potency of the Vaccine shall be not more than
twelve months from the date of manufacture.
1
[Multicomponent of Clostridial
Vaccine
1. Synonyms. – Combined anaculture of Clostridium perfringens type C and D, C1.
septicum and CI. oedematiens.
2. Definition – It consists of four highly antigenic components containing the toxoids
of C. perfringens type D, CI. Perfringens type C, Cl. oedematiens and CI. septicum which
are prepared in double strength and then combined in such a proportion that would invoke
adequate anti-toxin response in the vaccinated sheep against each antigen incorporated in the
vaccine
3. Preparation – The above strains are grown separately in suitable liquid media under
conditions which ensure maximum toxin production. The cultures are checked for purity and
toxicity in mice. Solution of Formaldehyde I.P. of analytical grade is added to a 0.5 per
cent final concentration and formalized cultures are kept at 37
o
C till the product is sterilized
and atoxic. The formalized anacultures are pooled, precipitated by the addition of Aluminium
Chloride, 20 per cent solution in distilled water to have a final concentration of the chemical
to 10 per cent and pH adjusted to 6.0.the sedimented toxoid is reconstituted to have its
original volume in normal saline.
1. Ins. by G.S.R. No. 659(E) ,dt. 31-8-1994
Drugs and Cosmetics Rules 1945
346
4 Standards
:
(a) Description – It is whitish liquid when shaken thoroughly to contain killed
bacteria and toxoid in suspension.
(b) Identification – When injected to susceptible animals it stimulates the
production of epsilon and beta antitoxins against CI. perfrigens type D and C and also
antitoxins against CI. septicum and toxin of CI. Oedematiens.
(c) Sterility Test – Complies with the test of sterility described in general
monograph on ―Bacterial Vaccines.‖
(d) Safety Test – Four sheeps each are inoculated with 10 ml. S/C of the product
and these are observed for 7 days during which period animals shall not show any local
or systemic reaction.
(e) Potency Test – Eight sheep each are inoculated with 2 doses of vaccines S/C at
an interval of 21 days and bled on 10th day after 2nd inoculation for collection of serum
for assessing the antitoxin titre against each antigen incorporated in the vaccine. The
post-inoculation serum should contain not less than 2 i.u. of epsilon and beta antitoxins
of CI. perfringens and 2.5 i.u. of CI. septicum antitoxin and 4 i.u. of CI. oedematiens
antitoxin.
5. Labelling and storage - Shall comply with the requirements regarding labelling
and storage as laid down in the general monograph on ―Bacterial Vaccine‖.
6. Expirty date – The expiry date of potency of vaccine shall not be more than 6 months
from the date of manufacture.
Haemorrhagic Septicaemia Vaccine – Alum Treated
1. Synonyms – Pasterulla multocida/(Yersinia Multocida) vaccine – Alum treated.
2. Definition -- The vaccine is a formalized culture of a virulent strain of Pasteurella
multocida in nutrient broth treated with potash alum.
3. Preparation -- A highly potent strain of Pasteurella multocida type I in Phase I is
grown on nutrient broth at 37
o
C. The pure growth is killed by the addition of a solution of
Formalin I.P in suitable concentration (0.5 per cent). This is treated with Potassium Alum I.P
to give a final concentration of 1 per cent.
4. Standard :
(a) Description – It is a white suspension containing dead bacteria and alum.
(b) Identification – It protects susceptible animals against infection with
P. multocida.
(c) Sterility Test -- It complies with the test for sterility described under general
monograph on ―Bacterial Vaccines‖.
(d) Safety Test -- Four healthy rabbits each weighting 1 to 1.5 kg. are inoculated
subcutaneously each with 5 ml. of the product. There shall be no untoward reaction
during the period of observation for 7 days except slight local swelling. Alternatively
two rabbits and six mice may be employed. The dose for mice will be 0.5 ml.
5. Labelling and Storage :-- Shall comply with the requirements of labelling and
storage as laid down in the general monograph on ―Bacterial Vaccines‖.
6. Expiry date – The date of expiry of potency of the vaccine shall be not more than
six months from the date of manufacture.]
(B) PROVISIONS APPLICABLE TO THE PRODUCTION OF VIRAL VACCINES
Drugs and Cosmetics Rules 1945
347
1. Definition- (i) This part of the Schedule applies to viral vaccines live or inactivated
made from any virus pathogenic to domestic animals and poultry and made from other
modified viruses which have any antigenic value.
(ii) For the purpose of this Part of the Schedule, a virus vaccine means a sterile
suspension or a freeze dried powder containing the modified living or inactivated virus
particles, which in its original unaltered stage, causes disease from which the vaccine derives
its name and which has been prepared from the blood or tissues of a suitable host in which it
has been grown in vivo or from tissue culture.
2. Staff of Establishment- The establishment in which viral vaccines are prepared
must be under the direction and control of an expert in bacteriology with specialized training
in virology and sufficient experience in the production of viral vaccines, and he shall be
assisted by a staff adequate for carrying out the tests required during the preparation and
standardisation of the vaccines.
3. Proper Name- The proper name of any viral vaccine shall be the name of the
disease which is caused by the particular virus from which the vaccine is produced followed
by the word ―vaccine‖ unless the Schedule otherwise provides, if there is no special provision
in the Schedule such other name as is approved by the Licensing Authority. Provided that in
the case of the undermentioned preparations the proper name of the vaccine shall be as
follows:
(i) Fowl Pox Vaccines, Chick Embryo Virus (Living).
(ii) Fowl Pox Vaccine, Pigeon Pox Virus (Living).
(iii) Horse Sickness Vaccine (Living)
(iv) Ranikhet Disease Vaccine (Living)
(v) Ranikhet Disease Vaccine F Strain (Living)
(vi) Rinderpest Goat Adapted Tissue Vaccine (Living)
(vii) Rinderpest Lapinised Vaccine (Living)
(viii) Rinderpest Lapinised Avianised Vaccine (Living)
(ix) Sheep and Goat Pox Vaccine (Living)
(x) Swine fever vaccine (crystal violet)
(xi) Swine fever vaccine lapinised (Living).
1
[(xii) Foot and Mouth Dieseas Vaccine (Inactivated).
(xiii) Canine Hepatitis Vaccine (Living).]
2
[4. Records- The seed virus used in the preparation of vaccine shall, before being used
for preparing a batch, be thoroughly tested for purity, safety, sterility and antigenicity by the
generally accepted tests applicable to a particular virus. It shall not be more than five passages
away from the stock seed virus, unless otherwise prescribed for a particular virus. The stock
seed virus shall be maintained by seed-lot system at specified passage level and tested for
bacterial, mycoplasmal and extraneous viral contamination. The permanent record which the
licensee is required to keep shall include a record of the origin, properties and characteristics
of the seed virus from which the vaccines are made.]
5. Tests- Viral vaccine shall be tested for sterility, safety and potency on suitable test
animals and for viability in the case of live vaccines.
(a) Sterility Test- All vaccines shall be tested for sterility in accordance with rules
115 to 119. If the vaccine contains added bactericides or bacteriostatic, a quantity of
medium sufficient to render the growth inhibitor ineffective is added to the sample or a
suitable substance is added in a concentration sufficient to render the growth inhibitor
ineffective but not itself to inhibit the growth of micro-organisms.
(b) Safety Test- Suitable laboratory animals or large animals or birds may be
employed to test the vaccine for safety. Details of the safety test are given in the
individual monograph.
1. Ins. by G.S.R. 659(E) ,dt. 31-8-1994.
2. Subs. by G.S.R. 659(E) ,dt. 31-8-1994.
Drugs and Cosmetics Rules 1945
348
(c) Potency Test- All virus vaccines for which potency test has been prescribed
shall be tested for potency and only those which pass the potency test shall be issued.
Details of the potency test are given in the individual monograph.
6. Storage- Live viral vaccines shall be stored, protected from light at sub-zero
temperature as required. Other viral vaccines shall be stored at 2 ˚ C to 4 ˚ C but shall not be
frozen.
7. Condition of housing of animals- (i) The animals used in the production of vaccine
must be housed in hygienic conditions in premises satisfactory for this purpose.
(ii) Only healthy animals may be used in the production of vaccine. Each animal
intended to be used as a source of vaccine must, before being passed for the production of
vaccine be subjected to a period of observation in quarantine for at least seven days. During
the period of quarantine the animal must remain free from any sign of disease and must be
well kept.
1
[(iii) The poultry birds from which eggs and cell culture for production of vaccines are
obtained should be housed in a manner so as to keep them free from extraneous infection and
shall be screened at frequent intervals for common bacterial, mycoplasmal and viral infection.
The record of the tests and their results shall be maintained by the manufacturers.]
8. Labelling- The provisions of ―Labelling‖ as laid down for Bacterial Vaccines shall
also apply to Viral Vaccines. The following additional information shall also be included on
the label of the outside container:
(i) The name and percentage of bacteriostatic agent contained in the
vaccine.
(ii) If the vaccine as issued for sale contains any substance other than the diluent,
the nature and strength of such substances.
9. Date of Manufacture- For the purpose of this part of the Schedule, the date of
manufacture shall be what is given unless otherwise stated in the individual monograph, as
defined in sub-clause (b) of sub-rule (3) of rule 109.
Fowl Pox Vaccine Chick- Embryos Virus
(Living
)
1. Synonym- Egg adapted Fowl Pox Vaccine (Living).
2. Definition- Fowl-pox Vaccine, Chick-Embryo Virus (Living) is a suspension of a
modified living virus (e.g. Mukteswar Strain) prepared from the chorioallantoic membrane
(CAM) of the infected embryo and is either freeze dried or is issued as glycerinated liquid
vaccine.
3. Preparation- Active chick-embryos obtained from Salmonella pullorum free flock,
are used.
1
[Twelve to thirteen days old embryos are injected with a suitable dilution of the
suspension of the infected membrane (seed virus) of chick embryo adopted fowl pox virus.]
The suspension of the stock seed virus is dropped on the CAM. After an incubation at 37˚C
for a suitable period membranes showing discrete or confluent lesions (pocks) are harvested.
These are homogenised with adequate quantity of antibiotics (penicillin and streptomycin)
ampouled in 0.5 ml. quantities and freeze dried.
4. Standard-
(a) Description- Light mauve coloured scales.
(b) Identification- When reconstituted vaccine is applied to scarified area of the
skin of a fowl it produces characteristic lesions of fowl pox. This product should afford
protection against fowl pox.
1. Ins. by. GSR 659(E) , dt. 31-8-1994.
Drugs and Cosmetics Rules 1945
349
(c) Moisture Content- Moisture Content in the finished product should not exceed
1.0 per cent.
(d) Safety Test- For testing each batch of fowl pox vaccine twelve healthy
cockerels, or other suitable young chicken each weighing not less than 400 g. from the
same source are taken. This group of twelve birds is immunized at least twenty-one days
previous to the test, with fowl pox vaccine. The vaccine under test is reconstituted in 5
ml. of 50 per cent glycerine saline and administered to fowls as follows:-
Three of the test birds are injected subcutaneously with 0.8 ml. or 10 times the field
doses of the vaccine under test. This group serves to indicate whether the product is free
from other viruses and bacteria causing septicaemia or not.
Three of the test birds are injected intratrecheally with 0.3 ml. or 10 times the field
dose of vaccine under test. This group serves to indicate whether the product is free from
the virus of infectious laryngotracheitis and similar disease.
1
[Three of the test birds are injected intranasally with 0.2 ml. of 10 times of
the field dose of the vaccine under test. This group serves to indicate whether the
product is free from the virus of infectious laryngotracheitis and similar disease.]
The three remaining birds serve as controls. They are isolated and kept under
observation for twenty-one days. The birds that succumb during the period of twenty-one
days are subjected to a careful postmortem examination. The product is withheld from
issue until the vaccine and the test birds are shown to be free from the causative agents
of any extraneous disease.
(e) Sterility test- Complies with the tests for sterility as described under the general
monograph on ―Viral Vaccines‖.
(f) Potency Test- For testing of potency three unsusceptible birds each weighing not
less than 400 g. are vaccinated using the field dose by the stick method and examined for
―takes‖. Three weeks after vaccination these birds along with two unvaccinated controls
are exposed to challenged virus and observed for fourteen days. The vaccinated birds
should not manifest any reaction, while the controls should show active ―takes‖.
5. Labelling- Should comply with the requirement for ―Labelling‖ as laid down in the
general monograph on ―Viral Vaccines‖.
6. Storage and Expiry date- Freeze dried vaccine shall be expected to retain its
potency for periods at temperatures as specified below:-
-15 ˚ C to - 20˚ C–Twenty-four months.
2˚ C to 4˚ C–Twelve months.
Room temperature– upto one month.
The liquid vaccine shall be expected to retain its potency for periods and temperatures as
specified below:
2˚ C to 4 ˚C – six months.
Room temperature– seven days.
1. Ins. by. GSR 659(E) , dt. 31-8-1994.
Drugs and Cosmetics Rules 1945
350
Fowl- Pox Vaccine, Pigeon Pox Virus (Living)
1. Synonym- Fowl Pox Vaccine (Pigeon pox scab).
2. Definition- Fowl Pox Vaccine, Pigeon-pox Virus (living) consists of pigeon pox
virus in scabs collected from artificially infected pigeons and dried.
3. Preparation- Healthy pigeon are scarified on the legs and breast, with a suitable
dilution of the suspension of pigeon-pox virus. The pigeons reacting satisfactorily and
showing good takes are selected and the superficial skin layer scraped by means of sharp
scalpel. The material so collected is freed from feathers, homogenised and dried or freeze
dried. The dried pulp is powdered, sieved and ampouled in 0.3 g. quantities and sealed
4. Standard-
(a). Description- Light cream coloured powder.
(b) Identification- When applied to feather follicles by vigorous rubbing, it
produces mild reaction in fowls. The product should afford protection to fowls upto six
weeks against fowl pox.
(c) Safety Test- For testing a batch of vaccine, twelve healthy cockerels, or other
suitable young chicken from the same source are made available at the same time. This
group of twelve birds is immunised at least twenty-one days previous to the test with
fowl pox vaccine. The vaccine under test is reconstituted in 10 ml. of 50 per cent
glycerine saline and administered to fowls as follows: -
Three of the test birds are injected subcutaneously with 0.3 ml. or 10 times the field
dose of the vaccine to be tested. This group serves to indicate whether the product is free
from organisms of septicaemia disease.
Three of the test birds are injected intranasally with 0.2 ml. of the vaccine to be
tested. This group serves to indicate whether the product is free from virus of Coryza and
similar diseases.
1
[Three of the test birds are injected intratricheally with 0.2 ml or 10 times of the
field dose of vaccine under test. This group serves to indicate whether the product is free
from the virus of infectious laryngotracheitis and similar diseases.]
The three remaining birds serve as controls. All the birds under test are isolated and
held under observation for twenty-one days. All those that succumb are subjected to
careful post-mortem examination. The product is withheld from issue until the vaccine
and test birds are shown to be free from the causative agents of any extraneous diseases.
(d) Sterility Test- Complies with the tests for sterility described under the general
monograph on ―Viral Vaccines‖.
(e) Potency Test- For testing the potency of a batch of vaccines three susceptible
birds each weighing not less than 400 g. are vaccinated using the field dose by the
follicular method and examined for ‗takes‘. Three weeks after vaccination these birds
and two healthy susceptible controls are exposed to challenge virus and are observed for
fourteen days. The vaccinated birds shall manifest no reaction, while the controls must
have active ―takes‖.
5. Storage and Labelling- Should comply with the requirements of ‗Labelling‘ as laid
down in the general monograph on ‗Viral Vaccines‘.
6. Expiry date- The vaccine shall be expected to retain its potency for periods at
temperature as specified below:-
-15 ˚ C to - 20 ˚C-- two years.
2˚ C to 4 ˚C-- twelve
months.
Room
temperature- Upto one month.
1. Ins. by. GSR 659(E) , dt. 31-8-1994.
Drugs and Cosmetics Rules 1945
351
Fowl Pox Vaccine- Pigeon Pox- Chick Embryos Virus (Living)
1. Synonym- Chick embryo adapted pigeon pox vaccine (Living).
2. Definition- Fowl pox vaccine (Pigeon Pox virus) chick embryo adapted virus
(living) is a suspension of a modified living virus prepared from the chorioallantoic
membranes of the infected embryos and is freeze dried.
3. Preparation- Active chick embryos obtained from Salmonella Pullorum free stock
are used. Twelve to thirteen days old embryos are injected with a suitable dilution of the
suspension of the infected membrane (stock seed virus) of chick embryo adapted pigeon pox
virus. The suspension of the stock seed virus is dropped on the membrane. The inoculated
eggs are incubated at 37 ° C for four days. One of the fourth day embryos that are living, are
removed to a refrigerator for chilling for about one hour. Membranes showing discrete lesions
(Pocks) are harvested. These are homogenised with adequate quantities of antibiotics,
ampouled in 0.5 ml. quantities and freeze dried.
4. Standards-
(a) Description- Light mauve coloured scales.
(b) Identification- When reconstituted vaccine is applied to scarified area of the
skin of a fowl, it produces characteristics lesions of Fowl Pox. This product should
afford protection against pox.
(c) Moisture content- Moisture content in the finished product should not
exceed 1.0 per cent.
(d) Safety test- For testing each batch of chicks aged four to six weeks from the
same source are taken. This groups of twelve birds is immunised at least twenty-one
days previous to the test, with fowl-pox vaccine. The vaccine under test is reconstituted
in 3 ml. of normal saline solution and administered as under:-
Three of the test chicks are injected subcutaneously with 0.3 ml. or 10 times the
field dose of the vaccine under test. This group serves to indicate whether the product is
free from other viruses and bacteria causing of septicaemia or not.
Three of the test chicks are injected intratracheally with 0.3 ml. or ten times the
field dose. This group serves to indicate whether the product is free from the viruses of
infections laryngeotracheitis and similar diseases.
Three of the test chicks are injected with 0.2 ml 1/N of the vaccine under test. This
group serves to indicate whether the product is free from the virus of coryza and similar
diseases.
The remaining three chicks serve as controls. They are isolated and kept under
observation for twenty-one days. The birds that succumb during the period of
observation are subjected to careful post-mortem examination. The product is withheld
from issue until the vaccine and the test birds are shown to be free from the causative
agents of any extraneous disease.
In addition to the above, similar groups of pigeons aged six to nine months old are
also injected in a similar way to eliminate psittacosis.
(e) Sterility Test- Should comply with the tests for sterility described under
the general monograph on ‗Viral Vaccine‘.
(f) Potency test- For testing potency of a batch of vaccine three susceptible
chicks of three to four weeks of age are vaccinated by feather forthicle method ( a
few forthicles on one leg are injected) and these are examined for ‗takes‘.
Three weeks after vaccination these chicks along with two unvaccinated chicks
are exposed to challenge virus (virulent fowl pox virus) and observed for fourteen
Drugs and Cosmetics Rules 1945
352
days. The vaccinated chicks should not manifest any reaction while controls should
show active ‗takes‘.
5. Labelling- Should comply with the requirements for ‗Labelling‘ as laid down in
the general monograph on ‗Viral Vaccines‘.
6 Storage- The freeze dried product is expected to retain its potency for periods at
temperatures as specified below:
-15 ° C to 20 ° C–two years.
2° C to 4 ° C–twelve months.
Room temperature- up to one month.
Sheep Pox Vaccine (Living)
1. Synonym- Sheep Pox vaccine; Goat pox vaccine.
2. Definition- Sheep pox vaccine consists of sheep pox virus collected from sheep
artificially infected with sheep pox virus and freeze dried.
3. Preparation- Healthy yearling sheep are infected artificially by subcutaneous
infection on the undersurface of the previously shaved abdomen with 200- 300 cc. of the
freeze dried sheep pox virus (seed material) diluted in 1 : 1 Normal saline solution. On the
sixth or seventh day after injection oedematous swelling develops in the injected area with
thermal reaction. The sheep which develop good swelling are slaughtered and the gelatinous
material present under the skin in the infected area is collected under sterile conditions. This
material is mixed with 2 parts by volume of sterile peptone broth of pH 7.2 and homogenised.
The homogenised suspension is filtered, ampouled in 0.5 ml. quantities and freeze dried.
4. Standard:
(a) Description- White scales.
(b) Identification- Reconstituted vaccine when applied over the scarified area
of the skin of the abdominal region of sheep will produce characteristic local lesion of
pox.
(c) Moisture content- The moisture content should not exceed 1.0 per cent.
(d) Safety test- Two rabbits each weighing not less than 1 kg. are injected
subcutaneously each with 1 ml. of 1 : 100 dilution of the vaccine in normal saline
solution. These animals are observed for fourteen days. The animals should remain
normal.
(e) Sterility Test- Complies with the tests for sterility described under the general
monograph on ‗Viral Vaccines‘.
(f) Potency Test- Four yearling sheep are vaccinated on the inner surface of the ear
by scarification method. The contents of one ampoule of F.D. Sheep Pox vaccine are
constituted in 10 cc. of 50 % glycerin saline solution, characteristic ‗takes‘ develop in the
scarified area with ulceration and scab formation. Three weeks later these and two more
susceptible sheep (Controls) are challenged by scarifying with a suspension of the
previous brow of the vaccine of the undersurface of the abdomen. The controls should
develop typical lesions of pox and the vaccinated should remain normal.
5.Labelling- Should comply with the requirements of ‗labelling‘ as laid down in the
general monograph in ‗Viral Vaccine‘.
6. Storage and expiry date- The vaccine is expected to retain potency for period and
temperature as specified below:-
-15 ° C to – 20 ° C– two years
2 ° C to 4 ° C–three months.
Room temperature- Fifteen days.
Drugs and Cosmetics Rules 1945
353
Horse Sickness Vaccine
(Living)
1. Synonym- African Horse Sickness Vaccine, Mouse adapted Polyvalent Horse
Sickness Vaccine (Living).
2. Definition- Horse sickness vaccine is a suspension of live mouse adapted strains of
Horse Sickness Virus (Onderstepoort) prepared from the brains of infected mice and is freeze
dried.
3. Preparation- Thirty to thirty-five days old white mice are infected intracerebrally
with 0.05 ml. of a suitable dilution of the seed virus (6 or 7 types, as the case may be). Groups
of large numbers of mice are injected separately with each type of the virus and are housed at
27 ° C to 32 ° C. A majority of these become paralytic on the third and fourth day when they
are sacrificed and their brains collected and stored at – 15 ° C to – 20 ° C till the day of
processing. For preparing the polyvalent vaccine, equal number of brains collected from mice
infected with different types of the virus are homogenised with 5-10 times its volume of
sterile lactose buffer medium (pH 7.2 ) containing antibiotics. The suspension is centrifuged
at 1500 r.p.m. for five minutes. The supernatant liquid is distributed in ampoules in suitable
quantities and freeze dried.
4. Standard:
(a) Description- White scaly material.
(b) Identification- This product affords protection to horse against horse sickness.
(c) Safety Test- Four healthy mice thirty to thirty-five days old are injected
intraperitoneally with 0.2 ml. of 10:1 dilution of the vaccine and kept under observation
for ten days. All the mice should remain normal throughout the period of observation.
(d) Sterility Test- Should comply with the test for sterility described under the
general monograph on ‗Viral Vaccines‘.
(e) Viability Test- Each batch of vaccine is titrated in tenfold dilutions using four
mice of thirty to thirty-five days old for each dilution. Each mouse is injected
intracerebrally with 0.05 ml and kept under observation for ten days. Mortality and
survival ratios are noted and LD
50
ml is determined. The minimum acceptable titre is
10–4 LD
50
per 0.05 ml.
(5) Labelling - Should comply with the requirements of ‗labelling‘ as laid down in
the general monograph in ‗Viral Vaccines‘.
(6) Storage- The vaccine may be expected to retain its potency for twelve months if
stored – 15 ° C to 20° C and about six months if stored in refrigerator at 2 ° C to 4° C.
Rabies Vaccine
(Inactivated)
1. Synonym- Antirabic Vaccine (Inactivated)
2. Definition- Rabies vaccine is a suspension of the brain tissue of animals, that have
been infected with a suitable strain of rabies fixed virus, inactivated with phenol or some
other suitable agent.
3. The following particulars relating to this vaccine are the same as those relating to
Antirabic vaccine described in Part D of Schedule F to these rules, namely:-
(i) Strain of fixed Rabies Virus to be used;
(ii) Staff of Establishment;
(iii) Condition and housing of animals;
(iv) Precaution to be observed in preparation;
(v) Records;
(vi) Issue.
Drugs and Cosmetics Rules 1945
354
4. Preparation- Healthy sheep or any other suitable species of animal are inoculated
subdurally or intracerebrally with an appropriate dose of suspension of a suitable strain of
rabbit brain passaged rabies fixed virus. The sheep or animals which get paralysed from the
sixth day onwards after the inoculation are sacrificed and their brains collected aseptically.
Brain tissue is weighed individually and a suspension of suitable concentration of brain tissue
prepared in buffered saline is strained through gauze. The suspension treated with phenol or
some other suitable inactivating agent is incubated for an appropriate period.
5. Standard-
(a) Description- A grey to pale yellow opalescent suspension.
(b) Identification- Appropriate doses protect mice against subsequent intracerebral
inoculation with suitable strain of fixed rabies virus.
(c) Safety test- Not less than five mice, each weighing at least 18 gm., are inoculated
intracerebrally with not less than 0.03 ml. of the suitably diluted vaccine. None of
the animals should show symptoms of rabies or die of the disease during period of
observation of three weeks.
(d) Sterility Test- Should comply with the test for sterility described under the
general monograph on ‗Viral Vaccine‘.
6. Labelling- Should comply with the requirements of ‗Labelling‘ as laid down in the
general monograph on ‗Viral Vaccines‘. In addition the label on the container shall
indicate the percentage of brain tissue present in the vaccine.
7. Storage- The vaccine may be expected to retain its potency for about six months if
stored in refrigerator at 2˚ to 4 ° C.
Rabies Vaccine
(Living)
1. Definition- Rabies vaccine (living) is a freeze-dried suspension of chick-embryo
tissue infected with a suitable attenuated strain of rabies virus.
2. Preparation- It may be prepared by the following method. Seed virus consisting
of
a suspension of the Flury or other suitable strain of chick adapted virus that has been
maintained by passage in chick embryos is injected into the yolk-sacs of fertile eggs
incubated for a suitable period. After incubation for a further ten days, the embryos are
harvested and grind in water for injection to give 33 percent suspension. The suspension is
centrifuged to remove coarse particles and the supernatant fluid is distributed into ampoules
in 3 millilitre quantities, and freeze dried. The vaccine is reconstituted immediately before use
by adding 3 millilitres of water for injection to the contents of an ampoule.
3. Standard- It complies with the requirements of general standard of viral vaccines
for abnormal toxicity, sterility, and labelling with the following additions.
(a) Description- Dry honey-coloured flakes or powder, readily dispersible in water.
(b) Identification- It protects guinea pig against a subsequent inoculation of
rabies street virus. It is distinguished from the inactivated Rabies vaccine by its ability to
produce rabies encephalitic on intracerebral injection into mice.
(c) Safety- The guinea pigs used in the test for potency should not show any marked
local or systemic reaction during the three weeks following injection with the vaccine.
(d) Sterility Test- Complies with the tests for sterility described under the
general monograph on ‗Viral Vaccines‘.
(e) Potency Test- The contents of an ampoule are dispersed in water for injection to
give a 5 per cent suspension and not fewer than twenty guinea pigs, drawn from a
uniform stock and each weighing 350 g. to 500 g., are each injected intramuscularly with
0.25 ml. of this suspension. Three weeks later, these guinea pigs and an equal number of
similar unvaccinated control guinea pigs are each inoculated with 0.1 ml. of a suitable
dilution of canine salivary gland suspension of street virus which is maintained as a 20
per cent suspension at 70 ° C or lower. The guinea pigs are observed for thirty days; not
less than 80 per cent of the control guinea-pigs die of rabies and not less than 70 per cent
of the vaccinated guinea-pigs are protected.
Drugs and Cosmetics Rules 1945
355
4. Storage- Freeze-dried vaccine should be stored at refrigeration temperatures of 2 °
C to 4 ° C.
5. Labelling- The life of the vaccine at room temperature and at refrigeration
temperature should be stated on the label.
6. (a) Action and uses- Rabies vaccine (living) is used for the prophylactic inoculation
of dogs against rabies; one injection should provoke a serviceable immunity lasting for at
least a year. The vaccine has been used to a limited extent on cattle.
(b) Dose- By intramusclar injection: Dogs, the contents of one ampoule reconstituted
in 3 ml. of water for injection; cattle five times the dog dose.
Ranikhet Disease Vaccine (Living)
1. Synonym- New Castle Disease Vaccine (Living); pheumoenteritis Vaccine
(Living).
2. Definition- Ranikhet Disease vaccine is a suspension of a modified living virus e.g.
(Mukteswar strain) prepared from infected embryos and fluids and is freeze dried.
3. Preparation- Good fertile eggs obtained from Salmonella pullorum free flock are
incubated in an egg incubator. Ten days old vigorous embryos are infected with 0.1 ml. of a
suitable dilution of a suspension of the virus. Inoculation is done in the allantoic cavity.
Embryos are incubated at a suitable temperature. Eggs showing dead embryos twenty-four
hours after incubation are discarded. After forty-eight hours incubation the eggs are candled
and those showing dead embryos are chilled for a suitable period of time, while embryos alive
beyond forty-eight hours are discarded. The fluids and embryos are then collected and spot
haemogglutination carried out. The material is homogenised in a blender and ampouled in
aliquots of 0.5 ml. quantities and freeze-dried.
4. Standards-
(a) Description- Light brown scales.
(b) Identification- This product affords protection to fowls against Ranikhet
Disease.
(c) Safety Test- For testing each batch of freeze dried Ranikhet Disease Vaccine,
twelve healthy young chickens, all from the same source each weighing not less than 100
g. are taken and immunised against Ranikhet Disease. Fourteen days later, these birds,
are tested as follows with the contents of one ampoule suspended in 100 ml. of normal
saline.
Three of the test birds are injected subcutaneously with 0.1 ml. equivalent to
ten times the field dose of the vaccine to be tested. This group serves to indicate whether
the product is free from viruses or organisms of speticaemia disease.
Three of the test birds are injected intratracheally with 0.1 ml. equivalent to ten
times the field dose of he vaccine to be tested. This group serves to indicate whether the
product is free from the virus of infectious laryngotracheitis,
1
[***] and similar
diseases.
The three remaining birds serve as controls.
2
[Three of the test birds are injected intranasally with 0.2 ml of the vaccine to be
tested. This group serves to indicate whether the product is free from virus of Coryza and
similar diseases.]
All the treated birds and controls are observed daily for fourteen days. All the test
birds that succumb are subjected to careful postmortem examination. The product is not
issued until the birds under test are shown to be free from the causative agents of any
extraneous diseases.
(e) Sterility Test- Should comply with the test for sterility described in the general
monograph on ‗Viral Vaccine‘.
1. The word ―Coryza‖ omitted by. GSR 659(E) ,dt.. 31-8-1994.
2. Ins. by G.S.R. 659(E) ,dt.. 31-8-1994
Drugs and Cosmetics Rules 1945
356
(f) Potency Test- Four susceptible birds eight to twelve weeks old and each
weighing not less than 400 g. are vaccinated by injecting subcutaneously 1 ml. of a 10
-5
dilution of the product. Two weeks after vaccination these birds and four non-protected
birds are challenged by injecting subcutaneously each with 1.0 ml. of a 1: 100 dilution of
virulent virus (liver and spleen suspension) or 1.0 ml. of a 1 : 100 dilution of fluid from
the embryo infected with virulent Ranikhet Disease virus. The non-protected birds
should show symptoms of Ranikhet Disease and die and all the protected birds should
remain normal during an observation period of fourteen days.
5. Labelling- Should comply with the requirements of ‗Labelling as laid down in the
general monograph on ‗Viral Vaccines‘.
6. Storage- The vaccine when stored at – 15° C to 20° C. may be expected to retain
the potency for about one year and about three months if stored in a refrigerator at 2° C to
4° C. The product should not be used if stored for more than ten days outside the refrigerator.
Ranikhet Disease Vaccine F strain (Living)
1. Synonyms- New castle disease vaccine F Strain (Living).
2. Definition- Ranikhet disease vaccine F. strain is a suspension of a naturally
modified living virus (F strain) prepared from the infected embryos, devoid of beaks and
eyes and fluids in a frozen state.
3. Preparation- Good fertile eggs obtained from Salmonella pullorum free flock are
incubated in an egg incubator. Eight days old vigorous embryos are infected with 0.1 ml. of
1 : 100 suspension of Ranikhet disease vaccine F strain virus. Inoculation is done via the
allantoic cavity. Embryos are incubated at 37° C. Eggs are candled every day upto four days
and the dead ones are discarded. Final candling of the embryos is carried out on the fourth
day and only the living ones are chilled in a refrigerator for one hour. The fluids embryos are
collected separately. The fluids are tested for spot haemagglutination and sterility test is
carried out. The beaks and eye balls of the embryos are removed. The materials are
homogenised with adequate quantities of antibiotics in a cool warning blender and ampouled
in aliquots of 0.5 ml. quantity and freeze dried.
4. Standard-
(a) Description- Light brown scales.
(b) Identification- This product affords protection to baby chicks against
Ranikhet disease.
(c) Moisture content- The moisture content should not exceed
1
[1.0] per cent.
(d) Potency test- For testing each batch of the vaccine twelve one-day old chicks
are given two drops 1/N o the field dose of the vaccine (5 ampoules selected at random
may be reconstituted in 50 ml.) of cold normal saline solution. These are observed for
fourteen days and the vaccinated chicks should remain normal throughout the period of
observation. This serves the safety test also.
On the fourteenth days the vaccinated chicks are challenged two drops with 1:50
virulent Ranikhet disease virus alongwith 8 control chicks. Four of the controls receive
two drops 1/N of the virulent virus while the rest of the four receive 0.5 ml. of the
virulent virus. The control chicks should succumb to the challenge virus showing
symptoms of Ranikhet Disease while the protected chicks should remain normal
throughout the observation period of fourteen days.
(e) Sterility Test- Should comply with the tests for sterility described in the general
monograph on ‗Viral Vaccines‘
5. Labelling- Should comply with the requirements of ―Labelling‖ as laid down in the
general monograph on ‗Viral Vaccines‘.
6. Storage- The vaccine when stored at – 15 ° C to –20 ° C may be expected to retain
the potency for about one year and about three months if stored in a refrigerator at 2 ° C to
4° C. When removed from the refrigerator, the product should not be used later than ten days.
1. Ins. by G.S.R. 659(E) ,dt.. 31-8-1994
Drugs and Cosmetics Rules 1945
357
Rinderpest Goat adapted Tissue Vaccine (Living)
1. Synonym- Goat-adapted Cattle Plague Vaccine; Goat Tissue Vaccine (Living).
2. Definition- Rinderpest Goat-adapted Tissue Vaccine is the homogenised freeze
dried preparation of spleen pulp of goats artificially infected with the suitable strain of
rinderpest virus.
3. Preparation- Healthy susceptible goats are quarantined for a period of ten days.
After this period a batch of selected goats are injected subcutaneously with 2 ml. of a suitable
dilution of the suspension of the seed virus. The donor goats are sacrificed after a suitable
period when the titre of the virus in the animal body is expected to be maximum, usually four
days, and the spleen from animals free from any pathological change or signs are collected
under sterile conditions. Smear from each spleen is examined microscopically to exclude
spleen which are contaminated from the production batch.
The spleen is freed from fat and fascia and is blended into a smooth pulp in a grinder.
The pulp is spread on a shallow dish of glass or stainless steel and is freeze dried.
The freeze dried pulp is then ground into a fine powder and sieved. The powder is
ampouled in 0.25 g. or 0.125 g. quantities and freeze dried.
4. Standard:
(a) Description- Dark brown or chocolate coloured scales or powder.
(b) Identification- The product affords protection to susceptible animals against
rinderpest.
(c) Moisture content- Not more than 1.0 per cent.
(d) Safety Test- Each batch of vaccine shall be tested for safety in laboratory
animals and cattle or buffalo calves as follows:-
(i) Small animals- At least two guinea pigs each weighing 300 g. to 450 g.
and two adult rabbits each weighing 1 kg. to 1.5 kg. should be injected each with
1 ml. of 1: 100 suspension of the vaccine subcutaneously and kept under
observation for seven days. None of the animals should die. Alternatively, a batch
of six white mice each weighing not less than 18 g. may be used, each mouse
receiving 0.5 ml. of a dilution 1 : 100 suspension subcutaneously. None of the
animals should die.
(ii) Large animals- Either cattle of good grade of susceptibility (hill cattle)
or buffalo calves may be employed. For each batch of vaccine, three animals
should be injected subcutaneously with 1 ml. of 1 : 8000 dilution of the vaccine.
These animals should be kept under observation for twelve to fourteen days. None
of the animals should show any untowards reactions.
(e) Sterility Test- Complies with the tests for sterility described under the general
monograph in ‗ Viral Vaccines‘.
(f) Potency Test- The animals receiving 1 ml. of 1 : 8000 dilution of vaccine
used under safety test mentioned above and kept under observation for fourteen days,
should be challenged with 1 ml. of 1 per cent suspension of stock Rinderpest Virulent
virus. None of the animals should die of rinderpest within a period of ten days. This test
serves as a short potency test for each of the batches.
For conducting a detailed potency test the following procedure may be followed:-
Dilution 1: 8000, 1: 12,000 and 1 : 16,000 shall be tested and for each dilution
three susceptible cattle or buffalo calves should be used. Each animal is inoculated
subcutaneously with 1 ml. of a dilution of the vaccine, followed twelve to fourteen
days later with a standard challenge dose of virulent rinderpest bull virus containing
Drugs and Cosmetics Rules 1945
358
in 1 ml. of a 1 : 100 suspension of spleen tissue. Two unvaccinated bovines, each
receiving the same quantity of the challenge dose acts as controls. These are kept
under observation for fourteen days. The end point of protection titre is assessed on
the death or survival rate and the dose contained in one gramme of vaccine
calculated on the basis of 20 to 40 minimum protective doses being equivalent to
one vaccinating dose.
(g) Virulence and Viability Test- Two to four goats each weighing not less than
18 kg. are injected with 2 ml. of 1 : 100 suspension of the vaccine and kept under
observation for ten days. These animals should show reaction characterised by pyrexia
(rise of about 2˚ C) anorexia and dullness.
5. Labelling- Should comply with the requirement of ‗Labelling‘ as laid down in the
general monograph on ‗ Viral Vaccines‘.
6. Storage- The vaccine may be expected to retain its potency for twelve months if
stored at - 15˚ C to -20˚ C or about three months if stored at 2˚C to 4 ˚ C.
Rinderpest Lapinised Vaccine (Living)
1. Synonym- Rabbit Adapted Cattle Plague Vaccine (Living) Lapinised Vaccine
(Living).
2. Definition- Rinderpest lapinised vaccine is a suspension of a modified living virus
(e.g. Nakamura III Strain) prepared with the blood, spleen and mesenteric lymph glands of
infected rabbits and is freeze dried.
3. Preparation- Adult rabbits possibly from a known stock, each weighing not less than
1 kg. free from cocidiosis and snuffles, are injected intravenously with 1 ml. of a suitable
dilution of a suspension of the stock seed virus. Donor rabbits are sacrificed after a suitable
period when the titre of the virus in the animals is expected to be the maximum usually the
third day.
Ten millilitres of blood is collected from each rabbit in a defibrinating flask under
aseptic condition. Later the animals are sacrificed and the spleen and mesenteric lymph
glands collected. Each rabbit is subjected to a thorough post-mortem examination to observe
lesions of rinderpest infection.
After harvesting, the blood and the organs (spleen and glands) are homogenised in a
suitable proportion if necessary. Adequate quantities of penicillin and streptomycin may be
added. The homogenized material is ampouled in suitable quantities and freeze dried.
4. Standard-
(a) Description- Dark chocolate coloured mass.
(b) Identification- This product affords protection to susceptible animals against
rinderpest.
(c) Moisture content- Not more than 1.0 per cent.
(d) Safety Test- For testing a batch 2 guinea pigs each weighing not less than 300
g. are injected subcutaneously with 1 ml. of a 1 : 100 suspension of the vaccine.
Alternatively, a group of six white mice each weighing not less than 18 g. is used. Each
animal receives subcutaneously 0.5 ml. of 1 : 100 suspension of the vaccine. None of the
test animals should die within a period of seven days.
(e) Sterility Test- Should comply with the tests for sterility described in the general
monograph on ‗Viral Vaccines‘. If antibiotics have been added the inoculum should be
neutralised before doing the test.
Drugs and Cosmetics Rules 1945
359
(f) Potency Test- Dilution 1: 100, 1 : 200, 1 : 400 and 1 : 800 shall be tested and
for each dilution 2 susceptible cattle ( hill bulls) or buffalo calves should be used. Each
animal is inoculated subcutaneously with 1 ml. of a dilution of the vaccine, followed
twenty-one days later with a standard challenge dose of a virulent rinderpest bulls virus
contained in 1 ml. of a 1 : 100 suspension of spleen tissue. Two unvaccinated bovines
each receiving the same quantity of the challenge virus serve as controls. These animals
are kept under observation for fourteen days. The end point of the protecting titre is
assessed on the death or survival rate and the dose contained in one gramme of vaccine
calculated on the basis of twenty minimum protective doses being equivalent to one
vaccinating dose.
(g) Virulence and Viability Test- Four rabbits each weighing 1 to 1.5 kg. are
injected subcutaneously with 1 ml. of 1 : 100 suspension of the vaccine. The animals
should react typically showing all the symptoms of rinderpest in rabbits.
5. Labelling- Should comply with the requirements of ‗Labelling‘ as laid down in the
general monograph on ‗Viral Vaccines‘.
6. Storage- The vaccine may be expected to retain its potency for six months if stored
at 15 ˚C to –20 ˚C or about a month if stored at 2 ˚C to 4 ˚C.
Rinderpest Lapinised Avianised Vaccine (Living)
1. Synonym- Lapinised Avianised Vaccine (Living).
2. Definition- Rinderpest Lapinised Avianised Vaccine is a suspension of a modified
live rinderpest virus of low virulence prepared either with the whole chick embryo or the
viscera of the infected chick embryo.
3. Preparation- Twelve or thirteen days old active chick embryos from a flock free from
Salmonella pullorum infection are injected intravenously with a suitable dilution of the
suspension of the stock seed virus in six per cent glucose solution. The embryos are incubated
at 38.5˚ C for five days. At the end of this incubation period, eggs which show living embryos
are selected for the preparation of the vaccine. The viscera of the chicks are harvested, care
being taken to reject the gizzard and gall bladders. The material is homogenised in a blender
with adequate quantities of antibiotics (penicillin and streptomycin added if necessary), and
primary freeze dried done. This freeze dried material is ground into a fine powder, ampouled
in suitable quantities and finally subjected to secondary freeze drying and sealed under
vacuum.
4. Standard-
(a) Description- Pale cream or yellow coloured sterile powder.
(b) Identification- This product affords good grade of immunity to susceptible
animals against rinderpest.
(c) Moisture content- Not more than 1.0 per cent.
(d) Safety Test- For testing each batch, a group of six mice each weighing not
less than 18g. is used. Each mouse is injected subcutaneously with 0.5 ml. of a 1 : 100
suspension. Alternatively, two guinea pigs each weighing not less than 300 g. and two
rabbits each weighing not less than 1 kg. are injected with 1 ml. of 1 : 100 suspension
subcutaneously. These animals should not show any untoward reaction during the period
of observation for seven days.
(e) Sterility Test- Should comply with the test or sterility as laid down in the
general monograph on ‗Viral Vaccines‘.
(f) Potency Test- Healthy highly susceptible cattle (hill bulls) or buffalo calves
should be used for testing the potency of each batch of vaccine in suitable dilution. For
each dilution two highly susceptible animals should be used. Each animal is inoculated
Drugs and Cosmetics Rules 1945
360
subcutaneously with 1 ml. of a dilution of the vaccine, followed twenty-one to twenty-
eight days after with a standard challenge dose of a virulent rindepest bull virus
contained in 1 ml. of a 1 : 100 suspension of spleen tissue. Two unvaccinated bovines,
each receiving the same quantity of the challenge virus serve as controls. All these
animals are kept under observation for fourteen days. The end point of protective titre is
assessed on the death or survival rate and the dose contained in one gramme of vaccine
calculated on the basis of forty minimum protective doses being equivalent to one
vaccinating dose.
5. Labelling- Should comply with the requirements of ‗Labelling‘ as laid down in the
general monograph on ‗Viral Vaccines‘.
6. Storage and Expiry date- The vaccine shall be expected to retain its potency for the
period at temperatures as specified below:-
-15˚ C to – 20˚ C .. Six months.
2˚ C to 4˚ C . .. One month.
Sheep and Goat Pox Vaccine (Living)
1. Synonym- Sheep Pox Vaccine. Goat Pox Vaccine (Living).
2. Definition- Sheep and Goat Pox Vaccine consists of the virus contained in the scabs
collected from sheep artificially infected with the virus.
3. Preparation- Healthy yearling sheep are infected artificially on the shaved portion of
the abdomen with a suitable dilution of the suspension of the stock seed virus 50 per cent
glycerine saline solution. The material from the semi-dried areas where the pock lesions are
evident is collected and dried over calcium chloride or phophorus pentoxide under vacuum.
Dry scabs are powdered, sieved, ampouled in suitable quantities and sealed.
4. Standard:
(a) Description- Light cream coloured powder.
(b) Identification- This product when applied to scarified area of the skin of the
sheep or goats produces characteristic local lesions of pox and should afford protection
to sheep and goat against Sheep and Goat Pox.
(c) Safety Test- Two rabbits each weighing not less than 1 kg. are injected
subcutaneously each with 1 ml. of a 1 : 100 dilution of the vaccine in normal saline
solution. These animals are observed for fourteen days. The animals should remain
normal.
(d) Sterility Test- Complies with the tests for sterility described under the general
monograph on ‗Viral Vaccines‘.
(e) Potency Test- Four yearling sheep are inoculated with 1 : 100 suspension of the
vaccine in 50 per cent glycerine saline on a scarified area on the abdomen. Fourteen days
later, these and two more susceptible sheep are inoculated by the same method with
stock virus and observed for a period of fourteen days. The control animals should
develop typical lesions of pox and vaccinated animals should remain normal.
5. Labelling- Should comply with requirement of ‗Labelling‘ as laid down in the
general monograph on ‗Viral Vaccines‘.
6. Storage and Expiry date- The vaccine shall be expected to retain its potency for
period at temperatures as specified below:-
-15˚ C to – 20˚ C : Twenty months.
2˚ C to 4˚ C : Three months.
Room Temperature : Fifteen days.
Drugs and Cosmetics Rules 1945
361
Fowl Spirochaetosis Vaccine ( Chick Embryo Origin)
1. Synonym- Tick Fever Vaccine.
2. Definition- The vaccine consists of a merthiolated suspension of chorioallantoic
membrane, internal viscera and blood of chick embryos infected with a vaccine strain of
spirochaetes and freeze dried.
3. Preparation- Eleven days old developing chick embryos are infected with 0.2 ml. of
sterile fresh blood containing spirochaetosis via the chorioallantoic membrane. The inoculated
embryos are incubated at 37 ˚C and candled daily and the dead one are discarded. On the
seventh day the living embryos are chilled in the refrigerator for two hours. The chilled
embryos are harvested separately and necrotic lesions in liver noted. Representative samples
of blood should be examined for teaming spirochaetes. The internal viscera, chorio-allantoic
membranes and the blood are collected. The material is pooled, weighed and held in deep
freeze at – 15 ˚C to –20 ˚C for a period of one week. Thereafter the material is blended with
equal quantity of Merthiolate (final concentration of merthiolate in the suspension should be 1
: 10, 000) thoroughly for three times, each time the motor running at full speed and the
vaccine is ampouled in 2 ml. quantities and freeze dried.
4. Standard-
(a) Description- Light brownish scales.
(b) Identification- The vaccine affords protection when inoculated into the fowls
against spirochetosis.
(c) Moisture content- The moisture content should not exceed 1.0 per cent.
(d) Safety and potency test- Six healthy cockerals ten to twelve weeks old are used
for this purpose. Each ampoule of vaccine is reconstituted in 10 ml. of cold distilled
water and the six cockerals are injected intramuscularly each with 1 ml. of the
reconstituted vaccine and the birds are observed for a period of ten days and the
vaccinated birds should remain normal throughout the period of observation. The
vaccinated birds are challenged with 0.2 ml. intramuscularly with virulent spirochaete
blood along with two susceptible controls. Temperature and blood smear examination of
the challenged birds and controls should be carried out daily for a period of ten days. The
blood smears of vaccinated birds should remain negative for spirochaetes during the
entire period of observation. The controls should react and show spirochaetes in the
blood.
(e) Sterility Test- Complies with the tests for sterility described in the general
monograph on ‗ Bacterial Vaccine‘.
5. Labelling- Should comply with the requirement of ‗Labelling‘ as laid down in the
general monograph on ‗Viral Vaccines‘.
6. Storage- The vaccine when stored at –15 ˚C to – 20 ˚C may be expected to retain
the potency for about one year and about two months if stored in refrigerator at 2 ˚C to 4 ˚C.
Swine Fever Vaccine Crystal Violet
1. Synonym- Crystal Violet Swine fever vaccine, Hog Cholera Vaccine.
2. Definition- Swine fever vaccine, crystal violet is a suspension of blood of swine that
have been infected with a suitable virulent antigenic strain of swine fever virus, inactivated
with 0.25 per cent crystal violet ethylene glycol at 37 ˚C for fourteen days.
3. Preparation- Susceptible healthy pigs of six to seen months of age belonging to a
well established strain or bred are used. Body weight of these animals at this age may vary
according to the breed but optimum weight is considered as between 75 to 100 kg. Animals
used for production may be procured from well established farms and kept under quarantine
Drugs and Cosmetics Rules 1945
362
for fourteen days. These are injected intramuscularly with a suitable dilution of the
suspension of the virulent blood viruses. Bleeding of the clinically injected animals is carried
out on the sixth day. The defibrinated blood from each animal is strained and stored
separately in sterile glass containers. To the four parts of defibrinated blood, one part of 0.25
per cent crystal violet- ethylene glycol is added and the suspension after thorough mixing, is
stored at 37˚ C (
+
0.5) for two weeks. The product is filled in 20 ml. volumes in sterile vials
and labelled on the completion of tests.
4. Standard-
(a) Description- Very dark violet suspension.
(b) Identification- This product affords protection against swine fever but not
against African Swine Fever.
(c) Safety Test- Two young pigs weighing about 15 to 30 kg. are injected
subcutaneously each with 40 ml. of the vaccine batch to be tested. In addition, one
unvaccinated susceptible pig is placed in contact.
(d) Sterility Test- Should comply with the test for sterility described under general
monograph on ‗Viral Vaccines‘.
(e) Abnormal toxicity test- Two guinea pigs are given 1 ml. of vaccine
intramuscularly.
Two guinea pigs are given 2 ml. of the vaccine intraperitoneally.
Two mice are given 0.5 ml. of the vaccine subcutaneously.
(f) Potency Test- Four susceptible pigs weighing between 20-30 kg. are injected
with 5 ml. of the vaccine subcutaneously. After twenty-one days these are challenged
with 1 ml. of suitable dilution of the challenge virus subcutaneously. The dose must
contain at least 1000 minimum infective doses. At least two control pigs should be used.
5. Labelling- - Should comply with requirement of ‗Labelling‘ as laid down in the
general monograph on ‗Viral Vaccines‘.
6. Storage- The vaccine may be expected to retain its potency for twelve months if
stored in refrigerator at 2 ˚C to 4 ˚C.
Swine Fever Vaccine Lapinised (Living)
1. Synonym- Lapinised swine fever vaccine, freeze dried lapinised swine fever
vaccine.
2. Definition- Swine fever lapinised vaccine consists of the suspension of a
modified live swine fever virus prepared from spleens of infected rabbits and is freeze dried.
3. Preparation- Healthy adult rabbits weighing approximately 1000 gms. or over, free
from coccidiosis snuffles etc. are injected intravenously with a suitable dose of a dilution of
the modified rabbit adapted virus. Rabbits are sacrificed at the height of reaction and spleens
are collected with sterile precautions. The collection is later homogenised in a blender using
ten per cent yolk phosphate buffer as a diluent. The suspension is ampouled in 0.5 ml.
quantities and freeze dried.
Drugs and Cosmetics Rules 1945
363
4. Standard-
(a) Description- Light scales.
(b) Identification- This product affords protection against swine fever.
(c) Moisture content- The moisture content should not exceed 1.0 per cent.
(d) Safety Test- Six mice are injected each with 0.5 ml. of a 1 : 100 suspension of
the vaccine. These are kept under observation for seven days. Non should die.
(e) Viability Test- Two healthy rabbits are injected intramuscularly with 1 ml. of
1 : 100 suspension of the vaccine. These animals show thermal reaction.
(f) Sterility Test- Should comply with the test for sterility described under the
general monograph on ‗Viral Vaccines‘.
(g) Potency Test- The vaccine batch under test should be tested on susceptible
healthy pigs weighing between 20-30 kg. Two animals for each dilution may be used.
The dilutions tested are 1 : 10, 1 : 25, 1 : 50 and 1 : 100. One millilitre of each of these
dilutions is injected subcutaneously. One healthy, susceptible, unvaccinated in contact
animal should be kept along with the vaccinated animals.
Fourteen to twenty-one days later these animals along with two controls are injected
subcutaneously with 1 ml. of the challenge virus containing at least 1000 minimum infective
doses.
5. Labelling- Should comply with requirements of ‗Labelling‘ as laid down in the
general monograph on ‗Viral Vaccines‘.
6. Storage- The vaccine may be expected to retain its potency for six months if stored at
temperature ranging between – 10˚ C to - 15˚ C and for seven days at 2˚ C to 4˚ C in the
refrigerator.
1
[Foot and Mouth Disease Vaccine (Inactivated)
1. Synonym. – Inactivated Tissue culture mono or polyvalent Foot and Mouth Disease
Vaccine.
2 Definition. – Foot and Mouth Disease Vaccine is a liquid product or preparation
containing one or more types of foot and mouth disease virus which have been inactivated in
such a way that its immunogenic property is maintained. It may also contain an adjuvant. The
vaccine is described as monovalent, bivalent, trivalent or polyvalent depending on the number
of types of virus used.
3. Preparation. – The virus is propagated in suitable cell culture. The cell culture is
infected with an appropriate inoculum of virus and incubated at a suitable temperature for
multiplication of virus. The virus is harvested and cellular debris removed by filteration.
Inactivation is carried out by a suitable agent such as formaldehyde solution or aziridine
compound. The adjuvant may be aluminium hydroxide and/or saponin. In case of inactivated
gel vaccine the antigen is concentrated by sedimentation at plus 4 degree C. For preparing a
polyvalent vaccine, monovalent antigens are mixed in appropriate quantities to give the final
mixture which is the formulated vaccine.
4. Standards :
(a) Description :- Aluminium hydroxide gel vaccines settle down to variable
degree on storage leaving the supernatant clear.
1. Ins. by G.S.R. No. 659(E) ,dt.. 31-8-1994.
Drugs and Cosmetics Rules 1945
364
(b) Identification – It protects cattle against Foot and Mouth Disease due to
homologous type/subtype of virus.
(c) Sterility test – It shall comply with the tests for sterility as prescribed under the
―general monograph on ―Viral Vaccines‖.
(d) Safety test - The test is carried out on fully susceptible cattle not less than 12
months of age and which have not been sensitized either by vaccination or previous
infection. Inoculate 3 susceptible cattles each with 2 ml. of finished product at multiple
sites on tongue by intradermal route and observe for 4 days. The same animals are
inoculated on 4th day with 3 cattle doses subcutaneously and are observed for a further
period of 6 days. The animals should not develop any signs of FMD and remain normal.
(e) Potency test – Each batch of the vaccine is to be tested in susceptible cattle of
not less than 15 months of age. The potency test in cattle can be done either by :–
(i) PD
50
Method : The vaccine shall be tested by the determination of PD
50
in
susceptible cattle by challenging animals vaccinated with appropriate dilution of the
vaccine made in adjuvanted or non-adjuvanted diluent as appropriate.
A minimum of 5 animals should be used per dilution and 2 unvaccinated
animals to be included as controls to the challenge. All animals are needle
challenged with 10,000 ID
50
of the homologous strain of virus by inoculation on the
tongue on the 21
st
day of post-vaccination.
The control animals are to be similarly challenged. Animals are observed for 10
days for the development of lesions. Unprotected animals show generalised lesions
due to FMD. Control animals must shown generalized lesions. From the number of
animals protected in each group the PD
50
content of the vaccine is calculated. The
vaccine passes the test if an observed PD
50
value of 3 or greater is obtained in the
test.
(ii) Percentage protection method in which groups of ten health susceptible
cattle are each injected subcutaneously with the vaccinating dose and 14 – 21 days
later the cattle are challenged by intradermal injection into three separate sites on
the tongue with 10,000 ID
50
of the strain of virus used in the preparation of the
vaccine. The vaccine can be passed if atleast seven out of the ten in the group are
protected against the development of generalized infection whereas all the controls
should react by developing primary and secondary lesions observable in the mouth
and feet.
For other reasons if cattle testing is not possible then the potency of the vaccine may be
assed in guineapigs either by Lucam ‗C‘ index or PD
50
method by challenging those which
have been previously vaccinated, provided that the correlation has been established between
guinea pig challenge test and cattle challenge results.
The estimation of the serum neutralizing antibody titre cattle may be considered as a
supportive test to evaluate potency of vaccine.
However, potency testing of vaccines, in cattle, of batches whenever by other accepted
methods of testing is in doubt, at aleast one out of every five batches, be undertaken.
5 Labelling :- It is labelled as described under the requirements of ‗labelling‘ as laid
down in the general monograph, with the additional requirements that the label on the
container states the virus types used in the preparation.
6. Storage :- It should be protected from the light and stored between 4
o
C to 8
o
C. Under
these conditions it may be expected to retain its potency for not less than 12 months. Freezing
of aluminium hydroxide vaccine must be avoided. The frozen product will not be fit for use.
Drugs and Cosmetics Rules 1945
365
Canine Hepatitis Vaccine (Living)
1. Synonyms : Infectious Canine Hepatitis Vaccine (Living), Canine Hepatitis Cell
Culture
Vaccine.
2. Definition : Canine Hepatitis Vaccine (Living) is a freeze dried preparation of
tissue culture fluid containing the cell culture adopted canine hepatitis virus.
3. Preparation : Canine hepatitis vaccine shall be prepared from virus bearing cell
culture fluid.
Only stock seed virus which has been established as pure, safe and immunogenic shall be
used in the preparation of the vaccine.
Immunogenicity test : Each lot of stock seed virus shall be tested for immunogenicity
as follows :
Thirteen canine hepatitis susceptible dogs, 8-14 weeks old shall be used for the test
(10 vaccinates and 3 controls). Blood samples may be drawn from these animals and
individual serum samples tested for the presence of antibodies, against canine hepatitis
virus. Ten dogs shall be injected subcutaneously with predetermined quantity of the virus
and remaining 3 dogs are kept as unvaccinated controls. The dose calculation will be
based on virus titration in suitable cell culture system. Not less than 14 days post
vaccination, the vaccinated and control shall each be challenged intravenously with
virulent infectious canine hepatitis virus and observed daily for 14 days. At least 2 out of
3 controls should die and the survivors shall show the clinical signs of canine hepatitis.
Nine out of ten vaccinated dogs shall survive and shall not show any signs of infectious
canine hepatitis during the observation period.
The stock seed virus shall be tested once in 5 years and maintained under standard
conditions as prescribed.
The stock seed virus may be inoculated on a suitable tissue culture system and may
be incubated for five to seven days.
The tissue culture fluid is then harvested and titrated in cell culture system for virus
content. After appropriate dilution and pooling, the material is stored at minus 20
o
C until
freeze dried. Each vaccine dose shall contain not less than 10
3.5
TCID
50
dose.
4. Standards
:-
(a) Description. – The dried product is a pinkish cream material readily dispersible
in water. The reconstituted vaccine is a pinkish liquid.
(b) Identification.- It causes characteristic cytopathic effect in dog, pig and ferret
kidney monolayers. This can be neutralized by specific antiserum. When
inoculated into dogs, the development of specific neutralizing antibodies can be
demonstrated by suitable serological tests.
(c) Moisture content.- In the finished product moisture content shall not exceed 1.0
per cent.
(d) Sterility Test.-- Shall comply with the tests of sterility as described under the
general monograph on ―Viral Vaccines‖.
(e) Safety Test.-- Mouse safety test – Vaccine prepared for use as recommended on
Drugs and Cosmetics Rules 1945
366
the label shall be tested. Eight mice shall be inoculated intracerebrally with 0.03
ml and 8 mice shall be inoculated intraperitoneally with 0.5ml. Both the groups
shall be observed for seven days. If unfavourable reaction attributable to the
product occurs in two or more mice in either group during their observation
period, the batch is unsatisfactory.
(f) Dog Safety Test.-- Each of the two susceptible pups aged 8 – 14 weeks shall be
injected with vaccine equivalent of 10 vaccinating doses from the batch
reconstituted with sterile diluent and administered in the manner recommended
on the label and observed for 21 days. None of the pups shall show any
unfavourable reaction during the period of observation.
(g)
Potency test, Virus Titration: – Samples of finished product shall be tested for
virus titre in suitable cell culture system. The batch shall have a virus titre of not
less than 10
3.5
TCID
50
dose.
(h)
Potency test in dog:– Two healthy susceptible dogs of 8-14 weeks of age shall be
injected subcutaneously with one Vaccine dose. 14 days after vaccination,
specific neutralizing antibodies from both the dogs shall be demonstrable by
serological tests.
5 Labelling: Shall comply with the requirement for labelling as laid down in the
general monograph on ―Viral Vaccines‖.
6 Storage: The dry product shall be stored at temperature of minus 20
o
C or below.
. The vaccine is expected to retain its potency for about 6 months in the
freezing chamber of the refrigerator (temperature) approximately minus
8
o
C
Duck Plague
Vaccine
1 Definition.- Duck plague vaccine is a suspension of modified living virus prepared
from infected chick embryos.
2 Preparation.- Fresh fertile hen‘s eggs obtained from salmonella free flocks are
. incubated in an incubator. Nine days old embryos are injected with
0.2 ml of the suitable dilution ( 1 in 100) of the suspension of the virus
on the CAM and incubated at 37
o
C for 5 days post-inoculation. Dead
embryos of the 3rd, 4th and 5th days post-inoculation are harvested.
The embryos (devoid of head and legs). Clear fluid and the membranes
are collected and homogenized in a Blender, ampoulded in 0.5ml
quantities and freeze dried.
3 Standards:-
(a) Description.- Light brown scales.
(b) Identification.- This product affords protection to the ducks against duck plague.
Drugs and Cosmetics Rules 1945
367
(c) Safety Test.- Four healthy, 8 to 12 weeks old ducks weighting not less than 600
gms are inoculated subcutaneously with 1ml of 10
-1
dilution of the vaccine and
observed for a period of 14 days. During the period of observation, the ducks shall
not show any untoward reaction.
(d) Sterility test.- Shall comply with the test for sterility described in the
general monograph on ―Viral Vaccines‖.
(e) Potency Test.- Six susceptible ducks 8 to 12 weeks old each weighing not less than
600 gms are inoculated subcutaneously with 1 ml of 10
-3
dilution of the vaccine.
The minimum virus contents in 1 ml. dose of the vaccine shall be 10
3.5
EID
50.
14
days later these ducks are challenged subcutaneously each with 1 ml. of 10
-2
dilution of the virulent duck plague virus (1000 DEID
50
) along with 2 unprotected
young ducks of about 8-12 weeks age. The unprotected ducks shall show symptoms
of duck plague and die within 10 days, while the protected ducks shall remain
normal during the observation period of 14 days.
4. Labelling.- Should comply with the requirements of labelling as laid down in the general
monograph on ―Viral Vaccine‖.
5. Storage.- Vaccine when stored at minus 15
o
C to minus 20
o
C may be expected to retain
its potency for one year and about three months if stored in the freezing
chamber of Refrigerator i.e. minus 5
o
C.
Avian Encephalomyelitis Vaccine (Living)
1. Synonyms.- Avin-encephalomyelitis Vaccine Freeze dried.
2. Definition.- A virus bearing tissue and fluid suspension from embryonated hen‘s legs.
3. Preparation.- The stock seed virus which has been established as pure, safe and
immunogenic shall be used for preparing the vaccine.
(i) Each lot of stock seed virus shall be tested for pathogenicity by chicken
embryo inoculation test:
(a) One dose of the seed lot shall be mixed with 9 volume of sterile heat
inactivated specific, antiserum to neutralize vaccine virus in the product.
(b) After neutralization, 0.2 ml of serum vaccine mixture shall be inoculated
into each of at least 20 fully susceptible chicken embryos (0.1ml of the
inoculum shall be inoculated on CAM of 9-11 days old embryos and
0.1 ml in the allantoic sac).
(c) Eggs shall be candled for 7 days. Deaths occurring during first 24 hours
shall be discarded but at least 18 viable embryos shall survive 24 hours post
inoculation for a valid test. All embryos and CAMs from embryos which
die after the first day shall be examined.
Drugs and Cosmetics Rules 1945
368
(d) If the death or abnormality attributable to inoculums occur, the seed lot is
unsatisfactory.
(ii) Immunogenicity test.- Avian encephalomyelitis susceptible chicks, all of same age
8 weeks old) shall be used 20 chickens shall be inoculated with the field dose of the
virus by prescribed route. Ten additional chickens of same age and flock shall be
held as unvaccinated controls.
At least 21 days post vaccination, the controls and vaccinates shall be
challenged intracerebrally with Virulent avian encephalomyelitis virus and observed
each for 21 days. At least 80 percent of controls shall show signs of avian
encephalomyelitis or die. At least 19 to 20 vaccinates shall remain free from clinical
avian encephalomyelitis during the observation period for the stock seed virus to be
satisfactory
4. Standards:-
(a) Description:- Greyish white flakes easily dispersible in the diluent.
(b) Identification:- At least 5–6 days old embryonated eggs (from hens with no history of
infection with avian encephalomyelitis) shall be inoculated with 0.1 ml of undiluted
vaccine into the yolk sac and kept in incubator and then transferred to the brooder
where they are allowed to hatch. The hatched chicks shall be raised for 7 days. More
than 5 per cent of hatched chicks shall manifest the typical symptoms (weak-leg, leg
paralysis tremor etc.) at the end of this period.
(c) Moisture Content: - Shall not exceed 1.0 per cent.
(d) Sterility Test: - Shall comply with the test for sterility described under general
monograph on ―Viral Vaccines‖.
(e) Safety Test: - At least 25 avian encephalomyelitis susceptible birds (6-10 weeks of
age) shall be vaccinated with 10 field doses by the recommended route and observed
each day for 21 days. If unfavourable reactions attributable to the vaccine occur
during the observation period, the batch of vaccine is unsatisfactory.
(f) Potency Test: -
(i) The vaccine shall be titrated for virus content. To be eligible for release, the
batch shall have a virus titre of at least 10
2.5
EID
50
per dose.
(ii) At least 10 susceptible chickens shall be vaccinated with the field dose of the
vaccine by prescribed route and 10 chickens from same batch and source shall
be kept as unvaccinated controls.
At least 21 days post-vaccination, both the groups shall be challenged
intracerebrally with Virulent avian encephalomyelitis virus and observed for 21
days. At least 8 out of 10 controls shall develop recognizable signs or lesions of
avian encephalomyelitis and at least 8 out of 10 vaccines should remain normal
5. Labelling: Shall comply with the requirement of labelling as laid down in
general monograph on ―Viral Vaccines‖.
Drugs and Cosmetics Rules 1945
369
Marek’s Disease Vaccine (Living)
1. Synonyms.- Herpes virus of Turkey Vaccine HVT vaccine (Living).
2. Definition:- Marek‘s disease vaccine is a suspension of cell free fluid containing live
virus.
3. Preparation.- The stock seed virus which has been established as pure, safe and
immunogenic in avian species shall be used for preparing the seed virus
for vaccine production.
(i) Safety Test – The stock seed virus shall be non-pathogenic for chickens as determined by
the following procedure:
The groups of at least 25 chickens each at one day of age shall be used. These
chickens shall be of the same source and batch be susceptible to Marek‘s disease
and be kept in isolated group.
Group 1: Each chicken shall be injected with 0.2 ml of 10 times as much viable virus as will
be contained in one dose of vaccine by intramuscular route.
Group II : Shall serve as controls. At least 20 chickens in each group shall survive for four
days postinjection. All chickens that die shall be necropsied and examined for
lesions of Marek‘s disease and cause of death. The test shall be judged according to
the following :
At 120 days o age, the remaining chicken in both the groups shall be weighted,
killed and necropoised. If at least 15 chicken in each of these two groups have not
survived the 120 days period if any of the chicken of Group-I have gross lesions of
Marek‘s disease at necroposy or if the average body weight of the chickens in
Group-I is significantly (statistically) different from the average of Group-II at the
end of 120 days, the lot of stock seed virus is unsatisfactory.
(ii)
(iii)
Purity test – Shall conducted in chickens and no lesions other than those typical of
Turkey Herpes virus shall be evidenced.
Immunologenicity test – Sixty susceptible day old chicks are used. Thirty of them
inoculated with the seed virus in a dose corresponding to the field dose of the final
vaccine and 14-21 days later challenged by intrabdominal route with virulent Marek‘s
diseas virus, alongwith the other 30 non-vaccinated control chicks. At the end of the
observation period when the chicks are 20 weeks old, the surviving chickens are
examined for the presence of antibody against Marek‘s disease by serological tests and
postmortem inspection for lesions of Marek‘s disease.
Any bird dead is thoroughly examined and the cause of death ascertained by
necropsy/histopathological examination. All the surviving birds are killed and necropsied.
The protection index (P1) is determined by following procedure :
1. Percent MD =
No. with MD lesions
x 100
No. with MD lesions + No. of –ve Surviviours (effective No.)
Drugs and Cosmetics Rules 1945
370
2. P.I. =
Percent MD in controls – Percent MD in vaccinated
x
100
Percent MD controls
Master seed virus should have P.1 of at least 80 per cent.
Eighty per cent of the chicks in the control group must fall ill specifically. If more than
80 per cent of the vaccinated chickens do not show symptoms or signs of Marek‘s disease, the
seed virus is regarded as sufficiently effective and can be used for production of vaccine.
The seed virus is propagated in duck embryo fibro-blast cell culture, chick embryo
fibroblast or any other suitable cell culture (specific pathogen free SPF flock) and when the
peak passage level is attained the cell monolayer is suspended in cold diluent of the following
composition:
SPGA Stablizer
0.218% Sucrose.
0.0038% monosodium phosphate.
0.0072% dipotassium phosphate.
L Monosodium glutanate 0.0049 M.
1 per cent bovine albumin fraction (V).
0.25 per cent EDTA (Sterilised by Seitz filteration and stored at minus 10
o
C). The virus
is freed from cell by ultrasonication for 3 minutes interrupted after every 30 seconds) at 100
MA and freeze dried at times 60
o
C preferably in shelf freeze dried in convenient volumes.
The doses per ampoule vial is calculated after titrating the freeze dried product in terms of
plaque forming units (PFU) in the corresponding cell monolayers.
4. Standards:
(a) Description: - The cell free freeze dried HVT vaccine look uniformly grayish in colour
and easily dispersible in the specified diluent.
(b) Identification. - The vaccine on inoculation in suitable cell culture system shall cause
cytopathic effect typical of Herpes virus of Turkey. Specific antiserum of Herpes virus of
Turkey shall neutralize the cytopathic effect.
(c) Moisture content. - Moisture content shall not exceed one per cent.
(d) Sterility test. - Shall comply with the test prescribed in general monograph on ―Viral
Vaccines‖.
(e) Safety Test.- At least 25 one day old chickens shall be injected with ten times of the
field dose of vaccine by intramuscular route. The chickens shall be observed each day for
21 days. Chickens dying during the period shall be examined, cause of death determined
and the results recovered as follows :
(i) If at least 20 chickens do not survive the observation period, the test is inconclusive.
(ii) If lesions of any disease or cause of death are directly attributable to the vaccine the
vaccine is unsatisfactory.
(f) Potency test. - The sample shall be titrated in the cell culture system. A satisfactory batch
shall contain at least 1500 plaque forming units (PFU) as per dose at the time of release
Drugs and Cosmetics Rules 1945
371
and maintain at least 1000 PFU till the end of expiry period.
5. Labelling. - Shall comply with the requirements of labelling as laid down in general
monograph on ―Viral Vaccines‖.
6. Storage and expiry date. - The freeze-dried cell free HVT vaccine may be stored at 4
o
C for
6 months.
Goat Pox Vaccine (Living Cell Culture)
1. Synonym. - Goat Pox Vaccine (living), Attenuated Goat Pox Vaccine.
2. Definition. - Goat Pox vaccine is freeze-dried preparation, prepared by growing attenuated
goat pox virus in kid kidney/testicular cell culture.
3. Preparation. - Primary kidney/testicular cell cultures of disease free kid are used. The
monolayers infected with the seed virus are incubated at 37
o
C. The cultures are harvested by
three cycles of freezing and thawings 6 to 7 days post infection when more than 80 per cent
cells show CPE. The suspension is centrifuged at 1000 rpm for 10 minutes to remove
cellular debris being stored at minus 20
o
C. The suspension is freeze dried after addition of
5 per cent Lactalbumin hydrolysate and 10 per cent sucrose.
4. Standards:
(a) Description. - Light yellow colour.
(b) Identification - The product affords protection to goat against goat pox.
(c) Moisture content. - The moisture content shall not exceed 1.0 per cent.
(d) Safety tests.-
(i) Laboratory animals. - Six mice, 3 guinea pigs and 3 rabbits are inoculated with
0.2ml intraperitoneally, 0.5 ml and 1.0 ml subcutaneously, respectively with 10
field doses of the vaccine. The inoculated animals during the observation period of
80 days shall remain normal.
(ii) Goat. - Two susceptible goats of 6 to 8 months of age are inoculated in postaxillary
region by subcutaneous route with one-hundred field doses of the vaccine. The
inoculated animals shall not develop more than a local reaction of 2 to 3 cms.
These animals shall be observed for 10 days.
(e) Sterility test.- Shall comply with the test for sterility described under the general
monograph on ―Viral Vaccines‖.
(f) Titration in cell culture.- Four randomly selected samples are inoculated in kid kidney
cell cultures using 5 tubes for each dilution. The titration shall be repeated thrice. One
thousands TCID
50
is used as a field dose.
(g) Potency Test.- The three susceptible goats (8-10 months) are inoculated with 1/10th field
dose and 3 susceptible goats (8-10 months) with one field dose, subcutaneously. Three
in contract controls are also kept with the inoculated goats. These animals are observed
for a period of 14 days and their body temperature recorded daily. The vaccinated
Drugs and Cosmetics Rules 1945
372
animals shall not show any termal, local or generalized reaction. Twenty one days post
infection, the vaccinated and controls and challenged with 10,000 TCID
50
of virulent
goat pox virus by intradermal route. The temperature of these goats are recorded for a
period of 14 days. The vaccinated goats shall not develop localized or generalized
reaction while control goats shall develop high fever, localized reaction or even
generalized reaction in some cases.
5. Labelling .- Shall comply with requirements of labelling as laid down in the general
monograph on ―Viral Vaccines‖.
6. Storage and expiry date.- The vaccine is expected to retain its potency for 12 months if
stored at minus 15
o
C to minus 20
o
C and for three months at 2
o
C to 4
o
C.
Sheep Pox Vaccine
(Inactivated)
1. Synonym .- Formal gel sheep pox vaccine.
2. Definition .- Sheep pox vaccine is a formaline inactivated gel treated tissue vaccine.
3. Preparation.- Healthy susceptible sheep of 8-12 months of age are inoculated
subcutaneously with 500 ml of the 1:100 dilution of the Russian Virulent Sheep Pox Virus.
Seven to eight day post inoculation skin of the abdomen alongwith the oedema is collected.
The infected tissues are homogenized in 10 percent concentration in phosphate buffer
(pH 7.4-7.6) which after the extraction of the virus is mixed with sterile gel and buffer in the
following proportion :-
6 percent aluminium hydroxide gel-50 per cent.
Phosphate Buffer (pH 7.6)- 35 per cent.
10 per cent suspension – 15 per cent
This is later formalized and kept at 20-25
o
C/10
o
C for varying periods.
4. Standards.-
(a) Description .- It is a greyish white suspension. During storage the gel settles at the bottom,
upper layer of the suspension is clear.
(b) Identification.- This product affords protection to sheep against sheep pox.
(c) Safety test.- This is carried out by inoculating 2 white mice with 0.2 ml., one guinea pig
with 1.0 ml and one rabbit with 3,0 ml of vaccine. The animals should remain clinically
healthy for 10 days.
(d) Sterility test.- This is done by seeding the vaccine on usual bacterial media. The plates and
tubes are incubated for 10 days at 37
o
C. If the pathogenic bacteria are found, the vaccine is
rejected while with non-pathogenic bacteria the vaccine is passed for field use.
(e) Potency test.- This is done by inoculating 4 non immune susceptible sheep preferably
exotic breed of 1-2 years with 3 ml of vaccine in the thigh, subcutaneously.
The vaccinated sheep are challenged 15 days after inoculation alongwith 3 controls each
with 0.1 ml of virulent virus containing 200 infective doses intradermally under the tail.
Drugs and Cosmetics Rules 1945
373
The sheep are observed for 10 days and their skin reaction recorded. The vaccine is
considered potent if all the vaccinated, sheep do not show thermal or local skin reaction.
Vaccine is also potent if 3 vaccinated animals do not develop any reaction and one shows
abortive skin reaction, while at least 2 of the 3 controls develop typical sheep pox reaction
at the site of inoculation.
5. Labelling.- Shall comply with the requirements of labelling as laid down in the general
monograph on ― Viral Vaccines‖.
6. Storage.- The vaccine shall be stored at 4
o
C to 5
o
C. it keeps well at above temperature upto
12 months.
Sheep Pox Vaccine (Living Cell Culture)
1. Synonym.- Sheep pox vaccine (Living), attenuated sheep pox vaccine.
2. Definition.- Sheep pox vaccine is freeze dried preparation prepared by growing attenuated
sheep pox virus in lamb kidney/testicular cell cultures.
3. Preparation.- Primary cell cultures prepared from kidney/testicles of disease free lambs are
used. The mono layers infected with the seed virus are incubated at 37
o
C. The cultures are
harvested by 3 cycles of freezing and thawing 6 to 7 days post infection when more than 80
per cent Cells show C.P.E. The suspension is centrifuged at 1000 r.p.m. for 10 minutes to
remove cellular debris before being stored at minus 20
o
C. The suspension is freeze dried
after addition of 5 per cent Lactalbumin hydrolysate and 10 per cent sucrose.
4. Standards:-
(a) Description.- Light yellow colour.
(b) Identification.- The product affords protection to sheep against sheep pox.
(c) Moisture contents.- The moisture contents should not exceed 1.00 per cent.
(d) Safety tests.-
(i) Six mice, 3 guinea pig and 3 rabbits are inoculated with 0.2 ml intraperitoneally
0.5ml and 1.0 ml subeutaneously, respectively containing 10 field doses of the
vaccine. The inoculated animals during the observation period of 10 days should
remain normal.
(ii) One hundred field doses of the vaccine are inoculated subcutaneously into each of
2 susceptibles sheep in postaxillary region. Inoculated animals shall not develop
more than a local reaction of 2 to 3 cms.
(e) Sterility test. - Shall comply with the test for sterility as described under the general
monograph on ―Viral Vaccines‖.
(f) Titration in cell culture. - Four randomly selected samples reconstituted in a
maintenance medium are inoculated in lamb kidney cell cultures using 5 tubes for each
dilution. The titrations shall be repeated thrice. The TCID
50
to be calculated by Read and
Muonch method. One thousand TCID
50
is calculated as one field dose.
(g) Potency test. - Three susceptible sheep 8-10 months old are inoculated with 1/10th, field
dose and 3 susceptible sheep with one field dose, subcutaneously. Three in contact
controls are also kept with the inoculated sheep. These animals are observed for a period
Drugs and Cosmetics Rules 1945
374
of 14 days and their temperature is recorded daily. The vaccinated animals should not
show any thermal, local or generalize reactions. Twenty-one days post infection the
vaccinated and controls are challenged with 10,000 ID
50
of virulent sheep poxvirus by
intradermal route. The temperature of these sheep are recorded for a period of 14 days.
The vaccinated sheep should not develop localised or generalized reaction while control
sheep should develop high fever, localized reaction or even generalized reaction in some
cases.
5. Labelling.- Shall comply with requirements of labelling as laid down in the general
monograph on ―Viral Vaccines‖.
6. Storage and expiry date.- The vaccine is expected to retain its potency for 12 months if
stored at minus 15
o
C to minus 20
o
C and three months at 2
o
C to
4
o
C
Tissue Culture Rinderpest Vaccine
1. Synonyms.- Cell Culture Rinderpest Vaccine.
2. Definition.- Tissue Culture Rinderpest Vaccine is a freeze dried preparation of live
modified rinderpest virus adapted to and propagated in cell culture.
3. Preparations.- Primary or secondary monolayer cultures of the kidney cells (Bovine or any
other suitable animals) taken from kidney from healthy animals free from any pathological
changes shall be used. When secondary cultures are used they shall have retained their
original morphology and Karyotype. Kabete ‗O‘ stain of Rinderpest virus developed by
East African veterinary Research Organisation (Plowrights strain between the passage levels
of 99th and 100th passages) shall be used. The virus harvested from cell monolayer culture
prepared from the kidneys of a single calf or serially cultivated bovine kidneys cells (Not
more than 10 passages away from the Primary) inoculated with the same seed and harvested
together, will be freeze dried with stabilizers in suitable quantities.
4. Standards.- It complies with the requirements of general standards of viral vaccines:
(a) Description.- Dry light yellow coloured flakes readily soluble in chilled and saline or
buffered saline.
(b) Identifications.-
(i) Protects cattle against a subsequent challenge with virulent or caprinised
rinderpest virus.
(ii) It is titrable in tissue culture systems capable of supporting the multiplication of
this virus. The test shall be made on at least three separate occasions using a cell
culture derived from different animals.
(iii) Specificity test shall be performed using an appropriate scrum neutralization test.
(c) Sterility test. - Each batch shall be tested for bacterial and mycotic sterility as given in
general monograph on ―Viral Vaccines‖.
(d) Innocuity test.- Shall be made on each batch in at least two guinea pigs and six mice.
These animals shall be observed for at least two weeks for any untoward reaction.
(e) Safety and efficacy test.- The test for safety and efficacy shall be performed using the
pooled reconstituted contents of not less than 4 ampoules taken at random. The vaccine
Drugs and Cosmetics Rules 1945
375
shall be injected subcutaneously into each of at least two susceptible cattle free from
specific antibodies using the quantity containing not less than 100 fields doses and two
further cattle and using 1/10th of the field dose (calculated on the basis of 1000 TCID
50
one field dose). The animals shall be housed with at least two unvaccinated animals and
observed for a period of three weeks. The vaccine passes the safety test if the cattle show
no signs of unusual clinical reactions.
At the end of three weeks all the four animals will be challenged alongwith two in contact
cattle with a challenge dose of not less than
10
4
ACID
50
of virulent Rinderpest virus. The vaccine
passes the potency/efficacy test if the in contact animals develop rinderpest and all the vaccinated
animals remain normal.
5 Labelling.- Shall comply with general monograph on ―Viral Vaccines‖. Each ampoule or
at least 50 percent ampoules in a lot shall contain at least following print :
(i) TCRP Volume.
(ii) Batch No. with year.
(iii) General instructions for use.
6 Storage .- The vaccine when stored at minus 20
o
C and plus 4 degree C will maintain its
titre for 2 years and 6 months respectively.
Canine Distemper
Vaccin
e
1. Synonyms.- Cannine Distemper Vaccine (Living)- Freeze-dried.
2. Definition.- It is freeze dried preparation of either tissues from chick embryo containing
eggs adapted strain of cannine distemper virus or the cell culture in which modified virus
has been cultivated.
3. Preparation.- Canine distemper vaccine shall be prepared from virus bearing cell culture,
fluid or infected chroioalantoic membrane. Only stock seed virus which has been
established as pure, safe and immunogenic shall be used for preparation of vaccine. Stock
seed virus propagated in chicken embryo shall be tested for pathogen by chicken embryo
test. One volume of the virus shall be mixed with 9 volume of specific sterile heat
inactivated serum to neutralize the virus. Mixture shall be inoculated into twenty (9 to 11
days old ) chicken embryo (with 0.1 ml on CAM and 0.1 ml in alantoic sac).
Embryonated eggs shall be candled for 7 days daily. Death occurring in the first 24 hours
shall be discarded. CAMS of embryos which die after 24 hours shall be examined. When
necessary embryo sub-culture shall be made to determine the cause of death. The test
should be concluded on the 7th day post inoculation.
The surviving embryos and their CAMS are examined. If deaths or abnormality
due to the inoculums occur, the seed virus is unsatisfactory.
Immunogenicity test : Thirteen susceptible dogs 8-14 weeks old shall be used for the test
(ten vaccinates and 3 controls). Blood samples are drawn from these animals and
individual sample is tested for antibodies against canine distemper. Ten dogs shall be
injected with a predetermined quantity of the virus and remaining 3 dogs are used as
unvaccinated controls. The dose shall be based on the virus tiltration. At least 21 days post
infection the vaccinated and controls shall be challenged intramuscularly with the same
dose of virulent canine distemper virus and the animals are observed each day for 21 days.
At least 2 out of 3 controls should die and survivor should show the symptoms typical of
canine distemper. At least 9 out of 10 vaccinated animals should survive and should not
show any clinical signs of canine distemper during the observation period. The stock seed
Drugs and Cosmetics Rules 1945
376
virus should be tested for immunogenicity at least once in 5 years, if maintained under
suitable conditions of storage. Eight days old chicken embryos from a healthy flock are
inoculated on their chorioallantoic membrane with bacteriologically sterile virus
suspension of egg adapted strain. After incubation for a period of five days, infected
membrane and embryos are harvested. The individual embryo is tested for bacterial
sterility. Those free from bacterial contamination are made into a 20 percent suspension
in
a suitable medium. The suspension is distributed in a single dose quantity into the
ampoules of vials and freeze-dried.
The ampoules are sealed under vacuum or with pure dry sterile nitrogen before sealing.
Alternatively, the virus may be grown on the suitable cell culture. Cells along with the
suspending fluid is harvested, distributed in single dose quantity in ampoules and freeze
dried.
4. Standard.-
(a) Description. - It is a dry product, pinkish cream material, readily dispersible in
water or a suitable solvent.
(b) Identification. - It infects CAM of fertile eggs. This is neutralized by canine
distemper antiserum. It does not cause distemper after injection into susceptible
ferrets or dogs but immunizes them against the disease.
(c) Moisture content. - Moisture content in the finished product shall not exceed
more than 1.0 per cent.
(d) Sterility test. - Shall comply with the test for sterility as described in the general
monograph on ―Viral Vaccines.‖
(e) Safety tests. - (i) Mice safety test: Reconstituted vaccine as recommended on the
label shall be tested.
Eight mice, 4 weeks old shall be inoculated intracerebally with 0.03 ml and 8
mice shall be inoculated intraperitoneally with 0.5ml. Both groups shall be observed for 7
days, if unfavourable reaction attributable to the product in either 2 or more mice in either
group is observed during observation period, the batch is unsatisfactory.
(ii) Dog Safety test.-Inject two healthy dogs eight to fourteen weeks old that have
previously been shown to be free from distemper virus-neutralising antibodies by the
recommended route with twice the dose stated on the label and observe for 21 days. No
significant local or general reaction develops.
(i) Potency test. - (i) Titration : Final samples of finished product shall be tested
for virus titre, and when tested at any time within the expiry period, it should
contain not less than 10
3
ID
50
per dose.
(ii) It shall be carried out in dogs. Two healthy susceptible dogs each of 8-14
weeks of age free from distemper neutralizing antibodies are injected
subcutaneously each with one vaccination dose. Serum samples shall be
collected from each dog 14 days after vaccination and these shall have specific
neutralizing antibodies at a dilution of 1: 100.
6. Labelling.- Shall comply with the requirements of labelling as laid down in the general
monograph on ―Viral Vaccines‖.
Drugs and Cosmetics Rules 1945
377
7. Storage and expiry date. - For the freeze-dried product the expiry date is one year
when stored at minus 20
o
C.
Avian Infectious Bronchitis Vaccine
(Living)
1. Synonyms. - Avian Infectious Bronchitis Vaccine (Living) freeze-dried.
2. Definition. - It is a freeze-dried product of low virulent Avian Infectious Bronchitis
Virus grown in embryonated hen‘s eggs of cultivated in cell culture.
3. Preparation. - Only stock seed virus which has been established as pure, safe
and immunogenic shall be used. Each jot of stock seed virus shall be tested for other
pathogens by chicken embryo inoculation tests as follows: -
A lot of seed virus shall be mixed with 9 volumes of sterile heat inactivated specific
anti- serum to neutralize and the vaccine virus serum mixture shall be inoculated into
each of at least 20 fully susceptible chicken embryos of 9-11 days old (0.1 ml on CAM
and 0.1 ml in the allantoic sac). Eggs are candled daily for 7 days. Deaths occurring
during first 24 hours shall be discarded but at least 18 viable embryos shall survive 24
hours post inoculation
for
a valid test. All embryo and CAMS from embryos shall be
examined which die after 24 hours. If necessary embryo subcultures shall be made to
determine the cause of death. The test shall be concluded on the 7th day post
inoculation and surviving embryos including the CAM shall be examined. If death and
or abnormality attributable to the stock seed virus occur, the seed lot is unsatisfactory.
Each lot of stock seed virus shall be tested for immunogenicity as below:
-
Bronchitis susceptible chickens of the same age and source shall be used. For each
method of administration recommended on the label and for each serotype against
which protection is claimed, 20 chicks shall be used as vaccinates. Ten additional
chickens for each serotypes against which protection is claimed shall be held as
unvaccinated controls.
21 to 28 days post vaccination all vaccinates and controls shall be challenged by eye
drops with virulent Bronchitis virus. A separate set of vaccinates and controls shall be
used for each serotype against which protection is claimed. The challenge virus shall
have a titre of at least 10
4.6
EID
50
per ml. Trachea swabs shall be taken once 5 days
post challenge from each vaccinated and controls. Each swab shall be placed in test
tube containing 3 ml of tryptose phosphate broth and antibiotics. The tubes and swabs
shall be swirled thoroughly and stored at minus 40
o
C pending egg inoculation. For
each chicken swabs at least 5 chicken embryos, 9-11 days old shall be inoculated in
the allantoic cavity with 0.2 ml of broth from each tube. All the embryos surviving 3rd
day post inoculation shall be used in evaluation. A tracheal swab shall be positive for
virus recovery when any of the embryos show typical infections bronchitis virus
lesions such as stunting, curling, kidney urates, clubbed down or death during 4-7 days
post inoculation period.
90 percent of the controls should prove positive for virus recovery. If less than 90
per cent of the controls are negative for virus recovery, the stock seed is
unsatisfactory. The stock seed virus should be tested for immunogenicity once in
5 years provided it is maintained under standard conditions of the bronchitis virus
storage.
4. Standards. -
(a) Descriptio: It is greyish-white product easily dispersible in the dil
uent.
Drugs and Cosmetics Rules 1945
378
(b) Identification: (i) The contents of the ampoule are suspended as per
the instructions for the field use. The 0.2ml of the suspension shall be inoculated in the
allantoic cavity of 9-11 days old chicken embryo and are incubated for 7 days. The lesions
typical of infectious bronchitis shall be observed in the embryos at the end of incubation
period. The allantoic fluid shall not agglutinate the chicken RBC's.
(ii) Specific antisera against avian infectious bronchitis virus should neutralize
the vaccine virus.
(c) Moisture content. - Moisture content in the finished product should not
exceed 1.0 per cent.
(d) Sterility test. - Complies with the test for sterility as described under the
general monograph on ―Viral Vaccines‖.
(e) Safety test. - Ten healthy susceptible chickens 5-10 days old from the
same source batch shall be vaccinated with ten field dose of the vaccine and along with five
chicks from same batch as unvaccinated controls by the prescribed route and observed 7 or
21 days post vaccination. Neither severe respiratory symptoms nor death shall occur to
more than one experimental chicks, none of the unvaccinated control shall show any clinical
symptoms.
(f) Potency test. - The minimum virus content of the freeze-dried product shall
not be less than 10
3.5
EID
50
per bird. The virus content of the vaccine shall be titrated as
below:
Serial ten-fold dilution of the freeze-dried material will be made in tryptose
phosphate broth. Three to five embryonated eggs (9-11 days old) shall be in inoculated
with 0.1 ml of each dilution into the allantoic cavity and observed daily for 7 days.
Deaths occurring during the first 24 hours shall be discarded. The surviving
embryos are examined for the evidence of infection and EID
50
shall be calculated by the
Reed and Muench Method/spearman and Karber method.
5. Labelling .- Shall comply with the requirement of labelling as laid down in the
general monograph on ―Viral Vaccine‖.
6. Storage and expiry date.- Shall be stored at 4
o
C for six months].
PART II
–
A
NTISERA
Provisions applicable to the production of all Sera from Living Animals
1. Definitions- (i) This Part of the Schedule applies to antibacterial sera, anti-viral sera
and anti-toxic sera which are prepared by injecting bacteria or viruses or their products into
buffalo- bulls or other suitable animals so as to produce active immunity which is
manifested by the formation of anti-body.
(ii) For the purpose of this Part of the Schedule an anti-serum means sterile liquid
anti- serum concentrated and unconcentrated, solutions of globulins or their derivatives
or solid forms which can be reconstituted when necessary.
2. Staff of Establishment- The establishment shall be under the direction and control of
a competent expert in bacteriology and serology with adequate training in immunology and
standardisation of biological products and knowledge of animal management. He shall be
assisted by a staff adequate for carrying out the tests required during the course of
preparation of the sera and standardisation of the finished products.
3. Proper Name- The proper name of he antiserum shall be the recognised scientific
name of the diseases or its causative organism or some generally recognised abbreviations
thereof preceded by the prefix ‗anti‘, and followed by the word ‗serum; as for example,
‗Anti- Anthrax serum‘. The proper name of any antitoxin may be formed from the word
‗Anti-toxin‘ preceded by the name of the organism from which the toxin was prepared, and
followed, if desired, by a term indicating the source or the strain of that organism provided
where there is no special provision in the Schedule, the name as approved by the
Licensing Authority may be adopted.
Drugs and Cosmetics Rules 1945
379
4. Records-
(1) The permanent records which the licensee is required to keep shall include
the following particulars: -
(a) As to the culture- Evidence of the identity and specificity of the cultures.
(b) As to the procedure used in immunising the animals;
(i) The method of preparing the cultures or antigen used for immunisation.
(ii) The dosage and methods employed in administering the culture or antigen.
(iii) The period in the course of immunisation at which blood is withdrawn
for the preparation of the serum.
(c) Any test which may have been applied to the serum to determine its content
of specific antibodies or its specific therapeutic potency and purity.
(2) If the licensee desired to treat the performance of any tests recorded under sub-
paragraph (i) (c) of this paragraph as determining the date of completion of manufacture
for the purpose of rule 109 he shall submit full particulars of the proposed test to the
Licensing Authority and obtain his approval.
5. Cultures- The cultures used in immunising the animals shall be at all times open to
inspection, and specimens shall be furnished for examination at the request of the Licensing
Authority.
6. Quantity -
(a) Any antiserum shall be issued for veterinary use in the form of either.
(i) Actual serum, i.e., the liquid product of decantation of the coagulated
blood or plasma without any addition, other than antiseptic or subtraction, or
(ii) A solution of the purified serum proteins containing the specific
antibodies.
(b) At the time of issue, the liquid shall be clear or show at the most a
slight opalescence or precipitate. Preparations of the natural serum shall not contain
more than 10 per cent of solid matter. A solution of serum protein shall not contain
more than 20 per cent of solid matter.
1. Precautions to be observed in preparations-
(i) Laboratories where sera are exposed to the air in the course of the
process of preparation must be separated by a sufficient distance from stables
and animals houses to avoid the risk of aerial contamination with bacteria from
animal excreta, and must be rendered fly proof to prevent such contamination by
insects. Such laboratories must have impervious walls and floors and must be
capable of being readily disinfected when necessary.
(ii) A special room with impervious walls must be provided for the
collection of blood from the living animals.
(iii) An efficient system of manure removal must be used which will
prevent its accumulation in the vicinity of any room where blood or serum is
collected or handled.
(iv) An adequate number of sterilizers must be provided for the sterilization of
all glassware or other apparatus with which the serum may come into contact in the
course of its preparation.
(v) All processes to which the serum is subjected during and after the
collection from the animals, must be designed to preserve its sterility, but in the case
of a artificially concentrated sera, it shall suffice that the process of concentration is
Drugs and Cosmetics Rules 1945
380
conducted with scrupulous cleanliness and in such a manner as to avoid unnecessary
dangerous contamination.
(vi) The laboratories in which the testing of sera for potency, sterility and
freedom from abnormal toxicity are carried out must be adequate for the purpose. An
adequate supply of animals for use in such tests and suitable housing for such
animals must be provided.
(vii) Provision must be made for complying with any special conditions which
may be laid down in the Schedule relating to the production and issue of the
particular serum, in respect of which the licence is granted.
8. Unhealthy or Infected Animals- If an animal used in the production of sera is
found to be suffering from an infection except one produced by living organisms against
which it is being immunized, or shows signs of serious or persistent ill health not reasonably
attributable to the process of immunisation, the licensee shall immediately report the matter to
the Licensing Authority and shall, if the authority orders an inspection and the Inspectors so
directs, cause such animals to be killed and a postmortem examination of it to be made, and
take steps to prevent any serum obtained from the animal being sold or offered for sale until
permission is given by the Licensing Authority. If the result of the postmortem is such as to
bring under suspicion, the health of any of the other animals used for the production of sera,
the Licensing Authority may prohibit the use of those animals for the production of sera or
may take such other steps as may be necessary to prevent the issue of sera which may be
dangerous to animal health.
Provided in the case of emergency, the person in charge of the establishment may
order the destruction of an animal used in the production of sera and suspected of infection,
and shall in that case given notice forthwith to the Licensing Authority and shall permit an
Inspector to be present at the postmortem examination.
9. Conditions and Housing of animals:
(i) The animals used in the production of sera should be adequately housed under
hygienic environments.
(ii) Only healthy animals free from disease should be used in the preparation of
sera.
(iii) Every animal intended to be used as the source of serum must be subjected
to a period of
observation
in quarantine for at least seven days before being
admitted to the animal sheds in which the serum yielding animals are housed.
(iv) In case of horses and other equidae, every animal used as source of serum
shall either be actively immunized against tetanus or shall be passively immunized
against the disease by injection of tetanus antitoxin in such doses as to ensure the
constant presence of that antitoxin in the blood during the whole period of the use of the
animals as a source of serum.
Anti-Sera and their General Standard
Anti-sera contain the immune substances that have a specific prophylactic or
therapeutic action when injected into animals exposed to or suffering from a disease due to a
specific microorganism or its toxin. Anti-sera are classified into three groups.
(i) Antitoxic sera (Antitoxin)
(ii) Antibacterial sera.
(iii) Antiviral sera.
Antisera are usually issued in an unconcentrated form for animal use but may be
concentrated and also freeze dried. However, for the purpose of the Schedule the word
‗antisera‘ is also used for the unconcentrated liquid sera only. A suitable bacteriostatic agent
in a concentration sufficient to prevent the growth of microorganisms is added to the liquid
serum.
Drugs and Cosmetics Rules 1945
381
General
Standard
1. Description- Liquid native or unconcentrated antisera are yellow or yellowish
brown in colour. They are initially transparent but may become turbid with age. They are
almost odourless except for the odour of any bacteriostatic agent that may have been added.
2. Identification- The test for identity is described in the individual monograph.
3. Acidity or Alkalinity- All native antisera have a pH of 7.0 to 8.5.
4. Abnormal Toxicity- All anti-sera shall comply with the following tests or freedom
from abnormal toxicity.
(a) Two healthy mice each weighing not less than 18 g. are injected
subcutaneously each with 0.5 ml. of the sample and observed for five days. None of the
mice should show any abnormal reaction or die.
(b) Two healthy guinea pigs each weighing 300 g. to 450 g. are injected
subcutaneously each with 5 ml. of the sample and observed for seven days. None of the
guinea-pigs should show any abnormal reaction or die.
5. Sterility- All anti-sera shall comply with the tests for sterility described in rules 115
to 119.
6. Potency- The potency of each preparation, when the available methods permit, is
determined by the appropriate biological assay, and it is described under the individual
monograph.
7. Total Solids- Native antisera should not contain more than 10 per cent solid matter.
8 Labelling- Should comply with the provisions for ‗Labelling‘ as laid down for
‗Bacterial Vaccines.‘
9. Storage- Liquid preparations of antisera shall be stored, protected from light at
temperature between 2 ˚C to 4 ˚C and shall not be frozen.
10 Date of Manufacture- The date of manufacture shall be unless otherwise specified
in the individual monograph in this part is as defined in clause (b) of sub-rule (3) of rule 109.
11. Containers- All antisera are distributed in sterilised containers of a material which is
inert towards the substance and which are sealed to exclude micro-organisms.
12. Expiry Date- The expiry date of potency of all sera shall not be more than twenty-
four months after the date of a manufacture.
Anti-Anthrax
Serum
1. Synonym- Bacillus Anthracis Anti-serum.
2. Definition- Anti-anthrax serum is the serum of animals that confers a specific
protection against Baccillus anthracis.
3. Preparation- The antiserum may be prepared in buffalo bulls after repeated
injections of cultures of B. anthracis of a virulent strain.
4. Standard- It complies with the requirements in the general provisions for
antisera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids,
Labelling, Storage and Expiry date.
Identification – It protects animals against infection with B. Anthracis
Anti-Blackquarter
Serum
1. Synonym- Blackleg Antiserum, Clostridium Chauvoei-Anti serum
2. Definition-Anti-Blackquarter serum is the serum of suitable animals containing the
Substances that have a specific neutralising effect on Clostridium Chauvoei.
Drugs and Cosmetics Rules 1945
382
3. Preparation- It is prepared by injecting subcutaneously or intramuscularly
increasing doses of formolised cultures of Cl. Chauvoei into buffalo bulls.
4. Standards- It complies with the requirements described in the general provisions
for antisera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids,
Labelling, Storage and Expiry date.
Identification- It protects susceptible animals against infection with virulent strains of
Cl. Chauvoei.
Anti-Fowl-Cholera Serum
1. Synonym- Pasteurella Septica Antiserum (Avian).
2. Definition- Fowl Cholera Antiserum is the serum of animals containing the
substances that confer a specific protection to fowls against virulent strain of Pasteurella
Septica (Avian).
3. Preparation- Antiserum is prepared from buffalo bulls after they have been
subjected to an injection of killed cultures of virulent strain of Pasteurella Septica (Avian)
followed by injections of living cultures of the same organism.
4. Standard- It complies with the requirements described in the general provision for
anti-sera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility, Solids,
Labelling, Storage and Expiry date.
Identification- It protects susceptible fowls against infection with Pasteurella Septica
(Avian) and its homologous strains.
Anti- Haemorrhagic Septicaemia Serum
1. Synonym- Pasteurella Septica Antiserum.
2. Definition- Anti-Haemorrhagic Septicaemia Serum is the serum of animals
containing the substances that confer a specific protection to susceptible animals against
virulent strains of Pasteurella Septica.
3. Preparation – The antiserum is prepared from buffalo bulls after they have been
subjected to repeated injections of formolised cultures of standard strain Pasteurella Septica
with adjuvants, followed by suitable doses of virulent culture of the organism.
4. Standard.-It complies with the requirements described in the general
provisions for antisera under Description, Acidity or Alkalinity, Abnormal Toxicity, Sterility,
Solids, Labelling, Storage and Expiry date.
Identification- It protects susceptible animals against infection with homologous
strains of Pasteurella Septica.
Anti-Rinderpest
Serum
1. Synonym- Cattle Plague Antiserum
2 Definition- Anti-Rinderpest Serum is the serum of buffalo bulls containing the
substances that confer a specific immunity to susceptible animals against virulent strains of
the virus of rinderpest
3. Preparation – The antiserum is prepared from buffalos who have reacted to a dose
of virulent rinderpest virus, which is injected simultaneously with a predetermined quantity
of anti rinderpest serum so as to control the severity of the reaction (serum-simultaneous-
method).
4 Standard- It complies with the requirements described in the general provisions for
antisera under Description, Acidity or Alkalinity, Abnormal Toxicity, Solids, Labelling,
Storage and Expiry date.
(i) Identification- It protects susceptible animals against rinderpest.
Drugs and Cosmetics Rules 1945
383
(ii) Potency-Five Buffalo-calves of about one year of age in good condition are used
for the test. Three are injected subcutaneously with the anti-rinderpest serum under test at the
rate of 10 ml. per 46 kg. body weight, subject to a minimum of 20 ml. per animal. These
together with the two remaining, are simultaneously injected subcutaneously at a different
site with 1 ml. of a 1: 100 dilution of spleen suspension of virulent bull-virus.
The animals should be observed for fourteen days during which time the serum
treated animals should exhibit no symptoms of rinderpest other than rise in temperature and
slight intestinal disturbances, while the controls develop more severe symptoms or die.
Salmonella Pullorum Anti Serum
1. Synonym- Salmonella Pullorum Anti Serum.
2. Definition- Salmonella Pullorum anti-serum is the sera from fowls and contains
antibodies against Salmonella Pullorum. It is used for standardizing batches of Salmonella
Pullorum antigens and also used as a control along with the sera suspected for pullorum
disease.
3. Preparation- The serum is prepared after intravenous inoculation with smooth
culture suspension of Salmonella Pulloram in healthy birds.
4. Standards- It complies with the requirements in the general provisions for anti-
sera under Description, Acidity, Alkalinity, Sterility, Solids, Labelling, Storage and Expiry date.
5 . Identification- It should give positive agglutination with Salmonella pullorum
antigen.
Standard Anti-Brucella Abortus
Serum
1. Synonym- National counterpart of standard anti-Brucella Abortus serum.
2. Definition- Standard Anti-Brucella abortus serum is the serum which contains
1000 International Units (I.U) per ml. and is used for standardizing batches of brucella
antigens and is also used as a control along with the sera suspected for brucellosis.
3. Preparation- The serum is prepared after intravenous inoculation of suspension
of smooth culture of B. abortus (strain 99) in rabbits or cattle and subsequently diluting it
suitably with brucella-free healthy serum so that when tested with standardized Brucella
abortus tube test antigen, it gives 50% agglutination at 1/500 final serum dilution.
4. Standard- It complies with the requirements in the general provision for anti-
sera under Description, Acidity, Alkalinity, Sterility, Solids, Labelling, Storage and Expiry
date.
Identification- It should give agglutination with Brucella antigen.
PART III- DIAGNOSTIC A
NTIGENS
Provisions Applicable to the Manufacture and Standardisation
of
Diagnostic Agents (Bacterial
Origin)
1 Definition- This Part of the Schedule applies to reagents of bacterial origin
employed for various tests.
2 Staff of establishment- A competent expert in bacteriology with sufficient
experience in the manufacture and standardisation of veterinary biological products shall be
in charge of the establishment responsible for the production of various diagnostic agents of
bacterial origin and he may be assisted by a staff adequate or carrying out the tests required
during the preparation and standardisation of various diagnostic agents.
3 Proper Name- The proper name of any diagnostic agent is the name of micro-
oraganism from which it is made, followed by the word ‗antigen‘ unless the Schedule
Drugs and Cosmetics Rules 1945
384
otherwise provides, or, it may be derived from the name of the organism responsible for the
causation of the disease or if there is no special provision in the Schedule, the name approved
by the Licensing Authority. In the case of the undermentioned preparations the proper name
of the diagnostic agent may be as follows:
1. Abortus Bang Ring (A.B.R. ) Antigen.
2. Brucella Abortus Coloured Antigen.
3. Brucella Abortus Plain Antigen.
4. Johnin.
5. Mallein.
6. Salmonella Abortus Equi ―H‖ Antigen.
7. Salmonella Pullorum Coloured Antigen.
8. Salmonella Pullorum Plain Antigen.
9. Tuberculin.
4. Records- Cultures used in the preparation of diagnostic agents of bacterial
origin must, before being manipulated into an agent be thoroughly tested for identity by the
generally accepted tests applicable to the particular micro-organism. The permanent record
which the licensee is required to keep shall amongst other include a record of the origin,
properties and characteristics of the cultures.
5. Preparation- Diagnostic agents of bacterial origin are prepared from selected
cultures after their careful examination for the identity, specificity, purity and antigenicity.
They may be prepared in the following manner:
(a) Formolised Antigens- The selected pure culture strain grown in a suitable
medium at an optimum temperature for an appropriate period. The pure growth is
then exposed to the action of a solution of Formaldehyde I.P. in a suitable
concentration and at an appropriate temperature for a suitable period.
(b) In some cases, the diagnostic agents are prepared by growing the
organisms on suitable media and then deriving specific protein constituents of the
bacteria by various methods.
6. General Standard:-
(a) Description- Diagnostic agents may be clear opalescent or coloured
liquids.
(b) Identification- Some exhibit specific agglutination when mixed with
the serum of the animals infected with homologous organisms and others when
injected into the animal body in appropriate doses cause specific reactions like
hypersensitiveness, local and general reaction, if the animal is infected with
homologous organisms.
(c) Sterility Test- All antigens shall be tested for sterility in accordance
with rules 114 to 119.
(d) Standardisation- It is carried out either by determining the definite
concentration in the product or by observing the general and local reactions in
healthy and artificially infected animals with various standard dilutions of the
product.
7. Labelling- As under general provisions for the bacterial vaccines with the addition
that it is meant for diagnostic purposes only.
Drugs and Cosmetics Rules 1945
385
8. Storage- All antigens are stored, protected from light at a temperature between 2 ˚ C
to 4 ˚ C.
9. Date of manufacture- The date of manufacture shall be unless otherwise specified
in the individual monograph in this part as defined in clause (b) of sub- rule (3) of rule 109.
Abortus Bang Ring (A.B.R.) Antigen
1. Synonym- Milk Ring Test Antigen.
2. Definition- The antigen is a suspension of pure growth culture of standard strain of
Brucella abortus strain 99 strained supravitally with 2,3,5, triphenyl tetrazolium chloride
suspended in 0.85 per cent saline containing 1 per cent glycerol and 1 per cent phenol.
3. Preparation- Smooth strain of Brucella abortus strain 99 is grown in potato
infusion agar for 48 to 72 hours in Roux flasks, at 37 ˚ C. Condensation fluid if any is
pipetted off before washing. Each flask is washed with about 20 ml. of normal saline. The
pooled washing is filtered through a gauze and the filtrate is collected in a measuring
cylinder. To every 500 ml. of the filtrate 1 g. of 2, 3, 5, triphenyl tetrazolium chloride is added
immediately. The container is shaken for thirty minutes till the tetrazolium salt is dissolved.
The product is taken out and kept at 37 ˚ C for two hours. After incubation the product is
heated at 65˚ C in a water bath for thirty minutes. It is cooled and centrifuged at 3000 r.p.m
for one hour. The supernatant is pipetted off and sediment is suspended in normal saline
containing 1 per cent glycerol and 1 per cent phenol and filtered through sterile cotton wool.
This forms concentrated antigens.
Standardization of the Strained Antigen
An aliquot portion of the microbial suspension stained with phenylte-trazolium is
taken, representing the initial undiluted suspension. 1 ml. per tube of this initial undiluted
stained suspension is added to six test tubes, followed by increasing quantities of the
glycerolphenol diluent as follows:-
Tube Undiluted Stained Suspension Diluent
1
1
0.6
2
1
0.8
3
1
1.0
4
1
1.2
5
1
1.4
6
1
1.6
The contents of each tube are then diluted tenfold with the same diluent and serve as
antigen for a tube agglutination test with the Standard Serum (or its national counterpart). In
this way, six sero-reactions will be carried out. During this procedure, the concentrated
strained microbial suspension should be kept in the refrigerator at 4 ˚ C.
The agglutination reactions are read after forty-eight hours at the agglutination titre of
the Standard Serum, previously determined with the usual unstained antigen in the tube test,
corresponding to the correct dilution of the standard antigen.
The next step, therefore, is to dilute the concentrated stained suspension to the same
extent as the tube whose tenfold dilution has given the correct agglutination titre, i.e. the
concentration of antigen in the tube before the tenfold dilution had been made.
4. Standard:
(a) Description- It is a red colour liquid containing dead bacteria in
suspension.
Drugs and Cosmetics Rules 1945
386
(b) Identification- It shows formation of a specific cherry red coloured ring in the
cream layer when mixed with pooled samples of milk taken from animals suffering from
burcellosis.
(c) Sterility Test- Should comply with tests for sterility described in the general
monograph on ‗Diagnostic Antigen‘. The test shall, however, be done before colouring.
5. Labelling and Storage- Should comply with the requirements of ‗Labelling‘ and
‗Storage‘ as laid down in the general monograph on ‗Diagnostic
Antigens‘.
6. Expiry Date- The date of expiry of potency shall be not more than nine months
from the date of manufacture when stored 2 ° C to 4° C.
Brucella Abortus Coloured Antigen
1. Synonym- Brucella abortus Cotton Strain 99 coloured Antigen.
2. Definition- Brucella Abortus colured Antigen, is a suspension of pure smooth
cultures of Brucella abortus strain 99 in phenolised glycerine saline, the bacteria being
coloured by the addition of crystal violet and brilliant green. This antigen is used for plate test
for serological diagnosis of brucella infection.
3. Preparation- Seventy-two hours old growth of Brucella Abortus strain ninety-nine
in smooth form on potato infusion agar medium in Roux flasks is washed with phenolised
glycerine saline (containing 12 per cent sodium chloride, 20 per cent glycerine and 0.5 per
cent phenol). The washed growth is filtered through a pad of absorbent cotton wool and the
suspension is coloured by the addition of 1 ml. each of 1 per cent aqueous solution of crystal
violet and brilliant green for very 250 ml. of the suspension. The product is heated for sixty
minutes in a water bath at 60° C before it is standardised.
4. Standard:
(a) Description- It is a greenish violet liquid containing dead bacteria in
suspension.
(b) Identification-It gives specific agglutination when mixed with the serum of the
animal infected with brucella organism.
(c) Sterility Test- Should comply with the tests for sterility described in the general
monograph on ‗Diagnostic Antigens‘
(d) Standardisation- 0.5 ml. of the antigen is mixed with 4.5 ml of normal saline
solution in Hopkins graduated tube. The mixture is centrifuged at 3000 r.p.m. for sixty
minutes and the percentage of bacterial cells present in the original antigen is assessed
by noting the height of the cell deposit. The antigen is then standardised so as to
contain 10 per cent cell deposit.
5. Labelling and Storage- Should comply with the requirements of ‗Labelling‘ and
‗Storage‘ as laid down in the general monograph on ‗Diagnostic Antigens‘.
6. Expiry Date- The date of expiry of potency shall be not more than nine months
from the date of manufacture when stored at 2 ° C to 4°C.
Brucella Abortus Plain Antigen
1. Synonym- Brucella Abortus Strain 99 Plain Antigen.
2. Definition- Brucella Abortus Plain Antigen is a suspension of a pure smooth culture
of Brucella abortus strain 99 in phenol-saline.
3. Preparation- Seventy-two hours old growth of Br. Abortus strain 99 in smooth
form on potato infusion agar medium in Roux flasks is washed with normal saline solution.
The washed growth is filtered through a pad of absorbent cotton wool and the suspension is
Drugs and Cosmetics Rules 1945
387
kept at 60 ° C per cent. for sixty minutes on a water bath to kill the organisms. It is then
preserved by the addition of phenol in a final concentration of 0.5 per cent.
4. Standard:
(a) Description- An opalescent liquid containing dead bacteria in suspension.
(b) Identification –It gives specific agglutination when mixed with the serum of
animals infected with brucella organism.
(c) Sterility Test- Should comply with the tests for sterility described in the
general monograph in ‗Diagnostic Antigen‘.
(d) Standardisation- Mix the concentrated antigen well and dilute 1 ml. with
0.5 per cent phenol saline until it corresponds to about Tube 4 of Brown‘s opacity
tubes. Further dilutions of the antigen adjusted to opacity tube No. 4 are made.
The particular dilution that gives 50 per cent agglutination with anti-brucella
abortus serum ( containing 1000 International Units) at 1 : 500 final serum
dilution, is assessed as the diluting factor for the concentrated antigen. The bulk
of the concentrated antigens is accordingly diluted for issue as standard antigen.
5. Labelling and Storage- Should comply with the requirements of ‗Labelling and
Storage‘ as laid down in the general monograph on ‗Diagnostic Antigen‘.
6. Expiry Date- The date of expiry of potency shall be not more than nine months
from the date of manufacture when stored at 2° C to 4° C.
Johnin
1. Definition- Johnin is a preparation of a fluid medium in which Mycobacterium
Paratuberculosis has been grown in artificial culture and which has been freed by
filtration from the bacilli.
2. Preparation- Young culture of selected strain of Myco-Paratuberculosis of
bovine origin is grown on synthetic medium and incubated at 37 ° C for ten to twelve
weeks. Flasks showing lucurient and pure growth are steamed for three hours thereafter
kept at room temperature overnight. The contents are filtered through fine meshed sieve.
The filtrate is concentrated over a steam bath to one-tenth of its original volume and kept
in cold storage for fourteen days before being filtered through Seitz filter. The product is
dispensed in ampoules and hermetically sealed.
3. Standards:-
(a) Description- A yellowish brown to brownish liquid.
(b) Identification- It produces hot, painful and oeodemateus swelling at the site
of inoculation in animals infected with Myco-paratuberculosis organism.
(c) Sterility Test- Should comply with the test for sterility described in the
general monograph on ‗Diagnostic Antigens‘.
(d) Potency Test- Two animals, previously infected with Myco-paratuberculosis
and two healthy animals are each injected intrademally in the neck region with 0.1
ml. of the product. Forty-eight hours later, the injection is repeated at the same site.
The product should produce a typical reaction in the infected animals in the form of a
hot painful and oedemetous swelling at the site of inoculation persisting for at least
forty-eight hours after the second injection. Control animals should not show such
reaction.
4. Labelling and Storage- Should comply with the requirements of ‗Labelling‘ and
‗Storage‘ as laid down in general monograph on ‗Diagnostic Antigens‘.
5. Expiry Date- The date of expiry of potency shall be not more than two years from
the date of manufacture when stored at 2 ˚ C to 4 ˚ C.
Drugs and Cosmetics Rules 1945
388
Malleins
1. Definition- (i) Malleins are preparations of fluids media in which the
Actinobacillus mellei has been grown in artificial culture and which have been freed by
filtration from the bacilli.
(ii) For the purposes of this Schedule malleins are classified into (a) Mallein-
subcutaneous and (b) Mallein intradermo-palpebral (I.D.P.)
2. Preparation:-
(a) Mallein Subcutaneous- Three to four weeks old pure growth of standard strain
of A. mallei grown on synthetic medium is steamed for one hour in Koch‘s steam
sterilizer. One part of 5 per cent phenol solution is added to every nine part of the dead
culture which is then filtered through Seitz filter.
(b) Mallein Concentrated. - The procedure is the same as for Mallein
Subcutaneous except, that the filtrate is evaporated in porcelain dish over steam to half
the original volume before addition of phenol. Five per cent phenol solution is added in
sufficient quantity to the concentrated product, to give a final concentrated of 0.5 per
cent.
3. Standards:
(a) Description- A yellowish to brown viscous liquid.
(b) Identification- It produces hot tense, painful swelling when injected into the
animals infected with A. mallei organisms.
(c) Sterility Test- Should comply with the tests for sterility described in the general
monograph on ‗Diagnostic Antigens‘.
(d) Potency Test: -
(i) Mallein subcutaneous- Two ponies, previously sensitised with A.
Mallei and controls, are injected each with 1 ml. of the product subcutaneously in the
neck region. The animals are observed for local reaction and rise in temperature.
Local reaction is manifested by a hot tense, painful swelling becoming prominent
within twenty-four hours. The rise in temperature is observed by recording the body
temperature at the time of inoculation and subsequently at short intervals. A rise in
temperature of 1˚ C or more above normal is indicative of infection.
(ii) Mallein Intra-dermo-Palpebral (I.D.P.)- Two ponies, previously
sensitized with A. mallei and two healthy ponies are injected intradermally with 0.2
ml. of the product near the rim of the lower eye lid of one eye. Typical reactions
such as painful swelling of the palpebral tissue with mucopurulent discharge from the
eye is indicative of infection. The two healthy ponies should not show such reactions.
Similar test in other eye is performed with a previously determined patient
mallein using as a standard. When the local reactions produced by intradermo
palpebral infections of the two preparations are comparable the batch is passed for
issue.
4. Labelling and Storage- Should comply with the requirement of ‗Labelling‘ and
‗Storage‘ as laid down in the general monograph on ‗Diagnostic
Antigen‘.
5. Expiry Date- The date of expiry of potency shall be not more than two years from
the date of manufacture when stored at 2 ˚ C to 4 ˚ C.
Salmonella Abortus Equi ‘H’ Antigen
1. Synonym- Equine Abortion Diagnostic Antigen.
2. Definition- Salmonella Abortus Equi Antigen is suspension of a pure smooth
culture of actively motile Salmonella Abortus equi in formal saline.
Drugs and Cosmetics Rules 1945
389
3. Preparation- Standard strain of S.abortus equi is grown on nutrient agar in Roux
flasks at 37 ˚ C for twenty-four hours. The pure growth in Roux flasks is washed with
normal saline and diluted to contain approximately 800 million organisms per ml. Solution
of Formaldehyde I.P. is added to give a final concentration 0.5 per cent and the formolised
product is incubated at 37 ˚ C for twenty-four hours. The final product is dispensed in
suitable containers.
4. Standards:-
(a) Description- A slightly opalescent liquid containing dead bacteria in
suspension.
(b)
Identification- It gives specific agglutination when mixed with the serum of the
animals infected with S.abortus equi organisms.
(c) Sterility Test- Should comply with the test for sterility described in the general
monograph on ‗Diagnostics Antigens‘.
5. Labelling and storage- Should comply with the requirements of ‗Labelling‘ and
‗Storage‘ as laid down in the general monograph on ‗Diagnostic Antigens‘.
6. Expiry Date- The date of expiry of potency shall be not more than nine months from the
date of manufacture when stored at 2 ˚ C to 4 ˚ C.
Salmonella Pullorum Coloured Antigen
1. Synonym- Bacillary White Diarrhoes (B.W.D) Antigen.
2. Definition- The antigen is a suspension in a solution containing 1 per cent
Formaline, 1 per cent KH
2
PO
4
and 0.85 per cent Sodium Chloride of pure smooth culture of
standard strain of Salmonella Pullorum.
3 Preparation- Standard strain of S. Pullorum is grown on sulphur agar medium in
Roux flasks for five days at 37 ˚ C. The pure growth is washed with 1.0 per cent Formal
Saline.
Standardisation
The antigenic cell suspension is then centrifuged (preferably in cold centrifuge) for
half an hour at 4000 rotations per minute and the packed cell volume determined. The
packed cell is then re-suspended in a solution containing 1 per cent formalin, 1 per cent KH
2
PO
4
and 0.85 per cent sodium chloride, 1 ml. of packed cell is suspended in 10 ml. of the
resuspendiary solution, mixed thoroughly and is passed through a cotton wool pad. The
turbidity of the antigenic suspension is usually between 100 to 125 times Mac Farland scale
standard and optimum 3 cc. of a 1 per cent aqueous solution of crystal violet are added to
100 ml. of the antigenic suspension. After making the dye the antigen is allowed to stand
forty-eight hours before use. The average yield per Roux flasks of culture medium is about
50 ml. The antigen should be bottled in 10 ml. or 20 ml. quantity in amber-coloured bottles
and corked with rubber caps and paraffin sealed and preserved until required for use within
the expiry period. This antigen reacts instantly with the blood of all carrier birds and remains
permanently negative with that of non-infected birds.
This antigen gives good reactions with positive sera whose titre is even as low as 1 : 20.
4. Standard:-
(a) Description- Violet coloured liquid containing dead bacteria in
suspension.
(b) Identification- It gives specific agglutination when mixed with the serum of
birds in infected with S. Pullorum infection. It is used for carrying out plate agglutination
tests for serological diagnosis for S. Pullorum infection in birds.
(c) Sterility Test- Should comply with the test for sterility described in the general
monograph on ‗ Diagnostic Antigen‘. The tests shall be done before addition of ‗Crystal
Violet‘.
5. Labelling and Storage- Should comply with the requirements of ‗Labelling‘ and
‗Storage‘ as laid down in the general monograph 0n ‗Diagnostic Antigens‘.
Drugs and Cosmetics Rules 1945
390
6. Expiry Date- A six month expiration date for this antigen is recommended.
However, it is advisable to use fresh ones as far as possible. This antigen should be preserved at
4 ˚ C to 6 ˚ C in dark place in the refrigerator and should not be exposed to hot weather
condition for longer than necessary before use in the field.
Salmonella Pullorum Plain Antigen
1. Synonym- Bacillary White Diarrhoes (B.W.D) Plain Antigen.
2. Definition- The antigen is a suspension of pure smooth culture of Salmonella
pullorum in phenol saline.
3. Preparation- Forty-eight hours old pure culture of smooth strain of S. Pullorum is
washed with 0.5 percent phenol saline and the pooled suspension is adjusted to contain
approximately 800 million organisms per ml. by the addition of more carbol saline. The
suspension is kept at room temperature of twenty-four hours, and dispensed in suitable
containers.
4. Standard: -
(a) Description- An opalescent liquid containing dead bacteria in
suspension.
(b) Identification- It gives specific agglutination when mixed with the serum of
birds infected with S. Pullorum.
(c) Sterility Test- Should comply with the tests for sterility described in the general
monograph on ‗Diagnostic Antigen‘.
5. Labelling and Storage- Should comply with the requirments of ‗Labelling‘ and
‗Storage‘ as laid down in the general monograph on ‗Diagnostic Antigens‘.
6. Expiry Date- The date of expiry of potency shall be not more than nine months
from the date of manufacture when stored at 2 ˚ C to 4 ˚ C.
Tuberculin
1. Definitions:
(i) Tuberculins are preparations of fluid media on which Mycobacterium tuberculosis
has been grown in artificial culture and which has been freed by filtration from the bacilli.
(ii) For the purposes of the Schedule tuberculins are classified in (a) Tuberculin-
Subcutaneous (b) Heat Concentrated Synthetic Medium (H.C.S.M) Tuberculin (c) Avian
tuberculin.
2. Preparation:-
(a) Tuberculin subcutaneous- Flasks containing Henley and Dorset synthetic
medium are inoculated with standard human strains of Myco-Tuberculosis previously
grown on glycerol- beef broth medium for ten days. After ten to twelve weeks of
incubation at 37 ˚ C, flasks containing pure growth are steamed for three hours. The
contents are filtered through fine meshed sieve and the volume is made up to its
original with phenolised distilled water such that the final concentration of phenol is
0.5 per cent. It is then filtered through Seitz filter.
(b) Heat Concentrated Sythetic Medium (H.C.S.M) Tuberculin- To the strained
liquid obtained after sieving as in the method of preparation of Tuberculin
subcutaneous, glycerol is added in the proportion of 122 ml. per litre of the original
volume of medium used. The mixture is evaporated to one-fifth of the original
volume on a steam bath. An equal volume of 1 per cent phenol in distilled water is
added after the mixture is cooled. The product is stored at 47 ˚ C for fourteen days
before it is filtered through Seitz filter. It is then dispensed in ampoules.
(c) Avian Tuberculin Concentrated- The procedure is the same as for Tuberculin
Concentrated (H.C.S.M) except that standard strain of Myco-tuberculosis (Avian) is
used in its preparation.
Drugs and Cosmetics Rules 1945
391
3. Standard:-
(a) Description- A yellowish brown viscous liquid.
(b) Identification- When injected intradermally into the animal infected with
tuberculosis diffused swelling occurs depending upon the allergic status of the animal, the
magnitude of dose and specificity of the product. In non-infected animals this reaction is
not observed.
(c) Sterility Test- Should comply with the test for sterility described in the general
monograph on ‗Diagnostic Antigens‘.
(d) Potency Test- (i) Tuberculin subcutaneous-Six large white guinea-pigs each
weighing not less than 300-450 g. are individually inoculated intramuscularly with 0.5
mg. (Moist growth from solid plants) of Mycobacterium tuberculosis three weeks prior to
test of each batch of tuberculin; the following dilutions of (a) test tuberculin and (b)
standard tuberculin are used:-
1 in 200, 1 in 400, 1 in 800 and 1 in 1600.
The six sensitized guinea pigs are depilated on one flank and after about twenty-
four hours each animal inoculated intradermally with 0.2 ml. of each dilution of the two
tuberculins in two rows. The reactions are read after twenty-four and forty-eight hours.
When the local reactions produced by the graded inter-dermal injections of the two
preparations are comparable the brew is passed for issue.
(ii) Heat Concentrated Synthetic Medium (H.C.S.M) Tuberculin-Six adult white
guinea-pigs each weighing not less than 300-450 g. and sensitized three weeks
previously with 0.5 mg. (moist growth from solid plants) of Myco-Tuberculosis bovine
type, injected intramuscularly are used for test of each batch. The following dilutions of
(a) test tuberculin and (b) standard tuberculin are used: -
1 in 500, 1 in 1000, 1 in 2000 and 1 in 4000.
The six sensitized guinea pigs are depilated on one flank and after about twenty-
four hours each animal is inoculated intradermally with 0.2 ml. of each dilution of the
two tuberculins in two rows. The reactions are read after twenty-four and forty-eight
hours. When the local reactions produced by the graded inter-dermal injections of the
two preparations are comparable, the test tuberculin is passed for issue. The tuberculin is
dispensed in ampoules.
(iii) Avian Tuberculin- Six adults fowls, with well developed wattles, sensitized at
least three weeks previously by intramuscular injection with 10 mg. moist weight (from
solid plants) of twenty-one days old culture of Mycobacterium tuberculosis (Avian
Type) are used for potency test of each batch. In each fowl, one wattle is inoculated with
0.2 ml. of undiluted test tuberculin and the other wattle with similar quantity of undiluted
standard tuberculin. The reactions in each fowl are read after twenty-four hours and
forty-eight hours and if comparable the product is passed for issue.
4. Labelling and Storage- Should comply with the requirments of ‗Labelling‘ and
‗Storage‘ as laid down in the general monograph on ‗Diagnostic Antigens‘.
5. Expiry Date- The date of expiry of potency shall be not more two years months
from the date of manufacture when stored at 2 ˚ C to 4 ˚ C.
PART
IV
GENERAL
1. For the purpose of this Schedule any test or method of testing described in the
1
[British
Pharmacopoeia (Veterinary)] shall be deemed to be a method approved by the
Licensing Authority.
2. The Licensing Authority shall publish in the official Gazette from time to time
particulars of any test or method of testing approved by him.]
1. Subs. by G.S.R. 647(E) dated 28-10-1998.
Drugs and Cosmetics Rules 1945
392
Synonyms:
1
[SCHEDULE F (II)
(See Rule
124-C)
STANDARDS FOR SURGICAL
DRESSINGS
Bandage Cloth, Bleached Bandage Cloth, Rolled Bandage, Open Wove Bandage,
Cotton Bandage Cloth.
Bandage Cloth consists of cotton cloth of plain weave made from machine spun yarn
of suitable count to comply with a bleached count between 20 tex and 25 tex for warp and
between 25 tex and 30 tex for weft. The fabric contains no filling, sizing or dressing material.
It may be supplied uncut and folded or cut to suitable size and rolled.
Description for uncut bandages:
Uncut bandages are cotton cloth of plain weave, in one continuous length showing no
joints or seams, with well-formed selvedges. The cloth is bleached to a good white, is clean
and odourless and reasonably free from weaving defects and from seed and leaf debris.
Description for cut bandage:
Same as for uncut bandages, except for selvedges which shall not be included in cut
bandages. In addition, both the extremes and edges of cut bandages shall be straight and
evenly cut, with reasonable freedom and loose threads.
Threads per dm: – Warp not less than 150 and weft not less than 85.
Weight in g/m
2
: - 57 ± 5.
Length and Width: - The length and width shall not be less than 99 per cent each of
the length and width stated on the label. For cut bandages, each of the bandages in a packing
complies with this requirement.
Foreign matter: - Not more than 2 per cent.
Fluorescence:
When viewed under screened ultra-violet light, not more than occasional points of
fluorescence are observed.
Packing, Labelling and Storage:
Bandage Cloth shall be packed securely so as to allow normal handling and transport
without tearing and exposing the contents. In packages of cut and rolled bandages, each
bandage shall also individually be wrapped in a suitable paper. The net content is stated on
the label in terms of length and width. Bandage Cloth must be stored in packed condition
protected from dust. The packings of Bandage Cloth shall be labelled prominently with the
words ―Non-Sterile‖.
Absorbent Gauze.
Synonyms.- Gauze; Unmedicated Gauze; absorbent Cotton Gauze.
Absorbent Gauze is cotton fabric of plain weave, supplied in various widths and
lengths. The Gauze is bleached and free from any sizing, dressing or filling material. The yarn
used is machine spun cotton yarn, of suitable count to comply with a bleached count between
17 and 25 tex in the finished fabric.
1. Ins. by G.S.R. No.318(E), dt.. 1-5-1985.
Drugs and Cosmetics Rules 1945
393
Description:
Cotton cloth, plain weave, with a simple selvedge present on both sides to prevent
unravelling of yarn. The cloth is bleached to a good white, is clean, odourless, reasonably free
from fabric defects and adhering sand debris from cotton seeds and leaves, or any other
foreign matter.
Threads per dm:.- Warp not less than 75 and weft not less than 55.
Weight in g/m
2
: - 30 ± 5.
Length and widt:- Not less than 98 per cent each of the length and width stated on the
label.
Absorbency:- Average sinking time not more than 10 seconds.
Fluorescence:- When viewed under screened ultra-violet light not more than
occasional points of fluorescence are observed.
Foreign matter:- Not more than 1 per cent.
Sterility:- If sterile, the contents comply with the test for sterility.
Packing, Labelling and Storage:
Absorbent Gauze is folded and packed with such materials and so securely as to
protect its absorbency and allow normal handling and transport without tearing and exposing
the contents. The net content is stated on the label in terms of length and width. The packages
shall be labelled prominently with the words ―Non-Sterile‖. If sterile, it shall be so stated on
the label, and the packing method and material shall be such as to maintain the sterility. The
Absorbent Gauze must also comply with the Sterility Test. Absorbent Gauze must be stored
in packed conditions protected from moisture and dust.
Defect in fabric:.
METHODS OF TEST
The sample is unfolded, opened and held against diffused daylight or spread on black
topped table to locate and identify prominently visible defects in yarn and fabric construction.
The fabric shall be reasonably free from holes, slubs, snarls and naps as well as the following:
-
Odour.- Misty odour, or any objectionable smell like that of chemicals or materials
used in sizing and bleaching.
Skewness.- (For Bandage Cloth only) A condition where warp and weft do not keep
at right angles to each other.
Defective Selvedge. - The selvedge tearing and allowing yarn to unravel and loop
formation at selvedge.
Cracks.- Prominent steaks of space or gaps between warp or weft yarns.
Double ends.- More warp threads woven as one, due to wrong draw.
Sloughing.- Entanglement in the fabric of a bulk of yarn that has slipped off the weft
yarn due to loose widing.
Measurement of length and width.
Length is the distance from end to end, along one edge of the fabric, and width is the
perpendicular distance from one edge to the opposite edge.
Length. - Fix a meter scale to a table or mark off the division of one metre on a table
edge. Starting from one end, spread the fabric flat on that table in a single layer keeping one
Drugs and Cosmetics Rules 1945
394
selvedge parallel to the scale; smoothen the fabric without stretching it, to avoid creases, and
mark off with a coloured pencil, on the selvedge exactly one metre. Shift the fabric and
measure the same way the second metre and so on for the entire length of the fabric making a
mark at each metre. Note down the total length in metres. Repeat this at the opposite
selvedge, as well as on the fabric folded approximately about the middle. The average of the
three readings is the length. For cut bandages, one measurement at the middle of the bandages
by folding it length-wise will suffice.
Width. - Lay the portion of the fabric to be measured flat and smooth on the tables,
but do not stretch fabric except sufficiently to render it creaseless. At the place where mark
had been made on the selvedge in measuring the length measure the perpendicular distance to
the opposite selvedge with a metre scale. Note the width, repeat this at every mark made in
measuring the length. The average of all the readings is the width of the fabric. For cut
bandages, width shall be measured at every 50 cms., and average reported as width.
Threads per dm.- (For examples not less than 15 m. in length).
Weft. - At the third metre from one extreme locate three places one at about 5 cm.
below the top selvedge, a second in the middle and third at about 5 cm. below the top
selvedge, a second in the middle and third about 5 cm. above the bottom selvedge, all three
in
a vertical row. Take a rectangular plate (made of suitable material such as plastic or
aluminium) with the rectangular opening of 5 cm. x 10 cm. cut in it. Keep the plate on the
fabric horizontally so that the left 5 cm. side and bottom (10 cm. side) edges of the opening
coincides with a weft and warp yarns respectively; count the number of weft yarns within the
opening for the length of 10 cm.. Repeat this at the other two selected places, and note down
the average of three readings. Repeat this at every third metre in the sample and calculate the
average weft per dm.
Warp.- Keep the rectangular plate, this time vertically with left (10 cm. side) and
bottom (5 cm. side) edge of opening coinciding with a weft and warp yarn respectively. Count
the number of warp yarns within the opening for 10 cm. and note down. Repeat this for about
10 selected places in the samples taking care that the same set of warp yarns is not counted
more than twice and calculate the average warp per dm. Magnifying glass mounted on stand
may be used for counting.
For samples less than 15 m. in length, locate as many different places as the
dimension of the fabric permits, the total being not less than 10 for each sample and calculate
the warp and weft per dm. as above.
For cut bandages, all the warp threads in the samples are counted, taking care to leave
5 mm at the cut edge, and weft is counted at every 50 cm. at any place about the middle of the
bandage.
Weight per unit area.
For samples not less than 15 m. in length, cut out pieces of fabric from the entire
length of sample, representative places being taken from areas at every third or fourth metre
so that the total area of all the pieces so collected is not less than 3 sq. metre. Weigh the
pieces accurately, measure the dimension of each of the pieces and calculate the area and
weight of all the pieces. From the average area and average of weight thus obtained, calculate
the area per sq. metre.
For samples less than 15 m. length, take pieces in such a manner that the total area of
the selected pieces is not less than 20 per cent of the total area of the sample.
For cut bandages, pieces of 50 cm. in length, cut from 5 different cut bandages in a
packing should be taken and weight calculated as an average of 5 readings.
Absorbency. - Take a glass trough of approximate size length 30 cm. x width 30 cm. x
depth 25 cm. with straight thick walls and flat bottom. Fill it almost full with distilled water
leaving only about 5 cm. from the top rim of trough. Maintain the water at 27
o
C ± 1
o
C.
Drugs and Cosmetics Rules 1945
395
Cut out from any five places located equidistant down the length of the entire sample,
square pieces, each weighting one gm. (±10 per cent). Fold each piece in such a manner that a
square of approximately 5 cm. x 5 cm. is obtained. Keep one of the folded test specimen
between two glass plates and place 1 kg weight on the top for 10 minutes. Remove the
weight. Lift the specimen with forceps and gently place it on to the surface of water (the
specimen should be lightly pinched in the middle with a blunt forceps having no serrations).
As soon as the specimen touches the water surface start a stopwatch which is stopped when
the entire sample disappears below the surface of the water. Record the time taken. Repeat the
test with the other four-test specimens. Calculate the average time in seconds.
Foreign Matter
Dry about 5 g. of the sample to constant weight at 105
o
C and weigh the dried sample
accurately. Extract the dried sample with chloroform for one hour in an apparatus for the
continuous extraction of drugs. Remove the extracted sample to a beaker and allow the
evaporation of residual chloroform. Wash the material 12 times with hot water, using about
1000 ml. for each washing and wringing the material by hand after each washing; pass all
water through a fine sieve (100 mesh). Place the washed material and any loose threads or
fibres from sieve in a beaker, cover with a 0.5 per cent aqueous solution of diastase and
maintain at 50
o
C until free from starch. Allow to cool, filter the solution through a sieve;
return sample and loose fibre to a beaker. Repeat the washing process as before with hot
water. Dry the material to constant weight at 105
o
C, and determine the loss in weight.
Calculate the percentage of foreign matter, which is equal to the loss in weight, with reference
to the sample dried to constant weight, at 105
o
C.
If the sample is tested with iodine and is known to be free from starch, the treatment
with solution of diastase and the second series of washing with hot water may be omitted.
Cloth for manufacture of Plaster of Paris Bandages, cut and uncut.
Synonyms.- Bleached Bandage Cloth for Plaster of Paris, Rolled Bandage for Plaster
of Paris.
Cloth for Plaster of Paris Bandages shall consist of cotton cloth of leno weave made
from yarn of suitable count. It may be supplied cut or uncut of various widths and lengths.
Description
(a) For uncut bandages.- Cotton cloth of leno weave, in one continuous length
showing no joints or seams, and with selvedges. The cloth is bleached to a good white, is
clean and odourless and reasonably free from weaving defects as well as from seed and leaf
debris; the cloth may be dressed if necessary and if so, shall not dust off when unrolled.
(b) For cut bandages. - Same as for uncut bandages except for selvedges which shall
not be included and the bandages shall be cut evenly with straight edges and be reasonably
free from loose threads.
Threads per dm:
Warp. - Average not less than 150/dm; and Weft.- average not less than 75/dm.
Weight in gm/m
2
: - 35 ± 5
Length and width:
The length and width for uncut bandages shall not be less than 98 per cent each of the
length and width stated. For cut bandages a tolerance of ±5 cm. in length and ±0.5 cm. in
width may be allowed, and each of the bandages in packing complies with these requirements.
Fluorescene
When viewed under screened ultra-violet light not more than occasional points of
fluorescence are observed.
Drugs and Cosmetics Rules 1945
396
Packing, Labelling and Storage
Bandage Cloth for Plaster of Paris shall be packed securely so as to allow normal
handling and transport without tearing and exposing the contents. In packages of cut and
rolled bandages, each bandage shall also individually be warpped in suitable paper. The
package shall be labelled as ―Cloth for Plaster of Paris Bandage‖. The net content is stated on
the label in terms of number of rolls and length and width. Bandage Cloth for Plaster of Paris
must be stored in packed condition protected from dust.
1
[SCHEDULE F (III)
(See rule 124-D)
STANDARDS
FOR
UMBILICAL
TAPES
(A) Standards for Sterilised Umbilical Polyster Tape.
Description. - A uniform strand of Polyester yarn prepared by braiding and may be
finished with a suitable silicone finishing material, white to yellowish-white in colour. Tape
shall be sterilized by Gamma Radiation or other suitable method approved by the Licensing
Authority.
Other requirements. - The Umbilical Polyester Tape shall conform to the claims
made on the label in respect of length and width.
Tensile strength. - The Umbilical Polyester Tape shall have Tensile strength of not
less than 4 kg. on straight pull.
Packing and labelling. - The Umbilical Polyester Tape shall be packed in sealed
Polythene bags or sealed plastic containers which ensure that when packed, the tape is sterile.
The packing shall protect the tape from contamination and damage. Every packing offered for
sale shall bear a clear and permanent marking with the following particulars: -
(i) The proper name of the drug i.e. Umbilical Polyester Tape ‗Sterile‘
(ii) Manufacturer‘s name and address.
(iii) Batch number.
(iv) Licence number under which the tape is manufactured.
(v) Date of manufacture and date of expiry.
(vi) Length and width of the Tape.
Storage condition. - It should be stored in a cool place protected from
light.
(B) Standards for Sterilised Umbilical Cotton Tape–
Description. - A uniform strand of cotton yarn prepared by braiding and may be
finished with a suitable silicone finishing material, white to yellowish-white in colour. The
tape shall be sterilized by Gamma Radiation or by any other suitable method approved by the
Licesing Authority.
Other Requirement. - The Umbilical Cotton Tape shall conform to the claims made
on the label in respect of length and width.
Tensile strength. - The Umbilical Cotton Tape shall have a Tensile strength of not
less than 4 kg. on straight pull.
Packing and labelling. - The Umbilical Cotton Tape shall be packed in sealed
Polythene bags or sealed plastic containers which ensure that when packed the tape is sterile.
The packing shall protect the tape from contamination and damage. Every packing offered for
sale shall bear a clear and permanent marking with the following particulars:-
(i) The proper name of drug i.e. Umbilical Cotton Tape ―Sterile‖.
(ii) Manufacturer‘s name and address.
1. Ins. by G.S.R. No.1115(E), dt.. 30-9-1986.
Drugs and Cosmetics Rules 1945
397
(iii) Batch number.
(iv) Licence number under which the tape is manufactured.
(v) Date of manufacture and the date of expiry.
(vi) Length and width of the Tape.
Storage condition.- It should be stored in a cool place protected from light.]
1
[SCHEDULE FF
( See rule
126-A)
Standards for ophthalmic preparations.
Part-A. Ophthalmic Solutions and suspensions.
Ophthalmic Solutions and Suspensions
shall-
(a) be sterile when dispensed or when sold in the unopened container of the
manufacturer, except in case of those ophthalmic solutions and
suspensions which are not specifically required to comply with the test for
‗Sterility‘ in the Pharmacopoeia;
(b) contain one or more of the following suitable substances to prevent the
growth of micro-organisms:-
(i) Benzalkonium Chloride, 0.01 per cent (This should not be used in
solutions of nitrates or salicylates).
(ii) Phenyl mercuric nitrate, 0.001 per cent.
(iii) Chlorbutanol 0.5 per cent.
(iv) Phenyl ethyl alcohol 0.5 per cent.
Provided that solutions used in surgery shall not have any preservative and be packed in
single dose container.
Provided further that the Licensing Authority may in his discretion authorise the use of
any other preservative or vary the concentration prescribed on being satisfied that its use affords
equal guarantee for preventing the growth of micro-organisms:-
(c) be free from foreign
m
atter;
(d) be contained in bottles made of either neutral glass or soda glass specially
treated to reduce the amount of alkali released when in contact of aqueous
liquids, or in suitable plastic containers which would not in any way be
incompatible with the solutions;
The droppers to be supplied with the containers of ophthalmic solutions and
suspensions shall be made of neutral glass or of suitable plastic material
and when supplied separately shall be packed in sterile cellophane, or other
suitable packings;
(e ) In addition to complying with the provisions of labelling laid down in the rules
the following particulars shall also be shown on the label:-
1. Added by Notification No. F-1-13/69-D , dt.. 3-1-1970.
Drugs and Cosmetics Rules 1945
398
(1) of the containers
(i) The statement ‗Use the solution within one month after opening the
container‘.
(ii) Name and concentration of the preservative, if used.
(iii) The words ‗NOT FOR INJECTION‘.
(2) of container or carton or package leaflet
(i)
Special instructions regarding storage, wherever applicable.
(ii) A cautionary legend reading as
―WARNING (i) if irritation persists or increases, discontinue
the use and consult the phycian.
(ii) Do not touch the dropper tip or other
dispensing tip to any surface since this may
contaminate solutions‖.
Part B: Ophthalmic Ointments
Ophthalmic Ointments shall-
(a) be sterile when dispensed or when sold in the unopened container of the
manufacturer;
(b) be free from foreign matter;
(c) in addition to complying with the provisions for labelling laid down in the
rules the following particulars shall be shown on the container or carton or
package leaflet-
(i) Special instructions regarding storage wherever applicable;
(ii) A cautionary legend reading
―Warning :- If irritation persists or increases discontinue the use and
consult Physicians‖].
Drugs and Cosmetics Rules 1945
399
Aminopterin
L-Asparaginase
Bleomycin
Busulphan; its salts
Carbutamide
Chlorambucil;its salts
1
[SCHEDULE G]
(See Rule
97)
Chlorothiazide and other derivatives of 1, 2, 4 benzothiadiazine
Chlorpropamide; its salts
Chlorthalidone and other derivatives of Chlorobenzene compound.
2
[(Cis-Platin)]
Cyclophosphamide; its salts
2
[(Cytarabine)]
Daunorubicin
Di-Isopropyl Eluorophosphate
Disodium Stilboestrol Diphosphate
Doxorubicin Hydrochloride
Ethacrynic Acid, its salts
Ethosuximide
Glibenclamide
Hydantoin; its salts; its derivatives, their salts
Hydroxyurea
Insulin, all types
2
[(Lomustine Hydrochloride)]
Mannomustine; its salts
Mercaptopurine; its salts
Metformin; its salts
Methsuximide
Mustine, its salts
Paramethadione
Phenacemide
Phenformin; its salts
5-Phenylhydantoin; its alkyl and aryl derivatives; its salts
Primadone
1
[(Procarpazine Hydrochloride])
1. Subs.. by G.S.R. No.462(E) , dt. 22-6-1982 (w.e.f. 22.6.1982).
2. Ins. by G.S.R. No.626(E) , dt. 2-7-1987 w.e.f. 2-7-1987.
Drugs and Cosmetics Rules 1945
400
Quinthazone
Sarcolysine
1
[(Sodium-2-Mercaptoethanesulfonate]
Tamoxiten Citrate
Testolactone
Thiotepa Tolbutamide
Tretamine; its salts
Troxidone
Antihistaminic substances the following, their salts, their derivatives,
salts of their derivatives
Antazoline
Bromodiphenhydramine
Buclizine
Chlorcyclizine
Chlorpheniramine Clemizole
Cyproheptadine
Diphenhydramine
Diphenylpyraline Doxylamine
Succinate Isothipendyl
Mebhydrolin Napadisylate
Meclozine
Phenindamine
Pheniramine
Promethazine
Thenalidine
Triprolidine
Substances being tetra-N-Subs. derivatives of Ethylene Diamine or Prophylenediamine.
Note . – Preparations containing the above substances excluding those intended for topical or external
use are also covered by this Schedule.]
1. Subs.. by G.S.R. No.462(E) , dt. 22-6-1982 (w.e.f. 22.6.1982).
Drugs and Cosmetics Rules 1945
401
1. Subs. by G.S.R. No.160(E), dated 16.3.2006 .
2. Omitted by G.S.R 588(E) dated 30-8-2013
3. Omitted by G.S.R 602(E) dated 19-7-2010
4. Omitted by G.S.R 724(E) dated 7-11-2013
1. Abacavir
2.
A
b
c
i
xi
m
a
b
3.
Acamprosate
calcium
4. Ac
eb
uto
l
h
y
dr
och
lor
ide
5. Ac
l
ar
ub
i
c
in
6. Albendazole
1
[
S
C
H
EDU
L
E - H
(Se
e
Rules 65 and
97)
P
RE
S
CR
I
P
T
I
ON DRUG
S
38.
A
rt
esu
n
a
t
e
39.
Articaine
hydrochloride
40.
Ate
no
lo
l
41.
Atracurium besylate in
j
ectio
n
42.
A
tor
v
a
st
a
ti
n
43. Auranofin
7.
Alclometasone
dipr
o
pio
n
at
e
8.
A
c
t
il
y
s
e
9.
A
c
y
c
l
ov
i
r
10.
A
d
en
o
s
i
n
e
11.
Adrenocorticotrophic
ho
r
m
on
e
(ac
t
h
)
12.
Alendronate
sodium
13.
Alo
pu
rin
o
l
14.
Al
ph
a
c
h
y
m
o
try
ps
in
15.
2
[
A
l
p
raz
o
l
a
m
16.
Alpr
o
s
ta
dil
17.
Amantadine
hydrochloride
18.
Amif
o
stin
e
19.
Amikacin
sulphat
e
20. Am
il
o
rid
e
hy
dr
o
c
h
l
o
r
i
de
21. Amin
e
ptin
e
22.
A
min
o
gl
u
te
thi
m
id
e
23.
Amino
sa
li
c
y
li
c
a
c
id
24.
Amiodarone
hydrochloride
25.
A
mitr
i
p
ty
l
ine
26.
Amlodipine
be
sy
l
at
e
27.
A
mosc
a
n
at
e
28. Am
o
x
o
pi
n
e
29. Amrin
on
e
l
acta
te
30.
A
n
a
l
gi
n
31.
Androgenic anabolic,
o
e
st
r
o
gen
ic
&
progestational
subs
ta
n
c
e
s
32. An
ti
b
i
o
tic
s
33. Apr
aclon
idi
n
e
34. Aprotinin
35.
Organic compound
of
ar
sen
ic
36.
Ar
teeth
e
r
37.
Ar
t
e
meth
e
r
44. Az
at
h
i
o
pr
i
n
e
45.
A
ztr
e
o
nam
46. B
a
c
a
m
p
i
c
illi
n
47. B
a
c
lo
f
e
n
48. B
als
a
l
azid
e
49. B
a
mb
utero
l
50. B
a
r
b
i
tu
ric acid
51. B
a
s
ili
x
i
m
a
b
52. B
e
n
aze
pr
il
hy
dro
c
h
l
o
r
i
de
53. B
e
n
i
dipi
n
e
hydrochloride
54.
Benserazide
hydrochloride
55.
Betahistine dih
y
dr
o
c
h
l
o
r
ide
56.
Bethanidine
sul
ph
at
e
57. B
e
zaf
ibr
a
te
58. Bic
a
l
ut
a
m
id
e
59. Bicloty
mo
l
monohydrate
/l
actat
e
60. B
i
f
on
a
zo
le
61. Bimatoprost
62.
Biperiden
hydrochloride
63. B
iph
e
n
y
l
a
c
e
ti
c
acid
64. B
i
tosca
n
at
e
65. B
l
e
o
my
c
in
66.
P
r
i
m
o
nid
i
n
e
tartrate
67.
Bromhexine
h
y
dro
c
lor
i
de
68.
Bromocriptine
mesylate
69.
Bu
des
on
i
d
e
70. B
ulaquin
e
71.
Bupivacaine
hydrochloride
72. Bupropion
73. B
u
spi
r
on
e
74.
Butenafine
hydrochloride
75. B
uto
r
ph
an
o
l
ta
rtr
at
e
Drugs and Cosmetics Rules 1945
402
1. Subs. by G.S.R. No.160(E), dated 16.3.2006 .
2. Omitted by G.S.R 588(E) dated 30-8-2013
3. Omitted by G.S.R 602(E) dated 19-7-2010
4. Omitted by G.S.R 724(E) dated 7-11-2013
76.
Cab
e
r
go
l
in
e
77.
Calcium
dob
e
sil
at
e
78. Candesartan
79.
Capec
it
ab
in
e
80. Captopril
81. Carbidopa
82.
Carbo
c
i
ste
in
e
83. Carboplatin
84.
C
ar
boquon
e
85.
Car
isopr
odo
l
86.
L
-
c
a
rni
tine
87.
Car
teo
lo
l
hydrochloride
88.
Carv
e
dilo
l
89.
C
e
f
ad
r
o
xy
l
90.
C
e
f
ato
x
i
me
s
od
iu
m
91.
Ce
f
a
zo
l
in sodium
92.
2
[
C
e
f
d
i
n
i
r
93.
Ce
f
e
pim
e
hydrochloride
94.
C
e
f
e
t
ame
t piv
o
xi
l
95.
C
e
f
p
i
rom
e
96.
C
e
f
podo
x
i
m
e
po
x
e
t
il
97.
Ce
f
taz
idi
m
e
pe
n
ta
hy
dr
a
te
98.
C
e
f
t
izo
x
i
m
e
so
d
i
u
m]
99.
C
e
f
u
ro
x
i
m
e
100.
C
e
l
e
c
o
xib
101. Centchroman
102. Centbutindole
103.
Ce
n
tpro
pazin
e
104.
Ce
tir
i
zin
e
hy
d
r
o
c
hlo
r
i
de
105.
2
[
C
h
l
o
rdi
a
z
e
po
xid
e
106.
C
hlorm
e
z
a
no
ne
107.
3
[
* * *]
108.
C
hl
o
rprom
a
z
i
ne
109.
C
hl
o
rz
o
x
a
z
o
ne
110.
C
i
c
l
op
i
ro
x
o
l
a
m
i
ne
111.
C
i
m
e
t
i
d
i
ne
112.
C
i
nna
ri
z
i
ne
113.
Ciprofloxacin
h
y
d
r
o
c
hlo
r
i
de
114. Cisplatin
115.
Citalopram
hydrobromide
116.
C
l
a
ri
t
h
rom
y
c
i
n
117. Cl
avu
lan
ic acid
118.
C
li
d
i
ni
u
m
b
rom
i
d
e
119.
C
li
ndamy
c
i
n
120.
C
l
ob
a
z
a
m
121.
Clob
e
ta
s
o
l
p
r
o
pe
n
at
e
122.
Clobetasone
17-buty
r
at
e
123.
2
[
C
l
o
f
a
z
i
m
i
ne]
124. Cl
o
f
i
b
r
a
te
125.
C
l
o
naze
p
a
m
126.
Clo
n
idi
n
e
hydrochloride
127.
C
l
op
a
m
id
e
128.
Clo
pidogr
e
l
b
isulph
at
e
129. Cl
o
s
te
b
ola
cet
a
te
130.
C
l
o
t
ri
m
a
z
o
l
e
131. Clozapine
132.
2
[
Co
d
e
in
e]
133.
Co
lc
h
i
c
i
n
e
134.
Cor
ti
co
st
e
r
o
i
ds
135.
C
o
t
ri
m
o
x
a
z
o
l
e
136. Cyclandelate
137.
C
ycl
osp
o
rin
s
138. D
a
c
li
z
u
m
a
b
139. D
a
nazo
l
e
140. D
ap
s
on
e
141.
De
slo
r
at
adi
n
e
142. D
esog
es
trol
143. D
e
x
raz
o
x
a
ne
144. D
e
xt
ra
no
m
e
r
145.
2
[
* * *]
146.
De
xtr
o
pr
opo
xy
ph
e
n
e
147.
2
[D
i
a
z
e
p
a
m]
148. D
i
a
z
o
x
i
d
e
149. Dic
l
o
f
e
n
ac
s
o
dium
/pot
assium/
acid
150.
Dicyclomin
hydrochloride
151. Did
an
o
s
in
e
152. D
i
go
x
i
ne
153.
Dilazep
hydrochloride
154. D
il
t
i
a
z
e
m
155. Din
op
r
ost
on
e
156.
2
[
Diphenoxylate,
it
s
salt
s]
157. Dip
iv
e
f
rin hydrochloride
158. Di-sodiumpamidronate
159. Disopyramide
160.
Do
c
e
taxe
l
161.
Do
m
pe
rid
on
e
162.
Do
n
e
pe
zi
l
hydrochloride
163.
Do
pam
i
n
e
hydrochloride
164.
Dothiepin
hydrochloride
165.
Doxapram
hy
d
r
o
c
h
lor
i
de
166.
Doxazosin
mes
y
l
at
e
167.
Doxepin
hydrochloride
Drugs and Cosmetics Rules 1945
403
1. Subs. by G.S.R. No.160(E), dated 16.3.2006 .
2. Omitted by G.S.R 588(E) dated 30-8-2013
3. Omitted by G.S.R 602(E) dated 19-7-2010
4. Omitted by G.S.R 724(E) dated 7-11-2013
168.
Doxorubicin
hydrochloride
169.
Dro
tr
e
c
o
gi
n
-alph
a
170.
Eb
as
ti
n
e
171. Econozole
172.
E
f
a
v
i
re
nz
173.
E
na
l
a
p
ri
l
m
e
l
ea
t
e
174.
E
n
f
e
na
mic
a
c
i
d
175.
E
pi
n
e
ph
rine
176. Epirubicine
177.
Ep
ti
f
ib
at
i
de
178.
Ergot, alkaloids
of w
h
e
th
e
r
hydrogenated
or
not, t
h
e
ir
homologoues,
sa
lt
s
179.
E
so
meprazo
l
e
180.
Estr
a
dio
l
suc
ci
n
at
e
181.
Est
r
am
us
ti
n
e
pho
sph
at
e
182.
Et
an
e
r
c
e
pt
183.
Ethacridine
lactate
184.
2
[
Et
h
am
b
uto
l
hydrochloride]
185.
Et
hamsy
l
at
e
186.
Et
h
i
n
ylo
e
stradio
l
187.
2
[
E
t
h
i
o
na
mid
e]
188.
Et
i
dr
on
ate
disodium
189. Etodolac
190. Etomidate
191.
Etoposi
d
e
192.
E
xe
m
e
s
t
ane
193.
F
a
mc
i
c
l
o
v
i
r
194.
Fa
mo
tidi
n
e
195.
Fe
nb
e
n
daz
o
le
196.
Fe
no
f
ibr
at
e
197.
Fe
x
o
f
e
n
ad
in
e
198. Finasteride
199.
Flavoxate
hydrochloride
200.
5
-f
lu
o
r
ou
r
a
c
il
201.
Flu
dar
ab
in
e
202.
Flufenamic
acids
203.
F
lu
n
a
r
i
z
ine
hd
r
o
c
h
l
o
rid
e
204.
Fluo
xe
ti
n
e
ydrochloride
205.
F
lu
p
e
nthixo
l
206.
Fluphenazine enanthate
and
d
ec
a
n
oa
t
e
207.
F
l
u
raz
e
p
a
m
208. Fl
ur
b
i
pr
o
f
e
n
209.
F
lut
amid
e
210.
Fluticasone
pr
o
pio
n
at
e
211.
F
luv
oxa
m
i
n
e
mal
e
ate
212.
Fo
r
me
stan
e
213.
Fo
s
f
e
str
il
sodium
214.
Fosinopril
sodium
215.
Fossphenytoin
sodium
216.
Fo
t
e
must
in
e
217.
Gab
ap
e
n
ti
n
218.
Galanthamine
hydrobromide
219.
Galamine,
it
s
salts,
it
s
quate
r
n
ar
y compound
220. Gancyclovir
221.
G
a
n
i
r
e
li
x
222.
G
a
t
i
f
l
o
x
a
c
i
n
223.
G
e
mc
i
t
a
b
i
ne
224.
G
e
m
f
i
b
ro
z
il
225.
G
e
m
t
u
z
u
m
a
b
226.
Ge
no
de
o
xy
c
ho
li
c
acid
227.
G
li
c
l
a
z
i
d
e
228.
G
li
m
e
p
i
r
i
d
e
229.
G
lu
c
a
gon
230. Glycopyrrolate
231.
G
l
y
d
i
a
z
i
na
m
i
d
e
232.
Go
se
r
e
li
n
ace
tate
233. Granisetron
234.
Gu
an
e
thidi
n
e
235. Gugulipid
236.
Halogenated
h
y
dr
oxyqui
no
li
n
e
s
237. H
alo
pe
r
i
do
l
238. H
e
p
arin
239.
Hepatitis b.
V
acc
in
e
240. Hy
al
u
r
on
ida
se
241.
Hydrocorisone 17-
b
uty
r
at
e
242. Hy
d
r
o
ta
lc
it
e
243. Hy
dro
x
i
zine
244. Ibuprofen
245.
I
d
ebe
non
e
246.
Indap
am
i
de
247.
I
m
i
p
ra
m
i
n
e
248.
Indinavir
sulph
at
e
249. In
dometh
a
c
in
250.
Insulin
human
251. In
ter
f
e
r
on
252.
Intravenous
fat emulsion
253. Io
b
it
r
i
do
l
254.
I
o
he
x
o
l
255. Io
pa
mi
do
l
256.
I
o
m
e
p
ro
l
257. Iopromide
258. Irbesartan
259.
Irinotecan
hydrochloride
Drugs and Cosmetics Rules 1945
404
1. Subs. by G.S.R. No.160(E), dated 16.3.2006 .
2. Omitted by G.S.R 588(E) dated 30-8-2013
3. Omitted by G.S.R 602(E) dated 19-7-2010
4. Omitted by G.S.R 724(E) dated 7-11-2013
260.
Iron preparation
for
parenteral use
261.
Is
e
pa
mi
c
i
n
e
262.
Is
o
c
a
r
b
oxsi
de
263.
Isof
lur
an
e
264.
Isonicotnic acid hydrazine
and
other-hydragine derivatives
of
isonicotinic
acid
265.
Isosorbide dinitrate/
mo
non
it
r
at
e
266.
Isotr
e
ti
no
in
267.
Iso
xsu
pr
in
e
268.
It
o
pr
i
de
269.
4
[
***]
270. Ketoconazole
271.
K
e
t
op
rof
en
272.
Ketorolactromethamine
273.
L
ab
e
ta
lo
l
hydrochloride
274. Lacidipine
275. Lamivudine
276.
L
a
m
o
tr
i
g
i
ne
277.
L
a
ta
n
opr
o
s
t
278.
L
e
f
uno
mide
279.
Lercanidipine
h
y
dr
o
c
h
l
o
r
ide
280.
L
e
tro
zo
le
281.
L
e
upr
o
li
de
ac
e
tate
282.
L
e
v
am
e
so
le
283.
L
e
v
ar
t
e
r
e
no
l
284. Levobunolol
285.
L
e
v
o
c
e
t
iri
z
ine
286.
Levod
op
a
287.
2
[
L
e
v
o
f
lo
xac
in]
288. Levovist
289.
L
i
do
f
laz
i
ne
290.
L
i
ne
z
p
li
d
291.
L
i
th
i
um
car
bon
a
te
292.
L
o
f
e
pr
am
in
e
de
c
an
o
at
e
293.
L
op
e
ramid
e
294.
L
o
raz
e
p
a
m
295.
Losartan
potassium
296.
L
o
t
e
pr
e
dno
l
297.
L
ov
a
st
at
in
298.
L
o
x
a
p
i
ne
299.
Meb
enda
zol
e
300.
Mebeverine
hydrochloride
301.
Medroxyprogesterone
ace
t
at
e
302.
Me
f
e
n
am
ic acid
303.
Mefloquine
hydrochloride
304.
Me
g
e
stro
l
ace
t
at
e
305.
Meglumine
i
o
c
arm
a
te
306.
Me
la
ge
n
in
a
307.
Elit
r
ac
e
n
hy
d
r
o
c
h
lor
i
de
308.
M
e
l
o
x
i
c
a
m
309.
Mephenesin,
it
s
e
st
e
r
s
310.
Me
ph
e
n
termin
e
311.
2
[Meropenam]
312.
M
est
er
olon
e
313.
Me
ta
x
al
on
e
314. Methicillin sodium
315.
Me
th
o
c
a
r
b
am
o
l
316. Methotraxate
317. Metoclopramide
318.
Me
to
p
r
o
lo
l
tartrate
319.
M
e
t
ri
z
a
m
i
d
e
320. Metronidazole
321.
Mexiletine
h
y
d
r
o
c
hlo
r
i
de
322.
Mianserin
hydrochloride
323. Miconazole
324.
2
[
M
i
d
a
z
o
l
a
m]
325.
Mi
f
e
priston
e
326.
Mi
lr
ino
n
e
la
c
t
at
e
327.
Mil
tef
o
s
in
e
328.
Mi
no
c
y
c
li
n
e
329.
M
i
no
x
i
d
il
330.
Mirt
a
z
ap
ine
331.
M
i
sop
r
ost
ol
332.
Mitoxantrone
hydrochloride
333.
Miz
o
la
st
in
e
334. Mocl
ob
e
mide
335.
Mometasone
f
ur
oat
e
336.
Montelukast
sodium
337.
Morphazinamide
hydrochloride
338.
M
o
s
ap
rid
e
339.
2
[
M
o
x
i
f
l
o
x
a
c
i
n]
340.
Mycophenolate mo
f
et
il
341. N
a
d
i
f
lox
a
c
i
n
342. N
ad
o
l
o
l
343.
Nafarelin
ace
t
at
e
344. N
a
li
d
i
x
i
c
a
c
i
d
345. N
a
p
ro
x
e
n
346.
Narcotics
drugs
l
isted
in Narcotic
Drugs
&
Psychotropic
Su
b
stan
c
e
s
Act,
1985
Drugs and Cosmetics Rules 1945
405
1. Subs. by G.S.R. No.160(E), dated 16.3.2006 .
2. Omitted by G.S.R 588(E) dated 30-8-2013
3. Omitted by G.S.R 602(E) dated 19-7-2010
4. Omitted by G.S.R 724(E) dated 7-11-2013
347. Natamycin
348.
Na
teg
li
n
i
de
349. N-butyl-2-cyanoacrylate
350.
Ne
biv
o
l
o
l
351.
Nebu
me
ton
e
352. N
e
l
f
inav
i
r
m
e
si
l
ate
353.
Netilmicin
su
lp
h
a
te
354.
Ne
v
ira
pi
n
e
355.
Ni
c
e
r
go
lin
e
356. Nic
o
r
a
ndi
l
357.
Ni
f
e
dipi
n
e
358. N
ime
s
ulid
e
359.
Nimustine
hydrochloride
360.
2
[N
i
t
raz
e
p
a
m]
361.
Ni
tr
o
gly
c
e
rin
362.
No
r
e
th
i
ste
r
on
e
e
n
an
th
at
e
363. N
o
r
f
l
o
x
ac
i
n
364.
Octylonium
bromide
365.
O
f
l
o
x
a
c
i
n
366. Olanzapine
367.
Om
e
p
r
a
z
o
l
e
368.
Orn
i
d
a
zo
l
e
369.
Orph
e
n
a
dr
i
n
e
370.
Orthoclone
ste
r
il
e
371.
O
x
a
z
e
p
a
m
372.
O
x
a
z
o
li
d
i
ne
373.
O
xc
a
r
b
a
ze
p
ine
374.
Oxe
th
az
a
in
e
hydrochloride
375.
O
xic
o
na
zo
l
e
376.
O
x
o
li
nic
a
c
i
d
377.
Ox
pr
e
no
lo
l
h
y
d
r
o
c
hlo
r
i
de
378.
Oxybutynin
chloride
379.
O
xy
f
e
drine
380.
O
xy
m
e
t
azo
li
ne
381.
Oxy
ph
e
nb
uta
zon
e
382.
O
xy
to
c
i
n
383. Ozothine
384.
P
a
c
li
t
a
x
e
l
385.
Pa
n
c
ur
on
i
um
bromide
386. Pantoprazole
387.
Para-amino benzene
s
ulph
on
am
i
de
,
it
s
salts
&
der
i
v
at
i
v
e
s
388.
Parp-amino
sal
icy
li
c
acid,
it
s
s
al
ts,
it
s
de
r
i
v
at
i
v
e
s
389.
Pa
r
e
c
o
xib
390.
Paro
xe
ti
ne
hydrochloride
391. D-
p
e
ni
c
il
a
m
i
ne
392.
2
[
Pe
n
ta
zo
c
in
e]
393.
P
e
nto
x
if
ylline
394.
Pe
pleo
my
c
in
395.
Phenelzineh
sulph
at
e
396.
Ph
e
nob
ar
b
it
al
397.
Phenothiazine, derivatives
of and
salts
of
it
s
der
i
v
at
i
v
e
s
398.
Ph
e
n
ylb
uta
zi
n
e
399.
P
i
m
o
z
i
d
e
400.
P
indo
lo
l
401.
Pioglitazone
hydrochloride
402.
P
i
r
a
c
e
tam
403.
P
i
ro
x
i
c
a
m
404.
Pituitory gland, active principles
of,
not
otherwise
spe
ci
f
ied
in this
schedule and
th
e
i
r
s
a
lt
s
405.
Po
li
doc
an
o
l
406.
Po
l
y
e
st
r
adi
ol
pho
sph
at
e
407.
Poractant
al
f
a
408.
P
r
a
z
iq
ua
nte
l
409.
Prednimustine
iothalamates
410.
Prednisolone
ste
a
r
o
ylg
ly
c
o
l
at
e
411.
Pre
no
xd
iazinh
y
dr
o
-c
h
lor
i
de
412.
Promazine
h
y
d
r
o
c
h
l
o
r
i
de
413.
Pr
o
m
e
g
e
s
ton
e
414.
Propafenon
hydrochloride
415.
Pr
o
pan
o
lo
l
hydrochloride
416.
Pr
opo
f
o
l
417.
Pr
o
tr
is
ty
li
n
e
hydrochloride
418.
2
[
P
y
raz
inam
i
d
e]
419. Pyrvinium
420.
Quetiapine
fumerate
421.
Q
u
i
na
p
ri
l
422.
Quinidine
sulph
at
e
423.
R
ab
e
pr
azo
le
424.
R
ac
e
cado
tr
il
425.
R
a
lo
xi
f
e
n
e
h
y
d
r
o
c
hlo
r
i
de
Drugs and Cosmetics Rules 1945
406
1. Subs. by G.S.R. No.160(E), dated 16.3.2006 .
2. Omitted by G.S.R 588(E) dated 30-8-2013
3. Omitted by G.S.R 602(E) dated 19-7-2010
4. Omitted by G.S.R 724(E) dated 7-11-2013
426.
Ramipril
h
y
dro
c
hl
o
rid
e
427.
R
an
it
idi
n
e
428.
R
au
w
o
lfi
a,
a
lka
l
o
ids
of,
their
salts,
de
r
iv
at
i
v
e
s
of
the alkaloids
or
rauwolfia
429.
R
e
boxe
ti
n
e
430.
R
e
pag
li
n
i
de
431.
R
e
pr
otero
l
hydrochloride
432.
R
il
m
e
ni
d
i
ne
433.
R
il
u
z
o
ne
434.
R
ispe
r
ido
n
e
435.
R
i
to
nav
ir
436.
Ritodrine
hydrochloride
437.
R
i
t
u
x
i
m
a
b
438.
R
i
v
a
st
ig
min
e
439.
R
o
c
uro
n
i
um
bromide
440.
R
o
pi
n
i
r
o
le
441.
Rosox
a
c
i
n.
442.
Rosiglitazone mel
ea
te
443.
Sal
b
uta
mo
l
s
ulph
at
e
444.
Sal
icy
l
-az
o-sul
ph
ap
yridin
e
445.
Salmon
calcitonin
446.
Saq
u
inav
i
r
447. Satranidazole
448.
S
e
cn
i
d
az
o
l
e
449.
Se
p
to
pa
l
beads
&
c
h
a
in
s
450.
Ser
r
at
iope
pt
id
ase
451.
Sertraline
hydrochloride
452.
Sibutramine
hydrochloride
453. Sil
de
n
a
f
il
c
it
r
at
e
454. Simvastatin
455.
S
ir
olim
u
s
456.
Sisomicin
s
ulph
at
e
457.
S-n
e
o
mi
noph
agen
458.
Sodiumpico
s
ulph
at
e
459. Sodium
cr
o
m
og
ly
c
a
te
460.
Sodium
h
y
alur
on
at
e
461.
Sodium
val
pr
oat
e
462.
Sodium and ma
glum
in
e
iot
h
a
la
ma
t
e
s
463. Somatostatin
464. Somatotropin
465.
S
ot
a
l
ol
466.
2
[
Spar
f
l
o
xac
in]
467.
Sp
e
c
tin
o
m
y
c
i
n
h
y
dr
o
c
h
l
o
r
i
de
468.
S
pir
on
ol
ac
t
on
e
469.
Stavudine
470.
S
ucr
a
lfat
e
471.
Sul
ph
ado
xin
e
472.
Sulph
ame
th
o
xin
e
473.
Sulphamethoxypyridazine
474.
Su
lph
a
ph
e
n
az
o
le
475.
Su
lpi
r
i
de
476.
Sulprostone
h
y
dr
och
l
o
r
i
de
477.
Su
matr
i
pt
an
478.
Tacrine
hydrochloride
479.
Tamsulosin
hydrochloride
480. Tr
a
pidi
l
481.
Tegaserod
ma
le
at
e
482. T
e
ico
p
la
n
in
483. T
e
lm
i
sar
ta
n
484. T
em
ozol
a
mi
de
485. T
e
r
az
o
sin
486. T
e
r
b
uta
l
in
e
sulph
at
e
487. T
e
r
f
e
n
ad
in
e
488. T
er
iz
idon
e
489. T
er
l
ipr
ess
in
490.
Testosteroneun decoan
o
a
te
491. Teratolol
h
y
dr
och
l
o
r
i
de
492.
Th
al
i
do
mi
de
493.
2
[
Th
ia
c
e
ta
zon
e]
494. T
h
i
o
col
ch
i
co
s
i
d
e
495.
Th
i
o
pr
opazat
e
,
it
s
sa
lt
s
496.
Th
y
mogen
e
497. Thymosin-alpha1
498. T
iapr
o
f
en
ic
a
c
id
499.
Ti
bo
l
on
e
500. Tim
o
lo
l
ma
le
at
e
501. Tinidazole
502. T
i
zani
di
ne
503. Tabramycin
504. T
o
l
f
e
n
am
ic
a
c
id
505. T
o
pir
amat
e
506.
Topotecan
hydrochloride
507.
2
[Tr
a
ma
do
l
h
y
dr
och
lor
ide]
508.
Tranexamic
acid
509.
Tranylcypromine,
i
ts
sa
lt
s
510. Tr
azo
don
e
Drugs and Cosmetics Rules 1945
407
1. Subs. by G.S.R. No.160(E), dated 16.3.2006 .
2. Omitted by G.S.R 588(E) dated 30-8-2013
3. Omitted by G.S.R 602(E) dated 19-7-2010
4. Omitted by G.S.R 724(E) dated 7-11-2013
Note:- 1. Preparations exempted under proviso to para 2 of Note to Schedule X shall also be covered
by this Schedule.
2. The salts, esters, derivatives and preparations containing the above substances excluding those
intended for topical or external use (except ophthalmic and ear / nose preparations con- taining
antibiotics and/ or steroids) are also covered by this Schedule.
3. The inclusion of a substance in this Schedule does not imply or convey that the substance is
exempted from the provisions of Rule 122A/122B.”
1
[SCHEDULE H1
(See Rules 65 and 97)
Alprazolam
Doripenam
Balofloxacin
Ertapenem
Buprenorphine
Ethambutol Hydrochloride
Capreomycin
Ethionamide
Cefdinir
Feropenam
Cefditoren
Gemifloxacin
Cefepime
Imipenem
Cefetamet
Isoniazide
Cefixime
Levofloxacin
Cefoperazone
Meropenem
Cefotaxime
Midazolam
Cefpirome
Moxifloxacin
Cefpodoxime
Nitrazepam
Ceftazidime
Pentazocine
Ceftibuten
Prulifloxacin
Ceftizoxime
Pyrazinamide
Ceftriaxone
Rifabutin
Chlorodiazepoxide
Rifampicin
Clofazimine
Sodium Para-aminosalicylate
Codeine
Sparfloxacin
Cycloserine
Thiacetazone
Diazepam
Tramadol
Diphenoxylate
Zolpidem
Note:- Preparations containing the above drug substances and their salts excluding those intended for
topical or extrenal use (except ophthalmic and ear or nose preparations) containing above substances
are also covered by this Schedule.
1. Ins. by G.S.R 588(E) , dt. 30.8.203.
511. Tr
e
ti
no
in
512. T
ri
f
l
u
pe
raz
i
ne
513. Tr
i
f
lupe
r
ido
l
hydrochloride
514. Tr
i
f
lu
sa
l
515.
Tri
m
e
t
az
i
di
n
e
di
h
y
dro
c
hlo
r
i
de
516. T
ri
m
i
p
r
a
m
i
n
e
517.
Tripotassium dicitrate
b
ismut
h
at
e
518. Tr
o
ma
n
ta
din
e
hydrochloride
519. Ur
o
kin
ase
520.
V
a
ls
ar
t
an
521.
V
as
op
r
e
s
si
n
522.
V
e
c
u
r
on
i
um
bromide
523.
V
e
n
la
f
ax
in
e
hydrochloride
524.
V
e
r
apa
m
il
hydrochloride
525.
V
e
r
te
po
r
f
in
526.
Vincristine
sulphat
e
527.
Vinblastine
sulph
at
e
528.
Vindesine sul
ph
at
e
529.
V
i
no
r
e
l
b
i
n
e
ta
tr
a
te
530.
X
i
p
a
m
i
d
e
531.
Zidovudine
hydrochloride
532.
Ziprasidone
hydrochloride
533.
Zoledronic
acid
534.
2
[Z
o
l
pi
d
e
m]
535. Z
opi
c
l
on
e
536. Z
uc
lo
pe
n
th
i
xo
l
Drugs and Cosmetics Rules 1945
408
1
SCHEDULE I
(Omited)
2
[SCHEDULE J
(See rule
106)
DISEASES AND AILMENTS (BY WHATEVER NAME DESCRIBED) WHICH A DRUG MAY
NOT PURPORT TO PREVENT OR CURE OR MAKE CLAIMS TO PREVENT OR CURE.
1. AIDS
2. Angina Pectoris
3. Appendicitis
4. Arteriosclerosis
5. Baldness
6. Blindness
7. Bronchial Asthma
8. Cancer and Benign tumour
9. Cataract
10. Change in colour of the hair and growth of new hair.
11. Change of foetal sex by drugs.
12. Congenital malformations
13. Deafness
14. Diabetes
15. Diseases and disorders of uterus.
16. Epilepticfits and psychiatric disorders
17. Encephalitis
18. Fairness of the skin
19. Form, structure of breast
20. Gangrene
21. Genetic disorders
22. Glaucoma
23. Goitre
24. Hernia
25. High/low Blood Pressure
26. Hydrocele
27. Insanity
28. Increase in brain capacity and improvement of memory.
29. Improvement in height of children/adults.
30. Improvement in size and shape of the sexual organ and in duration of sexual
performance
31. Improvement in the strength of the natural teeth.
32. Improvement in vision
33. Jaundice/Hepatitis/Liver disorders
34 Leukaemia
35. Leucoderma
36. Maintenance or improvement of the capacity of the human being for sexual pleasure.
37 Mental retardation, subnormalities and growth
38. Myocardial infarction
39. Obesity
40. Paralysis
1. Schedule I omitted by G.S.R 462(E) , dt. 22.6.1982
2. Subs. by G.S.R. 21(E) , dt. 11.1.1996.
Drugs and Cosmetics Rules 1945
409
41.
Parkinsonism
42. Piles and Fistulae
43. Power to rejuvinate
44. Premature ageing
45. Premature greying of hair
46. Rheumatic Heart Diseases
47. Sexual Impotence, Premature ejaculation and spermatorrhoea
48. Spondylitis
49. Stammering
50. Stones in gall-bladder, kidney, bladder
51. Vericose Vein.]
SCHEDULE K
(See rule 123)
Class of Drugs
Extent and Conditions of Exemption
1. Drugs falling under clause (b) (i) of Section 3
of the Drugs and Cosmetics Act, not intended for
medicinal use.
All the provisions of Chapter IV of the Act
and the Rules thereunder, subject to the
conditions that the drug is not sold for
medicinal use or for use in the manufacture of
medicines and that each container is labelled
conspicuously with the words ―NOT FOR
MEDICINAL USE.‖
1
[2.* * *]
2
[2A. Quinine and other antimalarial drugs.
3
[Persons selling the drugs by retail under
arrangements made by State Government for
sale and distribution of the drugs will be
exempted from the requirement to take out
licences for retail sale under clause (c) of
Section 18 of the Act.]
4
[3.* * *]
4
[4.* * *]
5
[5. Drugs supplied by a registered medical
practitioner to his own patient or any drug
specified in Schedule C supplied by a
registered medical practitioner at the request
of another such practioner if it is specially
prepared with reference to the condition and
for the use of an individual patient provided
the registered medical practitioner is not (a)
keeping an open shop or (b) selling across the
counter or (c) engaged in the importation,
manufacture, distribution or sale of drugs in
India to a degree which render him liable to
the provisions of Chapter IV of the Act and the
rules thereunder.
All the provisions of Chapter IV of the Act
and the Rules made thereunder, subject to the
following conditions :
5
[1. The drugs shall be purchased only from a
dealer or a manufacturer licensed under these
rules, and records of such purchases showing
the names and quantities of such drugs,
together with their batch numbers and names
and addresses of the manufacturers shall be
maintained. Such records shall be open to
inspection by an Inspector appointed under the
Act, who may, if necessary, make enquiries
about purchases of the drugs and may also take
samples for test.]
2. In the case of medicine containing a
substance specified in
6
[Schedule G, H or X]
of the following additional conditions shall be
complied with:-
a. the medicine shall be labelled with the
Drugs and Cosmetics Rules 1945
410
name and address of the registered medical
practitioner by whom it is supplied;
b. if the medicine is for external application
it shall be labelled with the words
7
[***]
―For external use only‖ or, if it is for
internal use with the dose;
c. the name of the medicine or ingredients of
the preparation and the quantities thereof,
the dose prescribed, the name of the
patient & the date of supply and the name
of the person who gave the prescription
shall be entered at the time of supply in
register to be maintained for the purpose;
d. the entry in the register shall be given a
number and that number shall be entered
on the label of the container;
e. the register and the prescription, if any, on
which the medicines are issued shall be
preserved for not less than two years from
the date of the last entry in the register or
the date of the prescription, as the case
may be.
8
[3. The drug will be stored under proper
storage conditions as directed on the label.]
9
[4. No drug shall be supplied or dispensed
after the date of expiration of potency recorded
on its container, label or wrapper or in
violation of any statement or direction
recorded on such container, label or wrapper.]
10
[5A. Drugs supplied by a hospital or
dispensary maintained or supported by
Government or local body
11
[***]
The provisions of Chapter IV of the Act and
the Rules thereunder which require them to be
covered by a sale licence, subject to the
following conditions :
(1) The dispensing and supply of drugs shall
be carried out by or under the supervision
of a qualified person;
(2) The premises where drugs are supplied or
stocked shall be open to inspection by an
Inspector appointed under the Drugs and
Cosmetics Act who can, if necessary, take
samples for test;
(3) The drugs shall be stored under proper
storage conditions.
(4)
12
[The drugs shall be purchased from a
manufacturer or a dealer licensed under
these rules or received as transferred
stocks from hospital stores for distribution.
Records of such purchases or receipts shall
be maintained.]
(5)
13
[No drug shall be supplied or dispensed
after the date of expiration of potency
recorded on its container, label or wrapper
Drugs and Cosmetics Rules 1945
411
or in violation of any statement or
direction recorded on such container, label
or wrapper.]
14
[5B. Whole Human Blood IP and / or its
components stored for transfusion by a First
Referral Unit, Community Health Centre,
Primary Health Centre and a Hospital.
The provisions of Chapter IV of the Act and
the rules made thereunder which require
obtaining of a licence for operation of a
Blood Ban k or processing Whole Human
Blood and / or its components, subject to the
following conditions, namely: -
(1) The First Referral Unit, Community Health
Centre, Primary Health Centre and / or any
Hospital shall be approved by the State /
Union Territory Licensing Authority after
satisfying the conditions and facilities
through inspection.
(2) The captive consumption of Whole Human
Blood IP or its components in the First
Referral Unit, Community Health Centre,
Primary Health Centre and / or any
Hospital shall not be more than 2000 units
annually.
(3) The Whole Human Blood an d / or its
components shall be procured only from
Government Blood Bank and / or Indian
Red Cross Society Blood Bank and / or
Regional Blood Transfusion Centre duly
licensed.
(4) The approval shall be valid for a period of
two years from the date of issue unless
sooner suspended or cancelled and First
Referral Unit, Community Health Centre,
Primary Health Centre and / or any
Hospital shall apply for renewal to the
State Licensing Authority three months
prior to the date of expiry of the approval.
(5) The First Referral Unit, Community Health
Centre, Primary Health Centre and / or any
Hospital shall have the following technical
staff for storage of blood or its
components:
(a) A trained Medical Officer for proper
procurement, storage and cross
matching of blood and / or its
components. He / she shall also be
responsible for identifying haemolysed
blood and ensure non-supply of date
expired blood or its components.
(b) A blood bank Technician with the
qualification and experience as
specified in Part XII B of Schedule F
or an experienced laboratory
technician trained in blood grouping
and cross matching.
Drugs and Cosmetics Rules 1945
412
(6) The First Referral Unit, Community Health
Centre, Primary Health Centre and / or any
Hospital shall have an area of 10 sq.
metres. It shall be well lighted, clean and
preferably air- conditioned. Blood bank
refrigerator of appropriate capacity fitted
with alarm device and temperature
indicator with regular temperature
monitoring shall be provided to store blood
units between 2° C to 8° C and if the
components are proposed to be stored,
specialized equipment‘s as specified in
Part XII B of Schedule F shall also be
provided.
(7) The First Referral Unit, Community Health
Centre, Primary Health Centre and / or any
Hospital shall maintain records and
registers including details of procurements
of Whole Human Blood IP and / or blood
components, as required under Part XII B
Schedule F.
(8) (8) The First Referral Unit, Community
Health Centre, Primary Health Centre and /
or any Hospital shall store samples of
donors blood as well as patients sera for a
period seven days after transfusion.
15
[6.* * *]
7.Quinine Sulphate
The provisions of sub-section (a) (i) of Section
18 of the Act to the following extent-
(i) the colour of the drug may be pink, owing
to its being coloured with an edible pink
colouring matter;
(ii) the B. P. tests for readily carbonisable
substances produce a yellow colour of an
intensity about four times the colour
produced with quinine sulphate
conforming to the B.P. standard;
(iii) other Cinchona alkaloids present shall not
exceed six per cent; and
(iv) the residue on incineration shall not exceed
0.14 per cent.
16
[8.* * *]
17
[9. Magnesium Sulphate
The provisions of sub-clause (i) of clause (a)
of Section 18 of the Act to the following
extent:-
Chlorides present in the salt shall not
exceed 0.12 per cent in the case of the produce
prepared from sea water.]
18
[10. The following substances which are
used both as articles of food as well as drugs -
(i) all condensed or powdered milk whether
All provisions of Chapter IV of the Act and
the
Rules thereunder
Drugs and Cosmetics Rules 1945
413
pure, skimmed or malted, fortified with
vitamins and minerals or otherwise.
(ii) Farex, Oats,
19
[***] and all other similar
cereal preparations whether fortified with
vitamins or otherwise excepting those for
parenteral use.
(iii) Virol, Bovril, Chicken essence and all
other similar predigested foods.
(iv)
20
[Ginger, Pepper, Cumin, Cinnamon and
all other similar spices and condiments
unless they are specially labelled as
conforming to the standards in the Indian
Pharmacopoeia or the Official
Pharmacopoeia and official compendia
of drug standards prescribed under the
Act and Rules made thereunder.]
21
[11.* * *]
22
[12. Substances intended to be used for
destruction of vermin or insects which cause
disease in human beings or animals, viz.
Insecticides and Disinfectants.]
The provision of Chapter IV of the Act and
Rules thereunder, which require them to be
covered by a sale licence
23
[subject to the
condition that provision of condition (17) of
Rule 65 of the Drugs and Cosmetics Rules,
1945 are complied with by the person stocking
or selling such substances.]
24
[13. The following household remedies,
namely-
(1)
25
[Aspirin tablets.]
(2)
26
[Paracetamol Tablets.]
(3) Analgesic Balms.
(4) Antacid preparations.
(5) Gripe Water for use of infants.
(6) Inhalers, containing drugs for
treatment of cold and nasal congestion.
(7) Syrups, lozenges, pills and tablets for
cough.
(8) Liniments for external use.
(9) Skin ointments and ointments for
burns.
(10) Absorbent cotton wool, bandages
absorbent guaze and adhesive plaster.
(11) Castor Oil, liquid Paraffin and Epsom
Salt.
(12) Eucalyptus Oil
(13) Tincture Iodine, Tincture Benzoi n
C o. and Mercurochrome in containers
not exceeding 100 ml.
(14) Tablets of Quinine Sulphate I.P.
(15) Tablets of Iodochlorohydroxy
quinoline-250 mg.
The provisions of Chapter IV of the Act and
the Rules thereunder which require them to be
covered with a sales licence in Form 20-A
subject to the following conditions—
(a) The drugs are sold only in a village
having population of not more than one
thousand persons and where there is no
licensed dealer under the Drugs and Cosmetics
Act;
(b) The drugs do not contain any substance
specified in
27
[Schedules G, H or X];
(c) The drugs are sold in the original
unopened containers of the licensed
manufacturers;
(d) When the drugs are sold under clause (a)
condition 3 under ―Conditions of licence‖ of
Form 20-B shall not apply.
28
[14. Mechanical Contraceptives
The provisions of Chapter IV of the Act and
Rules thereunder, which require them to be
Drugs and Cosmetics Rules 1945
414
covered by a sale licence
29
[subject to the
condition that the provisions of condition (17)
of Rule 65 of the Drugs and Cosmetics Rules,
1945, are complied with by the person
stocking or selling mechanical contraceptives.]
30
[14A. Vaginal contraceptive pessaries
containing Nonoxynol.
The provisions of Chapter IV of the Act and
the Rules made thereunder which require them
to be covered by a sale licence subject to the
condition that the provisions of clause (17) of
Rule 65 of the Drugs and Cosmetics Rules,
1945 are complied with by the person stocking
or selling this contraceptive.]
31
[15. Chemical contraceptive having the
following composition per tablet :
(1) DL-Norgestrel-0.30 mg.
Ethinyloestradiol-0.03 mg.
(2) Levonorgestrel-0.15 mg.
Ethinyloestradiol-0.03 mg.
(3) Centchroman-30mg.
(4)
32
[Desogestrel -0.150mg.
Ethinyloestradiol 0.030mg.
(5) Levonorgestrel 0.1mg.
Ethinyloestradiol 0.02mg
The provisions of Chapter IV of the Act and
the rules made thereunder which required them
to be covered by a sale licence.]
33
[16. Cosmetics
The provisions of Chapter IV of the Act and
the Rules made thereunder, which require
them to be covered by a licence for sale
provided that the cosmetics sold, if of Indian
origin, are manufactured by licensed
manufacturers.]
34
[17. Ophthalmic ointments of the
Tetracycline group of drugs
Persons authorised by the Government to
distribute or sell the drugs under the National
Trachoma Control Programme shall be
exempted from the provisions of Chapter IV of
the Act and the Rules made thereunder, which
require the drugs to be covered by a sale
licence.]
35
[18.* * *]
36
[19. Hair Fixers, namely mucilaginous
preparations containing gums, used by men for
fixing beard.
The provisions of Chapter IV of the Act and
the rules thereunder.]
37
[20. Radio Pharmaceuticals.
All the provisions of Chapter IV of the Act
and the rules made thereunder.]
38
[21. Tablets of Chloroquine Salts.
The provisions of Chapter IV of the Act and
Rules thereunder, which require them to be
covered by a sale licence, provided the drug in
strip pack is sold under the Commercial
Distribution Scheme of the National Malaria
Eradication Programme and duly labelled as
Drugs and Cosmetics Rules 1945
415
―National Malaria Eradication Programme-
Ministry of Health and Family Welfare,
Government of India.‖]
39
[22. Sales from restaurant cars of trains and
from coastal ships of household remedies,
which do not require the supervision of a
qualified person for their sale.
The provisions of Chapter IV of the Act and
the rules thereunder which require them to be
covered by a sale licence, subject to the
following conditions, namely -
(a) the records of purchase and sale of drugs
shall be maintained by the person in charge
of sale of such drugs, which shall be available
for inspection by an Inspector appointed under
the Act;
(b) the place where such drugs are stocked
shall be open to inspection by a n Inspector
appointed under the Act who can, if necessary,
takes samples for test.]
40
[23. Drugs supplied by ( i ) Multipurpose
Workers attached to Primary Health
Centres/Sub- Centres, (ii) Community Health
Volunteers under the Rural Health Scheme,
(iii) Nurses, Auxiliary Nurses, Midwives an d
Lady Health Visitors attached to Urban Family
Welfare Centres/Primary Health Centres/Sub-
Centres and
41
[(iv) Anganwadi Workers].
All The provisions of Chapter IV of the Act
and Rules thereunder, which require them to
be covered by a sale licence, provided the
drugs are supplied under the Health or Family
Welfare Programme of the Central or State
Government.]
42
[24. Homoeopathic medicines supplied
by a registered Homoeopathic medical
practitioner to his own patient or
Homoeopathic medicines supplied by a
registered Homoeopathic medical
practitioner at the request of another such
practitioner provided the registered
Homoeopathic medical practitioner is not (a)
keeping an open shop, or (b) selling across the
counter or, (c) engaged in the importation,
manufacture, distribution or sale of
Homoeopathic medicines in India to a degree
which renders him liable to the provisions of
Chapter IV of the Act and the rules made
thereunder
All the provisions of Chapter IV of the Act
and the rules made thereunder subject to the
following conditions:—
(1) The Homoeopathic medicines shall be
purchased only from a dealer or a
manufacturer licensed under the Drugs and
Cosmetics Rules, 1945.
(2) The premises where the Homoeopathic
Medicines are stocked shall be open to
inspection by an Inspector appointed under the
Act, who may, if necessary, ―take samples for
test.]‖
43
[25. Preparations applied to human body for
the purpose of repelling insects like
mosquitoes.
The provisions of Chapter IV of the Act and
Rules thereunder which require them to be
covered by a sale licence subject to the
conditions that such a product has been
manufactured under a valid drug
manufacturing licence.
44
[26. Medicated Dressing and
Bandages for First Aid.
The provisions of Chapter IV of the Act and
Rules thereunder which require them to be
covered by a sale licence subject to the
conditions that such a product has been
manufactured under a valid drug
manufacturing licence.]
Drugs and Cosmetics Rules 1945
416
45
[27. Oral Rehydration Salts (Manufactured
as per the following formula) :
o Sodium chloride 3.5 g/litre.
o Trisodium citrate dehydrate 2.9 g/litre
o Potassium Chloride 1.5 g/ litre.
May be replaced by Sodium
bicarbonate(Sodium hydrogen Carbonate) 2.5
g/ litre, when citrate salt is not available.
The provisions of Chapter IV of the Act and
Rules thereunder which required them to be
covered by a sale licence, subject to the
conditions that such a product has been
manufactured under a valid drug
manufacturing Licence.]
46
[28. White or Yellow Petroleum Jelly
I.P. (Non-perfumed).
The provisions of Chapter IV of the Act and
Rules thereunder which required them to be
covered by a sale licence, subject to the
condition that such a product has been
manufactured under a valid drug
manufacturing Licence.
47
[29. Morphine Tablets
The provisions of Chapter IV of the Act and
the rules made thereunder which require them
to be covered by a sale licence, subject to the
following conditions, namely: -
(i) The drug shall be supplied by the
Palliative Care Centres approved by the State
Government to terminally ill cancer patients
(ii) The drug shall be kept under the custody of
the Medical Officer in charge of the said
Centre.
(iii) The drug shall be purchased from a dealer
or a manufacturer who holds licence under
these rules and records of such purchases
showing the names and quantities together
with their batch numbers and names and
addresses of the manufacturers or dealers and
the names and addresses of the patients to
whom supplies have been made shall be
maintained. Such records shall be open to
inspection by an inspector appointed under the
Act, who may also take samples for test.
30. Whole Human Blood collected and
transfused by Centres r un by Armed Forces
Medical Services in border areas, small mid-
zonal hospitals including peripheral hospitals,
Field Ambulances, Mobile medical units and
other field medical units including blood
supply units in border, sensitive and field
areas.
All the provisions of Chapter IV of the Act
and rules made thereunder which require them
to be covered by a licence to operate a Blood
Bank for collection, storage and processing of
whole human blood for sale or distribution
subject to the following conditions:-
(i) These Centres shall collect, process and
transfuse blood in emergent situations which
require lifesaving emergency surgeries/or
transfusion.
(ii) These Centres shall be under the active
direction and personal supervision of a
qualified Medical Officer, possessing the
Drugs and Cosmetics Rules 1945
417
qualifications and experiences specified in
condition (i) of rule 122-G.
(iii) Each blood unit shall be tested before use
for freedom from HIV I and II antibodies,
Hepatitis B surface antigen, malarial parasites
and other tests specified under the monograph
―Whole Human Blood‖ in current edition of
Indian Pharmacopoeia
(iv) These Centres shall have adequate
infrastructure facilities for storage and
transportation of blood.
(v) The blood collected and tested by such
Centres shall be transfused by the Centre itself
and may be made available for use of other
peripheral Armed Forces hospitals or Centres
during operational circumstances.]
48
[31. The following Homoeopathic
Medicines, namely: -
49
[(a) ***
(b) Homoeopathic Ointments, each
50
[in 25gm.
Tube]:
(i) Arnica Montana
(ii) Calendula Officinalis
(iii) Cantharis
(iv) Rhus Toxicodendron
(c) Biochemic tissue remedies in tablet forms,
in generic names only, each in 20gm. Packing
in 3X and 6X trituration-
(i) Calcarea Phosphorica
(ii) Calcarea Sulphurica
(iii) Ferum Phosphoricum
(iv) Kali Muriaticum
(v) Kali Phosphoricum
(vi) Kali Sulphuricum
(vii) Magnesium Phophoricum
(viii) Magnesia Sulphurica
(ix) Natrum Muriaticum
(x) Natrum Phophoricum
(xi) Natrum Sulphuricum
(xii) Silica
(d) Homoeopathic medicines, mentioned
below, in pills, each in 30C potency, in sealed
original packing of manufacturer of 8 gms:
(i) Arnica Montana
(ii) Aconitum Napellus
(iii) Arsenicum Album
The provisions of Chapter IV of the Act and
the rules made thereunder which require them
to be covered with a sale licence in Form 20-
C, subject to the following conditions: -
(i) These homoeopathic medicines shall be
sold in the original sealed small quantity
packings of the licensed manufacturers.
(ii) These medicines may be stocked and sold
by retail of medicines licensed under rule 61.
(iii) These medicines shall be stored separately
from other allopathic drugs.
(iv) These medicines shall be purchased from
a manufacturer or a dealer licensed under these
rules.
(v) The purchase and sale records of these
medicines shall be maintained by the dealer
for minimum period of three years.
(vi) These medicines shall be labelled in
generic / pharmacopoeial names only.
Drugs and Cosmetics Rules 1945
418
(iv) Aloe Socotrina
(v) Apis Mellifica
(vi) Allium Cepa
(vii) Bryonia Alba
(viii) Borax
(ix) Belladonna
(x) Cantharis
(xi) Carbo Vegatabilis
(xii) Cina
(xiii) Colocythis
(xiv) Calendula Officinalis
(xv) Caulophyllum Thalictroides
(xvi) Cocculus Indicus
(xvii) Chamomilla
(xviii) Drosera Rotundifolia
(xix) Hypeicum Perforatum
(xx) Hepar Sulphur
(xxi) Ipecacuanha
(xxii) Ledum Palustre
(xxiii) Millefolium
(xxiv) Mercurius Solubilis
(xxv) Nux Vomica
(xxvi) Pulsatilla Nigricans
(xxvii) Podophyllum Peltatum
(xxviii) Plantago Major
(xxix) Rhus Toxicodendron
(xxx) Ruta Graveolens
(xxxi) Symphytum Officinalis
(xxxii) Veratrum Album
51
[(e) All biochemic and its combinations (1
to 28), in tablet forms, in sealed original
packing of the manufacture.]
52
[32. First Aid kit supplied along with motor
vehicle by the manufacturer or its distributors
at the time of first sale of vehicle.
The provisions of Chapter IV of the Act and
rules made thereunder which require them to
be covered by a sale licence, subject to the
condition that the drug items are procured
from a manufacturer or a dealer licensed under
the rules.]
53
[33. Nicotine gum
54
[and Lozenges]
containing upto 2 mg of nicotine
The provisions of Chapter IV of the Act and
the Rules made thereunder which require them
to be covered by a sale license subject to the
condition that such a product has been
manufactured under a valid drug
manufacturing license.]
55
[34. Production of Oxygen 93 per cent USP,
produced from air by the molecular sieve
process, by a hospital or Medical Institute for
their captive consumption.
The provisions of Chapter IV of the Act and
the Rules made thereunder which require them
to be covered by manufacturing licence under
the rules, provided that the production
facilities shall be open to inspection by an
Inspector appointed under the Act, who can, if
necessary, take samples For test‖.]
Drugs and Cosmetics Rules 1945
419
56
[35. Homoeopathic hair oils having active
ingredients up to 3X potency only
The provisions of Chapter IV of the Act and
the rules made thereunder which require them
to be covered with a sale licence
57
[***]
subject to the condition that such a product has
been manufactured under a valid
manufacturing licence and sold in the original
sealed packing of the licensed manufacturers.]
58
[36. Custom made devices
All provisions of Chapter IV of the Act and
the rules made thereunder, subject to the
condition that the device being specifically
made in accordance with a duly qualified
medical practitioner‘s written prescription
under his responsibility, in accordance with
specific design characteristics and is intended
for the sole use of a particular patient and the
label should bear the word ―custom made
device.‖
Explanation.–– Mass produced devices
which only need adoption to meet the specific
requirements of the medical practitioner or any
other professional user shall not be considered
to be custom made devices.]
1. Item 2 omitted by Government of India Notification No. F.1-56/47-D, dt. 16.1.1950).
2. Added by Notification No .F. I-2/47-D dt. 13-2-1950.
3. Amended by Notification No. F. I-22/59-D dt.. 9-4-1960.
4. Item 3 and 4 omitted by Notification No. F.I-6/62-D dt. 2-7-1969.
5. Subs. by G.S.R. 1074, dt: 19.8.1978.
6. Subs. by G.S.R. 462 (E), dt: 22.6.1982.
7. Certain words omitted by G.S.R. 462 (E), dt: 22.6.1982.
8. Ins. by G.S.R. 460 (E), dt: 20.6.1984.
9. Ins. by G.S.R. 592 (E), dt: 13.8.2008.
10. Added by notification No. F.1-22/59-D, dt: 9.4.1960.
11. Certain words omitted by G.S.R. 812 (E), dt: 14.11.1994.
12. Ins. by G.S.R. 648 (E), dt: 16.9.2002.
13. Ins. by G.S.R. 592 (E), dt: 13.8.2008.
14. Ins. by G.S.R. 909 (E), dt: 20.12.2001.
15. Item 6 omitted by G.S.R. 681 (E), dt: 5.12.1980.
16. Item 8 omitted by G.S.R.1185 (E), dt: 18.8.1964.
17. Added by notification No. F.1-19/50-D.S, dt: 30.3.1953.
18. Added by notification No. DR/Sch.Ddk/F.1-40/54-D.S., dt: 27.1.1955.
19. Omitted by G.S.R. 665 (E), dt: 6.5.1977.
20. Subs. by G.S.R. 19, dt: 15.12.1977.
21. Item 11 omitted by notification No. F.1-36/64-D (G.S.R 1188), dt: 17.8.1964.
22. Amended by notification No. F.1-20/60-D (S.O.400), dt: 24.1.1964.
23. Added by G.S.R. 926, dt: 24.6.1977.
24. Added by notification No. F.1-19/59-D, dt: 13.6.1961.
25. Subs by S.O. 2139, dt: 5.6.1972.
26. Subs. by G.S.R. 1060(E), dt: 5.9.1986.
27. Subs. by G.S.R. 462 (E), dt: 22.6.1982.
28. Added by notification No. F.1-39/61-D (S.O. 1057), dt: 23.3.1964.
29. Added by G.S.R. 926, dt: 24.6.1977.
30. Ins. by G.S.R. 784 (E), dt: 28.8.1989.
31. Subs by G.S.R. 730 (E), dt: 10.12.1991.
32. Ins. by G.S.R. 648 (E), dt: 16.9.2002.
33. Added by notification No. F.1-36/64-D (G.S.R 1183), dt: 17.8.1964.
34. Added by notification No. F.1-21/63-D (G.S.R 70), dt: 4.1.1965.
35. Item 18 is omitted by G.S.R. 1594, dt: 28.10.1976.
36. Added by S.O. 2139, dt: 5.6.1972.
37. Added by G.S.R. 926, dt: 24.6.1977.
Drugs and Cosmetics Rules 1945
420
38. Added by G.S.R. 697 (E), dt: 11.11.1977.
39. Ins. by G.S.R. 1241, dt: 15.9.1979.
40. Ins. by G.S.R. 540 (E), dt: 22.9.1980.
41. Ins. by G.S.R. 784 (E), dt: 28.8.1989.
42. Ins. by G.S.R. 680 (E), dt: 5.12.1980.
43. Ins. by G.S.R. 1060 (E), dt: 5.9.1989.
44. Ins. by G.S.R. 371 (E), dt: 24.3.1988.
45. Ins. by G.S.R. 677 (E), dt: 2.6.1988.
46. Ins. by G.S.R. 753 (E), dt: 4.11.1999.
47. Ins. by G.S.R. 6 (E), dt: 4.1.2001.
48. Ins. by G.S.R. 218 (E), dt: 28.3.2001.
49. Sub-item (a) relating to ―Arnica Montana Hair Oil‖ omitted by G.S.R. 917 (E), dt: 22.12.2009.
50. Subs. by G.S.R. 592 (E), dt: 13.8.2008.
51. Ins. by G.S.R. 592 (E), dt: 13.8.2008.
52. Ins. by G.S.R. 648 (E), dt: 16.9.2002.
53. Ins. by G.S.R. 549 (E), dt: 16.7.2003.
54. Ins. by G.S.R. 101 (E), dt: 18.2.2001.
55. Ins. by G.S.R. 734 (E), dt: 21.12.2005.
56. Ins. by G.S.R. 917 (E), dt: 22.12.2009.
57. The words ―in Form 20C‖ omitted by G.S.R. 107 (E), dt: 17.2.2015.
58. Ins. By G.S.R. 890 (E), dt: 25.9.2014.
Drugs and Cosmetics Rules 1945
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1
[SCHEDULE L
(Omitted)
2
[SCHEDULE L-I
(see rules 74, 78 and 150E)
GOOD LABORATORY PRACTICES AND REQUIREMENTS OF PREMISES AND
EQUIPMENTS
1. General Requirements:-
(a) The laboratory or the organisation of which it is a part must be an entity that is legally
authorised to function and can be held legally responsible.
(b) It is the responsibility of the management to ensure that the laboratory carry out its
testing, calibration, validation, and all other technical activities in such a way as to
meet Good Laboratory Practices (GLP) requirements.
(c) Laboratory management shall have a qualified individual to be known as quality
manager or technical manager for carrying out all technical activities and for the
implementation of documented quality system and shall report to the top management
directly.
(d) The quality manager shall prepare a schedule for technical audit of the laboratory for
GLP compliance by an expert or experts appointed by the top-management other than
the in-charge of the laboratory and shall ensure the maintenance of documented quality
system as per quality manual.
2. Premises:-
(a) (i) the laboratories shall be designed, constructed and maintained so as to prevent entry
of insects and rodents besides cross contamination;
(ii) interior surface (walls, floor, and ceilings) shall be smooth and free from cracks,
and permit easy cleaning and disinfection;
(iii) adequate provision is made not only for space and equipment for carrying out
necessary test but also for utilities like water, power and gas;
(iv) air ventilation system shall ensure dust free environment.
(b) The laboratories shall be provided with adequate lighting and ventilation and if
necessary, air- conditioning to maintain satisfactory temperature and relative humidity
that will not adversely affect the testing and storage of drugs or the accuracy of the
functioning of the laboratory equipments or instruments.
(c) The drainage system facilities shall be such as to facilitate proper maintenance and
prevent water logging in the laboratory.
(d) Tabletops shall be constructed with acid, alkali and solvent resistant material and shall
be smooth and free from crevices as far as possible.
(e) All bio-medical laboratory waste shall be destroyed as per the provisions of the Bio--
Medical waste (Management and Handling) Rules, 1996.
(f) Adequate space with proper storage conditions in the laboratory shall be provided for
keeping reference and working standards and be maintained by the quality control
department. Standard Operating Procedure (SOP) for the maintenance of reference
standards and evaluation of Working and Secondary standards shall be prepared by the
laboratory.
(g) The air circulation is maintained in the area where sterility test is carried out as per
Schedule‘M‘.
(h) Bio-burden shall be routinely maintained in the controlled and uncontrolled area, (e.g.
air locks)
1. Schedule L omitted by G.S.R. 462 (E), dt: 22.6.1982.
2. Ins. by G.S.R. 780 (E), dt: 10.11.2008.
Drugs and Cosmetics Rules 1945
422
(i) Animals House:-
(i) Animal House shall have the approval of the Committee for the Purpose of
Control and Supervision on Experiments on Animals (CPCSEA).
(ii) Designed in such a way that there is an arrangement to quarantine the new
animals procured or purchased and have a provision for clean corridor and
dirty corridor.
(iii) In case of a diseased animal proper diagnosis shall be done and proper record
of treatment shall be maintained.
(iv) Different types of animals shall be housed separately with proper identification.
(v) A Standard Operating Procedure shall be prepared for breeding and care of
animals, maintenance, cleaning or sanitation with suitable schedule for cleaning
of animal cages, racks, floor and other equipments.
(vi) The animal house shall have proper air-conditioning (temperature and
humidity) with proper lighting and be monitored regularly and documented
periodically.
3. Personnel-
(a) Staff in the laboratory shall possess necessary qualification, proper training and shall
have adequate, experience for the assigned duties.
(b) A training record of all the personnel shall be maintained.
(c) Head of the laboratory must be of high professional standing with experience in drug
analysis and laboratory management who is responsible for.
(i) ensuring the control and maintenance of documents including the quality system as
per the requirements of regulatory authorities which involves all raw data, SOPs,
documentation exhibits, protocols, training charts, etc;
(ii) planning and organising the audit of the quality system and initiation as well as
follow up action of the corrective actions, if any;
(iii) investigation of technical complaints;
(iv) taking finai responsibilities for recommending any regulatory action in the event of
noncompliance of tested samples.
4. Equipments:-
(a) The laboratory shall be furnished with all types of equipments as may be necessary for
carrying out the different activities within the laboratory.
(b) The analytical instruments shall be housed in dust-free environment and whenever
required, conditions of temperature and humidity shall be maintained and periodic
checks on temperature and humidity be made and recorded.
(c) The instruments, instrument bench and surrounding areas shall be kept clean and tidy at
ail times.
(d) Instruments requiring calibration shall be calibrated at regular intervals and records of
such calibration or maintenance be maintained and there shall be written instructions in
the form of Standard Operating Procedures for the operation, maintenance and
calibration of instruments.
(e) Equipment records shall be maintained and such records shall contain the following:-
(i) name of equipment or machine or apparatus;
(ii) manufacturer ‘s name, model number and type of identification;
(iii) serial number;
(iv) date on which equipment was received in laboratory;
(v) current location;
(vi) condition when received (e.g. new, used, re-conditioned);
(vii) copy of the manufacturer ‘s operating instructions;
(viii) frequency of calibration;
(ix) frequency of maintenance;
(x) log Book (day to day entry including status of the equipment)
(xi) staff responsible for monitoring the calibration and maintenance status of the
equipment;
Drugs and Cosmetics Rules 1945
423
(xii) calibrating records;
(xiii) list of authorised users or operators, if any;
(xiv) history of any damage, malfunction, modification or upgradation, repair and
calibration;
(xv) list of spares and accessories, if any.
(f) A progress register for non-functional equipments and action for procurement of spares
and accessories, monitoring thereof, shall be maintained.
(g) A Standard Operating Procedure for preventive maintenance of machine or equipment
or apparatus shall be prepared by the laboratory.
(h) Other equipments such as burettes, pipettes, volumetric flasks, weight boxes,
thermometers, etc., shall be thoroughly checked for accuracy of calibration before
acceptance for use.
(i) Maintenance procedure in the form of Standard Operating Procedures must be
prepared and regular servicing must be performed by the maintenance engineer or
specialist
(j) Equipments, instruments giving anomalous results or defective must be labeled as ‗out-
of- order‘ till they are repaired and after instrument is repaired it should be calibrated
before use.
(k) The maintenance of equipments for services like electricity, gas, water, steam, and
compressed gas shall be handled by competent person.
(l) Autoclaves must meet the requirements described for operations, safety and validation
procedures, and the validation carried out by the laboratory shall be recorded.
(m) Fume Cupboards.-
Work involving the evolution of harmful and obnoxious vapours shall be carried
out in a fume cupboard. The exhaust system of the fume cupboard shall be checked
frequently to ensure that it is in order. There should be a water drainage system inside the
fume cupboard and shall be checked frequently to ensure that there is no water logging and
it is in order.
5. Chemicals and Reagents:
(a) The storage and handling of chemicals and reagents shall be done in a manner
considering the physicochemical properties of these substances and the hazards
involved in their use.
(b) All reagents and solutions in the laboratory shall be properly identified with a label.
(c) A standardisation register shall be maintained by the laboratory along with its raw
data and Standard Operating Procedure for preparation and standardisation on
stock solutions, standard solutions, volumetric solutions must be prepared for the
guidance of staff.
(d) Containers of stock solutions and of standard solutions shall bear the following
details:-
(i) name of analytical chemist who prepared the solution;
(ii) date of preparation;
(iii) Each volumetric solution shall have ―use before date‖ depending upon the
stability of the solution; and
(iv) standardization records.
(e) The transfer of hazardous chemicals and regents from one container to another
container shall be carried out with suitable equipment by taking the care of safety
and no make-shift or hazardous methods must be resorted to.
6. Good house keeping and safety.-
(a) General and specific written down instructions for safety shall be circulated to each
staff member and the instructions be revised periodically as appropriate (e.g., poster
displays, audio- visual material and by seminars/conferences)
(b) Standard Operating Procedure for safety, house-keeping and loss prevention shall be
prepared in accordance with the various rules, and regulations of the Government of
India and include the following requirements, namely:-
(i) safety data sheets must be made available to staff before testing is carried out;
Drugs and Cosmetics Rules 1945
424
(ii) drinking, eating and smoking shall not be permitted in the laboratories; food for
human consumption shall not be kept in working or storage areas; food meant for
test animals shall be handled by the workers under the guidance of a veterinary
doctor or qualified person. In the animal house, the facilities for collection and
disposal of animal waste or safe sanitary storage of waste before removal from
testing be provided;
(iii) staff must wear laboratory coats or other protective clothing including gloves and
face masks and eye protection wherever required;
(iv) the laboratories shall have adequate first aid kit and fire fighting equipments
located at the right places and the staff must be familiar and trained with the use
of fire fighting equipment including fire extinguishers, fire blankets and gas
masks,
(v) operators carrying out sterility tests shall wear sterilised garments including
headgear, face masks and shoes;
(vi) the staff must be educated in the first aid techniques, emergency care and use of
antidotes; and
(vii) safety rules in handling cylinders of compressed gases must be observed and
staff must be familiar with relevant colour identification codes;
(c) Protective Precautions to be taken in Laboratories:
(i) water showers shall be installed at appropriate places in the laboratory;
(ii) rubber suction bulbs must be used on manual pipettes and siphons;
(iii) warnings, precautions, and written instructions must be given for work with
violent, uncontrollable or dangerous reactions (e.g. mixing water and acids,
biological such as infectious agents, etc.); .
(iv) appropriate facilities for the collection, storage, and disposal of wastes shall be
made available;
(v) staff must be aware of methods for safe disposal of corrosive or dangerous
products by neutralisation or deactivation and of the need for complete disposal
of mercury and its salts.
(vi) staff must also be aware about the safety precautions to be adopted while
handling potassium cyanide and cyanogen bromide.
(vii) a Standard Operating Procedure for handling, collection, disposal of chemical
and biological wastes be prepared.
7. Maintenance, calibration, and validation of equipments:-
(a) All equipments, instruments and other devices used in the laboratory shall use
appropriate methods and procedures for all tests or calibrations and they shall be
regularly calibrated and validated. The frequency of calibration may differ from
instrument to instrument.
(b) The original equipment manufacturer ‘s recommendations along with the experience of
the laboratory staff and the use of equipment per day may also be considered while
fixing the frequency of calibration.
(c) For most of the equipments and instruments, Standard Operating Procedures for
calibration and calibration schedule be prepared by the laboratory and a logbook shall
also be prepared by each laboratory for proper documentation of calibration results.
8. Reference materials:-
(a) Reference materials are necessary for the testing and, or calibration, validation or
verification of a sample or of equipment, instruments or other devices and all such
materials shall be traceable to agency authorised by Government of India or any other
International body .
(b) The laboratory shall prepare working standard by comparing with the reference
standards and shall be routinely checked for their purity by selecting parameters such
as identity, loss on drying or on water, impurity and assay, etc.
(c) Whenever, any new reference material is received by the laboratory, a code number
shall be assigned and this code number shall be quoted on the laboratory note book and
analytical work sheet. The working standard shall also be provided with identification
Drugs and Cosmetics Rules 1945
425
code.
(d) A register pertaining to reference and working materials must be maintained by the
laboratory. The following details may be mentioned in the register:
(i) source of supply;
(ii) code number of the reference material;
(iii) date of receipt;
(iv) batch number or identification number of the supplying agency;
(v) details like assay value, water content or any other information provided;
(vi) storage condition of the material; and
(vii) date of expiry, if any and date of manufacturing if possible
(e) All working standards shall be checked at appropriate intervals or before use to ensure
that it has not deteriorated or decomposed during storage. These observations be
recorded in a register: All the reference and working standards shall be stored at
appropriate storage condition; those requiring storage between 2-8°C shall be stored in
a refrigerator. Wherever recommended the material may not be allowed to be frozen.
9. Microbiological Cultures:-
(a) Standard Operating Procedure for maintenance of microbial culture and sub-culture
must be prepared by the laboratories.
(b) If the cultures have become non-viable or mutant, proper procedure shall be followed
to destroy these cultures by autoclaving under an authorised personnel for biological
testing. Preferably not more than five passages may be prepared.
(c) All activities be carried out in a aseptic area by authorised person.
(d) The laboratories shall perform standard biochemical tests on the sub-culture as given
in literature to ensure their viability.
10. Quality system.-
The quality system shall be designed to ensure the following objectives:-
(a) The measurements and calibrations shall fully conform to the compendial requirements
and the methods demonstrably based on validation protocols are followed.
(b) It shall be effective in providing necessary assurance that the activities or processes or
techniques or practices comply with planned arrangements.
(c) It helps in early detection and correction of non conformities.
(d) Remedial action on the observations by internal and external audits are taken
appropriately and
(e) It shall have a documented quality policy for the organisation.
11. Internal quality system audits.-
(a) Internal audits are done to assure the integrity of the analysis‘ and such audits shall be
conducted periodically with a predetermined schedule and procedure with appropriate
checklist, to verify that the operations continue to comply with the requirements of
quality system and requirements of regulatory authorities. Internal quality audits shall
be carried out by trained and qualified personnel who are independent of the activity to
be audited.
(b) The periodicity of quality audit shall be fixed by the Head of the laboratory so that
each activity is audited at least once in a year.
(c) Head of the laboratory will be responsible for initiation of the corrective action arising
from audits and verification of corrective action.
(d) Whenever any non-compliance or any diversion is noticed by the team in implementing
quality policy or quality system, protocols, the same will be attended by the Quality
Manager. The problem will be analysed and necessary actions will be taken with proper
documentation.
(e) The Quality Manager shall maintain all the records of the analysis being conducted
which includes test system, the type of analysis, date on which analysis is done, etc
and quality Manager shall also maintain copies of all protocols pertaining to different
activities being checked by the audit team.
12. Management review –
Quality system reviews shall be conducted by the top management at least once in every
Drugs and Cosmetics Rules 1945
426
twelve months and the agenda of review shall generally cover the following:-
(i) report or input of internal audits;
(ii) matter arising from previous reviews;
(iii) report of external audits, if any;
(iv) surveillance report, if any;
(v) result of proficiency testing;
(vi) complaints or feedback received from users of laboratory services;
(vii) details of in-house quality control checks;
(viii) need of amendment of the quality system and documentation;.
(ix) induction training of new staff; and
(x) any other requirements of the laboratory.
13. Standard Operating Procedures:-
(a) Standard Operating Procedures are written procedures for different activities being
conducted in a laboratory and shall include the following characteristics:
(i) they shall be written in a chronological order listing different steps leading to an
analysis of drugs or calibration of an instrument:
(ii) testing laboratories shall have Standard Operating Procedure manuals and have its
periodic review;
(iii) it shall be user friendly documents and shall include designation of the person
responsible for intended activity.
(b) Standard Operating Procedures in addition to those recommended under various
activities shall also be prepared to the minimum in respect of the following:
(i) sample handling and accountability;
(ii) receipt identification, storage, mixing and method sampling of the test and
control articles;
(iii) record keeping, reporting, storage and retrieval of data;
(iv) coding of different studies, handling of data including use of computerized data
system;
(v) operation of technical audit personnel in performing and reporting audits,
inspections and final report reviews;
(vi) routine inspection of cleaning, maintenance, testing, calibration and
standardisation of instruments;
(vii) action to be taken in respect of equipment failure;
(viii) analytical data methods;
(ix) the raw data;
(x) data handling and storage retrieval;
(xi) health and safety protection;
(xii) animal room preparations;
(xiii) animal care;
(xiv) storage and maintenance of microbial cultures;
(xv) maintenance of sterility room (i.e. constant maintenance and monitoring of
Aseptic condition of sterility room);
(xvi) use and storage of reference standards;
(xvii) procurement of stores and equipment;
(xviii) monitoring of testing of samples;
(xix) method of retention of unexpended samples, their location, maintenance and
disposal;
(xx) document control;
(xxi) redressal of technical complaints;
(xxii) housing-keeping;
(xxiii) corrective and preventing action;
(xxiv) working procedure (test methods);
(xxv) calibration Manual; and
(xxvi) training manual.
14. Protocols and specifications archive.-
Drugs and Cosmetics Rules 1945
427
(a) Every laboratory shall have a specification archive and. current versions of all
necessary specifications shall be kept as per the requirements of the Act and the rules
made thereunder and the National Pharmacopoeia (Indian Pharmacopoeia).
(b) All updates and corrections must be noted in the master volumes of Pharmacopoeias to
prevent the use of obsolete sections; supplement and addendum shall also be made
available in the laboratory.
(c) The specification archive shall contain the following :-
(i) list of all the pharmacopoeias;
(ii) a file on patent and proprietary medicines (non-pharmacopoeial) test methods
to specifications prepared and validated by the manufacturer or by the
laboratory itself. The test methods shall be submitted to the ·concerned Drug
Control Authority. The validated test methods developed by the manufacturer
or the laboratory shall stand to the requirements of compendial parameters in
regard to its precision, accuracy, reproducibility, specificity, linearity, and
ruggedness etc.
15. Raw data:-
(a) Raw data refers to the laboratory work sheet, note books or analysis sheet, records,
and other activities and such raw data shall include hand written notes, photographs,
software, drawings, computer printouts, spectral charts, dictated observations or
recorded data from automated equipments. The raw data also includes record on
receipt of animals, result of environmental monitoring, calibration, records of
equipments, integrator output from analytical equipment, including work-sheet used to
read a note, information from Light Emitting Diode (LED) display of any equipment.
(b) A single line shall strike through the data being changed; the correct information shall
be recorded along with the old data and the reason of change. The analyst making the
change shall be identified by his signature with date. In case of automated data
collection system, the person responsible shall be identified at the time of data output.
The original entry must be saved and the system have audit trial for all the data.
(c) Data integrity and security shall be maintained and the data shall not be accessible to
any unauthorised person.
16. Storage and archival.-
(a) The residual sample shall be retained in proper storage condition for a period of one
year after the final report.
(b) The laboratory must establish and maintain procedures for the identification collection,
indexing, retrieval, storage, maintenance, and disposal of all quality documents.
(c) All the raw data, documentation, Standard Operating Procedures, protocols, and final
reports are to be retained and there shall be archives for orderly storage and expeditious
retrieval of all raw data, documentation, protocols, interim and final report. The
archive shall provide a suitable environment that will prevent modification, damage, or
deterioration and/or loss.
(d) The condition under which the original documents are stored must ensure their security
and confidentiality,
(e) Paper documents shall not be kept for long periods under high humidity and raw data in
the form of tape and discs are to be preserved with care,
(f) In case of storage of only optical disc, the life of disc shall be longer than the storage
time,
(g) Raw data on thermal paper might fade away with time; therefore, a photocopy of the
thermal paper shall also be retained in the archive.
(h) Time for which records are retained shall be prescribed in the documents.
Drugs and Cosmetics Rules 1945
428
1
[SCHEDULE M
(See Rules 71, 74, 76 and
78)
GOOD MANUFACTURING PRACTICES AND REQUIREMENTS OF
PREMISES,
PLANT AND EQUIPMENT FOR PHARMACEUTICAL
PRODUCTS
Note: To achieve the objectives listed below, each licensee shall evolve appropriate
methodology, systems and procedures which shall be documented and maintained for
inspection and reference; and the manufacturing premises shall be used exclusively for
production of drugs
2
[and no other manufacturing activity shall be undertaken therein except
in respect of units licensed prior to 11th December, 2001].
PART
1
GOOD MANUFACTURING PRACTICES FOR PREMISES AND
MATERIALS
1 GENERAL REQUIREMENTS:
1.1. Location and surroundings.- The factory building(s) for manufacture of
drugs shall be so situated and shall have such measures as to avoid risk of contamination from
external environment including open sewage, drain, public lavatory or any factory which
produce disagreeable or obnoxious odour or fumes, excessive soot, dust, smoke, chemical or
biological emissions.
1.2. Buildings and premises.- The building(s) used for the factory shall be
designed, constructed, adapted and maintained to suit the manufacturing operations so as to
permit production of drugs under hygienic conditions. They shall conform to the conditions
laid down in the Factories Act, 1948 (63 of 1948).
The premises used for manufacturing, processing, warehousing, packaging, labelling
and testing purposes shall be –
(i) compatible with other drug manufacturing operations that may be carried out
in the same or adjacent area / section;
(ii) adequately provided with working space to allow orderly and logical
placement of equipment, materials and movement of personnel so as to:
(a) avoid the risk of mix-up between different categories of drugs or
with raw materials, intermediates and in-process material;
(b) avoid the possibilities of contamination and cross- contamination by
providing suitable mechanism;
(iii) designed / constructed / maintained to prevent entry of insects, pests, birds,
vermins and rodents. Interior surface (walls, floors and ceilings) shall be
smooth and free from cracks, and permit easy cleaning, painting and
disinfection;
1. Subs. by G.S.R. 894(E) , dt. 11.12.2001.- applicable to manufacturers licensed to manufacture drugs, for
the period up to 31.12.2003.
2. Subs. by Act 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
429
(iv) air-conditioned, where prescribed for the operations and dosage forms under
production. The production and dispensing areas shall be well lighted,
effectively ventilated, with air control facilities and may have proper Air
Handling Units (wherever applicable) to maintain conditions including
temperature and, wherever necessary, humidity, as defined for the relevant
product. These conditions shall be appropriate to the category of drugs and
nature of the operation. These shall also be suitable to the comforts of the
personnel working with protective clothing, products handled, operations
undertaken within them in relation to the external environment. These areas
shall be regularly monitored for compliance with required specifications;
(v) provided with drainage system, as specified for the various categories of
products, which shall be of adequate size and so designed as to prevent back-
flow and/or prevent insects and rodents entering the premises. Open channels
shall be avoided in manufacturing areas and, where provided, these shall be
shallow to facilitate cleaning and disinfection;
(vi) the walls and floors of the areas where manufacture of drugs is carried out
shall be free from cracks and open joints to avoid accumulation of dust.
These shall be smooth, washable, coved and shall permit easy and effective
cleaning and disinfection. The interior surfaces shall not shed particles. A
periodical record of cleaning and painting of the premises shall be
maintained.
1.3 Water System. - There shall be validt. system for treatment of water drawn from
own or any other source to render it potable in accordance with standards specified by the
Bureau of Indian Standards or Local Municipality, as the case may be, so as to produce
Purified Water conforming to Pharmacopoeial specification. Purified Water so produced shall
only be used for all the operations except washing and cleaning operations where potable
water may be used. Water shall be stored in tanks, which do not adversely affect quality of
water and ensure freedom from microbiological growth. The tank shall be cleaned
periodically and records maintained by the licensee in this behalf.
1.4. Disposal of waste. -
(i) The disposal of sewage and effluents (solid, liquid and gas) from the
manufactory shall be in conformity with the requirements of Environment
Pollution Control Board.
(ii) All bio-medical waste shall be destroyed as per the provisions of the Bio-
Medical Waste (Management and Handling) Rules, 1996.
(iii) Additional precautions shall be taken for the storage and disposal of rejected
drugs. Records shall be maintained for all disposal of waste.
(iv) Provisions shall be made for the proper and safe storage of waste materials
awaiting disposal. Hazardous, toxic substances and flammable materials
shall be stored in suitably designed and segregated, enclosed areas in
conformity with Central and State Legislations.
2. Warehousing Area:
2.1 Adequate areas shall be designed to allow sufficient and orderly warehousing of
various categories of materials and products like starting and packaging materials,
intermediates, bulk and finished products, products in quarantine, released, rejected, returned
or recalled, machine and equipment spare parts and change items.
Drugs and Cosmetics Rules 1945
430
2.2 Warehousing areas shall be designed and adapted to ensure good storage
conditions. They shall be clean, dry and maintained with acceptable temperature
limits. Where special storage conditions are required (e.g. temperature, humidity),
these shall be provided, monitored and recorded. Storage areas shall have appropriate
house-keeping and rodent, pests and vermin control procedures and records
maintained. Proper racks, bins and platforms shall be provided for the storage of
materials.
2.3 Receiving and dispatch bays shall protect materials and products from
adverse weather conditions.
2.4. Where quarantine status is ensured by warehousing in separate earmarked
areas in the same warehouse or store, these areas shall be clearly demarcated. Any
system replacing the physical quarantine, shall give equivalent assurance of
segregation. Access to these areas shall be restricted to authorized persons.
2.5. There shall be a separate sampling area in the warehousing area for active
raw materials and excipients. If sampling is performed in any other area, it shall be
conducted in such a way as to prevent contamination, cross-contamination and mix-up.
2.6. Segregation shall be provided for the storage of rejected, recalled or
returned materials or products. Such areas, materials or products shall be suitably
marked and secured. Access to these areas and materials shall be restricted.
2.7. Highly hazardous, poisonous and explosive materials such as narcotics,
psychotropic drugs and substances presenting potential risks of abuse, fire or explosion
shall be stored in safe and secure areas. Adequate fire protection measures shall be
provided in conformity with the rules of the concerned civic authority.
areas.
2.8. Printed packaging materials shall be stored in safe, separate and secure
2.9. Separate dispensing areas for β (Beta) lactum, Sex Hormones and
Cytotoxic substances or any such special categories of product shall be provided with
proper supply of filtered air and suitable measures for dust control to avoid
contamination. Such areas shall be under differential pressure.
2.10. Sampling and dispensing of sterile materials shall be conducted under
aseptic conditions conforming to Grade A, which can also be performed in a dedicated
area within the manufacturing facility.
2.11. Regular checks shall be made to ensure adequate steps are taken against
spillage, breakage and leakage of containers.
2.12. Rodent treatments (Pest control) should be done regularly and at least
once in a year and record maintained.
3. Production area:
3.1. The production area shall be designed to allow the production preferably in
uni-flow and with logical sequence of operations.
3.2. In order to avoid the risk of corss-contamination, separate dedicated and self-
contained facilities shall be made available for the production of sensitive pharmaceutical
products like penicillin or biological preparations with live micro-organisms. Separate
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dedicated facilities shall be provided for the manufacture of contamination causing and potent
products such as Beta-Lactum, Sex Hormones and Cytotoxic substances.
3.3. Working and in-process space shall be adequate to permit orderly and logical
positioning of equipment and materials and movement of personnel to avoid cross-
contamination and to minimize risk of omission or wrong application of any manufacturing
and control measures.
3.4. Pipe-work, electrical fittings, ventilation openings and similar service lines
shall be designed, fixed and constructed to avoid
1
[accumulation of dust]. Service lines shall
preferably be identified by colours and the nature of the supply and direction of the flow shall
be marked/indicated.
4. Ancillary Areas:
4.1 Rest and refreshment rooms shall be separate from other areas. These areas
shall not lead directly to the manufacturing and storage areas.
4.2 Facilities for changing, storing clothes and for washing and toilet purposes
shall be easily accessible and adequate for the number of users. Toilets, separate for males
and females, shall not be directly connected with production or storage areas. There shall be
written instructions for cleaning and disinfection of such areas.
4.3 Maintenance workshops shall be separate and away from production areas.
Whenever spares, changed parts and tools are stored in the production area, these shall be
kept in dedicated rooms or lockers. Tools and spare parts for use in sterile areas shall be
disinfected before these are carried inside the production areas.
4.4. Areas housing animals shall be isolated from other areas. The other
requirements regarding animal houses shall be those as prescribed in rule 150-C(3) of the
Drugs and Cosmetics Rules, 1945 which shall be adopted for production purposes.
5. Quality Control Area.
5.1. Quality Control Laboratories shall be independent of the production areas.
Separate areas shall be provided each for physico-chemical, biological, microbiological or
radio-isotope analysis. Separate instrument room with adequate area shall be provided for
sensitive and sophisticated instruments employed for analysis.
5.2 Quality Control Laboratories shall be designed appropriately for the
operations to be carried out in them. Adequate space shall be provided to avoid mix-ups and
cross-contamination. Sufficient and suitable storage space shall be provided for test samples,
retained samples, reference standards, reagents and records.
5.3. The design of the laboratory shall take into account the suitability of
construction materials and ventilation. Separate air handling units and other requirements
shall be provided for biological, microbiological and radioisotopes testing areas. The
laboratory shall be provided with regular supply of water of appropriate quality for cleaning
and testing purposes.
5.4. Quality Control Laboratory shall be divided into separate sections i.e. for
chemical, microbiological and wherever required, biological testing. These shall have
adequate area for basic installation and for ancillary purposes. The microbiology section
shall have arrangements such as airlocks and laminar air flow work station, wherever
considered necessary.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005.
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6. Personnel:
6.1. The manufacture shall be conducted under the direct supervision of competent
technical staff with prescribed qualifications and practical experience in the relevant dosage
form and / or active pharmaceutical products.
6.2 The head of the Quality Control Laboratory shall be independent of the
manufacturing unit. The testing shall be conducted under the direct supervision of competent
technical staff who shall be whole time employees of the licensee.
6.3. Personnel for Quality Assurance and Quality Control operations shall be
suitably qualified and experienced.
6.4. Written duties of technical and Quality Control personnel shall be laid and
followed strictly.
6.5. Number of personnel employed shall be adequate and in direct proportion to the
workload.
6.6. The licensee shall ensure in accordance with a written instruction that all
personnel in production area or into Quality Control Laboratories shall receive training
appropriate to the duties and responsibility assigned to them. They shall be provided with
regular in-service training.
7. Health, clothing and sanitation of workers:
7.1 The personnel handling Beta-lactum antibiotics shall be tested for Penicillin
sensitivity before employment and those handling sex hormones, cytotoxic substances and
other potent drugs shall be periodically examined for adverse effects. These personnel should
be moved out of these sections (except in dedicated facilities), by rotation, as a health
safeguard.
7.2 Prior to employment, all personnel, shall undergo medical examination including
eye examination, and shall be free from Tuberculosis, skin and other communicable or
contagious diseases. Thereafter, they should be medically examined periodically, at least
once
a year. Records shall be maintained thereof. The licensee shall provide the services of a
qualified physician for assessing the health status of personnel involved in different activities.
7.3 All persons prior to and during employment shall be trained in practices which
ensure personnel hygiene. A high level of personal hygiene shall be observed by all those
engaged in the manufacturing processes. Instructions to this effect shall be displayed in
change- rooms and other strategic locations.
7.4 No person showing, at any time, apparent illness or open lesions which may
adversely affect the quality of products, shall be allowed to handle starting materials,
packaging materials, in-process materials, and drug products until his condition is no longer
judged to be a risk.
7.5 All employees shall be instructed to report about their illness or abnormal
health condition to their immediate supervisor so that appropriate action can be taken.
7.6 Direct contact shall be avoided between the unprotected hands of personnel
and raw materials, intermediate or finished, unpacked products.
7.7 All personnel shall wear clean body coverings appropriate to their duties.
Before entry into the manufacturing area, there shall be change rooms separate for each sex
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with adequate facilities for personal cleanliness such as wash basin with running water,
1
[clean towels or hand dryers], soaps, disinfectants, etc. The change rooms shall be provided
with cabinets for the storage of personal belongings of the personnel.
7.8 Smoking, eating, drinking, chewing or keeping plants, food, drink and
personal medicines shall not be permitted in production, laboratory, storage and other areas
where they might adversely influence the product quality.
8. Manufacturing Operations and Control:
8.1 All manufacturing operations shall be carried out under the supervision of
technical staff approved by the Licensing Authority. Each critical step in the process relating
to the selection, weighing and measuring of raw material addition during various stages shall
be performed by trained personnel under the direct personal supervision of approved technical
staff.
The contents of all vessels and containers used in manufacture and storage during the
various manufacturing stages shall be conspicuously labelled with the name of the product,
batch number, batch size and stage of manufacture. Each label should be initialled and dt. by
the authorised technical staff.
Products not prepared under aseptic conditions are required to be free from pathogens
like Salmonella, Escherichia coli, Pyocyanea, etc.
8.2. Precautions against mix-up and cross-contamination:
8.2.1. The licensee shall prevent mix-up and cross-contamination of drug material
and drug product (from environmental dust) by proper air-handling system, pressure
differential, segregation, status labelling and cleaning. Proper records and Standard Operating
Procedures thereof shall be maintained.
8.2.2 The licensee shall ensure processing of sensitive drugs like Beta-Lactum
antibiotics, sex hormones and cytotoxic substances in segregated areas or isolated production
areas within the building with independent air-handling unit and proper pressure differentials.
1
[The effective segregation of these areas shall be validated with adequate records of
maintenance and services].
8.2.3 To prevent mix-ups during production stages, material under process shall be
conspicuously labelled to demonstrate their status. All equipment used for production shall be
labelled with their current status.
8.2.4 Packaging lines shall be independent and adequately segregated. It shall be
ensured that all left-overs of the previous packaging operations, including labels, cartons and
caps are cleared before the closing hour.
8.2.5 Before packaging operations are begun, steps shall be taken to ensure that the
work area, packaging lines, printing machines, and other equipment are clean and free from
any products, materials and spillages. The line clearance shall be performed according to an
approximate check list and recorded.
8.2.6 The correct details of any printing (for example of batch numbers or expiry
dates) done separately or in the course of the packaging shall be rechecked at regular
intervals. All printing and overprinting shall be authorized in writing.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005.
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8.2.7 The manufacturing environment shall be maintained at the required levels of
temperature, humidity and cleanliness.
8.2.8 Authorised persons shall ensure change-over into specific uniforms before
undertaking any manufacturing operations including packaging.
8.2.9
1
[There shall be segregated secured areas for recalled or rejected material
and for such material which are to be reprocessed or recovered.]
9. Sanitation in the Manufacturing Premises:
9.1 The manufacturing premises shall be cleaned and maintained in an orderly
manner, so that it is free from accumulated waste, dust, debris and other similar material. A
validt. cleaning procedure shall be maintained.
9.2 The manufacturing areas shall not be used for storage of materials, except for
the material being processed. It shall not be used as a general thoroughfare.
9.3 A routine sanitation program shall be drawn up and observed, which shall be
properly recorded and which shall indicate–
(a) specific areas to be cleaned and cleaning intervals;
(b) cleaning procedure to be followed, including equipment and materials to
be used for cleaning; and
(c) personnel assigned to and responsible for the cleaning operation.
9.4 The adequacy of the working and in-process storage space shall permit the
orderly and logical positioning of equipment and materials so as to minimize the risk of mix-
up between different pharmaceutical products or their components to avoid cross
contamination, and to minimise the risk of omission or wrong application of any of the
manufacturing or control steps.
9.5 Production areas shall be well lit, particularly where visual on-line controls
are carried out.
10. Raw Materials:
10.1 The licensee shall keep an inventory of all raw materials to be used at any
stage of manufacture of drugs and maintain records as per Schedule U.
10.2 All incoming materials shall be quarantined immediately after receipt or
processing. All materials shall be stored under appropriate conditions and in an orderly
fashion to permit batch segregation and stock rotation by a ‗first in/first expiry‘ – ‗first-out‘
principle. All incoming materials shall be checked to ensure that the consignment corresponds
to the order placed.
10.3 All incoming materials shall be purchased from approved sources under valid
purchase vouchers. Wherever possible, raw materials should be purchased directly from the
producers.
10.4 Authorized staff appointed by the licensee in this behalf, which may include
personnel from the Quality Control Department, shall examine each consignment on receipt
and shall check each container for integrity of package and seal. Damaged containers shall be
identified, recorded and segregated.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005.
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10.5 If a single delivery of material is made up of different batches, each batch
shall be considered as a separate batch for sampling, testing and release.
10.6 Raw materials in the storage area shall be appropriately labelled. Labels shall
be clearly marked with the following information:
(a) designated name of the product and the internal code reference, where
applicable, and analytical reference number;
(b) manufacturer‘s name, address and batch number;
(c) the status of the contents (e.g. quarantine, under test, released, approved,
rejected); and
(d) the manufacturing date, expiry date and re-test date.
10.7 There shall be adequate separate areas for materials ―under test‖, ―approved‖
and ―rejected‖ with arrangements and equipment to allow dry, clean and orderly placement of
stored materials and products, wherever necessary, under controlled temperature and
humidity.
10.8 Containers from which samples have been drawn shall be identified.
10.9 Only raw materials which have been released by the Quality Control
Department and which are within their shelf-life shall be used. It shall be ensured that shelf
life of formulation product shall not exceed with that of active raw materials used.
10.10 It shall be ensured that all the containers of raw materials are placed on the
raised platforms/racks and not placed directly on the floor.
11. Equipment:
11.1 Equipment shall be located, designed, constructed, adapted and maintained to
suit the operations to be carried out. The layout and design of the equipment shall aim to
minimise the risk of errors and permit effective cleaning and maintenance in order to avoid
cross-contamination, build-up of dust or dirt and, in general, any adverse effect on the quality
of products. Each equipment shall be provided with a logbook, wherever necessary.
11.2 Balances and other measuring equipment of an appropriate range, accuracy
and precision shall be available in the raw material stores, production and in-process control
operations and these shall be calibrated and checked on a scheduled basis in accordance with
Standard Operating Procedures and records maintained.
11.3 The parts of the production equipment that come into contact with the
product shall not be reactive, additive or adsorptive to an extent that would affect the quality
of the product.
11.4 To avoid accidental contamination, wherever possible, non-toxic/edible grade
lubricants shall be used and the equipment shall be maintained in a way that lubricants do not
contaminate the products being produced.
11.5 Defective equipment shall be removed from production and Quality Control
areas or appropriately labelled.
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12. Documentation and Records:– Documentation is an essential part of the Quality
assurance system and, as such, shall be related to all aspects of Good Manufacturing Practices
(GMP). Its aim is to define the specifications for all materials, method of manufacture and
control, to ensure that all personnel concerned with manufacture know the information
necessary to decide whether or not to release a batch of a drug for sale and to provide an audit
trail that shall permit investigation of the history of any suspected defective batch.
12.1 Documents designed, prepared, reviewed and controlled, wherever
applicable, shall comply with these rules.
12.2 Documents shall be approved, signed and dt. by appropriate and authorized
persons.
12.3 Documents shall specify the title, nature and purpose. They shall be laid out
in an orderly fashion and be easy to check. Reproduced documents shall be clear and legible.
Documents shall be regularly reviewed and kept up to date. Any alteration made in the entry
of a document shall be signed and dt..
12.4 The records shall be made or completed at the time of each operation in such
a way that all significant activities concerning the manufacture of pharmaceutical products are
traceable. Records and associated Standard Operating Procedures (SOP) shall be retained for
at least one year after the expiry date of the finished product.
12.5 Data may be recorded by electronic data processing systems or other reliable
means, but Master Formulae and detailed operating procedures relating to the system in use
shall also be available in a hard copy to facilitate checking of the accuracy of the records.
Wherever documentation is handled by electronic data processing methods, authorized
persons shall enter or modify data in the computer. There shall be record of changes and
deletions. Access shall be restricted by ‗passwords‘ or other means and the result of entry of
critical data shall be independently checked. Batch records electronically stored shall be
protected by a suitable back-up. During the period of retention, all relevant data shall be
readily available.
13. Labels and other Printed Materials:– Labels are absolutely necessary for identification
of the drugs and their use. The printing shall be done in bright colours and in a legible
manner. The label shall carry all the prescribed details about the product.
13.1 All containers and equipment shall bear appropriate labels. Different colour
coded labels shall be used to indicate the status of a product (for example under test,
approved, passed, rejected).
13.2 To avoid chance mix-up of printed packaging materials, product leaflets,
relating to different products, shall be stored separately.
13.3 Prior to release, all labels for containers, cartons and boxes and all circulars,
inserts and leaflets shall be examined by the Quality Control Department of the licensee.
13.4 Prior to packaging and labelling of a given batch of a drug, it shall be
ensured by the licensee that samples are drawn from the bulk and duly tested, approved and
released by the quality control personnel.
13.5 Records of receipt of all labelling and packaging materials shall be
maintained for each shipment received indicating receipt, control reference numbers and
whether accepted or rejected. Unused coded and damaged labels and packaging materials
shall be destroyed and recorded.
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13.6 The label or accompanying document of reference standards and reference
culture shall indicate concentration, lot number, potency, date on which containers was first
opened and storage conditions, where appropriate.
14. Quality Assurance:–This is a wide-ranging concept concerning all matters that
individually or collectively influence the quality of a product. It is the totality of the
arrangements made with the object of ensuring that products are of the quality required for
their intended use.
14.1 The system of quality assurance appropriate to the manufacture of
pharmaceutical products shall ensure that: –
(a) the pharmaceutical products are designed and developed in a way that takes
account of the requirements of Good Manufacturing Practices (hereinafter
referred as GMP) and other associated codes such as those of Good
Laboratory Practices (hereinafter referred as GLP) and Good Clinical
Practices (hereinafter referred as GCP);
(b) adequate arrangements are made for manufacture, supply and use of the
correct starting and packaging materials.
(c) adequate controls on starting materials, intermediate products and bulk
products and other in-process controls, calibrations, and validations are
carried out.
(d) the finished product is correctly processed and checked in accordance with
established procedures;
(e) the pharmaceutical products are not released for sale or supplied before
authorized persons have certified that each production batch has been
produced and controlled in accordance with the requirements of the label
claim and any other provisions relevant to production, control and release of
pharmaceutical products.
15. Self Inspection and Quality audit:– It may be useful to constitute a self-inspection
team supplemented with a quality audit procedure for assessment of all or part of a system
with the specific purpose of improving it.
15.1 To evaluate the manufacturer‘s compliance with GMP in all aspects of
production and quality control, concept of self-inspection shall be followed. The manufacturer
shall constitute a team of independent, experienced, qualified persons from within or outside
the company, who can audit objectively the implementation of methodology and procedures
evolved. The procedure for self-inspection shall be documented indicating self-inspection
results, evaluation, conclusions and recommended corrective actions with effective follow up
program. The recommendations for corrective action shall be adopted.
15.2 The program shall be designed to detect shortcomings in the implementation
of Good Manufacturing Practice and to recommend the necessary corrective actions. Self-
inspections shall be performed routinely and on specific occasions, like when product recalls
or repeated rejections occur or when an inspection by the licensing authorities is announced.
The team responsible for self-inspection shall consist of personnel who can evaluate the
implementation of Good Manufacturing Practice objectively; all recommendations for
corrective action shall be implemented.
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15.3 Written instructions for self-inspection shall be drawn up which shall include
the following: -
(a) Personnel.
(b) Premises including personnel facilities.
(c) Maintenance of buildings and equipment
(d) Storage of starting materials and finished products.
(e) Equipment.
(f) Production and in-process controls.
(g) Quality control.
(h) Documentation.
(i) Sanitation and hygiene.
(j) Validation and revalidation programmes.
(k) Calibration of instruments or measurement systems.
(l) Recall procedures.
(m) Complaints management.
(n) Labels control.
(o) Results of previous self-inspections and any corrective steps taken.
16. Quality Control System. - Quality control shall be concerned with sampling,
specifications, testing, documentation, release procedures which ensure that the necessary and
relevant tests are actually carried and that the materials are not released for use, nor products
released for sale or supply until their quality has been judged to be satisfactory. It is not
confined to laboratory operations but shall be involved in all decisions concerning the quality
of the product. It shall be ensured that all quality control arrangements are effectively and
reliably carried out.The department as a whole shall have other duties such as to establish,
evaluate, validate and implement all Quality Control Procedures and methods.
16.1 Every manufacturing establishment shall establish its own quality control
laboratory manned by qualified and experienced staff.
16.2 The area of the quality control laboratory may be divided into Chemical,
Instrumentation, Microbiological and Biological testing.
16.3 Adequate area having the required storage conditions shall be provided for
keeping reference samples. The quality control department shall evaluate, maintain and store
reference samples.
16.4 Standard operating procedures shall be available for sampling, inspecting and
testing of raw materials, intermediate bulk finished products and packing materials and,
wherever necessary, for monitoring environmental conditions.
16.5 There shall be authorized and dt. specifications for all materials, products,
reagents and solvents including test of identity, content, purity and quality. These shall
include specifications for water, solvents and reagents used in analysis.
16.6 No batch of the product shall be released for sale or supply until it has been
certified by the authorized person(s) that it is in accordance with the requirements of the
standards laid down.
16.7 Reference/retained samples from each batch of the products manufactured
shall be maintained in quantity which is at least twice the quantity of the drug required to
conduct all the tests, except sterility and pyrogen/Bacterial Endotoxin Test performed on the
active material and the product manufactured. The retained product shall be kept in its final
pack or simulated pack for a period of three months after the date of expiry.
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16.8 Assessment of records pertaining to finished products shall include all
relevant factors, including the production conditions, the results of in-process testing, the
manufacturing (including packaging) documentation, compliance with the specification for
the finished product, and an examination of the finished pack. Assessment records should be
signed by the in-charge of production and countersigned by the authorised quality control
personnel before a product is released for sale or distribution.
16.9 Quality control personnel shall have access to production areas for sampling
and investigation, as appropriate.
16.10 The quality control department shall conduct stability studies of the products
to ensure and assign their shell life at the prescribed conditions of storage. All records of such
studies shall be maintained.
16.11 The in-charge of Quality Assurance shall investigate all product complaints
and records thereof shall be maintained.
16.12 All instruments shall be calibrated and testing procedures validt. before these
are adopted for routine testing. Periodical calibration of instrument and validation of
procedures shall be carried out.
16.13 Each specification for raw materials, intermediates, final products, and
packing materials shall be approved and maintained by the Quality Control Department.
Periodic revisions of the specifications shall be carried out whenever changes are necessary.
16.14 Pharmacopoeia, reference standards, working standards, references, spectra,
other reference materials and technical books, as required, shall be available in the Quality
Control Laboratory of the licensee.
17. Specification
17.1 For raw materials and packaging materials. - They shall include-
(a) the designated name and internal code reference;
(b) reference, if any, to a pharmacopoeial monograph;
(c) qualitative and quantitative requirements with acceptance limits;
(d) name and address of manufacturer or supplier and original manufacturer of the
material;
(e) specimen of printed material;
(f) directions for sampling and testing or reference to procedures;
(g) storage conditions; and
(h) maximum period of storage before re-testing.
17.2 For product containers and closures:–
17.2.1 All containers and closures intended for use shall comply with the
pharmacopoeial requirements. Suitable validt. test methods, sample sizes, specifications,
cleaning procedure and sterilization procedure, wherever indicated, shall be strictly followed
to ensure that these are not reactive, additive, absorptive, or leach to an extent that
significantly affects the quality or purity of the drug. No second hand or used containers and
closures shall be used.
17.2.2 Whenever bottles are being used, the written schedule of cleaning shall be
laid down and followed. Where bottles are not dried after washing, they should be rinsed with
de-ionised water or distilled water, as the case may be.
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17.3. For in-process and bulk products. - Specifications for in-process material,
intermediate and bulk products shall be available. The specifications should be authenticated.
17.4 For finished products. - Appropriate specifications for finished products
shall include: -
(a) the designated name of the product and the code reference;
(b) the formula or a reference to the formula and the pharmacopoeial reference;
(c)
directions for sampling and testing or a reference to procedures;
(d) a description of the dosage form and package details;
(e) the qualitative and quantitative requirements, with the acceptance limits for
release;
(f) the storage conditions and precautions, where applicable, and
(g) the shelf-life.
17.5 For preparation of containers and closures. - The requirements mentioned in
the Schedule do not include requirements of machinery, equipments and premises required for
preparation of containers and closures for different dosage forms and categories of drugs. The
suitability and adequacy of the machinery, equipment and premises shall be examined taking
into consideration the requirements of each licensee in this respect.
18. Master Formula Records:
There shall be Master Formula records relating to all manufacturing procedures for
each product and batch size to be manufactured. These shall be prepared and endorsed by the
competent technical staff i.e. head of production and quality control. The Master Formula
shall include: -
(a) the name of the product together with product reference code relating to its
specifications;
(b) the patent or proprietary name of the product along with the generic name, a
description of the dosage form, strength, composition of the product and batch size;
(c) name, quantity, and reference number of all the starting materials to be used. Mention
shall be made of any substance that may ‗disappear‘ in the course of processing.
(d) a statement of the expected final yield with the acceptable limits, and of relevant
intermediate yields, where applicable.
(e) a statement of the processing location and the principal equipment to be used.
(f) the methods, or reference to the methods, to be used for preparing the critical
equipments including cleaning, assembling, calibrating, sterilizing;
(g) detailed stepwise processing instructions and the time taken for each step;
(h) the instructions for in-process control with their limits;
(i) the requirements for storage conditions of the products, including the container,
labelling and special storage conditions where applicable;
(j) any special precautions to be observed;
(k) packing details and specimen labels.
19. Packing Records:
There shall be authorised packaging instructions for each product, pack size and type.
These shall include or have a reference to the following: -
(a) name of the product;
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(b) description of the dosage form, strength and composition;
(c) the pack size expressed in terms of the number of doses, weight or volume of the
product in the final container;
(d) complete list of all the packaging materials required for a standard batch size,
including quantities, sizes and types with the code or reference number relating to the
specifications of each packaging material.;
(e) reproduction of the relevant printed packaging materials and specimens indicating
where batch number and expiry date of the product have been applied;
(f) special precautions to be observed, including a careful examination of the area and
equipment in order to ascertain the line clearance before the operations begin.
(g) description of the packaging operation, including any significant subsidiary
operations and equipment to be used;
(h) details of in-process controls with instructions for sampling and acceptance; and
(i) upon completion of the packing and labelling operation, a reconciliation shall be
made between number of labelling and packaging units issued, number of units
labelled, packed and excess returned or destroyed. Any significant or unusual
discrepancy in the numbers shall be carefully investigated before releasing the final
batch.
20. Batch Packaging Records:
20.1 A batch packaging record shall be kept for each batch or part batch
processed. It shall be based on the relevant parts of the packaging instructions, and the
method of preparation of such records shall be designed to avoid transcription errors.
20.2 Before any packaging operation begins, check shall be made and recorded
that the equipment and the work stations are clear of the previous products, documents or
materials not required for the planned packaging operations, and that the equipment is clean
and suitable for use.
21. Batch Processing Records
21.1 There shall be Batch Processing Record for each product. It shall be based on
the relevant parts of the currently approved Master Formula. The method of preparation of
such records included in the Master Formula shall be designed to avoid transcription errors.
21.2 Before any processing begins, check shall be performed and recorded to
ensure that the equipment and work station are clear of previous products, documents or
materials not required for the planned process are removed and the equipment is clean and
suitable for use.
21.3 During processing, the following information shall be recorded at the time
each action is taken and the record shall be dt. and signed by the person responsible for the
processing operations: -
(a) the name of the product,
(b) the number of the batch being manufactured,
(c) dates and time of commencement, of significant intermediate stages and of
completion of production,
(d) initials of the operator of different significant steps of production and where
appropriate, of the person who checked each of these operations,
(e) the batch number and/or analytical control number as well as the quantities of each
starting material actually weighed,
(f) any relevant processing operation or event and major equipment used,
(g) a record of the in-process controls and the initials of the person(s) carrying them out,
and the results obtained,
Drugs and Cosmetics Rules 1945
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(h) the amount of product obtained after different and critical stages of manufacture
(yield),
(i) comments or explanations for significant deviations from the expected yield limits
shall be given,
(j) notes on special problems including details, with signed authorization, for any
deviation from the Master Formula,
(k) addition of any recovered or reprocessed material with reference to recovery or
reprocessing stages.
22. Standard Operating Procedures (SOPs) and Records, regarding:
22.1 Receipt of materials:
22.1.1 There shall be written Standard Operating Procedures and records for the
receipt of each delivery of raw, primary and printed packaging material.
22.1.2 The records of the receipts shall include;
(a) the name of the material on the delivery note and the number of containers;
(b) the date of receipt;
(c) the manufacturer‘s and/ or supplier‘s name;
(d) the manufacturer‘s batch or reference number;
(e) the total quantity, and number of containers, quantity in each container
received;
(f) the control reference number assigned after receipt;
(g) any other relevant comment or information.
22.1.3 There shall be written standard operating procedures for the internal labelling,
quarantine and storage of starting materials, packaging materials and other
materials, as appropriate.
22.1.4 There shall be Standard Operating Procedures available for each instrument and
equipment and these shall be placed in close proximity to the related instrument
and equipment.
22.2 Sampling:
22.2.1 There shall be written Standard Operating Procedures for sampling which
include the person(s) authorized to take the samples.
22.2.2 The sampling instructions shall include:
(a) the method of sampling and the sampling plan,
(b) the equipment to be used,
(c) any precautions to be observed to avoid contamination of the material or
any deterioration in its quality,
(d) the quantity of samples to be taken,
(e) instructions for any required sub-division or pooling of the samples,
(f) the types of sample container to be used,
(g) any specific precautions to be observed, especially in regard to sampling of
sterile and hazardous materials.
22.3. Batch Numbering:
22.3.1 There shall be Standard Operating Procedures describing the details of the batch
Drugs and Cosmetics Rules 1945
443
(lot) numbering set up with the objective of ensuring that each batch of
intermediate, bulk or finished product is identified with a specific batch number.
22.3.2 Batch numbering Standard Operating Procedures applied to a processing stage
and to the respective packaging stage shall be same or traceable to demonstrate
that they belong to one homogenous mix.
22.3.3 Batch number allocation shall be immediately recorded in a logbook or by
electronic data processing system. The record shall include date of allocation,
product identity and size of batch.
22.4. Testing:
22.4.1 There shall be written procedures for testing materials and products at different
stages of manufacture, describing the methods and equipment to be used. The
tests performed shall be recorded.
22.5 Records of
analysis:
22.5.1 The records shall include the following data:
(a) name of the material or product and the dosage form,
(b) batch number and, where appropriate the manufacturer and/ or supplier,
(c) references to the relevant specifications and testing procedures,
(d) test results, including observations and calculations, and reference to any
specifications (limits),
(e) dates of testing,
(f) initials of the persons who performed the testing,
(g) initials of the persons who verified the testing and the detailed calculations,
(h) a statement of release or rejection, and
(i) signature and date of the designated responsible person.
22.5.2 There shall be written standard operating procedures and the associated records of
actions taken for:
(a) equipment assembly and validation
(b) analytical apparatus and calibration,
(c) maintenance, cleaning and sanitation;
(d) personnel matters including qualification, training, clothing, hygiene;
(e) environmental monitoring;
(f) pest control;
(g) complaints;
(h) recalls made; and
(i) returns received.
23. Reference Samples:-
23.1 Each lot of every active ingredient, in a quantity sufficient to carry out all the tests,
except sterility and pyrogens/Bacterial Endotoxin Test, shall be retained for a
period of 3 months after the date of expiry of the last batch produced from that
active ingredient.
23.2. Samples of finished formulations shall be stored in the same or simulated
containers in which the drug has been actually marketed.
Drugs and Cosmetics Rules 1945
444
24. Reprocessing and
Recoveries:
24.1. Where reprocessing is necessary, written procedures shall be
established and approved by the Quality Assurance Department that
shall specify the conditions and limitations of repeating chemical
reactions. Such reprocessing shall be validt..
24.2. If the product batch has to be reprocessed, the procedure shall be
authorized and recorded. An investigation shall be carried out into the
causes necessitating re- processing and appropriate corrective measures
shall be taken for prevention of recurrence. Re-processed batch shall be
subjected to stability evaluation.
24.3. Recovery of the product residue may be carried out, if permitted, in the
master production and control records by incorporating it in subsequent
batches of the product.
25. Distribution records:
25.1. Prior to distribution or dispatch of given batch of a drug, it shall be ensured
that the batch has been duly tested, approved and released by the quality
control personnel. Pre-dispatch inspection shall be performed on each
consignment on a random basis to ensure that only the correct goods are
dispatched. Detailed instructions for warehousing and stocking of Large
Volume Parenterals, if stocked, shall be in existence and shall be
complied with after the batch is released for distribution. Periodic audits
of warehousing practices followed at distribution centers shall be carried
out and records thereof shall be maintained. Standard Operating
Procedures shall be developed for warehousing of products.
25.2. Records for distribution shall be maintained in a manner
1
[so as] to
facilitate prompt and complete recall of the batch, if and when necessary.
26. Validation and process validation:
26.1. Validation studies shall be an essential part of Good Manufacturing
Practices and shall be conducted as per the pre-defined protocols. These
shall include validation of processing, testing and cleaning procedures.
26.2. A written report summarizing recorded results and conclusions shall be
prepared, documented and maintained.
26.3. Processes and procedures shall be established on the basis of validation
study and undergo periodic revalidation to ensure that they remain capable
of achieving the intended results. Critical processes shall be
validt., prospectively or retrospectively.
26.4. When any new Master Formula or method of preparation is adopted, steps
shall be taken to demonstrate its suitability for routine processing. The
defined process, using the materials and equipment specified shall be
demonstrated to yield a product consistently of the required quality.
26.5. Significant changes to the manufacturing process, including any
change in equipment or materials that may affect product quality and/or
the reproducibility of the process, shall be validt..
1. Subs. by G.S.R. 431(E), dt. 30.6.2005. for ― such that finished batch of a drug can be traced to the retail level‖.
Drugs and Cosmetics Rules 1945
445
27. Product Recalls:
27.1 A prompt and effective product recall system of defective products shall be
devised for timely information of all concerned stockists, wholesalers, suppliers,
upto the retail level within the shortest period. The licensee may make use of both
print and electronic media in this regard.
27.2. There shall be an established written procedure in the form of Standard Operating
Procedure for effective recall of products distributed by the licensee. Recall
operations shall be capable of being initiated promptly so as to effectively reach at
the level of each distribution channel.
27.3 The distribution records shall be readily made available to the persons designated
for recalls.
27.4 The designated person shall record a final report issued, including reconciliation
between the delivered and the recovered quantities of the products.
27.5 The effectiveness of the arrangements for recalls shall be evaluated from time to
time.
27.6 The recalled products shall be stored separately in a secured segregated area
pending final decision on them.
28. Complaints and Adverse Reactions:.
28.1 All complaints thereof concerning product quality shall be carefully reviewed and
recorded according to written procedures. Each complaint shall be
investigated/evaluated by the designated personnel of the company and records of
investigation and remedial action taken thereof shall be maintained.
28.2. Reports of serious adverse drug reactions resulting from the use of a drug along
with comments and documents shall be forthwith reported to the concerned
licensing authority.
28.3 There shall be written procedures describing the action to be taken, recall to be
made of the defective product.
29. Site Master File. –The licensee shall prepare a succinct document in the form of
‗Site Master File‘ containing specific and factual Good Manufacturing Practices about the
production and/or control of pharmaceutical manufacturing preparations carried out at the
licensed premises. It shall contain the following: -
29.1 General information:
(a) brief information of the firm;
(b) pharmaceutical manufacturing activities as permitted by the licensing authority;
(c) other manufacturing activities, if any, carried out on the premises;
(d) type of products licensed for manufacture with flow charts mentioning procedure
and process flow;
(e) number of employees engaged in the production, quality control, storage and
distribution;
(f) use of outside scientific, analytical or other technical assistance in relation to
manufacture and analysis;
(g) short description of the Quality Management System of the firm; and
(h) products details registered with foreign countries.
Drugs and Cosmetics Rules 1945
446
29.2 Personnel:
(a) organisational chart showing the arrangement for quality assurance including
production and quality control;
(b) qualification, experience and responsibilities of key personnel;
(c) outline for arrangements for basic and in-service training and how the records are
maintained;
(d) health requirements for personnel engaged in production; and
(e) personnel hygiene requirements, including clothing.
29.3 Premises:
(a) simple plan or description of manufacturing areas drawn to scale;
(b) nature of construction and fixtures/fittings;
(c) brief description of ventilation systems. More details should be given for critical
areas with potential risk of airborne contamination (schematic drawing of
systems). Classification of the rooms used for the manufacture of sterile products
should be mentioned;
(d) special areas for the handling of the highly toxic, hazardous and sensitizing
materials;
(e) brief description of water system (schematic drawings of systems), including
sanitation;
(f) description of planned preventive maintenance programs for premises and of the
recording system.
29.4 Equipment:
(a) brief description of major equipment used in production and Quality Control
Laboratories (a list of equipment
required);
(b) description of planned preventive maintenance programs for equipment and of the
recording system; and
(c) qualification and calibration including the recording systems and arrangements for
computerized systems validation.
29.5
Sanitation:
(a) availability of written specifications and procedures for cleaning manufacturing
areas and equipment.
29.6 Documentation. -
(a) arrangements for the preparation, revision and distribution of;
(b) necessary documentation for the manufacture;
(c) any other documentation related to product quality that is not mentioned elsewhere
(e.g. microbiological controls about air and water).
29.7 Production:.
(a) brief description of production operations using, wherever possible, flow sheets
and charts specifying important parameters;
(b) arrangements for the handling of starting materials, packaging materials, bulk
and
Drugs and Cosmetics Rules 1945
447
finished products, including sampling, quarantine, release and storage;
(c) arrangements for the handling of rejected materials and products;
(d) brief description of general policy for process validation.
29.8 Quality Control:
(a) description of the quality control system and of the activities of the Quality Control
Department. Procedures for the release of the finished products.
29.9 Loan licence manufacture and licensee:
(a) description of the way in which compliance of Good Manufacturing Practices by
the loan licensee shall be assessed.
29.10 Distribution, complaints and product recall:
(a) arrangements and recording system for distribution;
(b) arrangements for the handling of complaints and product
recalls.
29.11 Self inspection. -
(a) short description of the self-inspection system indicating whether an outside,
independent and experienced external expert was involved in evaluating the
manufacturer‘s compliance with Good manufacturing Practices in all aspects of
production.
29.12 Export of drugs. -
(a) products exported to different countries;
(b) complaints and product recall, if any.
PART
IA
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF STERILE
PRODUCTS,
PARENTERAL PREPARATIONS (SMALL VOLUME INJECTABLES AND
LARGE
VOLUME PARENTERALS) AND STERILE OPHTHALMIC
PREPARATIONS.
Note. - The general requirements as given in Part 1 of this Schedule relating to Requirements
of Good Manufacturing Practices for Premises and Materials for pharmaceutical products
shall be complied with, mutatis mutandis, for the manufacture of sterile products, Parenteral
preparations (Small Volume Injectables and Large Volume Parenterals) and Sterile
Ophthalmic Preparations. In addition to these requirements, the following specific
requirements shall also be followed, namely: -
1. General :
Sterile products, being very critical and sensitive in nature, a very high degree of
precautions, prevention and preparations are needed. Dampness, dirt and darkness are to be
avoided to ensure aseptic conditions in all areas. There shall be strict compliance in the
prescribed standards especially in the matter of supply of water, air, active materials and
in
the maintenance of hygienic environment.
Drugs and Cosmetics Rules 1945
448
2. Buildings and Civil Works:
2.1 The buildings shall be built on proper foundation with standardized materials
to avoid cracks in critical areas like aseptic solution preparation, filling and sealing rooms.
2.2 Location of services like water, steam, gases etc. shall be such that their
servicing or repair shall not pose any threat to the integrity of the facility. Water lines shall
not pose any threat of leakage to aseptic area.
2.3. The manufacturing areas shall be clearly separated into support areas (e.g.
washing and component preparation areas, storage areas etc.), preparation areas (e.g. bulk
manufacturing area, non-aseptic blending areas etc.) change areas and aseptic areas.
Operations like removal of outer cardboard wrappings of primary packaging materials shall
be done in the de-cartoning areas which are segregated from the washing areas. Wooden
pallets, fiber board drums, cardboard and other particle shedding materials shall not be taken
inside the preparation areas.
2.4. In aseptic areas –
(a) walls, floors and ceiling should be impervious, non-shedding, non-flaking and
non-cracking. Flooring should be unbroken and provided with a cove both at
the junction between the wall and the floor as well as the wall and the ceiling.
(b) walls shall be flat, and ledges and recesses shall be avoided. Wherever other
surfaces join the wall (e,g, sterilizers, electric sockets, gas points etc.) these
shall flush the walls. Walls shall be provided with a cove at the joint between
the ceiling and the floor;
(c) ceiling shall be solid and joints shall be sealed. Light-fittings and air-grills shall
flush with the walls and not hanging from the ceiling, so as to prevent
contamination;
(d) there shall be no sinks and drains in Grade A and Grade B areas;
(e) doors shall be made of non-shedding material. These may be made preferably
of Aluminium or Steel material. Wooden doors shall not be used. Doors shall
open towards the higher-pressure area so that they close automatically due to air
pressure;
(f) Windows shall be made of similar material as the doors, preferably with double
panel and shall be flush with the walls. If fire escapes are to be provided, these
shall be suitably fastened to the walls without any gaps;
(g) The furniture used shall be smooth, washable and made of stainless steel or
any other appropriate material other than wood.
2.5. The manufacturing and support areas shall have the same quality of civil
structure described above for aseptic areas, except the environmental standards which may
vary in the critical areas.
2.6 Change rooms with entrance in the form of air-locks shall be provided before
entry into the sterile product manufacturing areas and then to the aseptic area. Separate exit
space from the aseptic areas is advisable. Change rooms to the aseptic areas shall be clearly
demarcated into ‗black‘. ‗grey‘, and ‗white rooms‘ with different levels of activity and air
cleanliness. The ‗black‘ change room shall be provided with a hand-washing sink. The sink
Drugs and Cosmetics Rules 1945
449
and its drain in the un-classified (first) change rooms may be kept clean all the time. The specially
designed drain shall be periodically monitored to avoid presence of pathogenic micro-organisms.
Change room doors shall not be opened simultaneously. An appropriate inter-locking system and a
visual and/or audible warning system may be installed to prevent the opening of more than one door at a
time.
2.7. For communication between aseptic areas and non-aseptic areas, intercom
telephones or speak-phones shall be used. These shall be minimum in number.
2.8 Material transfer between aseptic areas and outside shall be through suitable airlocks or
pass-boxes. Doors of such airlocks and pass-boxes shall have suitable interlocking arrangements.
2.9. Personal welfare areas like rest rooms, tea room, canteen and toilets shall be outside
and separated from the sterile product manufacturing area.
2.10 Animal houses shall be away from the sterile product manufacturing area and shall not
share a common entrance or air handling system with the manufacturing area.
3. Air Handling System (Central Air-Conditioning):
3.1 Air Handling Units for sterile product manufacturing areas shall be different from
those for other areas. Critical areas, such as the aseptic filling area, sterilized components
unloading area and change room conforming to Grades B, C and D respectively shall have separate air
handling units. The filter configuration in the air handling system shall be suitably designed to achieve
the Grade of air as given in Table1. Typical operational activities for clean areas are highlighted in
Table II and Table III.
3.2 For products which are filled aseptically, the filling room shall meet Grade B conditions
at rest unmanned. This condition shall also be obtained within a period of about 30 minutes of the
personnel leaving the room after completion of operations.
3.3. The filling operations shall take place under Grade A conditions which shall be
demonstrated under working of simulated conditions which shall be achieved by providing laminar air
flow work stations with suitable HEPA filters or isolator technology.
3.4. For products, which are terminally sterilized, the filling room shall meet Grade C
conditions at rest. This condition shall be obtainable within a period of about 30 minutes of the
personnel leaving the room after completion of operations.
3.5. Manufacturing and component preparation areas shall meet Grade C
conditions.
3.6. After completion of preparation, washed components and vessels shall be protected
with
1
[Grade D background and should be handled in such a way that they are not recontaminated].
3.7. The minimum air changes for Grade B and Grade C areas shall not be less than 20
air changes per hour in a room with good air flow pattern and appropriate HEPA filters. For Grade A
laminar air flow work stations, the air flow rate shall be 0.3 meter per second ± 20% (for vertical flows)
and 0.45 meter per second ± 20% (for horizontal flows).
3.8. Differential pressure between areas of different environmental standards shall be at
least 15 Pascal (0.06 inches or 1.5 mm water gauge). Suitable manometers or gauges shall be
installed to measure and verify pressure differential.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005
Drugs and Cosmetics Rules 1945
450
3.9 The final change room shall have the same class of air as specified for the
aseptic area. The pressure differentials in the change rooms shall be in the descending order
from ‗white‘ to ‗black‘.
3.10 Unless there are product specific requirements, temperature and humidity in
the aseptic areas
1
[shall be 27 ± 2 degree centigrade and relative humidity 55% ± 5,
respectively].
1
[TABLE
I
AIR BORNE PARTICULATE CLASSIFICATION FOR
MANUFACTURE
OF STERILE
PRODUCTS
Grade
Maximum number of permitted particles per cubic metre equal t to or above
At rest
(b)
In operation (a)
0.5µm
5µm
0.5µm
5µm
A
3500
0
3500
0
B (a)
3500
0
3,50,000
2,000
C (a)
350,000
2,000
35,00,000
20,000
D (a)
35,00,000
20,000
Not defined (c)
Not defined (c)]
Notes :
(a)
In order to reach the B, C and D air grades, the number of air changes shall be
related to the size of the room and the equipment and personnel present in the
room. The air system shall be provided with the appropriate filters such as HEPA
for Grades A, B and C. The maximum permitted number of particles in the ―at rest‖
condition shall approximately be as under:
1
[Grade A and B corresponds with class 100 or M 3.5 or class 5]; Grade C with Class
10,000 or M 5.5 or ISO Class 7; Grade D with Class 1,00,000 or M 6.5 or ISO Class 8.
(b) The requirement and limit for the area shall depend on the nature of the operation carried
out.
(c) Type of operations to be carried out in the various grades are given in Table II and Table
III as under:
TABLE
II
TYPES OF OPERATIONS TO BE CARRIED OUT IN THE
VARIOUS
GRADES FOR ASEPTIC
PREPARATIONS
Grade
Types of operations for aseptic preparations
A
Aseptic preparation and filling
B
Background room conditions for activities requiring Grade A
C
Preparation of solution to be filtered
D
Handling of components after washing
1. Subs. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
451
TABLE
III
TYPES OF OPERATIONS TO BE CARRIED OUT IN THE
VARIOUS
GRADES FOR TERMINALLY STERILIZED
PRODUCTS
Grade
Types of operations for terminally sterilized products.
A
Filling of products, which are usually at risk.
C
Placement of filling and sealing machines, preparation of solutions when
1
[unusually at
risk]. Filling of product when unusually at risk.
D
Moulding, blowing (pre-forming) operations of plastic containers, preparations of
solutions and components for subsequent filling.
4. Environmental Monitoring:
4.1 All environmental parameters listed under para 3.1 to 3.10 shall be verified and
established at the time of installation and thereafter monitored at periodic intervals. The
recommended frequencies of periodic monitoring shall be as follows :-
(a) Particulate monitoring in air – 6 Monthly.
(b) HEPA filter integrity testing (smoke testing) – Yearly
(c) Air change rates – 6 Monthly.
(d) Air pressure differentials – Daily.
(e) Temperature and humidity – Daily
(f) Microbiological monitoring by settle plates and/or swabs in aseptic areas–
Daily, and at decreased frequency in other areas.
`Note: The above frequencies of monitoring shall be changed as per the
requirements and load in individual cases.
4.2 There shall be a written environmental monitoring program and
microbiological results shall be recorded. Recommended limits for microbiological
monitoring of clean areas ―in operation‖ are as given in the table below:
TABLE
RECOMMENDED LIMITS FOR
MICROBIOLOGICAL
MONITORING OF
CLEAN
AREAS ― IN
OPERATION‖
Grade
Air
samp
le
Cfu/m
2
Settle plates (dia.
90mm.
Cfu/2
hrs.
Contact
plates
(dia. 55mm) cfu
per
plate
Glove
points
(five fingers)
cfu
per
glove
A
<
1
<
1
<
1
<
1
B
10
5
5
5
C
100
50
25
--
D
500
100
50
--
Notes:
(a) These are average values.
(b) Individual settle plates may be exposed for not less than two hours in Grade B,
C and D areas and for not less than thirty minutes in Grade A area.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
452
4.3 Appropriate action shall be taken immediately if the result of particulate and
microbiological monitoring indicates that the counts exceed the limits. The Standard
Operating Procedures shall contain corrective action. After major engineering modification to
the HVAC system of any area, all monitoring shall be re-performed before production
commences.
5. Garments.
5.1 This section covers garments required for use by personnel working only in
aseptic area. Outdoor clothing shall not be brought into the sterile areas.
5,2 The garments shall be made of non-shedding and tight weave material.
Cotton garments shall not be used. The garments shall shed virtually no fibres or particulate
matter.
5.3 The clothing and its quality shall be adopted to the process and the work
place and worn in such a way as to protect the product from contamination. Garments shall be
single piece with fastenings at cuffs, neck and at legs to ensure close fit. Trouser legs shall be
tucked inside the cover boots. Suitable design of garments shall either include a hood (head-
cover) or a separate hood which can be tucked inside the over-all. Pockets, pleats and belts
shall be avoided in garments. Zips (if any) shall be of plastic material. Garments with
damaged zips shall not be used.
5.4. Only clean, sterilized and protective garments shall be used at each work
session where aseptic filtration and filling operations are undertaken and at each work shift
for products intended to be sterilized, post-filling. The mask and gloves shall be changed at
every work session in both instances.
5.5 Gloves shall be made of latex or other suitable plastic materials and shall be
powder-free. These shall be long enough to cover wrists completely and allow the over-all
cuff to be tucked in.
5.6. The footwear shall be of suitable plastic or rubber material and shall be daily
cleaned with a bactericide.
5.7. Safety goggles or numbered glasses with side extension shall be used inside
aseptic areas. These shall be sanitized by a suitable method.
5.8. Garment changing procedures shall be documented and operators trained in
this respect. A full size mirror shall be provided in the final change room for the operator to
verify that he is appropriately attired in the garments. Periodic inspection of the garments
shall be done by responsible staff.
6. Sanitation:
6.1. There shall be written procedures for the sanitation of sterile processing
facilities. Employees carrying out sanitation of aseptic areas shall be trained specifically for
this purpose.
6.2. Different sanitizing agent shall be used in rotation and the concentrations of
the same shall be as per the recommendations of the manufacturer. Records of rotational use
of sanitizing agents shall be maintained.
6.3. Distilled water freshly collected directly from the distilled water plant or
water maintained above 70 degree centigrade from the re-circulation loop shall be used for
dilution of disinfectants. Alternatively, distilled water sterilized by autoclaving or membrane
filtration shall be used. The dilution shall be carried out in the ‗white‘ change room.
Drugs and Cosmetics Rules 1945
453
6.4.
1
[Where alcohol or isopropyl alcohol is used for dilution of disinfectants for
use as hand sprays, the preparation of the same shall be done in the bulk preparation area in
grade C.]
6.5. Diluted disinfectants shall bear the label ‗use before‘, based on
microbiological establishment of the germicidal properties. The solutions shall be adequately
labelled and documents maintained.
6.6. Formaldehyde or any other equally effective fumigant is recommended for
the fumigation of aseptic areas or after major civil modifications. There shall be Standard
Operating Procedures for this purpose. Its use for routine purpose shall be discouraged and an
equally effective surface cleaning regime shall be followed.
6.7. Cleaning of sterile processing facilities shall be undertaken with air suction
devices or with non-linting sponges or clothes.
6.8. Air particulate quality shall be evaluated on a regular basis and record
maintained.
7. Equipment:
7.1 The special equipment required for manufacturing sterile products includes
component washing machines, steam sterilizers, dry heat sterilizers, membrane filter
assemblies, manufacturing vessels, blenders, liquid filling machines, powder filling machines,
sealing and labelling machines, vacuum testing chambers, inspection machines, lyophilisers,
pressure vessels etc. Suitable and fully integrated washing sterilizing filling lines may be
provided, depending upon the type and volume of activity.
7.2. Unit-sterilizers shall be double-ended with suitable inter-locking
arrangements between the doors. The effectiveness of the sterilization process shall be
established initially by biological inactivation studies using microbial spore indicators and
then at least once a year by carrying out thermal mapping of the chamber. Various
sterilization parameters shall be established based on these studies and documented. For
membrane filters used for filtration, appropriate filter integrity tests that ensure sterilization
shall be carried out before and after filtration.
7.3. Filling machines shall be challenged initially and then at periodic intervals by
simulation trials including sterile media fill. Standard Operating Procedures and acceptance
criteria for media fills shall be established, justified and documented. Special simulation trial
procedures shall be developed, validt. and documented for special products like ophthalmic
ointments.
7.4. The construction material used for the parts which are in direct contact with
products and the manufacturing vessels may be stainless steel 316 or Boro-silicate glass (if
glass containers) and the tubing shall be capable of being washed and autoclaved.
7.5 On procurement, installation qualification of each of the equipment shall be done
by engineers with the support of production and quality assurance personnel. Equipment for
critical processes like aseptic filling and sterilizers shall be suitably validt. according to a
written program before putting them to use.
7.6. Standard Operating Procedures shall be available for each equipment for its
calibration and operation and cleaning. Gauges and other measuring devices attached to
equipment shall be calibrated at suitable intervals against a written program. Calibration
status of equipment gauges shall be adequately documented and displayed.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
454
8. Water and Steam Systems:
8.1. Potable water meeting microbiological specification of not more than 500
cfu/ml and indicating absence of individual pathogenic micro-organisms. Escherichia coli,
Salmonella, Staphylococcus aureus and Pseudomonas aeruginosa per 100 ml sample shall be
used for the preparation of purified water.
8.2 Purified water prepared by de-mineralization shall meet the microbiological
specification of not more than 100 cfu per ml and indicate absence of pathogenic micro-
organisms in 100 ml. Purified water shall also meet IP specification for chemical quality.
Purified water shall be used for hand washing in change rooms. Containers, closures and
machine parts may be washed with potable water followed by suitably filtered purified water.
Purified water shall be stored in stainless steel tanks or plastic tanks.
8.3. Water for Injection (hereinafter as WFI) shall be prepared from potable water or
purified water meeting the above specifications by distillation. Water for Injection shall meet
microbiological specification of not more than 10 cfu per 100 ml. WFI shall also meet IP
specification for Water for Injection and shall have an endotoxin level of not more than
0.25 EU/Ml. Bulk solutions of liquid parenterals shall be made in WFI. Final rinse of product
containers and machine parts shall be done with WFI. Disinfectant solutions for use in aseptic
areas shall be prepared in WFI.
8.4. Water for Injection for the manufacture of liquid injectables shall be freshly
collected from the distillation plant or from a storage or circulation loop where the water has
been kept at above 70 degree centigrade. At the point of collection, water may be cooled
using suitable heat exchanger.
8.5 Water for non-injectable sterile products like eye drops shall meet IP
specifications for purified water. In addition, microbiologial specification of not more than 10
cfu per 100 ml and absence of Pseudomonas aeruginosa and Enterobacter coli in 100 ml
shall also be met.
8.6. Water for Injection shall be stored in steam jacketed stainless steel tanks of
suitable size and the tanks shall have hydrophobic bacterial retention with 0.22 µ vent filters.
The filters shall be suitably sterilized at periodic intervals. The distribution lines for purified
water and distilled water shall be of stainless steel 316 construction and shall not shed
particles.
8.7. There shall be a written procedure and program for the sanitation of different
water systems including storage tanks, distribution lines, pumps and other related equipment.
Records of sanitation shall be maintained.
8.8. There shall be written microbiological monitoring program for different types of
water. The results shall justify the frequency of sampling and testing. Investigation shall be
carried out and corrective action taken in case of deviation from prescribed limits.
1
[8.9 Steam coming in contact with the product, primary containers and other
product contact surfaces shall be sterile and pyrogen free.]
9. Manufacturing Process:
9.1. Manufacture of sterile products shall be carried out only in areas under
defined conditions.
1. Omitted by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
455
9.2. Bulk raw materials shall be monitored for bio-burden periodically. Bio-
burden of bulk solution prior to membrane filtration shall be monitored periodically and a
limit of not more than 100 cfu per ml is recommended.
9.3 The time between the start of the preparation of the solution and its
sterilization or filtration through a micro-organism retaining filter shall be minimized. There
shall be a set maximum permissible time for each product that takes into account its
composition and method of storage mentioned in the Master formula record.
9.4. Gases coming in contact with the sterile product shall be filtered through two
0.22 µ hydrophobic filters connected in-series. These filters shall be tested for integrity. Gas
cylinders shall not be taken inside aseptic areas.
9.5. Washed containers shall be sterilized immediately before use. Sterilized
containers, if not used within an established time, shall be rinsed with distilled or filtered
purified water and re-sterilized.
9.6. Each lot of finished product shall be filled in one continuous operation. In
each case, where one batch is filled in using more than one operation, each lot shall be tested
separately for sterility and held separately till sterility test results are known.
9.7. Special care shall be exercised while filling products in powder form so as not
to contaminate the environment during transfer of powder to filling machine-hopper.
10. Form-Fill-Seal Technology or Blow, Fill-Seal Technology:
10.1 Form-Fill-Seal units are specially built automated machines in which through
one continuous operation, containers are formed from thermoplastic granules, filled and then
sealed. Blow, fill-seal units are machines in which containers are moulded / blown (pre-
formed) in separate clean rooms, by non-continuous operations.
Note:
(i) These shall be installed in at least Grade C environment.
(ii) These shall comply with the limits as recommended in Table at Item 4.2.
10.2. Form-Fill-Seal/Blow, Fill-Seal machines used for the manufacture of
products for terminal sterilization shall be installed in at least Grade C environment and the
filling zone within the machine shall fulfil Grade A requirements.
10.3. Terminally sterilized products.–
10.3.1. Preparation of primary packaging material such as glass bottles, ampoules
and rubber stoppers shall be done in at least Grade D environment. Where there is unusual
risk to the product from microbial contamination, the above operation shall be done in Grade
C environment. All the processes used for component preparation shall be validt..
10.3.2. Filling of products requiring terminal sterilization shall be done under Grade
A environment with a Grade C background.
10.4 Preparation of solutions, which are to be sterilized by filtration, shall be done in
Grade C environment, and if not to be filtered, the preparation of materials and products shall
be in a Grade A environment with Grade B in background.
Drugs and Cosmetics Rules 1945
456
10.5 Filtration (Membrane).-
(i) Solutions for Large Volume Parenterals shall be filtered through a non-fibre releasing,
sterilizing grade cartridge/membrane filter of nominal pore size of 0.22 µ for aseptic
filling whereas 0.45 µ porosity shall be used for terminally sterilized products.
(ii) A second filtration using another 0.22 µ sterilizing grade cartridge / membrane filter
shall be performed immediately prior to filling. Process specifications shall indicate
the maximum time during which a filtration system may be used with a view to
precluding microbial build-up to levels that may affect the microbiological quality of
the Large Volume Parenterals.
(iii) The integrity of the sterilized filter shall be verified and confirmed immediately after
use by an appropriate method such as Bubble Point, Diffusive Flow or Pressure Hold
Test.
10.6 Sterilization (Autoclaving).–
10.6.1. Before any sterilization process is adopted, its suitability for the product and
its efficacy in achieving the desired sterilizing conditions in all parts of each type of load
pattern to be processed, shall be demonstrated by physical measurements and by biological
indicators, where appropriate.
10.6.2 All the sterilization process shall be appropriately validt.. The validity of the
process shall be verified at regular intervals, but at least annually. Whenever significant
modifications have been made to the equipment and product, records shall be maintained
thereof.
10.6.3 The sterilizer shall be double ended to prevent mix-ups.
10.6.4 Periodic bio-burden monitoring of products before terminal sterilization shall
be carried out and controlled to limits specified for the product in the Master Formula.
10.6.5 The use of biological indicators shall be considered as an additional method
of monitoring the sterilization. These shall be stored and used according to the manufacturer‘s
instructions. Their quality shall be checked by positive controls. If biological indicators used,
strict precautions shall be taken to avoid transferring microbial contamination from them.
10.6.6 There shall be clear means of differentiating ‗ sterilized‘ and ‗un-sterilized‘
products. Each basket, tray or other carrier of products or components shall be clearly labelled
with the name of the material, its batch number, and sterilization status. Indicators shall be
used, where appropriate, to indicate whether a batch (or sub-batch) has passed through the
sterilization process.
10.6.7 Sterilization records shall be available for each sterilization-run and may also
include thermographs and sterilization monitoring strips. They shall be maintained as part of
the batch release procedure.
10.7. Sterilization (By dry heat).–
10.7.1 Each heat sterilization cycle shall be recorded on a time/temperature chart
of a suitable size by appropriate equipment of the required accuracy and precision. The
position of temperature probes used for controlling and/or recording shall be determined
during the validation and, where applicable, shall also be checked against a second
independent temperature probe located in the same position. The chart shall form a part of the
Drugs and Cosmetics Rules 1945
457
batch record. Container mapping may also be carried out in the case of Large Volume
Parenterals.
10.7.2 Chemical or biological indicators may also be used, but shall not take the place
of physical validation.
10.7.3. Sufficient time shall be allowed for the load to reach the required
temperature before measurement of sterilization time commences. This time shall be
separately determined for each type of load to be processed.
10.7.4. After the high temperature phase of a heat sterilization cycle, precautions
shall be taken against contamination of sterilized load during cooling. Any cooling fluid or
gas in contact with the product shall be sterilized unless it can be shown that any leaking
container would not be approved for use. Air inlet and outlets shall be provided with bacterial
retaining filters.
10.7.5. The process used for sterilization by dry heat shall include air-circulation
within the chamber and the maintenance of a positive pressure to prevent the entry of non-
sterile air. Air inlets and outlets should be provided with micro-organism retaining filters.
Where this process of sterilization by dry heat is also intended to remove pyrogens, challenge
tests using endotoxins would be required as part of the validation process.
10.8. Sterilization (By Moist Heat).-
10.8.1 Both the temperature and pressure shall be used to monitor the process.
Control instrumentation shall normally be independent of monitoring instrumentation and
recording charts. Where automated control and monitoring systems are used for these
applications, these shall be validt. to ensure that critical process requirements are met. System
and cycle faults shall be registered by the system and observed by the operator. The reading
of the independent temperature indicator shall be routinely checked against the chart-recorder
during the sterilization period. For sterilizers fitted with a drain at the bottom of the chamber,
it may also be necessary to record the temperature at this position throughout the sterilization
period. There shall be frequent leak tests done on the chamber during the vacuum phase of the
cycle.
10.8.2 The items to be sterilized, other than products in sealed containers, shall be
wrapped in a material which allows removal of air and penetration of steam but which
prevents re-contamination after sterilization. All parts of the load shall be in contact with the
sterilizing agent at the required temperature for the required time.
10.8.3. No Large Volume Parenteral shall be subjected to steam sterilization cycle
until it has been filled and sealed.
10.8.4 Care shall be taken to ensure that the steam used for sterilization is of a
suitable quality and does not contain additives at a level which could cause contamination of
the product or equipment.
10.9. Completion/finalisation of sterile products–
10.9.1. All unit operations and processes in the manufacture of a batch shall have a
minimum time specified and the shortest validt. time shall be used from the start of a batch to
its ultimate release for distribution.
Drugs and Cosmetics Rules 1945
458
10.9.2. Containers shall be closed by appropriately validt. methods. Containers
closed by fusion e.g. glass or plastic ampoules shall be subjected to 100% integrity testing.
Samples of other containers shall be checked for integrity according to appropriate
procedures.
10.9.3 Containers sealed under vacuum shall be tested for required vacuum
conditions.
10.9.4 Filled containers of parenteral products shall be inspected individually for
extraneous contamination or other defects. When inspection is done visually, it shall be done
under suitably controlled conditions of illumination and background. Operators doing the
inspection shall pass regular eye-sight checks with spectacles, if worn, and be allowed
frequent rest from inspection. Where other methods of inspection are used, the process shall
be validt. and the performance of the equipment checked at suitable intervals. Results shall be
recorded.
11. Product Containers and Closures. –
11.1 All containers and closures intended for use shall comply with the
pharmacopoeial and other specified requirements. Suitable samples sizes, specifications, test
methods, cleaning procedures and sterilization procedures, shall be used to assure that
containers, closures and other component parts of drug packages are suitable and are not
reactive, additive, adsorptive or leachable or presents the risk of toxicity to an extent that
significantly affects the quality or purity of the drug. No second hand or used containers and
closures shall be used.
11.2 Plastic granules shall also comply with the pharmacopoeial requirements
including physio-chemical and biological tests.
11.3. All containers and closures shall be rinsed prior to sterilization with Water for
Injection according to written procedure.
11.4. The design of closures, containers and stoppers shall be such as to make
cleaning, easy and also to make airtight seal when fitted to the bottles.
11.5 It shall be ensured that containers and closures chosen for a particular
product are such that when coming into contact they are not absorbed into the product and
they do not affect the product adversely. The closures and stoppers should be of such quality
substances as not to affect the quality of the product and avoid the risk of toxicity.
11.6. Whenever glass bottles are used, the written schedule of cleaning shall be laid
down and followed. Where bottles are not dried after washing, these shall be finally
rinsed with distilled water or pyrogen free water, as the case may be, according to written
procedure.
11.7. Individual containers of parenteral preparations, ophthalmic preparations shall
be examined against black/white background fitted with diffused light after filling so as to
ensure freedom from foreign matters.
11.8 Glass Bottles. –
11.8.1 Shape and design of the glass bottle shall be rational and standardized.
Glass bottles made of USP Type-I and USP Type-II glass shall only be used. Glass bottles
shall not be reused. Before use, USP Type-II bottles shall be validt. for the absence of
particulate matter generated over a period of the shelf -life of the product and shall be
Drugs and Cosmetics Rules 1945
459
regularly monitored after the production, following statistical sampling methods. USP Type-
III glass containers may be used for non-parenteral sterile products such as Otic Solutions.
11.9. Plastic Containers. –
11.9.1 Pre-formed plastic containers intended to be used for packing of Large
Volume Parenteral shall be moulded in-house by one-continuous operation through an
automatic machine.
11.9.2. Blowing, filling and sealing (plugging) operation shall be conducted in
room(s) conforming to requirements as mentioned in Table III of Item 3.10. Entry to the area
where such operations are undertaken, shall be through a series of airlocks. Blowers shall
have an air supply which is filtered through 0.22µ filters. Removal of runners and plugging
operations shall be conducted under a laminar airflow workstation.
11.10 Rubber Stoppers.
–
11.10.1 The rubber stoppers used for Large Volume Parenterals shall comply with
specifications prescribed in the current edition of the Indian Pharmacopoeia.
12. Documentation:
12.1 The manufacturing records relating to manufacture of sterile products shall
indicate the following details:-
(1) Serial number of the Batch Manufacturing Record.
(2) Name of the product
(3) Reference to Master Formula Record.
(4) Batch/Lot number
(5) Batch/Lot size.
(6) Date of commencement of manufacture and date of completion of manufacture.
(7) Date of manufacture and assigned date of expiry.
(8) Date of each step in manufacturing.
(9) Names of all ingredients with the grade given by the quality control department.
(10) Quality of all ingredients.
(11) Control reference numbers for all ingredients.
(12) Time and duration of blending, mixing, etc. whenever applicable.
(13) pH of solution whenever applicable.
(14) Filter integrity testing records
(15) Temperature and humidity records whenever applicable
(16) Records of plate-counts whenever applicable.
(17) Results of pyrogen and/or bacterial endotoxin & toxicity.
(18) Records of weight or volume of drug filled in containers.
(19) Bulk sterility in case of aseptically filled products.
(20) Leak test records.
(21) Inspection records.
(22) Sterilization records including autoclave leakage test records, load details, date,
duration, temperature, pressure, etc.
(23) Container washing records.
(24) Total number of containers filled.
(25) Total numbers of containers rejected at each stage
(26) Theoretical yield, permissible yield, actual yield and variation thereof.
(27) Clarification for variation in yield beyond permissible yield.
(28) Reference numbers of relevant analytical reports.
(29) Details of reprocessing, if any.
Drugs and Cosmetics Rules 1945
460
(30) Name of all operators carrying out different activities.
(31) Environmental monitoring records.
(32) Specimens of printed packaging materials.
(33) Records of destruction of rejected containers and printed packaging materials.
(34) Signature of competent technical staff responsible for manufacture and testing.
Note:
(1)
Products shall be released only after complete filling and testing.
(2)
Result of the tests relating to sterility, pyrogens, and Bacterial
endotoxins shall be maintained in the analytical records.
(3)
Validation details and simulation trial records shall be maintained
separately,
(4)
Records of environmental monitoring like temperature, humidity,
microbilogical data, etc. shall be maintained. Records of periodic
servicing of HEPA filters, sterilizers and other periodic maintenance
of facilities and equipment carried out also be maintained.
(5)
Separate facilities shall be provided for filling-cum-sealing of Small
Volume Injectables and Large Volume Parenterals.
(6)
It is advisable to provide separate facilities for manufacture of
Large Volume Parenterals in glass containers and / or plastic
containers.
(7)
For manufacture of Large Volume Parenterals in plastic containers,
it is advisable to instal automatic (with all operations) Form–Fill-
Seal machines having one continuous operation.
PART
IB
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL SOLID
DOSAGE
FORMS (TABLETS AND
CAPSULES)
Note: - The General Requirements as given in Part 1 of this Schedule relating to
requirements of Good Manufacturing Practices for Premises and materials for
pharmaceutical products shall be complied with, mutatis mutandis, for the manufacture of oral
Solid Dosage Forms (Tablets and Capsules). In addition to these requirements, the following
Specific Requirement shall also be followed, namely :-
1. General:
1.1 The processing of dry materials and products creates problems of dust control
and cross-contamination. Special attention is therefore, needed in the design, maintenance
and use of premises and equipment in order to overcome these problems. Wherever
required, enclosed dust control manufacturing systems shall be employed.
1.2. Suitable environmental conditions for the products handled shall be
maintained by installation of air-conditioning wherever necessary. Effective air-extraction
systems, with discharge points situated to avoid contamination of other products and
processes shall be provided. Filters shall be installed to retain dust and protect the factory and
local environment.
Drugs and Cosmetics Rules 1945
461
1.3. Special care shall be taken to protect against subsequent contamination of the
product by particles of metal or wood. The use of metal detector is recommended.
Wooden equipment should be avoided. Screens, sieves, punches and dies shall be examined
for wear and tear or for breakage before and after each use.
1.4. All ingredients for a dry product shall be sifted before use unless the
quality of the input material can be assured. Such sifting shall normally be carried out at
dedicated areas.
1.5.
1
[Where the facilities are designed to provide special environmental
conditions of pressure differentials between rooms, these conditions shall be regularly
monitored and any deviation shall be brought to the immediate attention of the production
and quality assurance departments].
1.6. Care shall be taken to guard against any material lodging and remaining
undetected in any processing or packaging equipment. Particular care shall be taken to ensure
that any vacuum, compressed air or air-extraction nozzles are kept clean and that there is no
evidence of lubricants leaking into the product from any part of the equipments.
2. Sifting, Mixing and Granulation:
2.1. Unless operated as a closed system, mixing, sifting and blending equipments
shall be fitted with dust extractors
1
[or in a dedicated area for each operation].
2.2. Residues from sieving operations shall be examined periodically for evidence of
the presence of unwanted materials.
2.3. Critical operating parameters like time and temperature for each mixing,
blending and drying operation shall be specified in a Master Formula, monitored during
processing, and recorded in the batch records.
2.4. Filter bags fitted to fluid-bed dryer shall not be used for different products,
without being washed in-between use. With certain highly potent or sensitizing products, bags
specific to one product only shall be used. Air entering the dryer shall be filtered. Steps shall
be taken to prevent contamination of the site and local environment by dust in the air leaving
the dryer due to close positioning of the air-inlets and exhaust.
2.5. Granulation and coating solutions shall be made, stored and used in a manner
which minimizes the risk of contamination or microbial growth.
3. Compressions (Tablets):
3.1. Each tablet compressing machine shall be provided with effective dust control
facilities to avoid cross-contamination. Unless the same product is being made on each
machine, or unless the compression machine itself provides its own enclosed air controlled
environment, the machine shall be installed in separate cubicles.
3.2. Suitable physical, procedural and labelling arrangements shall be made to
prevent mix up of materials, granules and tablets on compression machinery.
3.3. Accurate and calibrated weighing equipment shall be readily available and
used for in-process monitoring of tablet weight variation. Procedures used shall be capable of
detecting out-of-limits tablets.
1. Ins. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
462
3.4. At the commencement of each compression run and in case of multiple
compression points in a compression machine, sufficient individual tablets shall be examined
at fixed intervals to ensure that a tablet from each compression station or from each
compression point has been inspected for suitable pharmacopoeial parameters like
‗appearance‘, ‗weight variation‘, ‗disintegration‘, ‗hardness‘, ‗friability‘ and ‗thickness‘. The
results shall be recorded as part of the batch documentation.
3.5. Tablets shall be de-dusted, preferably by automatic device and shall be
monitored for the presence of foreign materials besides any other defects.
3.6. Tablets shall be collected into clean, labelled containers.
3.7. Rejected or discarded tablets shall be isolated in identified containers and their
quantity recorded in the Batch Manufacturing Record.
3.8 In-process control shall be employed to ensure that the products remain within
specification. During compression, samples of tablets shall be taken at regular intervals of not
greater than 30 minutes to ensure that they are being produced in compliance with specified
in-process specification. The tablets shall also be periodically checked for additional
parameters such as ‗appearance‘, ‗weight variation‘, ‗disintegration‘, ‗hardness‘, ‗friability‘
and ‗thickness‘ and contamination by lubricating oil.
4. Coating (Tablets):
4.1. Air supplied to coating pans for drying purposes shall be filtered air and of
suitable quality. The area shall be provided with suitable exhaust system and environmental
control (temperature, humidity) measures.
4.2 Coating solutions and suspensions shall be made afresh and used in a manner,
which shall minimize the risk of microbial growth. Their preparation and use shall be
documented and recorded.
5. Filling of Hard Gelatin Capsule:
Empty capsules shells shall be regarded as ‗drug component‘ and treated accordingly.
They shall be stored under conditions which shall ensure their safety from the effects of
excessive heat and moisture.
6. Printing (Tablets and Capsules)
6.1. Special care shall be taken to avoid product mix-up during any printing of
tablets and capsules. Where different products, or different batches of the same product, are
printed simultaneously, the operations shall adequately be segregated. Edible grade colours
and suitable printing ink shall be used for such printing.
6.2. After printing, tablets and capsules shall be approved by Quality Control
before release for packaging or sale.
7. Packaging (Strip and Blister):
7.1. Care shall be taken when using automatic tablet and capsule counting, strip and
blister packaging equipment to ensure that all ‗rogue‘ tablets, capsules or foils from
packaging operation are removed before a new packaging operation is commenced. There
shall be an independent recorded check of the equipment before a new batch of tablets or
capsules is handled.
7.2. Uncoated tablets shall be packed on equipment designed to minimize the risk of
cross-contamination. Such packaging shall be carried out in an isolated area when potent
tablets or Beta-Iactum containing tablets are being packed.
1. Ins. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
463
7.3. The strips coming out of the machine shall be inspected for defects such as
misprint, cuts on the foil, missing tablets and improper sealing.
7.4. Integrity of individual packaging strips and blisters shall be subjected to
vacuum test periodically to ensure leak proofness of each pocket strip and blister and records
maintained.
PART
IC
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL
LIQUIDS
(SYRUPS, ELIXIRS, EMULSIONS AND
SUSPENSIONS)
Note: The General Requirements as given in Part I of this Schedule relating to
Requirements of Good Manufacturing Practices for Premises and Materials for
pharmaceutical products shall be complied with, mutatis mutandis, for the manufacture of
(Syrups, Elixirs, Emulsions and Suspensions). In addition to these requirements, the following
Specific Requirements shall also be followed, namely:-
1. Building and Equipment:.
1.1. The premises and equipment shall be designed, constructed and maintained to
suit the manufacturing of Oral Liquids. The layout and design of the manufacturing area shall
strive to minimize the risk of cross-contamination and mix-ups.
1.2. Manufacturing area shall have entry through double door airlock facility. It
shall be made fly proof by use of ‗fly catcher‘ and/or ‗air curtain‘.
1.3. Drainage shall be of adequate size and have adequate traps, without open
channels and the design shall be such as to prevent back flow. Drains shall be shallow to
facilitate cleaning and disinfecting.
1.4. The production area shall be cleaned and sanitized at the end of every
production process.
1.5. Tanks, containers, pipe work and pumps shall be designed and installed so
that they can be easily cleaned and sanitized. Equipment design shall be such as to prevent
accumulation of residual microbial growth or cross-contamination.
1.6. Stainless steel or any other appropriate material shall be used for parts of
equipments coming in direct contact with the products. The use of glass apparatus shall be
minimum.
1.7. Arrangements for cleaning of containers, closures and droppers shall be made
with the help of suitable machines/devices equipped with the high pressure air, water and
steam jets.
1.8. The furniture used shall be smooth, washable and made of stainless steel
1
[or
any other appropriate material which is scratch proof, washable and smooth].
2. Purified Water.
2.1. The chemical and microbiological quality of purified water used shall be
specified and monitored routinely. The microbiological evaluation shall include testing for
absence of pathogens and shall not exceed 100 cfu/ml (as per Appendix 12.5 of IP 1996.)
1. Added by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
464
2.2. There shall be a written procedure for operation and maintenance of the
purified water system. Care shall be taken to avoid the risk of microbial proliferation with
appropriate methods like re-circulation, use of UV treatment, treatment with heat and
sanitizing agent. After any chemical sanitisation of the water system, a flushing shall be done
to ensure that the sanitizing agent has been effectively removed.
3. Manufacturing:
3.1.
1
[Manufacturing personnel shall wear wherever required, non-fiber shedding
clothing to prevent contamination of the products].
3.2. Materials likely to shed fibre like gunny bags, or wooden pallets shall not be
carried into the area where products or cleaned-containers are exposed.
3.3. Care shall be taken to maintain the homogenecity of emulsion by use of
appropriate emulsifier and suspensions by use of appropriate stirrer during filling. Mixing and
filling processes shall be specified and monitored. Special care shall be taken at the beginning
of the filling process, after stoppage due to any interruption and at the end of the process to
ensure that the product is uniformly homogenous during the filling process.
3.4. The primary packaging area shall have an air supply which is filtered through
5 micron filters. The temperature of the area shall not exceed 30 degrees centigrade.
3.5. When the bulk product is not immediately packed, the maximum period of
storage and storage conditions shall be specified in the Master Formula. The maximum period
of storage time of a product in the bulk stage shall be validt..
PART
ID
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF TOPICAL PRODUCTS
,
i.e. EXTERNAL PREPARATIONS (CREAMS, OINTMENTS,
PASTES,
EMULSIONS, LOTIONS, SOLUTIONS, DUSTING POWDERS AND
IDENTICAL
PRODUCTS)
Note: The General Requirements as given in Part I of this Schedule relating to
Requirements of Good Manufacturing Practices for Premises and Materials for
pharmaceutical products shall be complied with, mutatis mutandis, for the manufacture of
Topical Products i.e. External preparations (Creams, Ointments, Pastes, Emulsions, Lotions,
Solutions, Dusting powders and identical products used for external applications). In
addition to these requirements, the following Specific Requirements shall also be followed,
namely: -
1. The entrance to the area where topical products are manufactured
shall be through a suitable airlock. Outside the airlock, insectocutors shall be
installed.
2. The air to this manufacturing area shall be filtered through at least 20µ
air filters and shall be air-conditioned.
2
[***].
3. The area shall be fitted with an exhaust system of suitable capacity to
effectively remove vapours, fumes, smoke, floating dust particles.
4. The equipment used shall be designed and maintained to prevent the
product from being accidentally contaminated with any foreign matter or
lubricant.
5.
3
[Suitable cleaning equipment and material] shall be used in the process
of cleaning or drying the process equipment or accessories used.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005.
2. The words ―The air shall be ventilated.‖ omitted by G.S.R. 431(E), dt. 30.6.2005.
3. Subs. by G.S.R. 431(E), dt. 30.6.2005, for ― no rags or dusters‖.
Drugs and Cosmetics Rules 1945
465
6. Water used in compounding shall be Purified Water IP.
7. Powders, wherever used, shall be suitably sieved before use.
8. Heating vehicles and a base like petroleum jelly shall be done in separate
mixing area in suitable stainless steel vessels, using steam, gas, electricity, solar
energy, etc.
9. A separate packing section may be provided for primary packaging of the
products.
PART
1E
SPECIFIC REQUIREMENTS FOR MANUFACTURE
OF
METERED-DOSE-INHALERS (MDI)
Note: The General Requirements as given in Part I of this Schedule relating to
Requirements of Good Manufacturing Practices for Premises and Materials for
pharmaceutical products shall be complied with, mutatis mutandis, for the manufacture of
Metered-Dose-Inhalers (MDI). In addition to these requirements, the following Specific
Requirements shall also be followed, namely: -
1. General:
Manufacture of Metered-Dose-Inhalers shall be done under conditions which shall
ensure minimum microbial and particulate contamination. Assurance of the quality of
components and the bulk product is very important. Where medicaments are in suspended
state, uniformity of suspension shall be established.
2. Building and Civil Works:
2.1. The building shall be located on a solid foundation to reduce risk of cracking
walls and floor due to the movement of equipment and machinery.
2.2 All building surfaces shall be impervious, smooth and non-shedding.
Flooring shall be continuous and provided with a cove between the floor and the wall as well
as the wall to the ceiling. Ceiling shall be solid, continuous and covered to walls. Light
fittings and air-grills shall be flush with the ceiling. All service lines requiring maintenance
shall be erected in such a manner that these are accessible from outside the production area.
2.3. The manufacturing area shall be segregated into change rooms for personnel,
container preparation area, bulk preparation and filling area, quarantine area and spray testing
and packing areas.
2.4. Secondary change rooms shall be provided for operators to change from
factory clothing to special departmental clothing before entering the manufacturing and filling
area.
2.5. Separate area shall be provided for de-cartoning of components before they
are air washed.
2.6. The propellants used for manufacture shall be delivered to the manufacturing
area distribution system by filtering them through 2µ filters. The bulk containers of
propellants shall be stored, suitably identified, away from the manufacturing facilities.
Drugs and Cosmetics Rules 1945
466
3. Environmental Conditions:
3.1. Where products or clean components are exposed, the area shall be supplied
with filtered air of Grade C.
3.2. The requirements of temperature and humidity in the manufacturing
area shall be decided depending on the type of product and propellants handled in the
facility. Other support areas shall have comfort levels of temperature and humidity.
3.3. There shall be a difference in room pressure between the manufacturing
area and the support areas and the differential pressure shall be not less than 15 Pascals (0.06
inches or 1.5 mm water gauge).
3.4. There shall be a written schedule for the monitoring of environmental
conditions. Temperature and humidity shall be monitored daily.
4. Garments:
4.1. Personnel in the manufacturing and filling section shall wear suitable single-
piece-garment made out of non-shedding, tight weave material. Personnel in support areas
shall wear clean factory uniforms.
4.2. Gloves made of suitable material having no interaction with the propellants
shall be used by the operators in the manufacturing and filling areas. Preferably, disposable
gloves shall be used.
4.3. Suitable department-specific personnel protective equipment like footwear
and safety glasses shall be used wherever hazard exists.
5. Sanitation:
5.1. There shall be written procedures for the sanitation of the MDI
manufacturing facility. Special care should be taken to handle residues and rinses of
propellants.
5.2. Use of water for cleaning shall be restricted and controlled. Routinely used
disinfectants are suitable for sanitizing the different areas. Records of sanitation shall be
maintained.
6. Equipment:
6.1. Manufacturing equipment shall be of closed system. The vessels and supply
lines shall be of stainless steel.
6.2. Suitable check weights, spray testing machines and labelling machines shall
be provided in the department.
6.3. All the equipment shall be suitably calibrated and their performance validt.
on receipt and thereafter periodically.
7. Manufacture:
7.1. There shall be an approved Master Formula Records for the manufacture of
metered dose inhalers. All propellants, liquids and gases shall be filtered through 2µ filters to
remove particles.
Drugs and Cosmetics Rules 1945
467
7.2. The primary packing material shall be appropriately cleaned by compressed
air suitably filtered through 0.2µ filter. The humidity of compressed air shall be controlled as
applicable.
7.3. The valves shall be carefully handled and after de-cartoning, these shall be
kept in clean, closed containers in the filling room.
7.4. For suspensions, the bulk shall be kept stirred continuously.
7.5. In-process controls shall include periodical checking of weight of bulk
formulation filled in the containers. In a two-shot-filling process (liquid filling followed by
gaseous filling), it shall be ensured that 100% check on weight is carried out.
7.6. Filled containers shall be quarantined for a suitable period established by the
manufacturer to detect leaking containers prior to testing, labelling and packing.
8. Documentation-
8.1. In addition to the routine good manufacturing practices documentation,
manufacturing records shall show the following additional information:-
(1) Temperature and humidity in the manufacturing area.
(2) Periodic filled weights of the formulation.
(3) Records of rejections during on-line check weighing.
(4) Records of rejection during spray testing.
PART
1F
SPECIFIC REQUIREMENTS OF PREMISES, PLANT
AND
MATERIALS FOR
MANUFACTURE OF
ACTIVE
PHARMACEUTIAL
INGREDIENTS
(BULK
DRUGS)
Note: The General Requirements as given in Part I of this Schedule relating to
Requirements of Good Manufacturing Practices for premises and Materials for
pharmaceutical products shall be complied with, mutatis mutandis, for the manufacture of
active pharmaceutical ingredients (Bulk Drugs). In addition to these requirements, the
following Specific Requirements shall also be followed, namely: -
1. Building and Civil Works:
1.1. Apart from the building requirements contained in Part I, General ante, the
active pharmaceutical ingredients facilities for manufacture of hazardous reactions, Beta-
Lactum antibiotics. Steroids and Steroidal Hormones / Cytotoxic substances shall be provided
in confined areas to prevent contamination of the other drugs manufactured.
1.2. The final stage of preparation of a drug, like isolation/filtration/drying/
milling / sieving and packing operations shall be provided with air filtration systems including
pre-filters and finally with a 5 micron filter. Air handling systems with adequate number of air
changes per hour or any other suitable system to control the air borne contamination shall be
Drugs and Cosmetics Rules 1945
468
provided. Humidity / Temperature shall also be controlled for all the operations wherever
required.
1.3. Air filtration systems including pre-filters and particulate matter retention air
filters shall be used, where appropriate, for air supplies to production areas. If air is re-
circulated to production areas, measures shall be taken to control re-circulation of floating
dust particles from production. In areas where air contamination occurs during production,
there shall be adequate exhaust system to control contaminants.
1.4. Ancillary area shall be provided for Boiler-house. Utility areas like heat
exchangers, chilling workshop, store and supply of gases shall also be provided.
1.5. For specified preparation like manufacture of sterile products and for certain
antibiotics, sex hormones, cytotoxic and oncology products, separate enclosed areas shall be
designed. The requirements for the sterile active pharmaceutical ingredient shall be in line
with the facilities required for formulation to be filled aseptically.
2. Sterile Products:
Sterile active pharmaceutical ingredient filled aseptically shall be treated as
formulation from the stage wherever the process demands like crystallization, lyophilisation,
filtration etc. All conditions applicable to formulations that are required to be filled aseptically
shall apply mutatis mutandis for the manufacture of sterile active pharmaceutical ingredients
involving stages like filtration, crystallization and lyophilisation.
3. Utilities / Services:
Equipment like chilling plant, boiler, heat exchangers, vacuum and gas storage
vessels shall be serviced, cleaned, sanitized and maintained at appropriate intervals to prevent
mal-functions or contamination that may interfere with safety, identity, strength, quality or
purity of the drug product.
4. Equipment Design, Size and Location:
4.1. Equipment used in the manufacture, processing, packing or holding of an
active pharmaceutical ingredient shall be of appropriate design, adequate size and suitably
located to facilitate operations for its intended use and for its cleaning and maintenance.
4.2. If equipment is used for different intermediates and active pharmaceutical
ingredients, proper cleaning before switching from one product to another becomes
particularly important. If cleaning of a specific type of equipment is difficult, the equipment
may need to be dedicated to a particular intermediate or active pharmaceutical ingredient.
4.3. The choice of cleaning methods, detergents and levels of cleaning shall be
defined and justified. Selection of cleaning agents (e.g. solvents) should depend on :
(a) the suitability of the cleaning agent to remove residues of raw materials;
intermediates, precursors, degradation products and isomers, as appropriate.
(b) whether the cleaning agent leaves a residue itself;
(c) compatibility with equipment construction materials like centrifuge/
filtration, dryer/fluid bed dryer, rotocone proton dryer, vacuum dryer, frit
mill, multi-mill/jet mills/sewetters cut sizing;
(d) test for absence of intermediate or active pharmaceutical ingredient in the
final
rinse.
Drugs and Cosmetics Rules 1945
469
4.4. Written procedures shall be established and followed for cleaning and
maintenance of equipment, including utensils used in the manufacture, processing, packing
or holding of active pharmaceutical ingredients. These procedures shall include but should
not be limited to the following :
(a) assignment of responsibility for cleaning and maintaining equipment;
(b) maintenance and cleaning program schedules, including where appropriate,
sanitizing schedules;
(c) a complete description of the methods and materials used to clean and
maintain equipment, including instructions for de-assembling and re-
assembling each article of equipment to ensure proper cleaning and
maintenance.;
(d) removal or obliteration of previous batch identification;
(e) protection of clean equipment from contamination prior to use;
(f) inspection of equipment for cleanliness immediately before use;
(g) establishing the maximum time that may elapse between completion of
processing and equipment cleaning as well as between cleaning and
equipment reuse.
4.5. Equipment shall be cleaned between successive batches to prevent
contamination and carry-over of degraded material or contaminants unless otherwise
established by validation.
4.6. As processing approaches the final purified active pharmaceutical ingredient,
it is important to ensure that incidental carry over between batches does not have adverse
impact on the established impurity profile. However, this does not generally hold good for
any biological, active pharmaceutical ingredient where many of the processing steps are
accomplished aseptically and where it is necessary to clean and sterilize equipment between
batches.
5. In-Process Controls:
5.1. In-process control for chemical reactions may include the following:
(a)
reaction time or reaction completion;
(b) reaction mass appearance, clarity, completeness or pH solutions;
(c) reaction temperature;
(d) concentration of a reactant;
(e) assay or purity of the product;
(f) process completion check by TLC / any other means.
5.2. In-process control for physical operations may include the following:
(a)
appearance and colour;
(b) uniformity of the blend;
(c) temperature of a process;
(d) concentration of a solution;
(e) processing rate or time;
(f) particle size analysis;
(g) bulk/tap density;
(h) pH determination;
(i) moisture content.
Drugs and Cosmetics Rules 1945
470
6. Product Containers and Closures:
6.1. All containers and closures shall comply with the pharmacopoeial or any
other requirement, suitable sampling methods, sample sizes, specifications, test methods,
cleaning procedures and sterilization procedures, when indicated, shall be used to assure that
containers, closures and other component parts of drug packages are suitable and are not
reactive, additive, adsorptive or leachable to an extent that significantly affects the quality or
purity of the drug.
6.2. The drug product container shall be tested or re-examined as appropriate and
approved or rejected and shall be identified and controlled under a quarantine system
designed to prevent their use in manufacturing or processing operations for which these are
unsuitable.
6.3 Container closure system shall provide adequate protection against
foreseeable external factors in storage / transportation and use that may cause deterioration or
contamination of the active pharmaceutical ingredient.
6.4. Bulk containers and closures shall be cleaned and, where indicated by the
nature of the active pharmaceutical ingredient, sterilized to ensure that they are suitable for
their intended use.
6.5. The container shall be conspicuously marked with the name of the product
and the following additional information concerning :
(a) quality and standards, if specified;
(b) manufacturing licence number/drug master file number (whichever
applicable), batch number;
(c) date of manufacture and date of expiry;
(d) method for container disposal (label shall give the methodology, if
required);
(e) storage conditions, if specified and name and address of the manufacturer, if
available.
6.6. Areas for different operation of active pharmaceutical ingredients (bulk
drugs) section shall have appropriate area which may be suitably partitioned for different
operations.
PART
II
REQUIREMENTS OF PLANT AND
EQUIPMENT
1. External Preparations:
The following equipment is recommended for the manufacture of ‗External
preparations‘ i.e. Ointments, Emulsion, Lotions, Solutions, Pastes, Creams, Dusting powders
and such identical products used for external applications, whichever is applicable, namely :-
(1)
1
[Mixing and storage tanks preferably of stainless steel or any other appropriate
material].
(2)
2
[Stainless steel container] (steam, gas or electrically heated).
(3) Mixer (electrically operated).
(4) Planetary mixer.
(5) A colloid mill or a suitable emulsifier.
(6) A triple roller mill or an ointment mill.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005; for ―mixing and storage tanks (Stainless steel)‖.
2. Subs. by G.S.R. 431(E), dt. 30.6.2005; for ―Jacketted Kettle‖.
Drugs and Cosmetics Rules 1945
471
(7) Liquid filling equipment (electrically operated).
(8) Jar or tube filling equipment
1
[***]
Area. - (1) A minmum area of thirty square meters for basic installation and ten
square meters for Ancillary area is recommended.
(2) Areas for formulations meant for external use and internal use shall be
separately provided to avoid mix-up.
2
[Note: The requirement for ancillary area in this part shall not apply to units registered
before 1st January, 2002.]
2. Oral Liquid Preparations:
The following equipments are recommended for the manufacture of oral/internal use
preparations i.e. Syrups, Elixirs, Emulsions and Suspensions, whichever is applicable,
namely: -
(1)
3
[Mixing and storage tanks preferably of Stainless steel or any other
appropriate material].
(2) Jacketted Kettle / Stainless steel tank (steam, gas or electrically heated).
(3) Portable stirrer (electrically operated).
(4) A colloid mill or suitable emulsifier (electrically operated).
(5) Suitable filtration equipment (electrically operated).
(6) Semi-automatic/automatic bottle filling machine.
(7) Pilfer proof cap sealing machine.
(8) Water distillation unit or deionizer.
(9) Clarity testing inspection units.
Area. - A minimum area of thirty square meters for basic installation and ten square
meters for Ancillary area is recommended.
2
[Note: The requirement for ancillary area in this part shall not apply to units registered
before 1st January, 2002.]
3. Tablets:
The Tableting section shall be free from dust and floating particles and may be air-
conditioned. For this purpose, each
4
[tablet compression machine] shall be isolated into
cubicles and connected to a vacuum dust collector or an exhaust system. For effective
operations, the tablet production department shall be divided into four distinct and separate
sections as follows: -
(a) Mixing, Granulation and Drying section.
(b) Tablet compression section.
(c) Packaging section (strip/blister machine wherever required).
(d) Coating section (wherever required).
3.1. The following electrically operated equipments are recommended for the
manufacture of compressed tablets and hypodermic tablets, in each of the above sections,
namely: -
(a) Granulation-cum-Drying section:
(1) Disintegrator and sifter.
(2) Powder mixer.
(3) Mass mixer/Planetary mixer/Rapid mixer granulator.
1. The word ‗electrically operated‘ Omitted by G.S.R. 431(E), dt. 30.6.2005.
2. Ins by G.S.R. 431(E), dt. 30.6.2005.
3 Subs. by G.S.R. 431(E), dt. 30.6.2005, for ―mixing and storage tanks (Stainless steel)‖.
4. Subs. by G.S.R. 431(E), dt. 30.6.2005, for ‗tablet machine‘.
Drugs and Cosmetics Rules 1945
472
(4)
1
[Granulator wherever required].
(5) Thermostatically controlled hot air oven with trays (preferably mounted on a
trolley)/Fluid bed dryer.
(6) Weighing machines.
(b) Compression section:
(1) Tablet compression machine, single/multi punch/rotatory.
(2) Punch and dies storage cabinets.
(3)
Tablet de-duster
(4) Tablet inspection unit/belt.
(5)
1
[Dissolution test apparatus wherever required].
(6) In-process testing equipment like single pan electronic balance, hardness tester,
friability and disintegration test apparatus.
(7) Air-conditioning and dehumidification arrangement (wherever necessary)
(c) Packaging section:
(1) Strip/blister packaging machine.
(2) Leak test apparatus (vacuum system).
(3) Tablet counters (wherever applicable).
(4) Air-conditioning and dehumidification arrangement (wherever applicable).
Area. – A minimum area of sixty square meters for basic installation and twenty
square meters for Ancillary area is recommended for un-coated tablets.
(d) Coating section:
(1) Jacketted kettle
2
[stainless steel container or any other appropriate material]
(steam, gas or electrically heated for preparing coating suspension).
(2) Coating pan (Stainless steel).
(3) Polishing pan (where applicable).
(4) Exhaust system (including vacuum dust collector).
(5) Air-conditioning and Dehumidification Arrangement.
(6) Weighing balance.
2
[Note: The requirement for ancillary area in this part shall not apply to units registered
before 1st January, 2002.]
3.2. The coating section shall be made dust free with suitable exhaust system to
remove excess powder and fumes resulting from solvent evaporation. It shall be air-
conditioned and dehumidified wherever considered necessary.
Area. – A minimum additional area of thirty square meters for coating section for
basic installation and ten square meters for Ancillary area is recommended.
Separate area and equipment for mixing, granulation, drying, tablet compression,
coating and packing shall be provided for Penicillin group of drugs on the lines indicated
above. In case of operations involving dust and floating particles, care shall be exercised to
avoid cross-contamination.
2
[Note: The requirement for ancillary area in this part shall not apply to units registered
before 1st January, 2002.]
3.3. The manufacture of Hypodermic tablets shall be conducted under aseptic
conditions in a separate air-conditioned room, the walls of which shall be smooth and
washable. The granulation, tableting and packing shall be done in this room.
1. Subs. by G.S.R. 431(E), dt. 30.6.2005.
2. Ins. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
473
3.4. The manufacture of effervescent and soluble
1
[***] tablets shall be carried out in air-
conditioned and dehumidified areas.
4. Powders:
The following equipment is recommended for the manufacture of powders, namely:-
(1) Disintegrator.
(2) Mixer (electrically operated).
(3) Sifter.
(4) Stainless steel vessels and scoops of suitable sizes.
(5) Filling equipment
1
[***].
(6) Weighing balance.
In the case of operation involving floating particles of fine powder, suitable exhaust
system shall be provided. Workers should be provided with suitable masks during operation.
Area. – A minimum area of thirty square meters is recommended to allow for the
basic installations. Where the actual blending is to be done on the premises, an additional
room shall be provided for the purpose.
2
[Note: The requirement for additional room in this part shall not apply to units registered
before 1st January, 2002.]
5. Capsules:
For the manufacture of capsules, separate enclosed area suitably air-conditioned and
dehumidified with an airlock arrangement shall be provided. The following equipment is
recommended for filling Hard Gelatin Capsules, namely: -
(1) Mixing and blending equipment (electrically or power driven).
(2) Capsules filling units
1
[***].
(3) Capsules counters (wherever applicable).
(4) Weighing balance.
(5) Disintegration test apparatus.
(6) Capsule polishing equipment.
Separate equipment and, filling and packaging areas shall be provided in penicillin
and non-penicillin sections. In case of operations involving floating particles of fine powder, a
suitable exhaust system shall be provided. Manufacture and filling shall be carried out in air-
conditioned area. The room shall be dehumidified.
Area. –A minimum area of twenty-five square meters for basic installation and ten
square meters for Ancillary area each for penicillin and non-penicillin sections is
recommended.
2
[Note: The requirement for ancillary area in this part shall not apply to units registered
before 1st January, 2002.]
6. Surgical Dressing:
The following equipment is recommended for the manufacture of Surgical Dressings
other than Absorbent Cotton Wool, namely:-
(1) Rolling machine.
1. Omitted by G.S.R. 431(E), dt. 30.6.2005.
2. Ins. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
474
(2) Trimming machine.
(3) Cutting equipment.
(4) Folding and pressing machine for gauze.
(5) Mixing tanks for processing medicated dressing.
(6) Hot air dry oven.
(7) Steam sterilizer or dry heat sterilizer or other suitable equipment.
(8) Work tables/benches for different operations.
Area. – A minimum area of thirty square meters is recommended to allow for the
basic installations. In case medicated dressings are to be manufactured, another room with a
minimum area of thirty square meters shall be provided.
7. Ophthalmic Preparations:.
For the manufacture of Ophthalmic preparations, separate enclosed areas with airlock
arrangement shall be provided. The following equipment is recommended for the manufacture
under aseptic conditions of Eye-Ointment, Eye-Lotions and other preparations for external
use, namely:-
(1) Thermostatically controlled hot air ovens (preferably double
ended).
(2)
Jacketted kettle/stainless steel tanks (steam, gas or electrically heated).
(3) Mixing and storage tanks of stainless steel/Planetary mixer.
(4) Colloid mill or ointment mill.
(5) Tube filling and crimping equipment (semi-automatic or automatic filling machines).
(6) Tube cleaning equipment (air jet type).
(7) Tube washing and drying equipment, if required.
(8) Automatic vial washing machine.
(9) Vial drying oven.
(10) Rubber bung washing machine.
(11) Sintered glass funnel, Seitz filter and filter candle (preferably cartridge and membrane
filters).
(12) Liquid filling equipment (semi-automatic or automatic filling machines).
(13) Autoclave (preferably ventilator autoclave).
(14) Air conditioning and dehumidification arrangement (preferably centrally air-
conditioned and dehumidification system).
(15) Laminar airflow units.
Area. – (1) A minimum area of twenty-five square meters for basic installation and
ten square meters for Ancillary area is recommended. Manufacture and filling shall be carried
out in air-conditioned areas under aseptic conditions. The rooms shall be further dehumidified
as considered necessary if preparations containing antibiotics are manufactured.
(2) Areas for formulations meant for external use and internal use shall be separately
provided to avoid mix up.
1
[Note: The requirement for ancillary area in this Part shall not apply to units registered
before 1st January, 2002.]
8. Pessaries and Suppositories:
(i) The following equipment is recommended for manufacture of Pessaries and
Suppositories, namely: -
(1) Mixing and pouring equipment
(2) Moulding equipment.
(3) Weighing devices.
1. Ins. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
475
Area. – A minimum area of twenty square meters is recommended to allow for the
basic installation.
(ii) In the case of pessaries manufactured by granulation and compression, the
requirements as indicated under ―Item 3 of Tablet‖, shall be provided.
9. Inhalers and Vitrallae:
The following equipment is recommended for manufacture of inhalers and vitrallae,
namely: -
(1) Mixing equipment.
(2) Graduated delivery equipment for measurement of the medicament during filling.
(3) Sealing equipment.
Area. – An area of minimum twenty square meters is recommended for the basic
installations.
10. Repacking of drugs and pharmaceutical chemicals:
The following equipment is recommended for repacking of drugs and
pharmaceuticals chemicals, namely:-
(1) Powder disintegrator.
(2) Powder sifter (electrically operated).
(3) Stainless steel scoops and vessels of suitable sizes.
(4) Weighing and measuring equipment.
(5) Filling equipment (semi-automatic / automatic machines).
(6) Electric sealing machine.
Area. – An area of minimum thirty square metres is recommended for the basic
installation. In case of operations involving floating particles of fine powder, a suitable
exhaust system shall be provided.
11. Parenteral Preparations
The whole operation of manufacture of parenteral preparations (small volume
injectables and large volume parenterals) in glass and plastic containers may be divided into
the following separate areas/rooms, namely: -
11.1 Parenteral preparations in glass containers: –
(1) Water management area: This includes water treatment and storage.
(2) Containers and closures preparation area: This includes washing and drying of
ampoules, vials, bottles and closures.
(3) Solution preparation area: This includes preparation and filtration of solution.
(4) Filling, capping and sealing area: This includes filling and sealing of ampoules and/or
filling, capping and sealing of vials and bottles.
(5) Sterilization area
(6) Quarantine area
(7) Visual inspection area.
(8) Packaging area
Drugs and Cosmetics Rules 1945
476
The following equipment is recommended for different above-mentioned areas,
namely: -
(a) Water management area:
(1) De-ionised water treatment unit.
(2) Distillation (multi-column with heat exchangers) unit.
(3) Thermostatically controlled water storage tank.
(4) Transfer pumps.
(5) Stainless steel service lines for carrying water into user areas.
(b) Containers and closures preparation area:
(1) Automatic rotary ampoule/vial/bottle washing machine having separate air, water
distilled water jets.
(2) Automatic closures washing machine,
(3) Storage equipment for ampoules, vials, bottles and closures.
(4) Dryer/sterilizer (double ended)
(5) Dust proof storage cabinets.
(6) Stainless steel benches/stools.
(c) Solution preparation area:
(1) Solution preparation and mixing stainless steel tanks and other containers.
(2) Portable stirrer.
(3) Filtration equipment with cartridge and membrane filters/bacteriological filters.
(4) Transfer pumps.
(5) Stainless steel benches/stools
(d) Filling, capping and sealing area:
(1) Automatic ampoule/vial/bottle filling, sealing and capping machine under laminar air
flow workstation.
(2) Gas lines (Nitrogen, Oxygen, Carbon dioxide) wherever required.
(3) Stainless steel benches / stools.
(e) Sterilization area:
(1) Steam sterilizer (preferably with computer control for sterilization cycle along with
trolley sets for loading/unloading containers before and after sterilization).
(2) Hot air sterilizer (preferably double ended).
(3) Pressure leak test apparatus.
(f) Quarantine area. –
(1) Storage cabinets.
(2) Raised platforms/steel racks.
(g) Visual inspection area:
(1) Visual inspection units (preferably conveyor belt type and composite white and black
assembly supported with illumination).
(2) Stainless steel benches/stools.
(h) Packaging area. -
(1) Batch coding machine (preferably automatic).
Drugs and Cosmetics Rules 1945
477
(2) Labelling unit (preferably conveyor belt type).
(3) Benches/stools.
Area. – (1) A minimum area of one hundred and fifty square meters for the basic
installation and an Ancillary area of one hundred square meters for Small Volume Injectables
is recommended. For Large Volume Parenterals, an area of one hundred and fifty square
meters each for the basic installation and for Ancillary area is recommended. These areas
shall be partitioned into suitable enclosures with airlock arrangements.
(2) Areas for formulations meant for external use and internal use shall be separately
provided to avoid mix up.
(3) Packaging materials for large volume parenteral shall have a minimum area of
100 square meters.
1
[Note: The requirement for ancillary area in this part shall not apply to units registered
before 1st January, 2002.]
11.2 Parenteral preparations in plastic containers by Form-Fill-Seal/Blow, Fill-
Seal Technology.-The whole operation of manufacture of large volume parenteral
preparations in plastic containers including plastic pouches by automatic (all operations in one
station) Form-Fill-Seal machine or by semi-automatic blow moulding, filling-cum-sealing
machine may be divided into following separate areas/rooms, namely: -
(1) Water management area.
(2) Solution preparation area.
(3) Containers moulding-cum-filling and sealing area.
(4) Sterilization area.
(5) Quarantine area .
(6) Visual inspection area.
(7) Packaging area.
The following equipment is recommended for different above mentioned areas
namely: -
(a) Water management area:
(1) De-ionised water treatment unit.
(2) Distillation unit (multi column with heat exchangers).
(3) Thermostatically controlled water storage tank.
(4) Transfer pumps.
(5) Stainless steel service lines for carrying water into user areas.
(b) Solution preparation area:
(1) Solution preparation and storage tanks.
(2) Transfer pumps.
(3) Cartridge and membrane filters.
(c) Container moulding-cum-filling and sealing area:
(1) Sterile Form-Fill-Seal machine (all operations in one station with built-in laminar air
flow workstation having integrated container output conveyor belt through pass box).
(2)
Arrangement for feeding plastic granules through feeding-cum-filling tank into the
machine.
1. Ins. by 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
478
(d) Sterilization area: Super heated steam sterilizer (with computer control for
sterilization cycle along with trolley sets for loading/unloading containers for
sterilization).
(e) Quarantine area:- Adequate number of platforms/racks with storage system.
(f) Visual inspection area. - Visual inspection unit (with conveyor belt and composite
white and black assembly supported with illumination).
(g) Packaging area:
(1) Pressure leak test apparatus (pressure belt or rotating disc type).
(2) Batch coding machine (preferably automatic).
(3) Labelling unit (preferably conveyor belt type).
Area. – (1) A minimum area of two hundred and fifty square meters for the basic
installation and an Ancillary area of one hundred and fifty square metres for large volume
parenteral preparations in plastic containers by Form-Fill-Seal technology is recommended.
These areas shall be partitioned into suitable enclosures with airlock arrangements.
(2) Areas for formulations meant for external use and internal use shall be separately
provided to avoid mix up.
(3) Packaging materials for large volume parenteral shall have a minimum area of
100 square meters.]
1
[Note: The requirement for ancillary area in this part shall not apply to units registered
before 1st January, 2002.]
1
[Note I: There are certain categories of drugs such as chemicals and pharmaceutical aids,
gauzes and bandages, medicinal gases, empty gelatin capsules, non- chemical/mechanical
contraceptives, diagnostic kits and reagents, medical devices, new dosage forms and their
delivery systems, disinfectant fluids, antacids, raw-materials manufactured from sea bittern,
veterinary biologicals including poultry vaccines, re-packing of drugs, etc. for which this
Schedule does not prescribe specific requirements of space and equipments. The Licensing
Authority, as the case may be, in respect of such categories of drugs, have the discretion to
modify the requirements of this Schedule, if he is of the opinion that having regard to the
nature off the products and extent of manufacturing operations and for reasons to be recorded
in writing, it is necessary to relax or alter them in the circumstances of a particular case and
direct the manufacturer to carry out necessary modifications in them and the modifications
having been made, approve the manufacturer of such categories of the drugs.
Note II: In case of manufacturers licensed to manufacture drugs prior to the 11th December,
2001, the requirements of this Schedule shall also apply to them from 1st July, 2005.]
1. Ins. by G.S.R. 431(E), dt. 30.6.2005.
Drugs and Cosmetics Rules 1945
479
1
[SCHEDUE M-I
[See Rule 85E
(2)]
GOOD MANUFACTURING PRACTICES AND REQUIREMENTS OF PREMISES,
PLANT AND EQUIPMENT FOR HOMOEOPATHIC MEDICINES
1.GENERAL REQUIREMENTS:
1.1 Location and Surroundings: - The premises shall be situated at a clean place which
shall not be adjacent to open drains, public lavatory or any factory producing
pollution of any kind, garbage dump, slaughter house or any other source likely
to cause contamination from the external environment. The premises shall be
located away from railway lines so that the performance of sensitive electronic
equipment is not affected by vibrations. There shall be no open drains inside or
outside the manufacturing premises. It shall be so designed that the entry of
rodents is checked. The drains shall facilitate easy flow of the effluent and shall
be cleared periodically.
1.2 Building: - The premises shall not be used for any purpose other than manufacture
of homoeopathic drugs and no part of the manufacturing premises shall be used
for any other purpose. Other facilities, if needed, could be provided in separate
building(s) in the same campus. Crude raw materials, packing materials, etc.
shall be stored and handled in places earmarked for them and shall not be taken
inside areas where critical operations of manufacture are done excepting
processed raw material. Heating, washing, drying, packing and labelling etc.
wherever needed, shall be done in dedicated ancillary areas adjacent to the
manufacturing sections concerned. The walls and floorings of manufacturing
areas shall be smooth and free from chinks, cracks and crevices and shall be
washable. The design of the windows, windowpanes and all fittings shall be
such that they will not facilitate accumulation / lodging of dust and other
contaminants.
1. Subs. by G.S.R. No. 678(E) , dt. 31-10-2006, for Schedule MI. Earlier Schedule MI was inserted by G.S.R. 507 (E), dt:
12.6.1987. Schedule M1, before substitution, stood as under.:
―
SCHEDUE M-I
[See Rule 85E
(2)]
1. Requirement of factory premises for manufacture of Homeopathic preparations-
(a) Location and surroundings. - The factory shall be situated in a place which shall not be adjacent
to an open sewage drain, public lavatory or any factory which produces a disagreeable or
obnoxious odour or fumes or large quantities of soot, dust or smoke. The factory shall be located in
a sanitary place, remove from filthy surroundings.
(b) Buildings. - The part of the building used for manufacturing shall not be used for a sleeping
place and no sleeping place adjoining to it shall communicate therewith except through open air
or through an intervening open space. The walls of the room in which manufacturing operations
are carried out shall, upto a height of six feet from the floor, be smooth, waterproof and shall be
capable of being kept clean. The flooring shall be smooth, even and washable and shall be such as
not to permit retention or accumulation of dust. There shall be no chinks or crevices in the walls or
floor.
(c) The building used for the factory shall be constructed so as to permit production under hygienic
conditions laid down in the Factories Act, 1948 (63 of 1948).
(d) Water Supply. - The water used in manufacture shall be pure and drinkable quality, free from
pathogenic microorganisms.
(e) Disposal of waste. - There should be adequate arrangement for disposal of waste-water and other
residues from the laboratory.
Drugs and Cosmetics Rules 1945
480
(f) The rooms should be airy and clean and the temperature of the room should be
moderately comfortable.
(g) Health, Clothing and Sanitary requirement of the Staff. - All workers shall be free from
contagious or obnoxious disease. Their clothing shall consist of a white or coloured uniform
suitable to the nature of the work and the climate, and shall be clean. Adequate facilities for
personal cleanliness, such as clean towels, soap and hand scrubbing brushes, shall be provided
separately for each sex. The workers shall be required to wash and change into clean footwear
before entering the rooms where the manufacturing operations are carried on. Workers shall be
required to wear either a clean cap or a suitable headgear so as to avoid any possibility of
contamination by air or perspiration.
(h) Medical services. - The manufacturer shall provide adequate facilities for First Aid, Medical
inspection of workers at the time of employment and periodically check-up thereafter at least
once a year.
(i) Working benches. - Working benches shall be provided for carrying out operations such as
filling, labelling, packing etc. Such benches shall be fitted with smooth, impervious tops
capable of being washed.
(j) Container management. - Where operations involving use of containers such as bottles,
phials and jars are conducted, there shall be adequate arrangements separated from
potentisation chamber for washing, cleaning and drying such containers, with
suitable equipment for the purpose. Wherever these are attended manually adequate precaution
of perfection in respect of cleanliness and avoidance of pollutants shall be taken.
2. Requirements of Plant and Equipment:
(a) Mother tinctures. External tinctures and Mother solution section. - The following plant and
equipment shall be provided namely: -
(i) Disintegrator.
(ii) Sieved Separator.
(iii) Balances and fluid measures.
(iv) Chopping boards and knives.
(v) Macerators with lids.
(vi) Percolators with lids and regulated discharge.
(vii) Moisture determination apparatus or other suitable arrangement.
(viii) Filtering arrangement.
(ix) Mixing vessels and suitable non-metallic storage containers.
(x) Portable stirrers.
(xi) Water still.
Note: (1) As far as possible metal contacts may be avoided once the drug is processed. (2) An area of
55 sq. meters is recommended for basic installations.
(3) Adequate separate storage facility should be provided for raw material
quarantine, storage and bonded room for alcohol where applicable.
(4) Separate and suitable storage facility should be provided for fresh herbs and
odorous raw materials.
(5) Adequate laboratory facility shall be provided for testing of raw materials and
finished products,
(b) Potentisation Section. - (1) The following arrangements are recommended for
container for closure preparation section namely:
(i) Washing tanks with suitable brushing arrangement manual or mechanical.
(ii) Purified Water rinsing tank
(iii) Closure macerating or washing tanks.
(iv) Drying chambers.
An area of 20 sq. meters is recommended for basic installations.
Drugs and Cosmetics Rules 1945
481
(2) The following arrangements are recommended for potency preparation section, namely:
–
(i) Working tables with washable top.
(ii) Facilities for separate storage of different grades of back potencies.
(iii) Suitable measuring devices for discharge of drug and diluent in potentisation vial,
(iv) Potentiser with counter or suitable manual arrangement.
Note: - (1) Different droppers shall be used for different drugs
po
te
ncies.
(2) All measuring devices shall be of metric system and be made of glass and shall be free from
metallic contents.
(3) It is desired that glass droppers etc. intended for re-use after cleaning should be
sterilized by autoclave or heating in a hot air oven.
(4) Plastics, rubber tubes, bulks etc. coming in contact with tinctures or back potencies should
not be re-used for other tincture and potencies.
(5) Method of potentisation will be adopted as specified in Homoeopathic
Pharmacopoeia of India Vol.
I.
3. Triturating, Tableting and Pill/Globules section
-
(3) The following arrangements are recommended: (i)
Triturating machine for suitable device.
(ii) Disintegrator.
(iii) Mass Mixer. (iv)
Granulator. (v)
Oven.
(vi) Tableting punches or machines.
(vii) Kettle (Steam/gas/electrically heated) for preparation solution. (viii) Dryers.
(ix) Sieved separator, tablet counters and balances.
Note: Tablet section shall be free from dust and floating particles. An area of 55 sq. meters is
recommended for basic installations.
(4) Ointments and lotion
section:
The following arrangements are recommended namely: -
(i) Mixing tank
(ii) Kettle (Steam, gas or electrically heated). (iii)
Suitable powder mixer
(iv) Ointment mill
(v) Filling equipment or arrangement.
An area of 20 sq. meters is recommended for basic installations. (5) Syrups
and tonics:
The following arrangements are recommended namely:- (i)
Mixing and storage tank.
(ii) Potable mixer.
(iii) Filtering equipment. (iv)
Water still / Deioniser.
(v) Filling and sealing equipment.
Drugs and Cosmetics Rules 1945
482
An area of 20 sq. meters is recommended for basic installations. (6)
Ophthalmic Preparations:
The following equipment is recommended for manufacture under aseptic conditions of Eye-
Ointments, Eye-Drops, Eye-lotions and other preparations for external use, namely: -
(i) Hot air even electrically heated with thermostatic control. (ii) Colloid
mill or ointment mill.
(iii) Kettle (gas or electrically heated) with suitable mixing arrangement. (iv) Tube
filling equipment.
(v) Mixing and storage tanks of stainless steel or of other suitable material.
(vi) Sintered glass funnel, Seitz filter or filter candle. (vii)
Liquid filling equipment.
(viii) Autoclaves.
Adequate precaution should be taken to ensure that the finished product is sterile. An area of 20 sq.
meters is recommended for basic installations.
(7) Adequate arrangements for space and equipment should be made for labelling and packing.‖
2. PLANT AND EQUIPMENT:
2.1 General: - The design of the plant shall be suitable for the nature and quantum
of the activities involved. Equipment shall be installed in such a manner as to
facilitate easy flow of materials and to check criss-cross movement of the personnel.
The entry to all manufacturing sections shall be regulated and persons not associated
with the activities in the sections shall not have access to them. There shall be
arrangements for personal cleanliness of workers and toilets. These shall be separate
for men and women workers. There shall be suitable arrangement, separate for men
and women, to change from their outside dress and footwear into the factory dress and
footwear. Uniforms of suitable colours and fabric which facilitate proper washing
and which do not shed fibres other contaminants shall be provided. Suitable head-
covers and gloves shall be provided to the workers. The manufacturing premises shall
not be used for dining. There shall be separate area for the personnel to take food or
rest. Toilets shall be located in or adjacent to any of the areas concerned with any
manufacturing activity. Spitting, smoking, chewing, littering, etc. in the
manufacturing or ancillary areas shall not be permitted. Standard operating practices
(SOPs) for cleaning and sanitation, personal hygiene of the workers, general and
specific upkeep of the plant, equipment and premises and every activity associated
with manufacture of drugs including procurement, quarantine, testing and
warehousing of material shall be written and adopted. No person with any contagious
disease shall be involved in any of the manufacturing activities. There shall be proper
arrangements for maintenance of the equipment and systems. The performance of
every equipment and system shall be properly validated and their use shall be
monitored. Dos and don‘ts in the matter of the use of the plant and equipment as may
be applicable shall be written and displayed in all places.
There shall be separate dedicated areas for each ancillary activity such as receipt,
cleaning, warehousing and issue of raw materials, packaging materials, containers and
closures, finished goods etc. Adequate measures shall be taken to prevent
entry/presence etc. of insects, rodents, birds, lizards and other animals into the raw
material handling areas. Every material shall have proper identification and control
numbers and inventory tags and labels displaying status of the quality being used, etc.
There shall be proper arrangements and SOPs for preventing mix-up of materials at
every stage of handling. There shall be separate arrangements for handling and
warehousing of materials of different origins. Materials with odour shall be kept in
tightly closed containers and shall be well protected from other materials. Fresh
materials and odorous materials shall, preferably be stored in separate dedicated areas.
Where bonded manufacturing and / or warehousing facilities are required as per
Drugs and Cosmetics Rules 1945
483
Excise laws, the facilities required shall be provided without compromise on the
requirements specified above.
A well equipped laboratory for quality control/quality assurance of raw materials
and finished products and for carrying out in-process controls shall be provided.
(a) Rooms: - The rooms shall be airy, ventilated, and maintained at temperatures
which are moderate and comfortable. Sections which are required to be sterile, air-
conditioned and provided with air handling system shall be designed accordingly. All
sections shall be free from insects, birds, rodents, worms etc. and suitable measures
shall be taken to prevent the same from finding ways to the sections and equipment.
(b) Water: - The water used for manufacture of drugs shall be of the quality as
prescribed in the rules or in the Homoeopathic Pharmacopoeia concerned, as the case
may be, and shall be prepared from pure drinking quality water, free from pathogenic
organisms.
(c) Disposal of waste: - Effluents, organic and inorganic wastes shall be disposed
of in such a manner as may be prescribed in the laws pertaining to pollution control
and if no such law exists in the place of manufacture, they shall be rendered harmless
and shall be disposed of in such a manner that they are not hazardous to health of the
public or cattle or plants.
(d) Factories Act: - The provisions of the Factories Act, 1948(Act 63 of 1948), as
applicable shall be adhered to.
(e) Medical Services:- All persons concerned with any activity pertaining to
manufacture of drugs including handling of raw materials, packing materials, packing
and labelling of drugs, etc. shall be medically examined for fitness at the time of
employment and subsequently at periodic intervals and records thereof shall be
maintained.
(f) Safety measures: - First-aid facilities shall be provided in such a manner that
they are easily accessible and staff shall be imparted knowledge and training in first-
aid measures as may be needed. Fire control equipment in suitable numbers shall be
provided at easily accessible places near all sections including stores and
warehouses.
(g) Workbenches: - Workbenches suitable to the nature and quantum of the work
involved shall be provided in all sections. Such work benches in general, shall have
smooth, washable and impervious tops and the parts shall not be rough or rusty or
damaged otherwise.
(h) Container management: - Proper arrangements shall be made for receiving
containers, closures and packing materials in secluded areas and for de-dusting the
same, removal of wastes, washing, cleaning and drying. Suitable equipment shall be
provided as may be needed, considering the nature of work involved. Where soaps
and detergents are used to wash containers and closures used for primary packing,
suitable procedure shall be prescribed and adopted for total removal of such materials
from the containers and closures. Plastic containers which are likely to absorb active
principle or which are likely to contaminate the contents may not be used.
Glass containers used shall be made of neutral glass. The closures and washers
used shall be of inert materials which shall not absorb the active principles or
contaminate the contents or which may otherwise be likely to cause deterioration of
quality. The containers, closures and packing materials shall protect the properties of
the medicines, Tablets, if blister-packed, shall have secondary protective packaging to
protect the medicines from moisture, odour etc. Neutral glass phials and epoxy-coated
closure shall be used for eye-drops. Transparent plastic containers may be used for
eye-drops containing only aqueous preparations. Sterile plastic nozzles may be
provided to eye-drops separately along with the medicine, whatever needed.
2.2. Personnel.- Manufacture of drugs shall be under the control of approved technical staff
that shall possess the qualifications prescribed in rule 85.
Drugs and Cosmetics Rules 1945
484
3. REQUIREMENT OF EQUIPMENT AND FACILITIES:
3.1 Mother tinctures and mother solutions:- The following equipment and facilities
shall be provided:-
(i) Disintegrator;
(ii) Sieved separator;
(iii) Balances, weights and fluid measures, all in metric system;
(iv) Chopping table/board and knives;
(v) Macerators with lids (all made of stainless steel of grade 304 or neutral glass);
(vi) Percolators (all made of stainless steel of grade 304);
(vii) Moisture determination apparatus;
(viii) Filter press/Sparkler filter (all metal parts shall be of stainless steel);
(ix) Mixing and storage vessels (Stainless steel of grade 304);
(x) Portable stirrers (Rod, blades and screws shall be of stainless steel);
(xi) Water still/water purifier;
(xii) Macerators and percolators for preparing mother solutions of materials of chemical
origin. These shall be of material, which will not react with the chemicals, used and
which do not bleach; and
(xiii) Filling and sealing machine.
The area and facilities for manufacture of mother tinctures and mother solutions shall be
separate and shall be 55 square meters for each for basic installations.
3.2 Potentisation section :- The section shall have the following facilities:-
(i) Work benches with washable impervious tops;
(ii) Facilities for orderly storage of different potencies and back-potencies of various
drugs;
(iii) Suitable devices for measuring and dispensing of potencies/back-potencies into the
potentisation phials;
(iv) Potentiser with counter.
An area of 20 square meters shall be provided for basic installations.
Note: -
(a) The requirement of potentiser is not mandatory. The process may be done
manually also with proper SOPs. Potentiser, if used, shall be properly validated and shall be
calibrated every time before commencement of work for proper performance.
(b) The manufactur er sh all use back-poten cies procur ed fr om Licen sed
manufacturers and the firm shall maintain proper records of purchase or shall prepare
own-back potencies . Every container of potencies and back-potencies shall be kept properly
labelled and there shall not be mix-up of different medicines and different potencies.
3.3 Containers and Closures Section: - Separate area for preparation of containers and
closures shall be provided adjacent to the potentisation section. This area shall have the
following facilities:-
(i) Washing tanks with suitable mechanical or hand operated brushes;
(ii) Rinsing tanks. Purified water shall be used for rinsing;
(iii) Closures washing / macerating tanks;
(iv) Driers;
Note: -
(a) Different droppers shall be used only for each different medicine and different
potency.
(b) All measures shall be in metric system. Measures used shall be of neutral glass.
Metal droppers and plastic droppers shall not be used.
(c) Glass droppers shall be reused only after proper cleaning and sterilization.
Drugs and Cosmetics Rules 1945
485
(d) Potentisation shall be done by the method(s) prescribed in the Homoeopathic
Pharmacopoeia of India.
3.4 Trituration, Tableting, Pills and Globules making sections:- The following basic
equipment and facilities shall be provided:-
(i) Triturating Machine;
(ii) Disintegrator;
(iii) Mass Mixer;
(iv) Granulator;
(v) Electrical Oven;
(vi) Tablets punching Machine;
(vii) Kettle (steam or electrically heated ) for preparing solutions;
(viii) Driers for drying granules and tablets;
(ix) Sieved separator (stainless steel);
(x) Tablet counter;
(xi) Balances;
(xii) Coating Pan with spray-gun;
(xiii) Multi-sifter
(xiv) Mill with perforations.
An area of 55 square meters shall be provided for basic installations. The area shall be
suitably divided into cubicles to minimize cross contamination, mix-up etc.
Note: - The section shall be free from insects, worms, rodents, dust and other floating
particles and moisture.
3.5 Syrups and other oral liquids section:- The following basic equipment and facilities shall
be provided:-
(i) Mixing and storage tanks (stainless steel of grade 304);
(ii) Portable stirrer (rod, blades and screws shall be of stainless steel);
(iii) Filter press / Sparkler filter (all metal parts shall be of stainless steel);
(iv) Filling and sealing machine;
(v) pH meter.
An area of 20 square meters shall be provided for basic installations. The section shall
be free from dust and other floating particles, cobwebs, flies, ants and other insects, birds,
lizards and rodents.
(1) Adequate number of workbenches shall be provided.
(2) Visual inspection table shall be provided. This shall comprise of a colour con trast
backgr ound with lamp for providing diffused ligh t, mounted on a suitable table.
3.6 Ointments and lotions section :- The following basic equipments and facilities shall be
provided:-
(i) Mixing tanks (Stainless steel)
(ii) Kettle (steam or electrically heated) for preparing solutions
(iii) Suitable powder / planetary Mixer
(iv) Ointment mill / colloidal Mill / Emulsifier
(v) Filling and sealing machine / Crimping machine
(vi) Filtering equipment
(vii) Balance and weights
A minimum area of 20 square meters shall be provided for basic installations. An
ancillary area for washing vessels and equipment shall be provided. An ancillary area for
heating purposes shall also be provided.
3.7 Ophthalmic preparations section:- The following basic equipment and facilities shall
be provided:-
(i) Hot air oven, electrically heated, with thermostatic control;
Drugs and Cosmetics Rules 1945
486
(ii) Laminar Air Flow bench;
(iii) Air Handling Unit with HEPA filters to provide filtered air and positive pressure to
the section and air-locks;
(iv) Ointment mill / colloidal mill;
(v) Mixing and storage tanks (Stainless steel of grade 304);
(vi) Pressure vessels, as may be needed;
(vii) Sintered glass funnels, Seitz Filter / Filter candle;
(viii) Vacuum pump;
(ix) Filling machines for liquids ointments etc.;
(x) Autoclaves with pressure and temperature gauges; and
(xi) Necessary workbenches, visual inspection bench, etc.
Area: Minimum area of 20 square meters shall be provided for basic installations.
Note: -
1. The section shall have a clean room facility of Class 100 specification.
2. The section shall be air-conditioned and humidity controlled.
3. Entry to the sections shall be regulated through air-locks with differential air
pressures with the air-lock adjacent to the section having higher pressure and the first one
through which entry is made with the least pressure.
4. Materials shall be passed to the sections through suitable hatches.
5. The personnel shall wear sterile clothing including headgear, which shall not shed
fibre.
6. Washing of phials shall be done in separate areas with proper equipment. Proper
facilities shall be provided in the area for washing vessels.
7. Separate area shall be provided for packing and labelling.
4. QUALITY CONTROL DIVISION:
4.1 Functions: - A separate quality control division shall be provided in the premises.
The section shall be under the control of an approved technical officer, independent of the
manufacturing division and directly responsible to the management. The section shall be
responsible for ensuring the quality of all raw materials, packing materials and finished goods.
The section shall also carry out in-process quality checks of the products. The section shall be
responsible for the stability of the products and for prescribing their shelf life wherever
applicable.
The functions of the division shall include:-
(1) To test the identity, quality and purity of the raw materials and to recommend
rejection of the material of poor quality and approve materials of the prescribed
quality only.
(2) To test the identity, quality and purity of the finished products and to recommend
rejection of the material of poor quality and to approve materials of the prescribed
quality only.
(3) To prepare and validate the methods of analysis, validate the equipment,
monitor their use, take steps for proper maintenance, etc.
(4) To approve or reject container s, closures and packaging materials in accordance
with the prescribed norms.
(5) To exercise / carry out in-process control of products.
(6) To prescribe SOPs on all matters concerning quality of materials and products.
(7) To monitor the storage and handling of raw materials, finished products,
containers, closures and packaging materials.
(8) To investigate complaints on quantity of products and take / recommend appropriate
measures and to examine returned goods and recommend their proper disposal.
4.2 Personnel: - The quality control staff shall be full-time personnel. Analysis and tests of
drugs, raw materials, etc. shall be done by qualified and approved technical staff. The
technical staff shall have the minimum qualification of degree in Homoeopathic Pharmacy
or Science with Chemistry or Botany as the principal subject and experience of not less than
Drugs and Cosmetics Rules 1945
487
two years in the test and analysis of medicines including handling of instruments.
4.3 Equipment: - The following equipment shall be provided:-
(i) Microscope of suitable magnification and photographic device;
(ii) Dissecting microscope;
(iii) TLC apparatus;
(iv) UV lamp viewer;
(v) Monopan Digital Electronic Balance;
(vi) Hot air oven;
(vii) Distillation apparatus;
(viii) Water Bath;
(ix) Polarimeter;
(x) Refractometer;
(xi) Melting point apparatus;
(xii) pH meter;
(xiii) Magnetic stirrer;
(xiv) Table Centrifuge;
(xv) Muffle furnace / electric Bunsen;
(xvi) Moisture determination apparatus;
(xvii) U.V. Spectrophotometer;
(xviii) Rotary microtome / Section cutting facilities;
(xix) Tablet Disintegration Machine.
5. RAW MATERIALS:
5.1 Raw materials of Plant Origin:-
(a) The raw materials of plant origin used for manufacture of drugs shall be of the following
specifications:-
(i) the materials shall be those recently collected and dried and shall be free from
moisture so as to eliminate the risk of deterioration and infestation with pests moulds, etc. The
materials shall be collected when the atmospheric temperature is suitable where its active
constituents are not changed / damaged / destroyed.
(ii) when fresh materials are to be used, the time lapse from the time of collection to
use shall be minimized to the extent possible;
(iii) the materials should be taken from healthy plants and shall be free from parasites,
moulds, etc.;
(iv) the materials shall be free of inorganic or organic foreign matter;
(v) when dry materials are procured, they shall be from healthy plants and shall be in
unprocessed form, free from all extraneous matters such as fungus, insects, moulds,
pathogenic organisms, etc. and should not be more than six months old. Plant materi alsof
Agaricaceae, which are perishable shall be used within one week of ollection.
(b) To facilitate proper identification and purity of the material and to exercise proper quality
control of the material, the following conditions must be satisfied:-
(i) a small twig of the plant with leaves shall be available if the part used is bark of the
plant;
(ii) an entire plant or part or aerial twig with leaves and some uncut roots /
rhizomes / bulbs shall be available if the part used is a root /rhizome / bulb;
(iii) if plants with flowers are to be used, a few dry flowers shall also be available
with the aerial twig;
(iv) if the material used is a mould or of the plant families Agaricaceae,
Polyporaceae/ amanitacaea / Boletaceae / Russulaceae, a whole specimen plant / mould shall
be available in properly dried form;
(v) the materials shall be free from insecticides, fungicides, etc;
(vi) the materials shall be in open mesh bags or in suitable material which permits
the passage of air inside;
(vii) each consignment of the material shall be accompanied by a statement of the
supplier‘s name; name of the plant with description of the part supplied. The
Drugs and Cosmetics Rules 1945
488
pharmacopoeial reference, place of collection /harvest, date and time of collection and
packaging and weight.
5.2 Raw material of Chemical origin: - They shall be of respective pharmacopoeial
standards and statements of their specification shall accompany the materials.
5.3 Raw materials of animal origin: - The materials shall be those collected from healthy
animals and shall be of pharmacopoeial specifications. The materials shall be those collected,
packed and transported under proper hygienic conditions and well protected from all
contamination. The materials shall be accompanied by statements as in para ‗a‘ above. In
case of drugs derived from a whole insect, bulk of such drugs along with some uncut whole
insect should be provided / maintained for records.
5.4 Sarcodes: - The materials shall be those collected from healthy animals and shall be of
pharmacopoeial specification. The materials shall be those collected, packed and transported
under proper hygienic conditions and well protected from all contamination. The materials
shall be accompanied by statements as in the Para ‗a‘ above. The materials shall be tested to
see that they are free from pathogenic organisms such as E. Coli, Salmonella, etc.
5.5 Nosodes: - These shall be of pharmacopoeial specifications. As these are derived from
diseased animals or human beings, they shall be autoclaved immediately after collection and
preserved and transported under proper hygienic conditions and well protected from all
contamination. Before use, these shall be sterilized by autoclaving and shall comply with the
test for sterility as specified in the Homoeopathic Pharmacopoeia.
6. PROCEDURES:
6.1 Manufacture of Mother tinctures: -
(a) Every material shall be identified and checked for its purity. They shall be cleaned
and processed by cutting, chopping, etc. for use in macerators / percolators. A specimen of
the material shall be preserved till approval of the product for release for sale.
(b) The design and procedures adopted shall ensure reproduction of the product of the
same quality every time.
(c) Mother tinctures shall be preserved in tight closed neutral containers at
temperatures preferably below 250 C, protected from light.
6.2 Manufacture of Attenuations: -
(a) Attenuations shall be prepared in a clean room environment with filtered air and
positive pressure inside suitable for the operations.
(b) The methods used shall be reproducible and shall be validated.
(c) The containers, tubings, etc. of the machines used for manufacture of attenuations
shall be thoroughly washed, cleaned and dried after attenuation of a drug. Regular checks shall
be carried out on the materials.
(d) The parts of the equipment that come into contact with the attenuation materials
shall be of neutral quality and shall not cause any contamination to the material.
(e) Attenuations shall be preserved in properly labeled glass containers.
(f) Alcohol and other vehicles used shall be of Homoeopathic pharmacopoeia
specification and shall be free from impurities.
6.3 Trituration: - Trituration technique is used to manufacture drugs from insoluble strains.
The procedure / method specified in the Homoeopathic pharmacopoeia shall be adopted.
6.4 Formulations:- Compound formulations shall preferably be in liquid and solid forms and
the potency of the ingredients shall be in detectable quantity preferably be in 3x except in case
of highly poisonous material and toxins which should not be below 6x. The ingredients shall
be compatible to each other. Complete pharmacopoeial name of each ingredient shall be
printed on the label along with composition.
6.5 Medicated Insert Pellets: - (a) Pellets shall be manufactured in clean rooms free from
particulate contaminants. The equipment used shall enable prevention of contamination and
cross- contamination.
(b) The procedures shall be validated.
7. LABORATORY CONTROLS:
Tests as per the pharmacopoeia and requirements shall be carried out on products and
materials. The stability of the products shall be established by proper methods. Sterility tests,
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wherever applicable, shall be carried out. Control samples shall be preserved for not less than
three years after the last sales.
8. PACKINGAND LABELLING:
A minimum area of 50 square meters shall be provided for packing and labeling section.
9. EXPIRYDATE:
Not exceeding sixty (60) months from the date of manufacture.
10. STANDARD OPERATING PRACTICES:
Standard Operating Practices (SOPs) shall be developed for various activities such as
receipt, identification, cleaning, drying, warehousing, issue, handling, sampling etc. of all
materials. Labels and packing materials shall be examined for correctness and compliance
with rules. Records shall be maintained for their printing, use, destruction etc.
11. RECORDSAND REGISTERS:
Records shall be maintained for all the activities. These shall include records of
production, records of raw materials, records of testing, records of sales and other supplies,
records of rejection, complaints and actions taken, SOPs and records in respect of compliance
thereof, log books of equipment, master formula records, records of medical examination and
fitness of personnel etc. All records shall be maintained for a period of one year after the
expiry of a batch or for three years whichever is later.
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1
[SCHEDULE M-II
[See Rule
139]
REQUIREMENTS OF FACTORY PREMISES FOR MANUFACTURE
OF COSMETICS
I. GENERAL REQUIREMENTS
(A) Location and surroundings.–The factory shall be located in a sanitary place and hygienic
conditions shall be maintained in the premises. Premises shall not be used for residence or be
interconnected with residential area. It shall be well ventilated and clean.
(B) Buildings.– The buildings used for the factory shall be constructed so as to permit production
under hygienic conditions and not to permit entry of insects, rodents, files, etc.
The walls of the room in which manufacturing operations are carried out, shall be up to a
height of six feet from the floor, be smooth, waterproof and capable of being kept clean.
The flooring shall be smooth, even and washable and shall be such as not to permit
retention or accumulation of dust.
(C) Water supply: - The water used in manufacture shall be of potable quality.
(D) Disposal of water. –- Suitable arrangements shall be made for disposal of waste-water.
(E) Health, clothing and sanitary requirements of the staff.– All workers shall be free from
contagious or infectious diseases. They shall be provided with clean uniforms, masks,
headgears, and gloves wherever required. Washing facilities shall also be provided.
(F) Medical Services. - Adequate facilities for first aid shall be provided.
(G) Work benches shall be provided for carrying out operations such as filling, labelling,
packing, etc. Such benches shall be fitted with smooth, impervious tops capable of being
washed.
(H) Adequate facilities shall be provided for washing and drying of glass containers if the same
are to be used for packing the product.
II. REQUIREMENTS OF PLANT AND EQUIPMENT
The following equipment, area and other requirements are recommended for the
manufacture of: −
A. Powders:− Face powder, cake make-up, compacts, face packs, masks and
rouges, etc.
1.
Equipment:
(a) Powder mixer of suitable type provided with a dust collector.
(b) Perfume and colour blender.
(c) Sifter with sieves of suitable mesh size.
(d) Ball mill or suitable grinder.
1. Ins. by G.S.R 723(E) , dt. 11-8-1992.
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(e) Trays and scoops (stainless steel).
(f) Filling and sealing equipment provided with dust extractor.
(g) For compacts: -
(i) a separate mixer, (ii) compact pressing machine.
(h) Weighing and measuring devices
(i) Storage tanks.
An area of 15 square meters is recommended. The section is to be provided with adequate
exhaust fans.
B. Creams, lotions, emulsions, pastes, cleansing milks, shampoos, pomade,
brilliantine, shaving creams and hair-oils etc.
(a) Mixing and storage tanks of suitable materials.
(b) Heating kettle – steam, gas or electrically heated.
(c) Suitable agitator.
(d) Colloidal mill or homogeniser (wherever necessary).
(e) Triple roller mill (wherever necessary).
(f) Filling and sealing equipment.
(g) Weighing and measuring devices.
An area of 25 square meters is recommended.
C. Nail Polishes and Nail lacquers.
1. Equipment:
(a) A suitable mixer.
(b) Storage tanks.
(c) Filling machine – hand operated or power driven.
(d) Weighing and Measuring devices.
An area of 15 square meters is recommended. The section shall be provided with flameproof
exhaust system.
2. Premises:–The following are the special requirements related to Nail
Polishes and Nail Lacquers: -
(a) It shall be situated in an industrial area.
(b) It shall be separate from other cosmetic-manufacturing areas by metal/brick partition
up to ceiling.
(c) Floors, walls, ceiling and doors shall be fireproof.
(d) Smoking, cooking and dwelling shall not be permitted and no naked flame shall be
brought in the premises.
(e) All electrical wiring and connections shall be concealed and main electric switch
shall be outside the manufacturing area.
(f) All equipment, furniture and light fittings in the section shall be flameproof.
(g) Fire extinguisher like foam and dry powder and sufficient number of buckets
containing sand shall be provided.
(h) All doors of the section shall open outwards.
3. Storage:
All explosive solvents and ingredients shall be stored in metal cupboards or in a
separate enclosed area.
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4. Manufacture:
(a) Manufacture of lacquer shall not be undertaken unless the above conditions are
complied with.
(b) Workers shall be asked to wear shoes with rubber soles in the section.
5. Other
r
e
quirements:
No objection certificate from the local Fire Brigade Authorities shall be furnished.
D. Lipsticks and Lip-gloss,
etc.
1. Equipment
(a) Vertical mixer.
(b) Jacketted kettle – steam, gas or electrically heated.
(c) Mixing vessel (stainless steel).
(d) Triple roller mill/Ball mill.
(e) Moulds with refrigeration facility.
(f) Weighing and measuring devices.
An area of 15 square meters is recommended.
E. Depilatories.
1. Equipment:
(a) Mixing tanks.
(b) Mixer
(c) Triple roller mill or homogeniser (where necessary).
(d) Filling and sealing equipment.
(e) Weighing and measuring devices.
(f) Moulds (where necessary).
An area of 10 square meters is recommended.
F. Preparations used for Eyes: - Such preparations shall be manufactured under strict
hygienic conditions to ensure that these are safe for use.
1. Eyebrows, Eyelashes, Eyeliners, etc.
1 Equipment:
(a) Mixing tanks.
(b) A suitable mixer.
(c) Homogeniser (where necessary)
(d) Filling and sealing equipment.
(e) Weighing and measuring devices.
An area of 10 square meters is recommended.
2. Kajal and Surma
1. Equipment:
(a) Base sterilizer.
(b) Powder sterilizer (dry heat oven).
(c) Stainless steel tanks.
(d) A suitable Mixer.
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(e) Stainless steel sieves.
(f) Filling and sealing arrangements.
(g) Weighing and measuring devices.
(h) Homogeniser (where necessary).
(i) Pestle and Mortar (for Surma).
An area of 10 square meters with a separate area of 5 square meters for base
sterilization is recommended.
Other requirements for 1 and 2:
(a) False ceiling shall be provided wherever required.
(b) Manufacturing area shall be made fly proof. An airlock or an aircurtain shall be
provided.
(c) Base used for Kajal shall be sterilized by heating the base at 150 degree C for
required time in a separate enclosed area.
(d) The vegetable carbon black powder shall be sterilized in a drying oven at 120 degree
C for required tim
e.
(e) All utensils used for manufacture shall be of stainless steel and shall be washed with
detergent water, antiseptic liquid and again with distilled water.
(f) Containers employed for ‗Kajal‘ shall be cleaned properly with bactericidal solution
and dried.
(g) Workers shall put on clean overalls and use hand gloves wherever necessary.
G. Aerosol.
1. Equipment: -
(a) Air-compressor (wherever necessary).
(b) Mixing tanks.
(c) Suitable propellant filling and crimping equipments.
(d) Liquid filling unit.
(e) Leak testing equipment.
(f) Fire extinguisher (wherever necessary)
(g) Suitable filtration equipment.
(h) Weighing and measuring devices.
An area of 15 square meters is recommended.
2. Other requirements: - No objection certificate from the Local Fire Brigade
Authorities shall be furnished.
H. Alcoholic Fragrance Solutions.
Equipment: -
(a) Mixing tanks with stirrer
(b) Filtering equipment.
(c) Filling and sealing equipment.
(d) Weighing and measuring devices.
An area of 15 square meters is recommended.
I. Hair Dyes.
Equipment:
(a) Stainless steel tanks.
(b) Mixer.
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(c) Filling Unit.
(d) Weighing and measuring devices.
(e) Masks, gloves and goggles.
An area of 15 square meters with proper exhaust is recommended.
J. Tooth powders and toothpastes, etc.:
1. Tooth-powder in General.
Equipment:
(a) Weighing and measuring devices.
(b) Dry mixer (powder blender).
(c) Stainless steel sieves.
(d) Powder filling and sealing equipments.
An area of 15 square meters with proper exhaust is recommended.
2. Toothpastes.
Equipment:
(a) Weighing and measuring devices.
(b) Kettle – steam, gas or electrically heated (where necessary).
(c) Planetary mixer with de-aerator system.
(d) Stainless steel tanks.
(e) Tube filling equipment.
(f) Crimping machine.
An additional area of 15 square meters with proper exhaust is recommended.
3. Tooth-powder (Black)
Equipment:
(a) Weighing and measuring devices.
(b) Dry mixer powder blender.
(c) Stainless steel sieves.
(d) Powder filling arrangements.
An area of 15 square meters with proper exhaust is recommended. Areas for
manufacturing ―Black‖ and ―White‖ tooth powders should be separate.
K. Toilet Soaps:
Equipment: -
(a) Kettles/pans for saponification.
(b) Boiler or any other suitable heating arrangement.
(c) Suitable stirring arrangement.
(d) Storage tanks or trays.
(e) Driers.
(f) Amalgamator/chipping machine.
(g) Mixer.
(h) Triple roller mill.
(i) Granulator.
(j) Plodder.
(k) Cutter.
(l) Pressing, stamping and embossing machine.
(m) Weighing and measuring devices.
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A minimum area of 100 square meters is recommended for the small-scale
manufacture of toilet soaps.
The areas recommended above are for basic manufacturing of different categories of
cosmetics. In addition to that separate adequate space for storage of raw materials, finished
products, packing materials shall be provided in factory premises.
1
[***]
Note No. I−The above requirements of the Schedule are made subject to modification at
the discretion of the Licensing Authority, if he is of the opinion that having regard to the
nature and extent of the manufacturing operations it is necessary to relax or alter them in the
circumstances of a particular case.
Note No. II.−The above requirements do not include requirements of machinery,
equipments and premises required for preparation of containers and clousers of different
categories of cosmetics. The Licensing Authority shall have the discretion to examine the
suitability and adequacy of the machinery, equipments and premises for the purpose of taking
into consideration of the requirements of the licensee.
Note No. III.−Schedule M-II specifies equipments and space required for certain
categories of cosmetics only. There are other cosmetics items, viz. Attars, perfumes, etc.,
which are not covered in the above categories. The Licensing Authority shall, in respect of
such items or categories of cosmetics have the discretion to examine the adequacy of factory
premises, space, plant and machinery and other requisites having regard to the nature and
extent of the manufacturing operations involved and direct the licensee to carry on necessary
modification in them.
1. The words ―A testing laboratory shall also be provided‖ omitted by G.S.R.285 (E) , dt. 16.7.1996.
Drugs and Cosmetics Rules 1945
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1
[SCHEDULE M-III
[See rules 69, 69A, 75, 75A and 76]
QUALITY MANAGEMENT SYSTEM –FOR NOTIFIED MEDICAL DEVICES AND IN-
VITRO DIAGNOSTICS
1. General Requirements:
1.1. This schedule specifies requirements for a quality management system that shall be used by
the manufacturer for the design and development, manufacture, packaging, labeling, testing,
installation and servicing of medical devices and in-vitro diagnostics. If the manufacturer does not
carry out design and development activity, the same shall be recorded in the quality management
system. The manufacturer shall maintain conformity with this Schedule to reflect the exclusions.
1.2. If any requirement in clause 7(product realisation) of this Schedule is not applicable due to
the nature of the medical device and in-vitro diagnostics for which the quality management system is
applied, the manufacturer does not need to include such a requirement in its quality management
system.
1.3. The processes required by this Schedule, which are applicable to the medical device and in-
vitro diagnostic devices, but which are not performed by the manufacturer are the responsibility of
the manufacturer and are accounted for in the manufacturer‘s quality management system.
1.4. If a manufacturer engages in only some operations subject to the requirements of this part,
and not in others, that manufacturer need only to comply with those requirements which are
applicable to the operations in which it is engaged.
1.5. It is emphasised that the quality management system requirements specified in this Schedule
are in addition to complementary to technical requirements for products.
1.6. Manufacturers of components or parts of finished devices and in-vitro diagnostics are
encouraged to use appropriate provisions of this regulation as guidance.
2. Applicability:
The provisions of this Schedule shall be applicable to manufacturers of finished devices, In-Vitro
Diagnostics, mechanical contraceptives (condoms, intrauterine devices, tubal rings), surgical
dressings, surgical bandages, surgical staplers, surgical sutures and ligatures, blood and blood
components collection bags with or without anticoagulants intended for human or animal use.
1. Subs.by G.S.R. 640 (E) , dt. 29.6.2016. Previously, Ins. by G.S.R. 109 (E) , dt. 22.2.1994.
Drugs and Cosmetics Rules 1945
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3. Terms and definitions:
3.1 Active implantable medical device.- Active medical device which is intended to be totally
or partially introduced, surgically or medically, into the human or animal body or by medical
intervention into a natural orifice and which is intended to remain after the procedure.
3.2 Active medical device.- Medical device relying for its functioning on a source of electrical
energy or any source of power other than that directly generated by the human or animal body or
gravity.
3.3 Advisory notice.- Notice issued by the manufacturer, subsequent to delivery of the medical
device and in-vitro diagnostic devices, to provide supplementary information or to advise what
action should be taken in or both in:-
a. the use of a medical device and in-vitro diagnostic devices;
b. the modification of a medical device and in-vitro diagnostic devices;
c. the return of the medical device and in-vitro diagnostic devices to the organization that
supplied it; or
d. the destruction of a medical device and in-vitro diagnostic devices.
3.4 Customer complaint.- Written, electronic or oral communication that alleges deficiencies
related to the identity, quality, durability, reliability, safety, effectiveness or performance of a
medical device and in-vitro diagnostic devices that has been placed on the market.
3.5 Implantable medical device.- Medical device intended:-
a. to be totally or partially introduced into the human or animal body or a natural orifice; or
b. to replace an epithelial surface or the surface of the eye;
by surgical intervention, and which is intended to remain after the procedure for at least
thirty days, and which can only be removed by medical or surgical intervention.
3.6 Component means any raw material, substance, piece, part, software, firmware, labeling, or
assembly which is intended to be included as part of the finished, packaged, and labeled device.
3.7 Design input means the physical and performance requirements of a device that are used as a
basis for device design.
3.8 Design output means the results of a design effort at each design phase and at the end of the
total design effort. The finished design output is the basis for the device master record. The total
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finished design output consists of the device, its packaging and labeling, and the device master
record.
3.9 Design review means a documented, comprehensive, systematic examination of a design to
evaluate the adequacy of the design requirements, to evaluate the capability of the design to meet
these requirements, and to identify problems.
3.10 Finished device means any device or accessory to any device that is suitable for use or
capable of functioning, whether or not it is packaged, labeled or sterilized.
3.11 In-vitro Diagnostic means in-vitro diagnostics referred in this Schedule including
diagnostics kits and reagents that fall under sub-clause (i) of clause (b) of section 3 of Drugs and
Cosmetics Act, 1940.
3.12 Management with executive responsibility means those senior employees of a manufacturer
who have the authority to establish or make changes to the manufacturer's quality policy and quality
system.
3.13 Medical device referred in this Schedule means devices that are notified under clause (iv) of
sub-section (b) of section 3 of Drugs and Cosmetics Act, 1940.
3.14 Quality audit means a systematic, independent examination of a manufacturer's quality
system that is performed at defined intervals and at sufficient frequency to determine whether both
quality system activities and the results of such activities comply with quality system procedures,
that these procedures are implemented effectively, and that these procedures are suitable to achieve
quality system objectives.
3.15 Quality policy means the overall intention and direction of an organization with respect to
quality, as established by management with executive responsibility.
3.16 Quality system means the organisational structure, responsibilities, procedures, processes,
and resources for implementing quality management.
3.17 Rework means action taken on a nonconforming product that will fulfill the specified
Device Master File requirements before it is released for distribution.
3.18 Specification means any requirement with which a product, process, service, or other
activity must conform.
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3.19 Validation means confirmation by examination and provision of objective evidence that the
particular requirement for a specific intended use can be consistently fulfilled;
3.19.1 Process validation means establishing by objective evidence that a process consistently
produces a result or product meeting its predetermined specifications.
3.19.2 Design validation means establishing by objective evidence that device specifications
conform with user needs and intended use(s).
3.20 Verification means confirmation by examination and provision of objective evidence that
specified requirements have been fulfilled.
4 Quality management system.-
4.1 General:
The manufacturer shall establish, document, implement and maintain a quality management system
and maintain its effectiveness in accordance with the requirements of this schedule.
The manufacturer shall;-
(a) identify the processes needed for the quality management system and their application
throughout the organization;
(b) determine the sequence and interaction of these processes;
(c) determine criteria and methods needed to ensure that both the operation and control of these
processes are effective;
(d) ensure the availability of resources and information necessary to support the operation and
monitoring of these processes;
(e) monitor, measure and analyse these processes; and
(f) implement actions necessary to achieve planned results and maintain the effectiveness of these
processes.
These processes shall be managed by the manufacturer in accordance with the requirements of this
Schedule. Where a manufacturer chooses to outsource any process that affects product conformity
with requirements, the manufacturer shall ensure control over such processes. Control of such
outsourced processes shall be identified within the quality management system.
NOTE: Processes needed for the quality management system referred to above shall include
processes for management activities, provision of resources, product realization and measurement.
4.2 Documentation requirements.-
4.2.1 General
The quality management system documentation shall include;-
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(a) documented statements of a quality policy and quality objectives;
(b) a quality manual;
(c) documented procedures required by this schedule;
(d) documents needed by the manufacturer to ensure the effective planning, operation and
control of its processes;
(e) records required by this schedule, and
where this schedule specifies that a requirement, procedure, activity or special arrangement be
―documented‖, it shall, in addition, be implemented and maintained.
For each type or model of medical device or In-vitro Diagnostics, the manufacturer shall establish
and maintain a file either containing or identifying documents defining product specifications and
quality management system requirements. These documents shall define the complete
manufacturing process and, if applicable, installation.
The manufacture shall prepare documentation for device or in-vitro diagnostics in a form of a
Device Master File containing specific information as referred to in Annexure-A appended to this
Schedule.
Data may be recorded by electronic data processing systems or other reliable means, but documents
and record relating to the system in use shall also be available in a hard copy to facilitate checking of
the accuracy of the records. Wherever documentation is handled by electronic data processing
methods, authorized persons shall enter or modify data in the computer. There shall be record of
changes and deletions. Access shall be restricted by ‗passwords‘ or other means and the result of
entry of critical data shall be independently checked. Batch records electronically stored shall be
protected by a suitable back-up. During the period of retention, all relevant data shall be readily
available.
4.2.2 Quality manual.-
The manufacturer shall establish and maintain a quality manual that includes:-
(a) the scope of the quality management system, including details of and justification for any
exclusion or non-application or both;
(b) the documented procedures established for the quality management system, or reference to
them; and
(c) a description of the interaction between the processes of the quality management system.
The quality manual shall outline the structure of the documentation used in the quality
management system.
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The manufacturer shall prepare documentation in a form of a Plant Master File containing specific
information about the facilities, personnel and other details as prescribed in Annexure B appended to
this Schedule.
4.2.3 Control of documents.-
Documents required by the quality management system shall be controlled. Records are a special
type of document and shall be controlled according to the requirements given in the control of
records. Documents shall be approved, signed and dated by the appropriate and the authorised
person.
A documented procedure shall be established to define the controls needed.-
(a) to review and approve documents for adequacy prior to issue;
(b) to review and update as necessary and re-approve documents;
(c) to ensure that changes and the current revision status of documents are identified;
(d) to ensure that relevant versions of applicable documents are available at points of use;
(e) to ensure that documents remain legible and readily identifiable;
(f) to ensure that documents of external origin are identified and their distribution controlled;
and
(g) to prevent the unintended use of obsolete documents, and to apply suitable identification to
them if they are retained for any purpose.
Changes to document shall be reviewed and approved. Change records shall be maintained which
will include a description of the change, identification of the affected documents, the signature of the
approving individual, the approval date, and when the change becomes effective.
The manufacturer shall ensure that changes to documents are reviewed and approved either by the
original approving functionary or another designated functionary which has access to pertinent
background information upon which to base its decisions.
The manufacturer shall define the period for which at least one copy of obsolete controlled
documents shall be retained. This period shall ensure that documents to which medical devices or in-
vitro diagnostics have been manufactured and tested are retained for at least one year after the date
of expiry of the medical device or in-vitro diagnostic as defined by the manufacturer.
4.2.4 Control of records.-
Records shall be established and maintained to provide evidence of conformity to the requirements
and of the effective operation of the quality management system. Records shall remain legible,
readily identifiable and retrievable. A documented procedure shall be established to define the
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controls needed for the identification, storage, protection, retrieval, retention time and disposition of
records.
The manufacturer shall retain the records for a period of time at least one year after the date of
expiry of the medical device or in-vitro diagnostics as defined by the manufacturer, but not less than
two years from the date of product release by the manufacturer.
5 Management responsibility.-
5.1 Management commitment:
Top management of the manufacturer shall provide evidence of its commitment to the development
and implementation of the quality management system and maintaining its effectiveness by:-
(a) communicating to the employees the importance of meeting customer as well as statutory and
regulatory requirements;
(b) establishing the quality policy;
(c) ensuring that quality objectives are established;
(d) conducting management reviews; and
(e) ensuring the availability of resources.
5.2 Customer focus:
Top management of the manufacturer shall ensure that customer requirements are determined and
are met.
5.3 Quality policy:
Top management of the manufacturer shall ensure that the quality policy:-
(a) is appropriate to the purpose of the manufacturing facility;
(b) includes a commitment to comply with requirements and to maintain the effectiveness of the
quality management system;
(c) provides a framework for establishing and reviewing quality objectives;
(d) is communicated and understood within the manufacturer‘s organization; and
(e) is reviewed for continuing suitability.
5.4 Planning.-
5.4.1 Quality objectives:
Top management of the manufacturer shall ensure that quality objectives, including those needed to
meet requirements for product, are established at relevant functions and levels within the
manufacturing organization. The quality objectives shall be measurable and consistent with the
quality policy.
5.4.2 Quality management system planning:
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Top management of the manufacturer shall ensure that.-
(a) the planning of the quality management system is carried out in order to meet the specified
requirements, as well as the quality objectives; and
(b) the integrity of the quality management system is maintained when changes to the quality
management system are planned and implemented.
5.5 Responsibility, authority and communication.-
5.5.1 Responsibility and authority:
Top management of the manufacturer shall ensure that responsibilities and authorities are defined,
documented and communicated within the manufacturing organisation.
Top management of the manufacturer shall establish the interrelation of all personnel who manage,
perform and verify work affecting quality, and shall ensure the independence and authority
necessary to perform these tasks.
5.5.2 Management representative:
Top management shall appoint a member of management who, irrespective of other responsibilities,
shall have responsibility and authority that includes:-
(a) ensuring that processes needed for the quality management system are established,
implemented and maintained;
(b) reporting to top management on the performance of the quality management system and any
need for improvement; and
(c) ensuring the promotion of awareness of regulatory and customer requirements throughout
the manufacturing organization.
5.5.3 Internal communication:
Top management shall ensure that appropriate communication processes are established within the
Manufacturing organization and that communication takes place regarding the effectiveness of the
quality management system.
5.6 Management review.-
5.6.1 General:
Top management shall review the organization‘s quality management system, at planned intervals,
to ensure its continuing suitability, adequacy and effectiveness. This review shall include assessing
opportunities for improvement and the need for changes to the quality management system,
including the quality policy and quality objectives. Records from management reviews shall be
maintained.
5.6.2 Review input:
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The input to management review shall include information on:-
(a) results of audits,
(b) customer feedback,
(c) process performance and product conformity,
(d) status of preventive and corrective actions,
(e) follow-up actions from previous management reviews,
(f) changes that could affect the quality management system,
(g) recommendations for improvement, and
(h) new or revised regulatory requirements as and when issued.
5.6.3 Review output:
The output from the management review shall include any decisions and actions related to:-
(a) improvements needed to maintain the effectiveness of the quality management system and
its processes,
(b) improvement of product related to customer requirements, and
(c) resource needs.
6 Resource management.-
6.1 Provision of resources:
The manufacturing organization shall determine and provide the resources needed
(a) to implement the quality management system and to maintain its effectiveness, and
(b) to meet regulatory and customer requirements.
6.2 Human resources.-
6.2.1 General:
Personnel performing work affecting product quality shall be competent on the basis of appropriate
education, training, skills and experience. Number of personnel employed shall be adequate and in
direct proportion to the workload. Prior to employment, all personnel, shall undergo medical
examination including eye examination, and shall be free from communicable or contagious
diseases. Thereafter, they should be medically examined periodically, at least once a year. Records
shall be maintained thereof.
6.2.2 Competence, awareness and training:
The manufacturer shall:-
(a) determine the necessary competence for personnel performing work affecting product
quality,
(b) provide training or take other actions to satisfy these needs,
(c) evaluate the effectiveness of the actions taken,
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(d) ensure that its personnel are aware of the relevance and importance of their activities and
how they contribute to the achievement of the quality objectives,
(e) maintain appropriate records of education, training, skills and experience, and
(f) establish documented procedures for identifying training needs and ensure that all personnel
are trained to adequately perform their assigned responsibilities.
6.3 Infrastructure:
The organisation shall determine, provide and maintain the infrastructure needed to achieve
conformity to product requirements. Infrastructure includes, as applicable:-
(a) buildings, workspace and associated utilities.
(b) process equipment (both hardware and software), and
(c) supporting services (such as transport or communication).
The manufacturer shall establish documented requirements for maintenance activities, including
their frequency, when such activities or lack thereof can affect product quality. Records of such
maintenance shall be maintained.
6.4 Work environment:
The organisation shall determine and manage the work environment needed to achieve conformity to
product requirements. The following requirements shall apply, namely:-
(a) the manufacturer shall establish documented requirements for health, cleanliness and clothing
of personnel if contact between such personnel and the product or work environment could
adversely affect the quality of the product;
(b) if work environment conditions can have an adverse effect on product quality, the
manufacturer shall establish documented requirements as per Annexure-C of this schedule
for the work environment conditions and documented procedures or work instructions to
monitor and control these work environment condition;
(c) the manufacturer shall ensure that all personnel who are required to work temporarily under
special environmental conditions within the work environment are appropriately trained and
supervised by a trained person;
(d) if appropriate, special arrangements shall be established and documented for the control of
contaminated or potentially contaminated product in order to prevent contamination of other
product, the work environment or personnel.
(e) all personnel shall bear clean body covering appropriate to their duties. Smoking, eating,
drinking, chewing or keeping food and drink shall not be permitted in production, laboratory
and storage areas.
7 Product realisation.-
7.1 Planning of product realization:
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The manufacturer shall plan and develop the processes needed for product realization. Planning of
product realization shall be consistent with the requirements of the other processes of the quality
management system.
In planning product realisation, the manufacturer shall determine the following, as
appropriate:-
(a) quality objectives and requirements for the product;
(b) the need to establish processes, documents, and provide resources specific to the product;
(c) required verification, validation, monitoring, inspection and test activities specific to the
product and the criteria for product acceptance;
(d) records needed to provide evidence that the realisation processes and resulting product meet
requirements.
The output of this planning shall be in a form suitable for the manufacturer‘s method of operations.
The manufacturer organisation shall establish documented requirements for risk management (as per
the IS or ISO 14971) throughout product realisation. Records arising from risk management shall be
maintained.
7.2 Customer-related processes.-
7.2.1 Determination of requirements related to the product:
The manufacturer shall determine:-
(a) requirements specified by the customer, including the requirements for delivery and post-
delivery activities,
(b) requirements not stated by the customer but necessary for specified or intended use, where
known;
(c) statutory requirements related to the product, and
(d) any additional requirements determined by the manufacturer.
7.2.2 Review of requirements related to the product:
The manufacturer shall review the requirements related to the product. This review shall be
conducted prior to the manufacturer's commitment to supply a product to the customer and shall
ensure that:-
(a) product requirements are defined and documented;
(b) contract or order requirements differing from those previously expressed are resolved; and
(c) the manufacturer has the ability to meet the defined requirements.
Records of the results of the review and actions arising from the review shall be maintained.
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Where the customer provides no documented statement of requirement, the customer requirements
shall be confirmed by the manufacturer before acceptance.
Where product requirements are changed, the manufacturer shall ensure that relevant documents are
amended and that relevant personnel are made aware of the changed requirements.
7.2.3 Customer communication:
The manufacturer shall determine and implement effective arrangements for communicating with
customers in relation to:-
(a) product information;
(b) enquiries, contracts or order handling, including amendments;
(c) customer feedback, including customer complaints; and
(d) advisory notices.
7.3 Design and development.-
7.3.1 Design and development planning:
The manufacturer shall establish documented procedures for design and development. The
manufacturer shall plan and control the design and development of product. During the design and
development planning, the manufacturer shall determine :-
(a) the design and development stages;
(b) the review, verification, validation and design transfer activities that are appropriate at each
design and development stage; and
(c) the responsibilities and authorities for design and development.
The manufacturer shall manage the interfaces between different groups involved in design and
development to ensure effective communication and clear assignment of responsibility.
Planning output shall be documented, and updated as appropriate, as the design and development
progresses.
NOTE: Design transfer activities during the design and development process ensure that design and
development outputs are verified as suitable for manufacturing before becoming final production
specifications.
7.3.2 Design and development inputs:
Inputs relating to product requirements shall be determined and records maintained. The design
requirements relating to a device are appropriate and address the intended use of the device,
including the needs of the user and patients.
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These inputs shall include:-
(a) functional, performance and safety requirements, according to the intended use;
(b) applicable statutory and regulatory requirements;
(c) where applicable, information derived from previous similar designs;
(d) other requirements essential for design and development; and
(e) output(s) of risk management.
These inputs shall be reviewed for adequacy and approved by designated individual.
Requirements shall be complete, unambiguous and not in conflict with each other.
7.3.3 Design and development outputs:
The outputs of design and development shall be provided in a form that enables verification against
the design and development input and shall be documented, reviewed, and approved prior to release.
Design and development outputs shall:-
(a) meet the input requirements for design and development;
(b) provide appropriate information for purchasing, production and for service provision;
(c) contain or reference product acceptance criteria; and
(d) specify the characteristics of the product that are essential for its safe and proper use.
Records of the design and development outputs shall be maintained.
Records of design and development outputs can include specifications, manufacturing procedures,
engineering drawings, and engineering or research logbooks.
7.3.4 Design and development review:
At suitable stages, systematic reviews of design and development shall be performed in accordance
with planned arrangements:-
(a) to evaluate the ability of the results of design and development to meet requirements; and
(b) to identify any problems and propose necessary actions.
Participants in such reviews shall include representatives of functions concerned with the design and
development stage being reviewed, as well as other specialist personnel.
Records of the results of the reviews and any necessary actions shall be maintained
7.3.5 Design and development verification:
Verification shall be performed in accordance with planned arrangements to ensure that the design
and development outputs have met the design and development input requirements. Records of the
results of the verification and any necessary actions shall be maintained.
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7.3.6 Design and development validation:
Design and development validation shall be performed in accordance with planned arrangements to
ensure that the resulting product is capable of meeting the requirements for the specified application
or intended use.
Design validation shall be performed under defined operating conditions on initial production units,
lots, or batches or their equivalence. Design validation shall include software validation and risk
analysis, where appropriate validation shall be completed prior to the delivery or implementation of
the product.
Records of the results of validation and any necessary actions shall be maintained.
As part of design and development validation, the manufacturer shall perform clinical evaluations
and/or evaluation of performance of the medical device or In-vitro Diagnostics.
NOTE 1.- If a medical device or In-vitro Diagnostic can only be validated following assembly and
installation at point of use, delivery is not considered to be complete until the product has been
formally transferred to the customer.
NOTE 2.- Provision of the medical device for purposes of clinical evaluations and/or evaluation of
performance is not considered to be delivery.
7.3.7 Control of design and development changes:
Design and development changes shall be identified and records maintained. The changes shall be
reviewed, verified and validated, as appropriate, and approved before implementation. The review of
design and development changes shall include evaluation of the effect of the changes on constituent
parts and product already delivered. Records of the results of the review of changes and any
necessary actions shall be maintained.
Note.-Each manufacturer shall establish and maintain a Design History File for each type of device.
The Design History File shall contain or reference the records necessary to demonstrate that the
design was developed in accordance with the approved design plan and the requirements of design
and development.
7.4 Purchasing.-
7.4.1 Purchasing process:
The manufacturer organisation shall establish documented procedures to ensure that purchased
product conforms to specified purchase requirements. The type and extent of control applied to the
supplier and the purchased product shall be dependent upon the effect of the purchased product on
subsequent product realisation or the final product.
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The manufacturer shall evaluate and select suppliers based on their ability to supply product in
accordance with the manufacturer‘s requirements. Criteria for selection, evaluation and re-evaluation
shall be established.
Records of the results of evaluations and any necessary actions arising from the evaluation shall be
maintained.
7.4.2 Purchasing information:
Purchasing information shall describe the product to be purchased, including where appropriate:-
(a) requirements for approval of product, procedures, processes and equipment;
(b) requirements for qualification of personnel; and
(c) quality management system requirements.
The manufacturer shall ensure the adequacy of specified purchase requirements prior to their
communication to the supplier.
To the extent required for traceability, the manufacturer shall maintain documents and records of
relevant purchasing information.
7.4.3 Verification of purchased product:
The manufacturer shall establish and implement the inspection or other activities necessary for
ensuring that purchased product meets specified purchase requirements. Where the manufacturer
intends to perform verification at the supplier‘s premises, the manufacturer shall state the intended
verification arrangements and method of product release in the purchasing information. Records of
the verification shall be maintained.
7.5 Production and service provision.-
7.5.1 Control of production and service provision:
7.5.1.1 General requirements:
The manufacturer shall plan and carry out production and service provision under controlled
conditions. Controlled conditions shall include, as applicable:-
(a) the availability of information that describes the characteristics of the product,
(b) the availability of documented procedures, documented requirements, work instructions; and
reference materials and reference measurement procedures as necessary;
(c) the use of suitable equipment;
(d) the availability and use of monitoring and measuring devices;
(e) the implementation of monitoring and measurement;
(f) the implementation of release, delivery and post-delivery activities; and
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(g) the implementation of defined operations for labeling and packaging.
The manufacturer shall establish and maintain a record for each batch of medical device or In-vitro
Diagnostic devices that provides traceability and identifies the amount manufactured and amount
approved for distribution. The batch record shall be verified and approved.
7.5.1.2 Control of production and service provision — Specific requirements
7.5.1.2.1 Cleanliness of product and contamination control:
The manufacturer shall establish documented requirements for cleanliness of product if:-
(a) product is cleaned by the manufacturer prior to sterilisation or its use; or
(b) product is supplied non-sterile to be subjected to a cleaning process prior to sterilisation or
its use; or
(c) product is supplied to be used non-sterile and its cleanliness is of significance in use; or
(d) process agents are to be removed from product during manufacture.
If the product is cleaned in accordance with (a) or (b) above, the requirements content in clause 6.4
(a) and (b) do not apply prior to the cleaning process
7.5.1.2.2 Installation activities:
If appropriate, the manufacturer shall establish documented requirements which contain acceptance
criteria for installing and verifying the installation of the medical device or In-vitro Diagnostic
device.
If the agreed customer requirements allow installation to be performed other than by manufacturer or
its authorised agent, the manufacturer shall provide documented requirements for installation and
verification. Records of installation and verification performed by the manufacturer or its authorized
agent shall be maintained.
7.5.1.3 Particular requirements for sterile medical devices:
The manufacturer shall maintain records of the process parameters for the sterilisation process which
was used for each sterilisation batch. Sterilisation records shall be traceable to each production batch
of medical device.
7.5.2 Validation of processes for production and service provision.-
7.5.2.1 General:
The manufacturer shall validate any processes for production and service provision where the
resulting output cannot be verified by subsequent monitoring or measurement. This includes any
processes where deficiencies become apparent only after the product is in use. Validation shall
demonstrate the ability of these processes to achieve planned results.
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The manufacturer shall establish arrangements for these processes including, as applicable:-
(a) defined criteria for review and approval of the processes;
(b) approval of equipment and qualification of personnel
(c) use of specific methods and procedures,;
(d) requirements for records; and
(e) revalidation.
The manufacturer shall establish documented procedures for the validation of the application of
computer software (and its changes to such software or its application) for production and service
provision that affect the ability of the product conform to specified requirements. Such software
applications shall be validated prior to initial use.
Records of validation shall be maintained.
7.5.2.2 Particular requirements for sterile medical devices:
The manufacturer shall establish documented procedures for the validation of sterilization processes.
Sterilisation processes shall be validated prior to initial use. The records of validation of each
sterilisation process shall be maintained.
7.5.3 Identification and traceability.-
7.5.3.1 Identification:
The manufacturer shall identify the product by suitable means throughout product realization, and
shall establish documented procedures for such product identification. The manufacturer shall
establish documented procedures to ensure that medical devices and In-vitro Diagnostics returned to
the manufacturer are identified and distinguished from conforming product.
7.5.3.2 Traceability.-
7.5.3.2.1 General:
The manufacturer shall establish documented procedures for traceability. Such procedures shall
define the extent of product traceability and the records required.
Where traceability is a requirement, the manufacturer shall control and record the unique
identification of the product.
NOTE.- Configuration management is a means by which identification and traceability can be
maintained.
7.5.3.2.2 Particular requirements for active implantable medical devices and implantable
medical devices:
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In defining the records required for traceability, the manufacturer shall include records of all
components, materials and work environment conditions, if these could cause the medical device not
to satisfy its specified requirements.
The manufacturer shall require that its agents or distributors maintain records of the distribution of
active implantable medical devices and implantable medical devices to allow traceability and that
such records are available for inspection. Records of the name and address of the shipping package
consignee shall be maintained.
7.5.3.3 Status identification:
The manufacturer shall identify the product status with respect to monitoring and measurement
requirements. The identification of product status shall be maintained throughout production,
storage, implant, usage and installation of the product to ensure that only product that has passed the
required inspections and tests (or released under an authorized concession) is dispatched, used or
installed.
7.5.4 Customer property:
The manufacturer shall exercise care with customer property while it is under the manufacturer‘s
control or being used by the manufacturer. The manufacturer shall identify, verify, protect and
safeguard customer property provided for use or incorporation into the product. If any customer
property is lost, damaged or otherwise found to be unsuitable for use, this shall be reported to the
customer and records maintained.
NOTE.- Customer property can include intellectual property or confidential health information.
7.5.5 Preservation of product:
The manufacturer shall establish documented procedures or documented work instructions for
preserving the conformity of product during internal processing and delivery to the intended
destination. This preservation shall include identification, handling, packaging, storage and
protection. Preservation shall also apply to the constituent parts of a product.
The manufacturer shall establish documented procedures or documented work instructions for the
control of product with a limited shelf-life or requiring special storage conditions. Such special
storage conditions shall be controlled and recorded.
7.6 Control of monitoring and measuring devices:
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The manufacturer shall determine the monitoring and measurement to be undertaken and the
monitoring and measuring devices needed to provide evidence of conformity of product to
determined requirements.
The manufacturer shall establish documented procedures to ensure that monitoring and measurement
can be carried out and are carried out in a manner that is consistent with the monitoring and
measurement requirements.
Where necessary to ensure valid results, measuring equipment shall be:-
(a) calibrated or verified at specified intervals, or prior to use, against measurement standards
traceable to Bureau of Indian Standards wherever available ; where no such standards exist,
the basis used for calibration or verification shall be recorded;
(b) adjusted or re-adjusted as necessary;
(c) identified to enable the calibration status to be determined;
(d) safeguarded from adjustments that would invalidate the measurement result;
(e) protected from damage and deterioration during handling, maintenance and storage.
In addition, the manufacturer shall assess and record the validity of the previous measuring results
when the equipment is found not to conform to requirements. The manufacturer shall take
appropriate action on the equipment and any product affected. Records of the results of calibration
and verification shall be maintained.
When used in the monitoring and measurement of specified requirements, the ability of computer
software to satisfy the intended application shall be confirmed. This shall be undertaken prior to
initial use and reconfirmed as necessary.
8 Measurement, analysis and improvement.-
8.1 General:
The manufacturer shall plan and implement the monitoring, measurement, analysis and
improvement processes needed:-
(a) to demonstrate conformity of the product;
(b) to ensure conformity of the quality management system; and
(c) to maintain the effectiveness of the quality management system.
This shall include determination of applicable methods, including statistical techniques, and the
extent of their use.
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Note.- If relevant Indian standards are not available, International standards are applicable. In case
no Indian or International standards are available, validated testing process of the manufacturer is
applicable.
8.2 Monitoring and measurement.-
8.2.1 Feedback:
As one of the measurements of the performance of the quality management system, the
manufacturer shall monitor information relating to whether the manufacturer has met customer or
regulatory requirements. The methods for obtaining and using this information shall be determined.
The manufacturer shall establish a documented procedure for a feedback system to provide early
warning of quality problems and for input into the corrective and preventive action processes.
8.2.2 Internal audit:
The manufacturer shall conduct internal audits at planned intervals to determine whether the quality
management system:-
a) conforms to the planned arrangements, to the requirements of this schedule and to the
quality management system requirements established by the manufacturer, and
b) is effectively implemented and maintained.
An audit programme shall be planned, taking into consideration the status and importance of the
processes and areas to be audited, as well as the results of previous audits. The audit criteria, scope,
frequency and methods shall be defined. Selection of auditors and conduct of audits shall ensure
objectivity and impartiality of the audit process. Auditors shall not audit their own work.
The responsibilities and requirements for planning and conducting audits, and for reporting results
and maintaining records shall be defined in a documented procedure. The management responsible
for the area being audited shall ensure that actions are taken without undue delay to eliminate
detected nonconformities and their causes. Follow-up activities shall include the verification of the
actions taken and the reporting of verification results.
8.2.3 Monitoring and measurement of processes:
The manufacturer shall apply suitable methods for monitoring and, where applicable, measurement
of the quality management system processes. These methods shall demonstrate the ability of the
processes to achieve planned results. When planned results are not achieved, correction and
corrective action shall be taken, as appropriate, to ensure conformity of the product.
8.2.4 Monitoring and measurement of product.-
8.2.4.1 General requirements:
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The manufacturer shall monitor and measure the characteristics of the product to verify that product
requirements have been met. This shall be carried out at appropriate stages of the product realisation
process in accordance with the planned arrangements and documented procedures.
Evidence of conformity with the acceptance criteria shall be maintained. Records shall indicate the
person(s) authorizing release of product. Product release shall not proceed until the planned
arrangements have been satisfactorily completed.
8.2.4.2 Particular requirement for active implantable medical devices and implantable medical
Devices wherever applicable:
The manufacturer shall record the identity of personnel performing any inspection or testing.
8.3 Control of nonconforming product
The manufacturer shall ensure that product which does not conform to product requirements is
identified and controlled to prevent its unintended use or delivery. The controls and related
responsibilities and authorities for dealing with nonconforming product shall be defined in a
documented procedure.
The manufacturer shall deal with nonconforming product by one or more of the following ways:
(a) by taking action to eliminate the detected nonconformity;
(b) by authorizing its use, release or acceptance under concession;
(c) by taking action to preclude its original intended use or application.
The manufacturer shall ensure that nonconforming product is accepted by concession only if
regulatory requirements are met. Records of the identity of the person authorisng the concession
shall be maintained.
Records of the nature of nonconformities and any subsequent actions taken, including concessions
obtained, shall be maintained.
When nonconforming product is corrected it shall be subject to re-verification to demonstrate
conformity to the requirements. When nonconforming product is detected after delivery or use has
started, the manufacturer shall take action appropriate to the effects, or potential effects, of the non-
conformity.
If product needs to be reworked (one or more times), the manufacturer shall document the rework
process in a work instruction that has undergone the same authorisation and approval procedure as
the original work instruction. Prior to authorisation and approval of the work instruction, a
determination of any adverse effect of the rework upon product shall be made and documented.
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8.4 Analysis of data:
The manufacturer shall establish documented procedures to determine, collect and analyze
appropriate data to demonstrate the suitability and effectiveness of the quality management system
and to evaluate whether improvement of the effectiveness of the quality management system can be
made.
This shall include data generated as a result of monitoring and measurement and from other relevant
sources.
The analysis of data shall provide information relating to:-
(a) feedback
(b) conformity to product requirements;
(c) characteristics and trends of processes and products including opportunities for preventive
action; and
(d) suppliers.
Records of the results of the analysis of data shall be maintained.
8.5 Improvement.-
8.5.1 General:
The manufacturer shall identify and implement any changes necessary to ensure and maintain the
continued suitability and effectiveness of the quality management system through the use of the
quality policy, quality objectives, audit results, analysis of data, corrective and preventive actions
and management review.
The manufacturer shall establish documented procedures for the issue and implementation of
advisory notices. These procedures shall be capable of being implemented at any time. Records of
all customer complaint investigations shall be maintained. If investigation determine that the
activities outside the manufacturer‘s organisation contributed to the customer complaint, relevant
information shall be exchanged between the organisations involved.
If any customer complaint is not followed by corrective or preventive action, the reason shall be
recorded and approved. Manufacturer shall notify the adverse event to the regulatory authority and
establish documented procedures for the same.
8.5.2 Corrective action:
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The manufacturer shall take action to eliminate the cause of nonconformities in order to prevent
recurrence. Corrective actions shall be appropriate to the effects of the nonconformities encountered.
A documented procedure shall be established to define requirements for:-
(a) reviewing nonconformities (including customer complaints);
(b) determining the causes of nonconformities;
(c) evaluating the need for action to ensure that nonconformities do not recur
(d) determining and implementing action needed, including, if appropriate, updating
documentation;
(e) recording of the results of any investigation and of action taken; and
(f) reviewing the corrective action taken and its effectiveness.
8.5.3 Preventive action:
The manufacturer shall determine action to eliminate the causes of potential nonconformities in
order to prevent their occurrence. Preventive actions shall be appropriate to the effects of the
potential problems. A documented procedure shall be established to define requirements for
(a) determining potential nonconformities and their causes,
(b) evaluating the need for action to prevent occurrence of nonconformities,
(c) determining and implementing action needed,
(d) recording of the results of any investigations and of action taken, and
(e) reviewing preventive action taken and its effectiveness.
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Annexure ‗A‘
(refer para 4.2.1)
The manufacturer shall prepare a succinct document in the form of Device Master File containing
specific information about the device manufacturing in the premises.
1.0 Executive Summary:
An executive summary shall be provided by the manufacturer and shall contain:
Introductory descriptive information on the medical device or In-vitro Diagnostics, the intended use
and indication for use, Class of Device, novel features of the device (if any), shelf life of the device
and a synopsis on the content of the dossier information regarding sterilisation of the device
(whether it is sterile or non-sterile; if sterile, mode of sterilisation)
2.0 Device Description And Product Specification, Including Variants And Accessories:
2.1 Device Description
2.2 Product Specification
2.3 Reference to predicate and/or previous generations of the device
3.0 Labelling
4.0 Design And Manufacturing Information:
4.1 Device Design
4.2 Manufacturing Processes
5.0 Essential Principles (EP) Checklist
6.0 Risk Analysis And Control Summary
7.0 Product Verification And Validation:
7.1 Biocompatibility
7.2 Medicinal Substances
7.3 Biological Safety
7.4 Sterilisation
7.5 Software Verification and Validation
7.6 Animal Studies
7.7 Shelf Life/Stability Data
7.8 Clinical Evidence
7.9 Post Marketing Surveillance Data (Vigilance Reporting)
8. Additional information in case of the diagnostic kits:
Product dossier showing the:
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8.1 The details of source antigen or antibody as the case may be and characterization of the
same.
Process control of coating of antigen or antibody on the base material like Nitrocellulose
paper, strips or cards or enzyme-linked immunosorbent assay (ELISA) wells etc.
Detailed composition of the kit and manufacturing flow chart process of the kit showing the
specific flow diagram of individual components or source of the individual components.
8.2 Test protocol of the kit showing the specifications and method of testing. In house
evaluation report of sensitivity, specificity and stability studies.
8.3 The detailed test report of all the components used/packed in the finished kit.
8.4 Pack size and labelling.
8.5 Product inserts.
Specific evaluation report, if done by any laboratory in India, showing the sensitivity and specificity
of the kit.
Specific processing like safe handling, material control, area control, process control, and stability
studies, storage at quarantine stage and finished stage, packaging should be highlighted in the
product dossier.
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Annexure `B`
(refer para 4.2.2)
The manufacturer shall prepare a succinct document in the form of Plant Master File containing
specific information about the production and/or control of device manufacturing carried out at the
premises. It shall contain the following information:
1. General Information:
(i) brief information on the site (including name and address), relation to other sites;
(ii) manufacturing activities;
(iii) any other operations carried out on the site
(iv) name and exact address of the site, including telephone, fax numbers, web site URL and
e-mail address;
(v) type of medical devices handled on the site and information about specifically toxic or
hazardous substances handled, mentioning the way they are handled and precautions
taken;
(vi) short description of the site (size, location and immediate environment and other
activities on the site);
(vii) number of employees engaged in Production, Quality Control, warehousing, and
distribution;
(viii) use of outside scientific, analytical or other technical assistance in relation to the design,
manufacture and testing;
(ix) short description of the quality management system of the company;
(x) devices details registered with foreign countries;
2. Personnel:
(i) organisation chart showing the arrangements for key personne;l
(ii) qualifications, experience and responsibilities of key personnel;
(iii) outline of arrangements for basic and in-service training and how records are maintained;
(iv) health requirements for personnel engaged in production
(v) personnel hygiene requirements, including clothing.
3. Premises and Facilities:
(i) layout of premises with indication of scale;
(ii) nature of construction, finishes/fixtures and fittings;
(iii) brief description of ventilation systems. More details should be given for critical areas
with potential risks of airborne contamination (including schematic drawings of the
systems). Classification of the rooms used for the manufacture of sterile products should
be mentioned;
(iv) special areas for the handling of highly toxic, hazardous and sensitizing materials;
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(v) brief description of water systems (schematic drawings of the systems are desirable)
including sanitation;
(vi) maintenance (description of planned preventive maintenance programmes for premises
and recording system);
4. Equipment:
(i) Brief description of major production and quality control laboratories equipment (a list of
the equipment is required);
(ii) maintenance (description of planned preventive maintenance programmes and recording
system);
(iii) qualification and calibration, including the recording system. Arrangements for
computerized systems validation.
5. Sanitation:
Availability of written specifications and procedures for cleaning the manufacturing areas and
equipments.
6. Production:
(i) Brief description of production operations using, wherever possible, flow sheets and
charts specifying important parameters ;
(ii) arrangements for the handling of starting materials, packaging materials, bulk and
finished products, including sampling, quarantine, release and storage;
(iii) arrangements for reprocessing or rework;
(iv) arrangements for the handling of rejected materials and products;
(v) brief description of general policy for process validation.
7. Quality Assurance:
Description of the Quality Assurance system and of the activities of the Quality Assurance
Department. Procedures for the release of finished products.
8. Storage:
Policy on the storage of medical device.
9. Documentation:
Arrangements for the preparation, revision and distribution of necessary documentation,
including storage of master documents.
10. Medical Device Complaints and Field Safety Corrective Action:
(i) Arrangements for the handling of complaints ;
(ii) Arrangements for the handling of field safety corrective action
11. Internal Audit:
Short Description of the internal audit system.
12. Contract Activities:
Description of the way in which the compliance of the contract acceptor is assessed.
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Annexure ‗C‘
Environmental requirement for Notified medical devices and in-vitro diagnostics
Name of Device
Type of Operation
ISO Class (At rest)
Cardiac stent/Drug Eluting
Stent
Primary Packing and Crimping
5
Washing, Ultrasonic cleaning &Drug
coating
7
Assembly, Wrapping & Packaging
8
Laser cutting, Descaling, Annealing &
Electro polishing
9
Heart Valves
Valve Packing
5
Ultrasonic Cleaning & Visual Inspection
7
Frame & Disc Assembly
7
Intra Ocular Lenses
Packing & Sealing
5
Final Inspection
7
Power Checking& Final Cleaning
8
Tumble Polishing & Lathe Cutting
9
Bone Cements
Final Product Filling
5
Sieving & Calcinations
7
Powder Preparation, Granulation
&Drying
8
Internal Prosthetic
Replacement
Packing
5
Product Preparation
7
Component Preparation
8
Orthopedic Implants
Polishing &Cleaning & packaging (to be
sterilized in factory premises)
7
Polishing , cleaning & packaging (Non
Sterile- to be sterilized in Hospital)
8
Cutting, lathing
9
Catheters /Ablation Device / I
V Cannulae / Scalp Vein Set/
Hypodermic Syringes/
Hypodermic Needles /
Perfusion Sets
Assembly, Coating, Wrapping &
Packing
7
Component Preparation & Cleaning
8
Moulding
9
Condom
Compounding
Well ventilated area with
minimum 5 micron filter
Moulding
Well ventilated area with
minimum 5 micron filter
Vulcanising
Normal air
Packing
Air conditioned
Intra Uterine Devices
Moulding
Well ventilated area with
minimum 5 micron filter
Assembling
7
Packaging
7
Tubal ring
Extrusion
7
Cutting and Assembly
7
Packaging
7
Blood bags
Moulding/Extrusion of components
8
Assembly
7
Filing
5
Suture
Extrusion
9
Assembly
8
Packing
8
Staplers
Staple formation
9
Staple assembly
8
Drugs and Cosmetics Rules 1945
524
Staple final pack
8
Ligatures
Extrusion
9
Cutting and assembly
8
Final Pack
8
Surgical dressings
Weaving
9
Assembly and Gauzing
9
Final pack
9
In-vitro diagnostics
Kit/Reagents
Dry, Liquid Reagent Preparation
Well Lighted and
Ventilated controlled
temperature & humidity as
per process or product
requirement
Coating of sheets etc.
Assembly and primary packing
Filling
Well Lighted and
Ventilated controlled
temperature and humidity
as per process or product
requirement. Provision of
Laminar hood if required,
Clean Room class 8 or class
9 as per product/process
requirement
Secondary Packing
Well Lighted and
Ventilated controlled
temperature if required
Storage
As per recommended
storage condition of the
product].
Drugs and Cosmetics Rules 1945
525
1
[SCHEDULE N
[See Rule
64(1)]
LIST OF MINIMUM EQUIPMENT FOR THE EFFICIENT
RUNNING
OF A
PHARMACY
1. Entrance. - The front of a pharmacy shall bear an inscription ―Pharmacy‖ in front.
2. Premises. - The premises of a pharmacy shall be separated from rooms for private
use. The premises shall be well built, dry, well lit and ventilated and, of sufficient dimensions
to allow the goods in stock, especially medicaments and poisons to be kept in a clearly visible
and appropriate manner. The areas of the section to be used as dispensing department shall be
not less than 6 square meters for one pharmacist working therein with additional 2 square
meters for each additional pharmacist. The height of the premises shall be at least 2.5 meters.
The floor of the pharmacy shall be smooth and washable. The walls shall be plastered
or tiled or oil painted so as to maintain smooth, durable and washable surface devoid of holes,
cracks and crevices.
A pharmacy shall be provided with ample supply of good quality water.
The dispensing department shall be separated by a barrier to prevent the admission of
the public.
3. Furniture and apparatus. - The furniture and apparatus of a pharmacy shall be
adopted to the uses for which they are intended and correspond to the size and requirements
of the establishment.
Drugs, chemicals, and medicaments shall be kept in a room appropriate to their
properties and in such special containers as will prevent any deterioration of the contents or of
contents of containers kept near them. Drawers, glasses and other containers used for keeping
medicaments shall be of suitable size and capable of being closed tightly to prevent the entry
of dust.
Every container shall bear a label of appropriate size, easily readable with names of
medicaments as given in the Pharmacopoeias.
A pharmacy shall be provided with a dispensing bench, the top of which shall be
covered with washable and impervious material like stainless steel, laminated or plastic, etc.
A pharmacy shall be provided with a cupboard with lock and key for the storage of
poisons and shall be clearly marked with the work ‗POISON‘ in red letters on a white
background.
Containers of all concentrated solution shall bear special label or marked with the
words ―To be diluted‖.
A Pharmacy shall be provided with the following minimum apparatus and books
necessary for making of official preparations and prescriptions:-
1.Subs. by S.O.2139 , dt. 12.8.1972.
Drugs and Cosmetics Rules 1945
526
Apparatus: -
Books :
Balance, dispensing, sensitivity 30 mg.
Balance, counter, capacity 3 Kgm., sensitivity 1 gm.
Beakers, lipped, assorted sizes.
Bottles, prescription, ungraduated assorted sizes.
Corks assorted sizes and tapers.
Cork, extracter.
Evaporating dishes, porcelain.
Filter paper.
Funnels, glass.
Litmas paper, blue and red.
Measure glasses cylindrical 10 ml, 25 ml, 100 ml and 500 ml.
Mortars and pestles, glass.
Mortars and pestles, wedgwood.
Ointment pots with bakelite or suitable caps.
Ointment slab, porcelain
Pipette graduated, 2 ml, 5 ml and 10
ml.
Ring, stand (retort) iron, complete with rings.
Rubber stamps and pad
Scissors
Spatulas, rubber or vulcanite
Spatulas, stainless steel.
Spirit lamp
Glass stirring rods.
Thermometer, 0
o
C to 200
o
C.
Tripod stand.
Watch glasses.
Water bath.
Water distillation still in case Eye drops and Eye lotions are prepared.
Weights, Metric, 1 mg. to 100 gm.
Wire Gauze.
*Pill finisher, boxwood.
* Pill Machine.
* Pill Boxes.
* Suppository mould.
The Indian Pharmacopoeia (Current Edition).
National Formulary of Indian (Current Edition).
The Drugs and Cosmetics Act, 1940.
The Drugs and Cosmetics Rules, 1945.
The Pharmacy Act, 1948.
The Dangerous Drugs Act, 1930.
Drugs and Cosmetics Rules 1945
527
4. General provisions. - A pharmacy shall be conducted under the continuous
personal supervision of a Registered Pharmacist whose name shall be displayed
conspicuously in the premises.
The Pharmacist shall always put on clean white overalls.
The premises and fittings of the pharmacy shall be properly kept and everything shall
be in good order and clean.
All records and registers shall be maintained in accordance with the laws in force.
Any container taken from the poison cupboard shall be replaced therein immediately
after use and the cupboard locked. The keys of the poison cupboard shall be kept in the
personal custody of the responsible person.
Medicaments when supplied shall have labels conforming to the provisions of laws in
force.
Note: - The above requirements are subject to modifications at the discretion of the
licensing authority, if he is of opinion that having regard to the nature of drugs dispensed,
compounded or prepared by the licensee. It is necessary to relax the above requirements or to
impose additional requirements in the circumstances of a particular case. The decision of the
licensing authority in that regard shall be final.
* These items are to be provided only by those who intend to dispense pills or
suppositories, as the case may be.]
Drugs and Cosmetics Rules 1945
528
1
[SCHEDULE O
[See Rule
126]
STANDARD FOR DISINFECTANT
FLUIDS
2
[PART I
PROVISION APPLICABLE TO BLACK FLUIDS AND WHITE
FLUIDS
The standards for disinfectants shall conform to the Indian Standards specification (IS
1061:1997) laid down from time to time by the Bureau of Indian Standards.]
1. Subs. by G.S.R. 1243, dared 19-09-1979, for Schedule O (w.e.f. 6-10-979). EARLIER Schedule O was added y
Notification No. F.1-20/60-D, dated 24-01-1964.
2. Subs. by G.S.R. 735(E), dated 21-12-2005, for
―PART I
Provision applicable to Black Fluids and White Fluids
1.Classification - The disinfectants shall be classified as follows: -
(a) Black fluids
(b) White fluids
(A) Black fluids.– These shall be homogeneous dark brown solution of coal tar acid or
similar acids derived from petroleum with or without hydrocarbon, and/or other
phenolic compounds, and their derivatives and a suitable emulsifier.
(B) White fluids.– These shall be finely dispersed homogeneous white to off- white
emulsion consisting of coal tar acids or similar acids derived from petroleum, with or
without hydrocarbons, and/or other phenolic compounds, and their derivatives.
2.Gradation – Each of the above classes of disinfectant fluids shall be graded on the basis of the
minimum requirements in respect of:
Rideal Walker (RW) Coefficient as follows: -
Grade Rideal Walker (RW) Coefficient (Minimum)
1. 18
2. 10
3. 5
3.Type - Each of the above grades of disinfectant fluids shall be stable in the range of temperature
indicated against each type. -
Type Stable in the range of
(I) Normal 15
o
C to 45
o
C.
(II) Winter 5
o
C to
30
o
C
4.Requirements - All classes and grades of disinfectant fluids shall comply with the following
requirements, namely: -
(1) Stability after dilution - When tested by the method described hereinafter the
disinfectant fluid shall be miscible with artificial hard water (for Black fluids) or with artificial sea
water (for White fluids) in all proportion from 1 per cent to 5 per cent by volume, to give
Drugs and Cosmetics Rules 1945
529
emulsion which shall not break or show more than traces of separation of either top or bottom oil
when kept for 6 hours at 15
o
C to 45
o
C for Type (I) (Normal) and 5
o
C to 30
o
C for Type (II)
(Winter).
(2) Germicidal Value.– Rideal Walker Coefficient – Black fluids and White fluids shall
be tested for determination of Rideal Walker Coefficient (R.W.Coefficient) by the method
described hereinafter.
(3) Storage.– Disinfectant fluids of all classes shall be stored in mild steel, tinned mild steel or
other suitable containers. These shall not be stored in containers made of galvanized iron.
(4) Labelling. -Subject to the other provisions in these rules, the label on the container shall
state-
(i) the name of the product,
(ii) the name and full address of the manufacturer,
(iii) grade, type, R.W. Coefficient of product,
(iv) date of manufacture,
(v) quantity present in the container,
(vi) indications and mode of use, and
(vii) date up to which the product can be used.
5.Method of testing - (1) Preparation of sample - The sample of disinfectant fluid to be tested
should be mixed thoroughly taking care that no air is beaten into the fluid immediately before
withdrawing any portion for testing. The rest portion should be withdrawn from the middle of the
sample.
(2) Method of resting stability after dilution. - (a) Preparation of Artificial Hard Water: 40
ml of I N Hydrochloric Acid (Analytical Reagent Quality) is neutralized with a slight excess of
Calcium Carbonate and filtered. The filtrate is diluted to 1000 ml with distilled water, 10 parts
of this solution is further diluted to 100 parts with distilled water.
(b) Preparation of Artificial Sea Water: 27G of Sodium Chloride (Analytical Reagent
Quality) and 5 G of Magnesium Sulphate (Analytical Reagent Quality) are dissolved in distilled
water and diluted to 1000 ml. The solution is filtered before use.
(c) Procedure: Take 1 ml and 5 ml portions of the sample in duplicate in 100 ml stoppered
measuring cylinder (IS: 878 – 1956) by means of pipettes. Dilute the sample with artificial Hard
water or Artificial Sea water (as the case may be) upto 10 ml mark. Mix thoroughly by inverting the
cylinders 5 times. Keep the cylinders containing the diluted fluids for 6 hours at the extremes of the
temperature range specified for the particular type. The sample complies with the test if the solution
shows not more than a trace of separation at its top and bottom.
(3) Method of determination of Rideal Walker Coefficient
(R.W.C)-
Apparatus – A loop, 4 mm in internal diameter is made at the end of 28 swg (0.376 mm)
wire of platinum or platinum iridium alloy, 38 mm long from the loop to the holder. The loop is bent
at such an angle to the length of the wire as will facilitate in removal vertically from the surface of
the liquid while keeping the place of the loop horizontal.
Incubator – Set and maintained at 37
o
C ± 1
o
C
Pipettes – Standard graduated pipettes of capacity 10 ml; 5 ml and 1 ml
Dropping Pipette – Made of delivery 0.2 ml
Medication tubes – 5 sterile plugged rimless test tubes 125 mm x 22 mm
(5 inch x ¾ inch) made of hard neutral glass.
Both tubes – About 2 dozens of the same description as medication tubes.
Drugs and Cosmetics Rules 1945
530
Standard measuring cylinders stopped and graduated—500 ml graduated in
10 ml–;one 100 ml graduated 1 ml– five. All apparatus must be scrupulously clean and
sterile; immediately before use.
Reagents– (a) Broth.– Prepare a mixture of the following ingredients:
Meat extract (Microbiological grade) 20 g Peptone (Micro biological grade) 20g. Sodium
Chloride (Regent Quality) 10 g Distilled Water- 1000 ml.
Dissolve the solids in distilled water. Add sufficient sodium hydroxide to neutralize the
solution; then boil it to bring down phosphates and filter while hot. The broth thus prepared
is then adjusted to pH 7.6 with normal Hydrochloric acid. The broth is then sterilized by
autoclaving at 15 lbs pressure for 20 minutes. It is then filtered and placed in 5 ml quantities in
sterilized broth tubes. The tubes of media thus prepared are sterilized by autoclaving at 15 lbs
pressure for 10 minutes. The final pH of the medium should lie between 7.3 and 7.5. Further
resterilization in bulk or in tubes is not permissible.
(b) Test Organism- Test organism used is Salmonella typhi (NCTC 786) of which suitable
culture shall be obtained from the Director, Central Drugs Laboratory, Calcutta. This culture is
maintained by weekly sub-culture on a nutrient agar slope (made by dissolving 2.5 per cent Agar
Agar (Bacteriological grade) in broth prepared as above), incubating the sub- culture for 24 hours
at 37
O
C and then storing in refrigerator at a temperature below 22
o
C. For the purpose of the test a
little of the growth from the most recent sub-culture in nutrient agar slope is placed in tube of R.W.
broth and incubated for 23 hours at 38
o
C. A standard loopful is then transferred to a second tube
and incubated as before. This is done at least three times before a test is carried out. Sub-culturing
in broth is limited to 14 days.
(c) Standard phenol: 5 per cent W/V solution in sterile distilled water of chemically pure
phenol having a crystallizing point of not less than 40.5
o
C is prepared. Test dilutions are prepared
from this stock solution containing 1 g of phenol in each 95, 100, 105, 115 ml of the solution made.
These dilutions shall be used within a week of preparation.
(d) Test dilutions of Disinfectant (sample)- The sample is prepared as described under
―Preparation of samples‖. A test portion of 5 ml is withdrawn and discharged into about 480 ml of
sterile distilled water in a 500 ml glass stoppered sterile measuring cylinder and the pipette is
rinsed three times or more in the clear liquid. The whole is then made up to 500 ml with sterile
distilled water, the cylinder is stoppered and the contents thoroughly mixed by inverting the
cylinder several times. Suitable test dilutions in sterile distilled water are then immediately
prepared from this stock solution.
Procedure: 5 ml of 4 chosen dilutions of the disinfectant are placed in 4 medication tubes
which are then placed in a rack provided with water bath maintained at a constant temperature
between 17
o
C and 19
o
C, with the strongest dilution on the left. The fifth medication tube
containing 5 ml of the particular phenol dilution is placed on the right. When the content on the
medication tubes and broth culture of the test organism have reached the temperature of the water
bath, starting at Zero time, 0.2 ml of the culture is added to the left hand medication tube and the
tube is shaken gently. After 30 seconds the next tube is inoculated similarly and the process is
repeated with each successive tube at intervals of 30 seconds until the phenol control has been
inoculated. Thirty seconds after this last addition (that is 2-1/2 minutes from zero) a loopful of
the well-shaken content of the tube at the extreme left is withdrawn and placed in tube
containing 5 ml of the broth medium. Thirty seconds after this similar operation is performed
on the second medication tube. The procedure is repeated at an interval of 30 seconds with
each of the 5 medication tubes working from left to right until 4 sets of cultures have been made
i.e. at 2-1/2, 5, 7-1/2 and 10 minutes respectively after exposure. In each withdrawal care should
Drugs and Cosmetics Rules 1945
531
be taken to ensure that the loop is removed vertically from the surface of the liquid with its plane
horizontally and without touching the side of the test tubes. The loop shall be sterilized by flaming
between each operation, care being taken that the loop is cooled before being again used.
The inoculated broth tubes are incubated for not less than 48 hours and not more than 72 hours at
37
o
C when the tubes showing growth of the test organisms will be recognized by turbidity of the
broth.
Calculation of Coefficient – The R.W. Coefficient is obtained by dividing that
dilution of the disinfectant which shows life of test organism in 2-1/2 and 5 minutes but no life
thereafter by that dilution of the phenol which gives the same response.A typical set of sample is
given below:
Sample disinfectant Time of exposures in minutes
Dilutions 2½ 5 7½ 10
1:1000
−
−
−
−
1:1100
+
−
−
−
R.W. Coefficient
1:1200
+
+
−
. −
=
1200
=
12
1:1300
1:100 Pheno control
+
+
+
+
+
−
−
−
100
(+ = growth − = No growth)
PART II
Provisions applicable to other disinfectant
fluids:
Disinfectant fluids which are made with chemicals other than those specified under Part I of this
Schedule shall conform to the formula or list of ingredients shown on the label.
Labelling : Subject to the provisions of rules on labelling, the label of container shall state:
(i) the name of the product;
(ii) the name and full address of the manufacturer;
(iii) the full formula or list of ingredients of the preparation;
(iv) date of manufacture;
(v) date up to which the product can be used;
(vi) quantity present in the container; and
(vii) indications and mode of use.
Cautionary note:
Mercury compounds shall be strictly excluded from all grades.]
Drugs and Cosmetics Rules 1945
532
1
[SCHEDULE
P
[See Rule
96]
LIFE PERIOD OF
DRUGS
Sl.
No.
Name of the drug Period in months (unless
otherwise specified)
between
date of
manufacture and date of
expiry which the labelled
potency period of the drug
shall not exceed under the
conditions of storage
specified in Column No.4
Condition of storage
1 2 3 4
ANTIBIOTICS
1.
Adramycin
30
In a cool place
2.
Ampicillin
36
In a cool place
3.
Ampicillin Capsules
24
4.
Ampicillin Dry Syrup
24
5.
Ampicillin Injection
24
6.
Ampicillin Sodium
36
In a cool place
7.
Ampicillin Trihydrate
30
In a cool place
8.
Amoxycillin Trihydrate
36
In a cool place
9
Amoxycillin Trihydrate Capsules
24
10.
Amoxycillin Trihydrate Dry Syrup
18
11.
Bacitracin
18
In a cool place
12.
Bacitracin or Zinc Bacitracin Tablets
12
13.
Bacitracin Lozenges
12
14.
Carbenicillin Sodium Injection
24
At temperature not
Exceeding 5°C
15.
Carbenicillin Sodium Powder
24
At temperature not
Exceeding 5°C
16.
Cephalexin
24
In a cool place
17.
Chloramphenicol
60
In a cool place
18.
Chloramphenicol Capsules & Tablets
48
19.
Chloramphenicol Palmitate
48
20.
Chloramphenicol Palmitate Oral Suspension
36
21.
Chloramphenicol Eye drops
24
22.
Chloramphenicol Sodium Succinate Powder
48
In a cool palace
23.
Chloramphenicol Sodium Succinate Injection
36
In a cool place
24
Chlortetracycline Hydrochloride
60
In a cool place
25.
Chlortetracycline Hydrochloride Capsules
60
26.
Chlortetracycline Hydrochloride Tablets
24
27.
Chlortetracycline Hydrochloride Ointment
24
28.
Cloxacillin (Oral)
36
In a cool place
29.
Cloxacillin Sodium (Injection Grade)
36
In a cool place
1. Subs. by G.S.R. 17(E) , dt. 7.1.1986 ( w.e.f. 7.1.1986 ).
Drugs and Cosmetics Rules 1945
533
1 2 3 4
30.
Colistin Sulphate
60
Protected from light
31.
D-Cycloserine
48
In a cool place
32.
Dimethyl Chlortetracycline Hydrochloride
48
33.
Dimethyl Chlortetracycline Hydrochloride Capsules
36
34.
Daunoblastin Injection.
36
35.
Doxycycline Hydrochloride
48
In a cool place
36.
Doxcycline Monohydrate
36
In a cool place
37.
Doxycyline Monohydrate for Oral Suspension.
24
38.
Doxycycline Monohydrate Capsules.
36
39.
Erythromycin Estolate
36
In a cool place
40.
Erythromycin Ethylsuccinate
60
In a cool place
41.
Erythromycin Oral Suspension
36
42.
Erythromycin Estolate for Oral Suspension
36
43.
Erythromycin Ethyl Succinate Tablet
24
44.
Erythromycin Estolate Tablets
24
45.
Erythromycin Stearate
36
In a cool place
46.
Framycetin Sulphate
48
In a well closed container
with temperature not
exceeding 30°C
47.
Framycetin Sulphate Eye drops
24
In a well closed container
with temperature not
exceeding 30°C
48.
Framycetin Sulphate Ointment
24
In a well closed container
with temperature not
exceeding 30°C
49.
Gentamycin Sulphate
60
In a cool place.
50.
Gentamycin Sulphate Injection
36
51.
Gramicidin
60
In a cool place
52.
Griseofulvin
48
In a cool place
53.
Griseofulvin Tablets
36
54.
Kanamycin Sulphate Injection.
24
55.
Kanamycin Acid Sulphate Powder
48
In a cool place
56.
Mitomycin C
48
In a cool place
57.
Neomycin Sulphate.
48
In a cool place
58.
Nystatin
36
At temperature not exceeding
5°C
59.
Oleandomycin Phosphate sterile
24
In a cool place
60.
Oleandomycin Phosphate non sterile
36
In a cool place
61.
Oxytetracline Hydrochloride
36
In a cool place
62.
Oxytetracycline Hydrochloride Capsules.
36
63.
Oxytetracycline Hydrochloride Tablets
24
64.
Oxytetracycline Hydrochloride Injection
24
65.
Oxytetracycline Hydrochloride Ointment
36
66.
Penicillin Crystalline
36
In a cool place
67.
Penicillin Tablets
18
In a cool place
68.
Procaine Penicillin G
36
In a cool place
Drugs and Cosmetics Rules 1945
534
1 2 3 4
69.
Benzathin Penicillin G
48
In a cool place
70.
Potassium Phenoxy Methyl Penicillin
48
In a cool place
71.
Potassium Phenoxy Methyl PenicillinTablets
24
72.
Polymixin B Sulphate
48
In a cool place
73.
Polymixin B Sulphate Ointment or Powder
24
In a cool place
74.
Rifampicin
36
In a cool place
1
[75
Rifampicin Capsules
36]
76.
Spramycin Base
24
In a cool place
77.
Strepromycin Injection.
36
78.
Streptomycin Ointment
24
79.
Streptomycin Tablets
24
80.
Streptomycin Sulphate
48
At temperature not exceeding 20oC
81.
Tetracycline Base
24
In a cool place
82.
Tetracycline Hydrochloride
36
In a cool place
83.
Tetracycline Hydrochloride Capsules
36
84.
Tetracycline Tablets
24
85.
Tyrothricin
60
In a cool place.
VITAMINS
1.
Vitamin A Injection
24
2.
Vitamin B1 Injection
24
3.
Thiamine Mononitrate Tablets
36
4.
Thiamine Hydrochloride
48
In a well closed container, protected
from light, in a cool place.
5.
Thiamine Mononitrate
48
In a well closed container, protected
from light, in a cool place.
6.
Riboflavin
60
In a well closed container, protected
from light, in a cool place.
7.
Riboflavin-5-Phosphate
24
In a well closed container, protected
from light, in a cool place.
8.
Riboflavin Tablets
36
9.
Vitamin B2 Injection
24
10.
Vitamin B6
60
In a well closed container, protected
from light, in a cool place.
11.
Vitamin B6 tablets
36
12.
Cyanacobalamin
48
In a well closed container, protected
from light, in a cool place.
13.
Hydroxycobalamin
48
In a well closed container, protected
from light, in a cool place.
14.
Vitamin B12 Injection
36
15.
Calcium Pantothenate
36
In a well closed container, protected
from light, in a cool place.
16.
Vitamin C Injection
24
17.
Calcium Pantothenate Tablets
36
2
18.
Vitamin C
48
In a well closed container, protected
from light, in a cool place.
1. Subs. by G.S.R. 250(E), dt. 4.4.2002
2. Subs. by G.S.R. 626(E), dt. 14.10.1991
Drugs and Cosmetics Rules 1945
535
1 2 3 4
19.
Vitamin D
2
D
3
36
In a well closed container, protected from
light, in a cool place.
20.
Vitamin E or E-Acetate
60
In a well closed container, protected from
light, in a cool place.
21.
Folic Acid
60
In a well closed container, protected from
light, in a cool place.
22.
Folic Acid Tablets
36
23.
Vitamin K
60
In a well closed container, protected from
light, in a cool place.
24.
Vitamin K Injection
36
25.
Niacinamide
60
In a well closed container, protected from
light, in a cool place.
26.
Niacinamide Tablets
36
27.
D-Panthenol
60
In a well closed container, protected from
light, in a cool place.
INSULIN PREPARATIONS
1.
Globuline Zinc Insulin Injection
24
At temperature between 2
o
C and 8
o
C,
must not be allowed to freeze.
2.
Insulin Injection
24
At temperature between 2
o
C and 8
o
C,
must not be allowed to freeze.
3.
Insulin Zinc Suspension
24
At temperature between 2
o
C and 8
o
C,
must not be allowed to freeze.
4.
Isophane Insulin Injection.
24
At temperature between 2
o
C and 8
o
C,
must not be allowed to freeze.
1
[5.
Human Insulin Injection
30
At temperature between 2
o
C and 8
o
C,
must not be allowed to freeze.
NORMAL HUMAN PLASMA
1. Subs. by G.S.R. 626(E) , dt. 14.10.1991.
2. Subs. by G.S.R. 626(E) , dt. 14.10.1991.
1.
Anti-Haemophillic Human Globulin
12
In a cool place
2.
Dried Plasma
60
At a temperature not exceeding
25
o
C
3.
Dried Normal Human Serum Albumin
60
At a temperature not exceeding
25
o
C
4.
Frozen Plasma
60
In deep freeze
5.
Liquid Plasma
24
In cold place
6.
Liquid Normal Human Serum Albumin.
60
In cold place.
2
[7.
Whole Human Blood-
(a) Collected in ACD solution
21days
At temperature between 4
o
C and
6
o
C
(b) Collection in CPDA solution.
35days
At temperature between 4
o
C and
6
o
C]
Drugs and Cosmetics Rules 1945
536
SERA TOXIN AND TOXOID
1. Alum Precipitated Diphtheria Toxoid 24 In cold place.
2. Alum Precipitated Diphtheria and
Tetanus toxoid and Pertusis vaccine combined 18 In cold place
3.
Alum Precipitated Tetanus Toxoid
24
In a cold place
4.
Aluminium Hydroxide
24
In a cold place.
Absorbed Diphtheria Toxoid
5.
Aluminium Hydroxide
Absorbed
18
In a cold place
Diphtheria Tetanus Toxoid and Pertussis
Vaccine combined.
6. Aluminium Phosphate Absorbed Diphtheria
Toxoid.
7. Aluminium Phosphate absorbed
Diphtheria and Tetanus Toxoid
8. Aluminium phosphate absorbed diphtheria
Toxoid Tetanus Toxoid and
Pertussis vaccine combined.
24 In a cold place.
24 In a cold place.
18 In cold place
9. Diagnostic Diphtheira Toxin (Schick Test) 12 In cold place
10. Cobra venom in solution 3 Between 2
o
C and 5
o
C protected
from light.
at the lower limit.
o
C preferable
1[
11.
Diphtheria Toxoid
24
In cold place
12.
Inactivted Diagnostic Diphtheria Toxin.
12
In cold place
13.
Liquid serum
12
Between 2
o
C and 10
14.
Lyophilised anti-snake venom serum
60
15.
Lyophilised Schick test Toxin and control
60
16
Old Tuberculin
60
In cold place
17.
Thrombin (Bovine origin)
36
In cold place.
18.
Tetanus Toxoid
36
In cold place]
19.
uberculin PPD
60
In cold place
Drugs and Cosmetics Rules 1945
537
OTHER VACCINES
1. Subs. by G.S.R. 26(E) , dt. 19.01.2006.
2. Subs. by G.S.R. 174(E) , dt. 16.03.2005.
1.
Alum precipitatd pertussis Vaccine.
18
In cold place
2
[2.
BCG Vaccine
24
In cold place]
3.
Cholera Vaccine
18
In cold place
4.
DHL Vaccine (for dog)
12
In cold place
5.
Measles Vaccine
24
In cold place
6.
Plague Vaccine
36
In cold place
7.
Polio Vaccine
24
When stored at minus 20
o
C
6
When stored at Zero
o
C
3
When stored at 4
o
C
8.
Rabies vaccine
6
In cold place
9.
Typhoid vaccine
18
In cold place
10.
Typhoid and Para Typhoid Vaccine.
18
In cold place
11.
Typhoid Para Typhoid A and B vaccine.
18
In cold place
Drugs and Cosmetics Rules 1945
538
1 2 3 4
12.
Typhoid Para Typhoid A,B & C Vaccine
18
In cold place
13.
Typhoid Para Typhoid A, B & C and
18
In cold place
Tetanus Vaccine.
14.
Typhus vaccine
12
In cold place
15.
Yellow Fever Vaccine
12
In cold place
1
[16. Anti-Rabies Vaccine (Cell Culture) 24 In cold place.]
ANTITOXIN
(For serum extracted preparations)
20% Excess potency
12
In cold place
30% Excess potency
24
In cold place
40% Excess potency
36
In cold place
50% Excess potency (for enzyme preparations)
48
In cold place
5% Excess potency
12
In cold place
10% Excess potency
24
In cold place
15% Excess potency
36
In cold place
20% Excess Potency
48
In cold place
MISCELLANEOUS DRUGS
.
Note : (1) The term ―cool place‖ means place having a temperature between 10
o
C and 25
o
C.
(2) The term ―cold place‖ means a place having a temperature not exceeding 8
o
C.
(3) Capsules should be kept in a well-closed container at temperature not exceeding
30
o
C.
(4) Wherever condition of storage is not specified in Column 4, it may be stored under normal room
temperature.]
1. Ins. by G.S.R. 215(E) , dt. 19. 3. 1999.
2. Subs. by G.S.R. 174(E) , dt. 16. 3.2005.
2
[1.
Andrenaline for Injection
12
[As prescribed in Indian Pharmacopoeia]
2.
Chorionic Gonadotrophin for
36
At temperature not exceeding 20
o
C
Injection (Lyophilised)
3.
Corticotrophin
24
In cold place
4.
Corticotrophin Lyophilised
36
In cold place
5.
Heparin Injection
36
In a cool place.
6.
Liquid Extract of Ergot
12
In cold place
7.
Liver Extract Crude Injection
24
In a cool place
8.
Oxytocin Injection
24
In cold place
9.
Paraldehyde Injection
6
In cool place protected from light.
10.
Pituitary Injection
24
In cold place.
11.
Vasopressin Injection
24
In cold place.
Drugs and Cosmetics Rules 1945
539
1
[SCHEDULE P1
[See Rule
109]
PACK SIZES OF
DRUGS
Name of the Drug Dosage form Pack size
1 2 3
Albendazole Suspension
10ml
Atenolol
Tablets
14
Anti-Haemmorhoidal Topicals
Rectal Capsules
20
Aspirin (Low-dose)
Tablets
14
Cholecalciferol or Ergocalciferol
Granules
1 gm. Sachet
Ciclopiroxolamine
Vaginal Cream
30 gms.
Catalin
Ophthalmic drops
15 ml
Famotidine
Tablets
14
Glyceryl Trinitrate
Spansules (Long Acting)
25
Isosorbide Dinitrate
Spansules (Long Acting)
25
Isoniazide
Syrup
200 ml
Ipecacuanha
Syrup
10 ml
Oral Rehydration Salt (ORS)
Powder
Pouches to be reconstituted
to one litre in one pack or
in 5 unit dose sachets in
one pack.
Piperazine
Granules
5 gm.
Syrup
30 ml
Pyrantel Pamoate
Syrup
8 ml or 10 ml
Potassium Chloride.
Syrup
60 ml and 200 ml.
Progestogen Qestrogen
(Combinations for Oral Contraception)
Tablets
21 or 22 with or without
placebo.
7
Roxatidine Acetate Hydrochloride
Tablets
14
Vitamin A Oral Drops
Drops
7.5 ml.]
2
[Co-trimoxazole
Suspension
50 ml.
Haloperidol
Oral Solution
15 ml.
Loxapine
Oral Liquid Concentrate
15 ml.]
1. Ins. by G.S.R. 796(E) , dt. 1.10.1992 (w. e. f. 1.1.1993).
2. Ins. by G.S.R. 753(E), dt. 4.11.1999.
Drugs and Cosmetics Rules 1945
540
1
[SCHEDULE Q
(See rules 134 and 144)
2
[PART
I]
3
[LIST OF DYES, COLOURS AND PIGMENTS PERMITTED TO BE USED IN COSMETICS AND
SOAPS AS GIVEN UNDER IS : 4707
(PART I)-1988
(AS AMENDED BY THE BUREAU OF INDIAN STANDARDS)
Common name of the
colour
Colour
Index
Number
Chemical name of the colour
1 2 3
Guinea Green B 42085 Monosodium salt of 4-(N-ethyl-p-sulfobenzylamino)–
diphenylmethylone-(1-(N-ethyl-N-p-sulfoniumbenzyl)∆ 2,5-
cyclohexadienimine).
Light Green SF Yellowish
42095
Disodium salt of 4-[4-(N-ethyl-p-sulfobenzylamine)-phenyl)-4-
sulphoniumphenyl) methylene]-2(-(N-ethyl-N-sulfobenzyl)
∆
2,5-Cyclohexadienimine.
Tartrazine
19140
Trisodium salt of 3-carboxy-5-hydroxy-1-p-sulfophenyl-4-p-
sulfophenylazo-pyrazole.
Sunset yellow FCF
Ponceau 3R
15985
16155
Disodium salt of 1-p-sulfophenylazo-2- naphthol-6-sulfonic
acid.
Disodium salts of a mixture of 1-alkyl- phenylazo-2-napthol 3,
6-disulfonic acids.
Amarnath.
16185
Trisodium salt of 1-(4-sulfo-1- napthylazo) 2-naphthol 3, 6-
disulfonic acid.
Erythrosine.
45430
Disodium salt of 9-0-carboxyphenyl-6- hydroxy 2,4,5, 7-
tetraiodo-3- isoxanthone.
Ponceau SX.
14700
Disodium salt of 2-(5 sulfo-2, 4-xylyl- azo)-1-naphthol-4-
sulfonic acid.
Brilliant Blue FCF
42090
Disodium salt of 4-(9-4-(N-ethyl-p-sulfobenzylamino)-phenyl)-
2-sulfonium phenyl)- methylene)-(1-(N-ethyl-N-p-sulfobenzyl)-
∆ 2, 5-cyclohexadienimine).
Indigocarmine.
73015
Disodium salt of 5,5‘-indigotindisulfonic acid.
Wool Violet 5 BN
(Acid- violet 6B)
42640
Monosodium salt of 4-(N-ethyl-p-sulfobenzylamino)-phenyl)-(4-
(N-ethyl-p-(sulfonium-benzylamine)-phenyl) methylene)-(N, N-
dimethyl-∆ 2,5-cyclohexadienimine)
Light Green SF
Yellowish
42095
Calcium salt of 4-(4-(N-ethyl-p-sulfobenzyl) (minophenyl)
(4- sulfonium-phenyl)methylene), (1-(N-ethyl-N-p-sulfobenzyl)-
∆
2,5-cyclohexadienimine).
1. Inserted by Notification F.-1-36/64 D, dated 17.8.1964.
2. Renumbered as Part I by G.S.R. 11(E) , dated 7.1.1991.
3. Substituted by G.S.R. 811(E) , dated 14.11.1994.
Drugs and Cosmetics Rules 1945
541
1 2 3
Alizarin Cyanine Green F
61570
Disodium salt of 1,4-bis (O-sulfo-p-toluino) anthraquinone
Quinazarine Green SS
61565
1,4-bis-(p-Toluino)-anthraquinone
Fast Green FCF
42053
Disodium salt of 4-(4-(ethyl-p-sulfobenzylamino)-phenyl) (4-
hydroxy-2 sulphoniumphenyl) methylene)-(1-N-ethyl-N-p-
sulfobenzyl) ∆ 2, 5, cyclohexadienimine).
Acid Fast Green 42100 Monosodium salt of 4-(4-N-ethyl-p-sulfobenzylomino) phenyl)-
(o-chlorophenyl)-methylene)- 1-(N-ethyl-N- p-sulfonium-
Pyranine Concentrated
59040
benzyl- ∆ 2,5, cyclohexadienimine).
Trisodium salt of acid.
Quinoline Yellow WS
47005
Disodium salt of disulfonic acid of 2-(2-Quinolyl)-1, 3-
indandione.
Quinoline Yellow SS
47000
2-(2-quinolyl)-1, 3 indandiene.
Poneceau 2 R
16150
Disodium salt of 1-xylylazo-2-naphthol-3, 6-disulfonic acid.
Lithol Rubin B.
15850
Monosodium salt of 4-(o-sulfo-p-tolylazo)3 hydroxy-2-naphthoic
acid.
Lithol Rubin BCA
15850
Calcium salt of 4-(o-sulfo-p-tolylazo)-3-hydroxy-2-naphthoic
acid
Lake Red D.
15500
Monosodium salt of 1-0-carboxyphenylazo-2-naphthol.
Lake Red DBA
15500
Barium salt of 1-o-carboxyphenylazo-2-naphthol.
Lake Red DCA.
15500
Calcium salt of 1-o-carboxyphenylazo-2-naphthol.
Toney Red.
26100
I-p-phenylazophenylazo-2-naphthol.
Oil Red OS.
26125
I-Xylylazoxylylazo-2-napththol
Tetrabromofluorescein
45380
2,4,5,7-Tetrabromo-3, 6-flurandiol.
Eosin TS
Eosin YSK. .
45380
45380
Disodium salt of 2,4,5,7-tetrabromo-9-0 carboxyphenyl-6-
hyroxy-3-isoxanthone.
Dipotassium salt of 2,4,5,7-tetrabromo-9-0 carboxyphenyl-
6-hyroxy-3-isoxanthone
Tetrachlorofluorescein NA
45366
2,4,5,7- tetrachloro-S, 6-Fluorandiol
Tetrachlorofluorescein K.
45366
Disodium salt of 9-0-carboxyphenyl-2,4,5,7-tetrachloro-6-
hydroxy-3-isoxanthone.
Tetrachloro Tetrabromo
fluorescein
45410
2,4,5,7-Tetrabromo-12,13,14,15-tetrachloro-3,
6-fluorandiol.
Phloxine B
45410
Disodium salt of 2,4,5,7-tetrabromo-9 (3,4,5,6-tetra chloro-
o-carboxyphenyl)-6-hydroxy-3-isoxanthone
Bluish Orange T.R.
45457
1,4,5,8, 15-Pentabromo-2, 7-dicarboxy-3, 6-fluoran diol.
Helindone Pink CN.
73360
5, 5-Dichloro-3, 3‘ dimethyl-thioindigo
Drugs and Cosmetics Rules 1945
542
1 2 3
Deep Maroon (Fanchon Maroon)
Toluidine Red. .
15880
12120
Calcium salt of 4-(I-sulfo-2-naphthylazo 3- hydroxy-2-
naphthoic acid.
1-(o-Nitro-p-tolylazo)-2-naphthol.
Flaming Red.
12085
I- (o-Chloro-p-nitrophenylazo)-2-naphthol
Deep Red (Maroon).
Alba Red.
12350
13058
3-Hydroxy-N- (m-nitrophenyl)-4-(o-nitro-p-tolylazo)-2-
naphthamide.
o-(p,β,β-Dihydroxy-diethylamino)- phenylazo)-benzoic
acid.
Orange G.
Orange II
16230
15510
Disodium salt of 1-phenylazo-2-naphthol-6-8-disulfonic
acid.
Monosodium salt of 1-p-sulfophenylazo-2-naphthol.
Dichlorofluorescein
45365
4,5-Dichloro-3, 6-fluorandiol.
Dichlorofluorescein. NA
45365
Disodium salt of 9-o-carboxyphenyl-1-4,5- dichloro-6-
hydroxy-3-isoxanthone
Diiodofluorescein.
45425
4,5 –Diiodo-3, 6-fluorandiol
Erythrosine Yellowish NA.
45425
Disodium salt of 9-o-carboxyphenyl-6- hydroxy-4, 5-
diiodo-3-isoxanthone.
Erythrosine Yellowish K.
45425
Dipotassium salt of 9-o-carboxyphenyl-6-hydroxy-4, 5-
diiodo-3-isoxanthone.
Erythrosine Yellowish NH
45425
Dipotassium salt of 9-o-carboxyphenyl-6-hydroxy-4, 5-
diiodo-3-isoxanthone
Orange TR
45456
4,5, 15-Tribromo 2, 7-dicarboxy-3, 6- fluorandiol.
Alizarin.
58000
1,2- Anthraquinonediol.
Dibromodiiodofluorescein.
45371
4 ,5- Dibromo-2, 7-diiodo-3, 6-fluorandiol.
1
[***]
Alphazurine FG.
42090
Diammonium salt of 4-(N-ethyl-p- sulfobenzyl amino)-
phenyl)-(2-sulfoniumphenyl)-Methytlene)-(-(1 (N-ethyl-N-
p-sulfobenzyl) ∆ 2 ,5-cyclohexadienimine).
Allarin Astrol B.
61530
Monosodium salt of 1-methylamino-4-(o-sulfo-p-toluino)-
anthroquinone.
Indigo.
73000
Indigotin.
Patent Blue NA. .
42052
Monosodium salt of 4-(4- (N-ethyl- benzyl-amino)-phenyl –
(5-hydroxy-4-sulfo-2-sulfoniumphenyl-methylene)(N-ethyl-
Benzyl- ∆ 2, 5-cyclohexadienimine).
Patent Blue CA.
42052
Calcium salt of 4-(4- (N-ethyl- benzyl-amino)-phenyl)-(5
hydroxy-4-sulfo-2-sulfoniumphenyl, methylene)- (N-ethyl-
N-benzyl- ∆ 2- 5-cyclohexadienimine).
Carbrantherene Blue 69825 3, 3- Dichloroindanthrene.
1. Omitted by G.S.R. 203(E), dated 18-03-2015.
Drugs and Cosmetics Rules 1945
543
1 2 3
Napthol Blue
Black
20470
Disodium salt of 8-amino-7-p- nitrophenylazo 3-
phenylazo-1- naphthol-3, 6-disulfonic acid
Alizurol purple SS
60725
I-hydroxy-4-p-toluino-anthraquinone.
Acid Red 89
23910
----
Acid Red 97
22890
----
Acid Blue 1
42045
----
Food Blue 3
42045
----
Natural Orange
75480
----
Solvent Blues 4
44045
----
Solvent Yellow 18
12740
----
Food Yellow 12.
12740
----
1
[***]
----
Solvent Yellow 32.
48045
----
Fanchon Yellow
(Hansa Yellow G).
11680
(α) -(O-Nitro-p-tolylazo)
accetoacetanilide
2
[Part II
LIST OF COLOURS PERMITTED TO BE USED IN SOAPS.
Common name of the Colour Index Chemical name of the colour
Colour No.
Phthalocyanine Blue 74160 (phthalocyninate (2--) copper.
Iragalite Red CVPB
Paste or
Pigment
Orange 5
12075 1-(2,4-dinithro phenylazo)-2-Naphthalenol.
Citrus Red No.2. 12156 1-2(2,5-dimethoxy phenylazo) 2-naphthol.
Rhodamine B 500 45170 3-ethochloride of 9-0 carboxy-ethenyl-6-diethylamino-
3-ethylamine-3-isoxanthene.
Aqueous Green Paste 74260 Polychloro copper Phthalocyanine.
Pigment Yellow 3 11710 2-(4-Chloro-2-nitrophenyl)-azo-N-(-2-Chloro-
phenyl)-3- Oxobutamide.
Irgalite Carmine F-P Powder
or Pigments Red 5.
Monolite Red 4R HV Paste
or
Pigment Red 7.
12490 N-(5-Chloro-2, 4-dimethoxy-phenyl)-4-(CS-
diathylamine) Sulfonyl-2-methoxyphenyl)azo-
3-hydroxy-2-naphthalene carboxamide.
12420 N-(4-Chloro-2-methylphenyl-4-(-4-Chloro-2-methylphenyl)
Azo
3-hydroxy-2-naphthalenol Carboxamide.
Oil Red No.1 or Solvent
Red 24 or
Oil Red 3R.
26105 4-0-Tolylazo-Toluidine azo 2-naphthalenol.]
*This list of colour for use in soaps is in addition to those colours already given in
Schedule Q and are used
for soaps.]
1. Omitted by G.S.R. 203(E) dated 18-03-2015
2. Ins. by G.S.R. 11(E) , dt. 7.1.1991.
Drugs and Cosmetics Rules 1945
544
1
[SCHEDULE R
[See Rule
125]
STANDARDS FOR CONDOMS MADE OF RUBBER LATEX INTENDED FOR SINGLE
USE
AND OTHER MECHANICAL
CONTRACEPTIVES
I-Condoms
1. Description - Condoms consist of cylindrical rubber sheaths with one end open. The
open end shall terminate with an integral rim. The closed end may have a receptacle. They
may be supplied rolled and shall be free from tackiness and shall be capable of being unrolled
readily.
2. Materials - (1) Condoms shall be manufactured from good quality rubber latex and
shall be free from embedded grit and shall be opaque or translucent prior to the application of
dusting materials or lubricants.
(2) The rubber latex, colours used and any dusting materials or lubricants applied to the
condoms shall neither contain nor liberate substances which are known to have toxic or other
harmful effects under normal conditions of use. Any dusting material or lubricant or colour
used shall not have deleterious effect on the condoms or be harmful to the users.
3. Procedure for sampling during production − (1) Specimens constituting the test
samples shall be taken at random successively from each quantum of production that is, from
the quantity produced from the same finished rubber latex and under the same processing
and finishing conditions of manufacture and samples from each quantum shall be tested
separately to ascertain conformity of quantum with the specified requirements in accordance
with the tests described in this Schedule.
(2) (a) The number of samples drawn from each quantum shall be not less than 0.5 per
cent of the number.
(b) The number of samples drawn from each quantum shall be tested for Burst
Volume and Pressure Test and Water Leakage Test in accordance with the method prescribed
in paras 9 and 10 of this Schedule. 75 per cent of the samples drawn will be tested for Water
Leakage Test and 25 per cent will be tested for Burst Volume and Pressure Test.
(c) The number of test samples ‗N‘ and the number of rejected samples ‗R‘ from a
sequence of production quanta shall be recorded in a register. The cumulative total of test
samples ‗N‘ and the cumulative total of rejects ‗R‘ from the test shall be recorded and the
condoms shall be deemed to comply with the requirements if the cumulative total of rejects
‗R‘ is not more than
2
[0.0025N+3 x √0.0025N] for Water Leakage Test, and
2
[0.015N+3 x
√0.015N] for Burst Volume and Pressure Test.
(3) Each unit of 100 test samples shall be distributed for the various tests as follows: -
25 for Burst Volume Pressure Test, and;
75 for Water Leakage Test.
1 Subs. by G.S.R. 495(E) , dt. 9.6.1995.
2. Subs. by G.S.R. 353(E), dt. 26.4.2000.
Drugs and Cosmetics Rules 1945
545
(4) Where the number of test samples is a multiple of 100 the distribution scale
mentioned above shall be prorated.
(5) If the cumulative total sample rejected exceeds the number of allowables at any
point in the sequence of quanta, the quantum at which this occurs shall be liable to rejection.
The assessment of quality of further production quanta shall include all previous test results
starting from quantum number 1 and approval of production shall be in suspense until the
condition required by the scheme is again fulfilled.
(6) At least one sample shall be taken at random from each production quantum not
exceeding 10,000 condoms and shall satisfy all requirements regarding dimensions as
specified in paragraph 8 of this Schedule.
4. Procedure for sampling and testing of finished products by a manufacturer –
A. Water Leakage Test.- (1) Statistical sampling for quality control assessment of the finished
product in respect of Water Leakage Test shall be done in accordance with the plan set out in
Annexure 1 to this Schedule.
(2) A test sample failing in the above test is to be considered as defective. If the
cumulative total of rejects ‗R‘ is found to be equal to or greater than the number shown against
‗R‘ in Annexure-I, the batch or lot shall be declared as not of standard quality.
B. Bursting Volume and Pressure Test.- (1) Sample condoms shall be tested for
Bursting Volume and Pressure Test. Statistical sampling for this test shall be done in
accordance with the plan set out in Annexure III to this Schedule.
Condoms shall not leak or burst at a volume of less than that specified or at a
pressure less than 1.0 kpa (gauge), when tested as per paragraph 9, both before and after oven
conditioning as specified in Annexure V. Bursting Volume minimum limit in litres shall be
equal to [mean condom width (mm)
2
] rounded to the nearest 0.5 litre.
151.8
(2) A test sample failing in the above test is to be considered defective. If the
cumulative total of rejects ‗R‘ is found to be equal or greater than the number shown against
‗R‘ in Annexure III, the batch or lot shall be declared as not of standard quality.
C. Dimensions. - At least 2 samples drawn from the lot or batch shall satisfy the requirements
regarding dimensions as specified in paragraph 8 of this Schedule.
5. Procedure for sampling and testing of condoms by a purchaser -
A. Water Leakage Test- (1) Statistical sampling of condoms by a purchaser for Water Leakage
Test shall be done in accordance with the plan set out in Annexure II to this Schedule;
(2) A test sample failing in the above test is to be considered as defective. If the
cumulative total of rejects ‗R‘ is found to be equal to or greater than the number shown
against ‗R‘ in the Annexure-II, the batch or lot shall be declared as not of standard quality.
B. Bursting Volume and Pressure Test - Sample condoms shall be tested for Bursting
Volume and Pressure Test. Statistical sampling for this test shall be done in accordance with
the plan set out in Annexure III to this Schedule. If the cumulative total of rejects ‗R‘ is found
Drugs and Cosmetics Rules 1945
546
to be equal to or greater that the number shown against ‗R‘ in Annexure III, the batch or lot
shall be declared as not of standard quality.
Condom shall not leak or burst at a volume of less than that specified or at a pressure
less than 1.0 kpa (gauge), when tested as specified in paragraph 9, both before and after oven
conditioning as per specified in Annexure V. Bursting volume minimum limit in litres shall be
equal to
[mean condom width
(mm)
2
] rounded to the nearest 0.5 litre.
151.8
C. Dimensions. - At least two samples from the lot or batch shall satisfy the requirements
regarding dimensions as specified in paragraph 8 of this Schedule.
6. Sampling plan for a Drugs Inspector - (1) Where an Inspector under the Act desires
to take test samples from the premises of manufacturer or a distribution depot; twenty containers
from each batch of production may be selected by him on a random basis and from each of the
containers, five samples shall be taken. The hundred samples so selected shall be distributed for
various tests as specified in paragraph 7 of this Schedule. In case the number of container is less
than twenty, the number of samples to be taken from each container shall be proportionately
increased.
(2) Where an Inspector under the Act desires to take samples from a sales premises, he
shall take hundred samples from each batch of production in accordance with the procedure as
specified in sub- paragraph (1).
7. Sampled condoms drawn under sub-paragraph.- (1) shall be distributed for various tests
as follows: - Two samples for thickness, length and width;
Forty-five samples for Water Leakage Test;
Forty-five samples for Bursting Volume and Pressure Test; and
Eight samples as reserve.
The samples shall be declared as not of standard quality, if, - (i) the number of
condoms found defective in the Water Leakage Test exceeds one; (ii) the number of condoms
found defective in Bursting Volume and Pressure Test exceeds two; (iii) samples fail to
conform to the requirements of dimensions as specified in paragraph 8 of this Schedule.
8. Dimensions - (1) The length when unrolled (excluding test) shall be not less than -
(i) 170 mm.
(ii) 180 mm.
(2) The width of a condom which laid flat and measured at any point within 85 mm
from the open end shall be,–
(i) 49 ± 2 mm for 170 mm length.
(ii) 53 ± 2 mm for 180 mm length.
(3) The single-wall thickness of a condom when measured at three points, one at 30 ±
2mm from the open end, 30 ± 5mm from the close end excluding the reservoir tip and at the
mid distance between these two point shall be from 0.045 mm to 0.075 mm.
NOTE 1. - The single-wall thickness shall be determined with a suitable micrometer
dial gauge graduated in intervals of 0.01 mm.
NOTE 2. - Condoms shall, prior to the measurement of thickness, have the dusting
powder or the lubricant or both removed by means of water or Isopropanol.
Drugs and Cosmetics Rules 1945
547
9. Bursting Volume and Pressure Test - Determination of Bursting Volume and
Pressure Test shall be done as specified in Annexure IV.
10. Water Leakage Test - Unroll the condom and fit the open end on a suitable
mount, the condom thus being suspended open end upwards. Fill it with 300 ml water at room
temperature and inspect it after a period of at least 1 minute for leakage up to 25.mm from the
open end. If, because of distension of the condom the water does not extend to 25 mm from the
open end, raise the closed end until the water level reaches this distance. After at least 1
minute, inspect the newly-wetted part of the condom for leakage. The condom shall be deemed
to be defective if it bursts during test or shows any evidence of leakage or seepage of micro-
droplets or does not hold 300 ml water.
11. Quantity of Lubricant - (1) The condoms shall be dressed with silicone lubricant.
The quantity required on each individual condom should not be less than 200 mg and
minimum viscosity shall be 200 centistokes.
(2) Lubricated condoms in individual foil packages shall be weighed on an Analytical
Balance. Each condom shall be removed from its foil package and both condom and its foil
package shall be washed in denatured ethanol or isopropanol, dried and then weighed again.
All weights shall be recorded to the nearest milligram (mg.). Compliance with the
requirement shall be determined by subtracting the weight of the washed and dried condom
and its foil package from the weight of sample condom in individual foil package prior to the
removal of lubricant. Washing and drying may be required upto a total of four times if
the lubricant quantity is less than the required minimum.
(3) At least thirteen samples shall be drawn from the lot or batch and the samples shall
satisfy the requirements regarding the quantity of lubricant.
12. Colour Fastness - Not less than ten samples taken at random from each batch of
coloured condoms shall pass the following test for colour fastness, namely :-
Thoroughly wet inside and outside of the condom with distilled water. Make no
attempt to remove any dusting material or lubricant. Wrap the wet condom in white absorbent
paper so that the largest possible surface area of the condom is in contact with the paper and
seal the whole in a suitable container to prevent loss of moisture. Allow the container and its
contents to stand for 16 hours to 24 hours at room temperature. After removing the absorbent
paper from the container, examine it visually in the natural daylight for any indication of
staining. No part of the absorbent paper shall be stained. If there is any indication of staining of
the absorbent paper by any colouring agent present in any of the condoms or any dusting
material or lubricant, the entire batch shall be declared to be not of standard quality.
13. Labelling, packing and storage - (1) The condoms shall be individually wrapped
and sealed in laminates containing at least eight microns of aluminium foil. The individual
condom shall be packed in square (non-squeeze condition) / rectangular aluminium foil. The
packing shall protect the condoms from contamination and mechanical damage. The smallest
packing offered to the consumer shall bear a clear permanent marking with the following
particulars, namely: -
Drugs and Cosmetics Rules 1945
548
(i) Manufacturer‘s name and address and the trade name of the condoms, if any;
(ii) Batch number;
(iii) Date of manufacture (Month and year only);
(iv) Date of expiry (Month and year only) which shall not be more than thirty-six
months from the date of manufacture;
(v) The words ―For single use only‖
(2) The condoms shall be stored in a cool dry place away from heat and direct sunlight.
14. Integrity of individual package seals - Sample condoms in individual packages shall be
placed in a sealed, transparent container (such as a laboratory Bell jar) and subjected to vacuum
of 50± 10 kpa (gauge) for a period of one minute.
Condom packages that do not inflate or remain inflated for the period of the test shall be
deemed non- compliers. In doubtful cases, the test may be repeated, and both the inflation and
deflation of packages may be observed on application and removal of vacuum. An AQL of 2.5
per cent will be applied in assessing the results of this test. Thirty-two samples of condoms for a
batch size less than 5 lakhs and fifty samples of condoms for batch size more than 5 lakhs shall
be tested for integrity test of individual package seals and compliance limit or acceptance
number shall be not more than two or three condoms respectively.
II- Other Mechanical
Contraceptive
15. Standards for other mechanical contraceptive - Standards for ‗Copper T‘ and ‗Tubal
Ring‘shall be as laid down in Annexure VI.
1
[ANNEXURE
I
[See Paragraph
4-A]
SAMPLING PLAN FOR QUALITY CONTROL OF CONDOMS AT MANUFACTURER’S
LEVEL
.
BATCH SIZE: 35,001 TO 1.5
LAKH
Single Sampling Plan
Sample Size 200: AQL - 0.25
AC - 1
R
-
2
1. Subs. by. G.S.R. 353(E) , for ― Annexures I to III‖ dt. 26-4-2000.
Drugs and Cosmetics Rules 1945
549
Single Sampling Plan
BATCH SIZE: 150001 TO 5 LAKHS
Sample Size 315 : AQL - 0.25
AC -
2
R
-
3
BATCH SIZE: OVER 5 LAKHS
Single Sampling Plan.
Sample Size 500: AQL - 0.25
AC -
3
R
-
4
Note : AQL denotes Acceptance Quality Level;
AC denotes Acceptance Number i.e. the maximum allowable
number of defectives for acceptance of the Batch; and
R denotes Rejection Number i.e., the minimum number of
defectives for rejection of the Batch.
ANNEDURE
II
[See Paragraph
5A]
SAMPLING PLAN FOR QUALITY CONTROL OF CONDOMS AT PURCHASER‘S
LEVEL.
BATCH SIZE: 35,001 TO 1.5
LAKHS
Single Sampling Plan
Sample Size 200:
AQL
- 0.25
AC
- 1
R
-
2
BATCH SIZE : 15,001 TO 5 LAKHS
Single Sampling Plan.
Sample Size 315:
AQL
- 0.25
AC
- 2
R
-
3
BATCH SIZE : OVER 5 LAKHS
Single Sampling Plan
Sample Size 500:
AQL
- 0.25
AC
- 3
R
-
4
Note: AQL denotes Acceptance Quality Level;
AC denotes Acceptance Number i.e. the maximum allowable number of defectives for
acceptance of the Batch; and
R denotes Rejection Number i.e., the minimum number of defectives for rejection of the
Batch.
Drugs and Cosmetics Rules 1945
550
ANNEXURE
III
[See Paragraph 4-B and
5-B]
SAMPLING PLAN FOR BURSTING VOLUME AND PRESSURE
TES
T
.
Single Sampling Plan.
BATCH SIZE: 35,001 TO 1.5 LAKH.
Sample Size 200: AQL - 1.5
AC -
7
R -
8
BATCH SIZE: 150001 LAKHS TO 5 LAKHS
Single Sampling Plan.
Sample Size 315: AQL - 1.5
AC -
10
R -
11
Single Sampling Plan.
BATCH SIZE: OVER 5 LAKHS
Sample Size 500: AQL - 1.5
AC - 14
R
-
15
Note : AQL denotes Acceptance Quality Level;
AC denotes Acceptance Number i.e. the maximum allowable number of defectives
for acceptance of the Batch; and
R denotes Rejection Number i.e., the minimum number of defectives for rejection of the
Batch.]
ANNEXURE
IV
(See Paragraph
9)
DETERMINATION OF BURSTING VOLUME AND
PRESSURE
1. Principle - Inflation of constant length of the condom with air and recording
the volume and pressure at the moment of bursting.
2. Apparatus - (1) Apparatus suitable for inflating the condom with clean air at a
specified rate and provided with equipment for measuring volume and pressure.
(2) Suitable mount for fitting the condoms to the apparatus as shown in the figure annexed.
(3) Rod, 140 mm in length having a smooth sphere 20 mm in diameter at its top (see
the figure) for hanging the unrolled condom when fixed to the apparatus.
3. Procedure - (1) Unroll the condom, hang it on the rod (2.3), affix to the mount
(2.2) and inflate with air at a rate of 0.4 to 0.5 litre/sec. (24 to 30 litres/min.)
(2) Measure and note the bursting volume, in litres rounded to the nearest 0.5
litre and the bursting pressure, in kilopascals rounded to the nearest 0.1 kpa.
4. Test report - The test report shall include the following particulars:
(a) the identification of the sample;
(b) the bursting volume and bursting pressure of each tested condom;
(c) the date of testing.
Drugs and Cosmetics Rules 1945
551
ANNEXURE
V
[See Paragraphs 4(B) and 5 (B)
OVEN CONDITIONING
1. Principle of the Method - The test consists in subjecting test samples to controlled
deterioration by air at an elevated temperature and at atmospheric pressure after which burst
volume and pressure limits are measured.
2. Apparatus - The air oven shall be of such a size that the total volume of the test
samples does not exceed 10 per cent of the free air space of the oven. Provision shall be
made for slow circulation of air in the oven of not less than three changes and not more than
ten changes per hour. The temperature of the oven shall be thermostatically controlled so that
the test samples are kept within ± 2
o
C of the specified ageing temperature. A thermometer
shall be placed near the centre of the ageing test samples to record the actual ageing
temperature.
Note: - Copper or copper alloys shall not be used for the material of construction of the oven
prescribed.
3. Test sample - The foil laminations of individual packages should remain intact
throughout all laboratory handling including over conditioning.
4. Temperature of the oven – Maintain the oven at 70 ± 2
o
C.
5. Duration of test - 96 hours.
6. Procedure - Condition the requisite number of unopened packages of rubber condoms in
the oven at 70 ± 2
o
C for 96 hours. After heating, keep the packages at 23 ± 5
o
C for at least
12 hours but not more than 96 hours. Open the packages and examine conditioned condoms
for tackiness, brittleness, or other signs of deterioration. Within 96 hours but not sooner than
12 hours after conditioning, do the bursting volume and pressure Test as described in this
Schedule.
ANNEXURE
VI
(See Paragraph
15)
1. Standards for Copper T (200B) (IS-12418) (part 4)-1991-UDC 615.477.87) -
Contraceptive Device Copper T (200 B) shall conform to the Indian Standards laid down
from time to time by the Bureau of Indian Standards.
2. Standards for Contraceptive Tubal Ring (IS 13009 : 1990-UDC 615.472.6 :
611.656) - Contraceptive Device Tubal Ring shall conform to the Indian Standards laid
down from time to time by the Bureau of Indian Standards.]
Drugs and Cosmetics Rules 1945
552
1
[SCHEDULE R1
(See Rules 109A, 109, 109C and
125A)
The medical devices shall conform to the Indian Standards laid down from time to
time by the Bureau of Indian Standards. If there are no Bureau of Indian Standards then it
shall conform to the International Standards, like International Organisation for
Standardisation, or other International Pharmacopeia Standards and such other standards as
may be specified for this purpose. In case national or international standards are not available,
the device shall conform to the manufacturer‘s validated standards.]
2
[SCHEDULE
S
[See Rule
150-A]
STANDARDS FOR COSMETICS
Standards for cosmetics in finished form − The following cosmetics in finished form
shall conform to the Indian Standards specifications laid down from time to time by the
3
[Bureau of Indian Standards (BIS)].
1. Skin Powders.
2. Skin Powder for infants.
3. Tooth Powder.
4. Toothpaste.
5. Skin Creams.
6. Hair Oils.
7. Shampoo, Soap-based.
8. Shampoo, Synthetic-Detergent based.
9. Hair Creams.
10. Oxidation hair dyes, Liquid.
11. Cologne.]
4
[12. Nail Polish (Nail
Enamel).
13. After Shave Lotion.
14. Pomades and Brilliantines.
15. Depliatories Chemical.
16 Shaving Creams.
17. Cosmetic Pencils.
18. Lipstick.]
5
[19. Toilet
Soap.
20. Liquid Toilet Soap.
21. Baby Toilet Soap.
22. Shaving Soap.
23. Transparent Toilet Soap.]
1. Subs. by G.S.R. 690(E), dt. 25.9.2014.
2. Ins. by G.S.R. 510(E) , dt. 26.07.1982.
3. Subs. by G.S.R. 673(E), dt. 27.10.1993.
4. Ins. By G.S.R. 731(E) dated 23-08-1990
5. Ins. By G.S.R. 673(E) dated 27-10-1993
Drugs and Cosmetics Rules 1945
553
1
[24. Lipsalve IS:10284.
25. Powder Hair Dye IS: 10350.
26. Bindi (Liquid) IS: 10998.
27. Kum Kum Powder IS: 10999.
28. Henna Powder IS: 11142.]
2
[29. Bathing Bars IS: 13498: 1997
3[30. Sindoor IS: 14649: 1999
4
[31. Liquid Foundation makeup IS 14318
4[32. Cold Wax Hair remover IS 15152
4
[33. Face pack IS 15153
4
[34. Kajal IS 15154
4
[35. Oxidation Hair Dyes (Emulson Type) IS 15205
4[36. Cream Bleach IS 15608
1. Ins. by G.S.R. 553(E), dt. 20.7.1995.
2. Ins. by G.S.R. 592(E), dt.13.8.2008.
3. Ins. by G.S.R. 724(E), dt. 07.11.2013.
4. Ins. by G.S.R. 203(E), dt.18.03.2015.
5
[SCHEDULE
T
(See rule
157)
GOOD MANUFACTURING PRACTICES FOR
AYURVEDIC,
SIDDHA AND UNANI
MEDICINES
The Good Manufacturing Practices (GMP) are prescribed as follows in Part I and Part II
to ensure that:
(i) Raw materials used in the manufacture of drugs are authentic, of prescribed
quality and are free from contamination.
(ii) The manufacturing process is as has been prescribed to maintain the standards.
(iii) Adequate quality control measures are adopted.
(iv) The manufactured drug which is released for sale is of acceptable quality.
(v) To achieve the objectives listed above, each licensee shall evolve methodology
and procedures for following the prescribed process of manufacture of drugs
which should be documented as a manual and kept for reference and
inspection. However, under IMCC Act 1970 registered Vaidyas, Siddhas and
Hakeems who prepare medicines on their own to dispense to their patients and
not selling such drugs in the market are exempted from the purview of G.M.P.
5. Subs. by G.S.R. 560(E), dt. 07.3.2003.
Drugs and Cosmetics Rules 1945
554
PART
I
GOOD MANUFACTURING PRACTICES
1.1 Factory Premises:
The manufacturing plant should have adequate space for: -
(i)Receiving and storing raw material.
(ii)Manufacturing process areas.
(iii)Quality control section.
(iv)Finished goods store.
(v)Office.
(vi)Rejected goods/drugs store.
1.1 General Requirements:
1.1(A) Location and surroundings - The factory building for manufacture of
Ayurveda, Siddha and Unani medicines shall be so situated and shall have such
construction as to avoid contamination from open sewerage, drain, public lavatory for any
factory which produces disagreeable or obnoxious odour or fumes or excessive soot, dust
and smoke.
1.1(B) Buildings - The buildings used for factory shall be such as to permit
production of drugs under hygienic conditions and should be free from cobwebs and
insects/rodents. It should have adequate provision of light and ventilation. The floor and
the walls should not be damp or moist. The premises used for manufacturing, processing,
packaging and labelling will be in conformity with the provisions of the Factory Act. It
shall be located so as to be:
(I) Compatible with other manufacturing operations that may be carried out in
the same or adjacent premises.
(II) Adequately provided with working space to allow orderly and logical
placement of equipment and materials to avoid the risk of mix-up between
different drugs or components thereof and control the possibility of cross
contamination by other drugs or substances and avoid the risk of omission of
any manufacturing or control step.
(III) Designed, constructed and maintained to prevent entry of insects and rodents.
Interior surface (walls, floors and ceilings) shall be smooth and free from
cracks and permit easy cleaning and disinfection. The walls of the room in
which the manufacturing operations are carried out shall be impervious to and
be capable of being kept clean. The flooring shall be smooth and even and
shall be such as not to permit retention or accumulation of dust or waste
products.
(IV) Provided with proper drainage system in the processing area. The sanitary
fittings and electrical fixtures in the manufacturing area shall be proper and
safe.
(V) Furnace/Bhatti section could be covered with tin roof and proper
ventilation, but sufficient care should be taken to prevent flies and dust.
Drugs and Cosmetics Rules 1945
555
(VI) There should be fire safety measures and proper exits should be there.
(VII) Drying Space: -There should be separate space for drying of raw material,
in process medicine or medicines which require drying before packing. This
space will be protected from flies/ insects/dust etc., by proper flooring, wire-
mash window, glass panels or other material.
1.1(C) Water Supply - The water used in manufacture shall be pure and of potable
quality. Adequate provision of water for washing the premises shall be made.
1.1(D) Disposable of Waste - From the manufacturing section and laboratories
the waste water and the residues which might be prejudicial to the workers or public health
shall be disposed off.
1.1(E) Container‘s Cleaning - In factories where operations involving the use of
containers such as glass bottles, vials and jars are conducted, there shall be adequate
arrangements separated from the manufacturing operations for washing, cleaning and
drying of such containers.
1.1(F) Stores - Storage should have proper ventilation and shall be free from
dampness. It should provide independent adequate space for storage of different types
of material, such as raw material, packaging material and finished products.
1.1. (F)(A) Raw Materials - All raw materials procured for manufacturing will be
stored in the raw materials store. The manufacture based on the experience and the
characteristics of the particular raw material used in Ayurveda, Siddha and Unani system
shall decide the use of appropriate containers which would protect the quality of raw
materials as well as prevent it from damage due to dampness, microbiological
contamination or rodent and insect infestation, etc. If certain raw materials require such
controlled environmental conditions, the raw materials stores may be sub-divided
with proper enclosures to provide such conditions by suitable cabinization. While
designing such containers, cupboard or areas in the raw materials store, care may be
taken to handle the following different categories of raw materials:-
1. Raw material of metallic origin.
2. Raw material of mineral origin.
3. Raw material from animal source.
4. Fresh herbs.
5. Dry herbs or plant parts
6. Excipients etc.
7. Volatile oils/perfumes and flavours
8. Plant concentrates/ extracts and exudates/resins.
Drugs and Cosmetics Rules 1945
556
Each container used for raw material storage shall be properly identified with the
label which indicates name of the raw material, source of supply and will also clearly state
the status of raw material such as ‗UNDER TEST‘ or ‗APPROVED‘ or ‗REJECTED‘.
The labels shall further indicate the identity of the particular supply in the form of Batch
No. or Lot No. and the date of receipt of the consignment.
All the raw materials shall be sampled and got tested either by the in-house
Ayurvedic, Siddha and Unani experts (Quality control technical person) or by the
laboratories approved by the Government and shall be used only on approval after
verifying. The rejected raw material should be removed from other raw material store and
should be kept in separate room. Procedure of ‗First in first out‘ should be adopted for raw
materials wherever necessary. Records of the receipt, testing and approval or rejection and
use of raw material shall be maintained.
1.1. (F)(B) Packaging Materials. - All packaging materials such as bottles, jars,
capsules etc. shall be stored properly. All containers and closure shall be adequately
cleaned and dried before packing the products.
1.1. (F)(C) Finished Goods Stores. - The finished goods transferred from the
production area after proper packaging shall be stored in the finished goods stores within
an area marked ―Quarantine‖. After the quality control laboratory and the experts have
checked the correctness of finished goods with reference to its packing/labelling as well as
the finished product quality as prescribed, then it will be moved to ―Approved Finished
Goods Stock‖ area. Only approved finished goods shall be dispatched as per marketing
requirements. Distribution records shall be maintained as required.
If any Ayurvedic, Siddha and Unani drug needs special storage conditions, finished
goods store shall provide necessary environmental requirements.
1.1(G) Working space. - The manufacturing area shall provide adequate space
(manufacture and quality control) for orderly placement of equipment and material used in
any of the operations for which these employed so as to facilitate easy and safe working
and to minimize or to eliminate any risk of mix-up between different drugs, raw materials
and to prevent the possibility of cross contamination of one drug by another drug that is
manufactured, stored or handled in the same premises.
1.1(H) Health Clothing, Sanitation and Hygiene of Workers.- All workers
employed in the Factory shall be free from contagious diseases. The clothing of the
workers shall consist of proper uniform suitable to the nature of work and the climate and
shall be clean. The uniform shall also include cloth or synthetic covering for hands, feet
and head wherever required. Adequate facilities for personal cleanliness such as clean
towels, soap and scrubbing brushes shall be provided. Separate provision shall be made for
lavatories to be used by men and women, and such lavatories shall be located at places
separated from the processing rooms. Workers will also be provided facilities for changing
their clothes and to keep their personal belongings.
Drugs and Cosmetics Rules 1945
557
1.1. (I) Medical Services: The manufacturer shall also provide:-
(a) adequate facilities for first aid;
(b) medical examination of workers at the time of employment and periodical
check up thereafter by a physician once a year, with particular attention being
devoted to freedom from infections. Records thereof shall be maintained.
1.1(J) Machinery and Equipments - For carrying out manufacturing depending on
the size of operation and the nature of product manufactured, suitable equipment either
manually operated or operated semi-automatically (Electrical or steam based) or fully
automatic machinery shall be made available. These may include machines for use in
the process of manufacture such as crushing, grinding, powdering, boiling, mashing,
burning, roasting, filtering, drying, filling, labelling and packing etc. to ensure ease in
movement of workers and orderliness in operations a suitably adequate space will be
ensured between two machines or rows of machines. These equipments have to be properly
installed and maintained with proper cleaning. List of equipments and machinery
recommended is indicated in Part II-A.
Proper Standard Operational Procedures (SOPs) for cleaning, maintaining and
performance of every machine should be laid down.
1.1(K) Batch Manufacturing Records - The licensee shall maintain batch
manufacturing record of each batch of Ayurvedic, Siddha and Unani drugs manufactured
irrespective of the type of product manufactured (classical preparation or patent and
proprietary medicines). Manufacturing records are required to provide an account of the
list of raw materials and their quantities obtained from the store, tests conducted during
the various stages of manufacture like taste, colour, physical characteristics and chemical
tests as may be necessary or indicated in the approved books of Ayurveda, Siddha and
Unani mentioned in the First Schedule of the Drugs and Cosmetics Act, 1940 (23 of
1940). These tests may include any in-house or pharmacopoeial test adopted by the
manufacturer in the raw material or in the process material and in the finished product.
These records shall be duly signed by Production and Quality Control Personnel
respectively. Details of transfer of manufactured drug to the finished products store
including dates and quantity of drugs transferred along with record of testing of the
finished product, if any, and packaging, records shall be maintained. Only after the
manufactured drugs have been verified and accepted quality shall be allowed to be cleared
for sale.
It should be essential to maintain the record of date, manpower, machine and
equipments used and to keep in process record of various shodhana, bhavana, burning and
fire and specific grindings in terms of internal use.
Drugs and Cosmetics Rules 1945
558
1.1(L) Distribution Records - Records of sale and distribution of each batch of
Ayurveda, Siddha and Unani Drugs shall be maintained in order to facilitate prompt and
complete recall of the batch, if necessary.The duration of record keeping should be the
date of expiry of the batch. Certain category of Ayurvedic, Siddha and Unani medicines
like Bhasma, Rasa, Kupi-pakva, Parpati, Sindura, Karpu/Uppu/Puram, Kushta, Asava-
arishta etc. do not have expiry date in contrast their efficacy increases with the
passage of time. Hence, records need be maintained upto five years of the exhausting of
stock.
1.1(M) Record of Market Complaints - Manufacturers shall maintain a register to
record all reports of market complaints received regarding the products sold in the market.
The manufacturer shall enter all data received on such market complaints, investigations
carried out by the manufacturers regarding the complaint as well as any corrective action
initiated to prevent recurrence of such market complaints shall also be recorded. Once in a
period of six months the manufacturer shall submit the record of such complaints to the
licensing authority. The Register shall also be available for inspection during any
inspection of the premises.
Reports of any adverse reaction resulting from the use of Ayurvedic, Siddha and
Unani drugs shall also be maintained in a separate register by each manufacturer. The
manufacturer shall investigate any of the adverse reaction to find if the same is due to any
defect in the product, and whether such reactions are already reported in the literature or it
is a new observation.
1.1(N) Quality Control. - Every licensee is required to provide facility for
quality control section in his own premises or through Government approved testing
laboratory. The test shall be as per the Auurveda, Siddha and Unani pharmacopoeial
standard. Where the tests are not available, the test should be performed according to the
manufacturers‘ specification or other information available. The quality control section
shall verify all the raw materials, monitor in-process quality checks and control the quality
of finished product being released to finished goods store/warehouse. Preferably for such
quality control there will be a separate expert. The quality control section shall have the
following facilities:–
(1) There should be 150 sq. feet area for quality control section.
(2) For identification of raw drugs, reference books and reference samples
should be maintained.
(3) Manufacturing record should be maintained for the various processes.
(4) To verify the finished products, controlled samples of finished products of
each batch will be kept till the expiry date of product for 3 years.
(5) To supervise and monitor adequacy of conditions under which raw
materials, semi- finished products and finished products are stored.
(6) Keep record in establishing shelf life and storage requirements for the drugs.
Drugs and Cosmetics Rules 1945
559
(7) Manufacturers who are manufacturing patent and proprietary Ayurveda,
Siddha, and Unani medicines shall provide their own specification and control
references in respect of such formulated drugs.
(8) The record of specific method and procedure of preparation, that is,
―Bhavana‖, ―Mardana‖ and ―Puta‖ and the record of every process carried out
by the manufacturer shall be maintained.
(9) The standards for identity, purity and strength as given in respective
pharmacopoeias of Ayurveda, Siddha and Unani systems of medicines
published by Government of India shall be complied with.
(10) All raw materials will be monitored for fungal, bacterial contamination
with a view to minimize such contamination.
(11) Quality control section will have a minimum of: –
1
[(i) (a) Expert in Ayurveda or Sidha or Unani medicine who possesses a
degree qualification recognized under Schedule II of Indian Medicine Central
Council Act 1970;
(b) Chemist, who shall possess at least Bachelor Degree in Science or
Pharmacy or Pharmacy (Ayurveda), awarded by a recognized University; and
(c) Botanist (Pharmacognosist), who shall possess at least Bachelor Degree in
Science (Medical) or Pharmacy or Pharmacy (Ayurveda) awarded by a
recognized University.]
(ii) The manufacturing unit shall have a quality control section as explained
under Section 35 (ii). Alternatively, these quality control provisions will be met
by getting testing etc., from a recognised laboratory for Ayurveda, Siddha and
Unani drugs; under Rule 160-A of the Drugs and Cosmetics Act. The
manufacturing company will maintain all the record of various tests got done
from outside recognised laboratory.
(iii) List of equipments recommended is indicated in Part II C.
1.2. Requirement for Sterile Product:
(A) Manufacturing Areas: – For the manufacture of sterile Ayurvedic, Unani and
Siddha drugs, separate enclosed areas specifically designed for the purpose shall be
provided. These areas shall be provided with air locks for entry and shall be essentially
dust free and ventilated with an air supply. For all areas where aseptic manufacture has to
be carried out, air supply shall be filtered through bacteria retaining filters (HEPA Filters)
and shall be at a pressure higher than in the adjacent areas. The filters shall be checked for
performance on installation and periodically thereafter the record of checks shall be
maintained. All the surfaces in sterile manufacturing areas shall be designed to facilitate
cleaning and disinfection. For sterile manufacturing routine microbial counts of all
Ayurvedic, Siddha and Unani drug manufacturing areas shall be carried out during
operations. Results of such count shall be checked against established in-house
standards and record maintained.
1. Subs. by G.S.R. 463(E) dated 08-07-2005.
Drugs and Cosmetics Rules 1945
560
Access to manufacturing areas shall be restricted to minimum number of
authorized personnel. Special procedure to be followed for entering and leaving the
manufacturing areas shall be written down and displayed.
For the manufacturing of Ayurvedic, Siddha and Unani drug that can be sterilized
in their final containers, the design of the areas shall preclude the possibility of the
products intended for sterilization being mixed with or taken to be products already
sterilized. In case of terminally sterilized products, the design of the areas shall preclude
the possibility of mix-up between non-sterile products.
(B) Precautions against contamination and mix:
(a) Carrying out manufacturing operations in a separate block of adequately
isolated building or operating in an isolated enclosure within the building,
(b) Using appropriate pressure differential in the process area.
(c) Providing a suitable exhaust system.
(d) Designing laminar flow sterile air system for sterile products.
(e) The germicidal efficiency of UV lamps shall be checked and recorded
indicating the burning hours or checked using intensity.
(f) Individual containers of liquids and ophthalmic solutions shall be
examined against black-white background fitted with diffused light after
filling to ensure freedom from contamination with foreign suspended matter.
(g) Expert technical staff approved by the Licensing Authority shall
check and compare actual yield against theoretical yield before final
distribution of the batch.
All process controls as required under master formula including room
temperature, relative humidity, volume filled, leakage and clarity shall be checked and
recorded.
PART
II
A. LIST OF RECOMMENDED MACHINERY, EQUIPMENT AND
MINIMUM
MANUFACTURING PREMISES REQUIRED FOR THE MANUFACTURE
OF
VARIOUS CATEGORIES OF AYURVEDIC, SIDDHA SYSTEM OF
MEDICINES
One machine indicated for one category of medicine could be used for the manufacturing
of other category of medicine also. Similarly some of the manufacturing areas like
powdering, furnace, packing of liquids and Avaleha, Paks, could also be shared for these
items.
Drugs and Cosmetics Rules 1945
561
Sl.No. Category of Medicine Minimum manufacturing
space required
Machinery/equipment
recommended
(1) (2) (3)
(4)
1200 Square feet
covered area with
separate cabins or
partitions for each
activity. If Unani
medicines are
manufactured in same
premises an additional
area of 400 sq. feet will
be required.
1. Anjana/Pisti 100 sq. feet. Karel/mechanized/motorized, karel.
End runner/Ball-Mill
Sieves/Shifter.
2. Churna / Nasya/
Manjan/Lepa/
Kwath Churn
200 sq feet Grinder/disintegrator/Pulveriser/
Powder mixer/sieves/shifter.
3. Pills/Vati /Gutika
Matirai and tablets
100 sq. feet Ball Mill, Mass mixer/powder
mixer, Granulator, drier, tablet
compressing machine, pill/vati
cutting machine, stainless steel
trays/container for storage and
sugar coating, polishing pan in case
of sugar-coated tablets,mechanised
chattoo (for mixing guggulu) where
required.
4. Kupi pakava/Ksara/
Parpati/LavanaBhasm
a Satva/Sindura
Karpu/ Uppu / Param
150 sq. feet Bhatti, Karahi/Stainless steel
Vessels/Patila Flask, Multani
Matti/Plaster of Paris, Copper Rod,
Earthern container, Gaj Put Bhatti,
Mufflefurnace(Electrically
operated) End/EdgeRunner, Exhaust
Fan, Wooden/S.S.Spatula.
5. Kajal 100 sq. feet Earthern lamps for collection of
Kajal, Triple Roller Mill, End
Runner, Sieves, S.S.Patila, Filling/
packing and manufacturing room
should be provided with exhaust fan
and ultra violet lamps.
6. Capsules 100 sq. feet Air Conditioner, De-humidifier,
hygrometer, thermometer, Capsule
filling machine and chemical
balance.
7. Ointment/Marham
Pasai
100sq. feet Tube filling machine, Crimping
Machine/Ointment Mixer, End
Runner/ Mill (Where required) S.S.
Storage Container S.S.Patila.
Drugs and Cosmetics Rules 1945
562
Sl.No. Category of Medicine Minimum manufacturing
space required
Machinery/equipment
recommended
(1) (2) (3)
(4)
8. Pak/Avaleh/Khand/
Modak/Lakayam
100 sq. feet
Bhatti section fitted with
exhaust fan and should be fly
proof, Iron Kadahi/S.S. Patila and
S.S. Storage container.
9.
Panak, Syrup / Pravahi
Kwath Manapaku
150 sq, feet
Tincture press, exhaust fan
fitted and fly proof, Bhatti section,
Bottle washing machine, filter
press / Gravity filter, liquid
filling machine P.P. Capping
Machine
10.
Asava / Arishta
200 sq. ft
Same as mentioned above.
Fermentation tanks, containers and
distillation plant where necessary,
Filter Press.
11.
12.
Sura
Ark Tinir
100 sq. ft
100 sq. ft
Same as mentioned above plus
Distillation plant and Transfer
pump.
Maceration tank, Distillation plant,
Liquid filling tank with tap /
Gravity filter/Filter
press, Visual
inspection box.
13. Tail/Ghrit Ney 100 sq. ft Bhatti, Kadahi/S.S. Patila
S.S.Storage Containers, Filtration
equipment, filling tank with
tap/Liquid filling machine.
14. Aschyotan / Netra Malham
Panir/Karn Bindu/Nasa-
bindu
100 sq. ft Hot air oven electrically
heated with thermostatic control,
kettle gas or electrically heated
with suitable mixing arrangements,
collation mill, or ointment mill,
tube filling equipment, mixing and
storage tanks of stainless steel or
of other suitable material
sintered glass funnel, seitz filter or
filter candle, liquid filling
equipment, autoclave.
15. Each manufacturing unit will
have a separate area for
Bhatti, furnace boilers, puta,
etc. This will have proper
ventilation, removal of
smoke, prevention of flies,
insets, dust etc. The furnace
200 sq. ft
section could have tin roof.
Drugs and Cosmetics Rules 1945
563
B. LIST OF MACHINERY, EQUIPMENT AND MINIMUM MANUFACTURING
PREMISES REQUIRED FOR THE MANUFACTURE OF VARIOUS
CATEGORIES OF UNANI SYSTEM OF MEDICINES
One machine indicated for one category of medicine could be used for the manufacturing
of other category of medicine also. Similarly some of the manufacturing areas like
powdering, furnace, packing of liquids could also be shared for these items.
Sl.No.
Category
of
Medicine
Minimum manufacturing space
required
Machinery/equipment recommended
(1)
(2)
(3)
(4)
1200 square feet covered area
with separate cabins,
partitions for each activity. If
Ayurveda / Siddha
medicines are also
manufactured in same
premises an additional area of
400 square feet will be
required.
1.
Itrifal
Tirya/majoon/
Laooq/Jawarish
Khamiras
100 sq. feet
Grinder/ Pulveriser, Sieves, powder
mixer (if required), S.S. Patilas,
Bhatti and other accessories, plant
mixer for Khamiras.
2.
Arq.
100 sq. feet
Distillation Plant (garembic)
S.S. storage tank, Boiling Vessel,
Gravity filter, Bottle filling machine,
Bottle washing machine, Bottle
drier.
3.
Habb (Pills) and
tablets.
100 sq. feet
Ball Mill, Mass Mixer/Powder
mixer, Granulator drier, tablet
compressing machine, pill/vati
cutting machine, stainless steal
trays/ container for storage and
sugar coating, polishing pan in
case of sugar-coated tablets,
mechanized chattoo, (for
mixing guggul) where required.
Drugs and Cosmetics Rules 1945
564
4.
Sufoof (Powder)
200 sq. feet
Grinder / pulveriser, Sieves, Trays,
Scoops, Powder mixer
(where required).
5.
Raughan (oils) (Crushing
and boiling)
100 sq. feet
Oil Expeller, S.S. Patilas Oil filter
bottle, Filling machine, Bottle drier,
Bhatti.
6.
Shiyaf, Surma, Kajal
100 sq. feet
End runner, mixing S.S. Vessel..
7. Marham, Zimad
(Ointment)
8. Qurs (Tab.)
100 sq. feet
100 sq. feet
Kharal, Bhatti, End runner, Grinder,
Pulveriser, Triple Roller Mill (if
required).
Grinder/Pulveriser, Sieves, Powder
mixer (where needed), Granulator,
Drier, Tablet Compressing Machine,
Die punches Trays, O.T. Apparatus,
Balance with weights, Scoops, Sugar
Coating Pan, polishing pan, Heater.
9. Kushta 100 sq. feet Bhatti, Kharal, Sil Batta, Earthen pots.
10. Murabba 100 sq. feet. Aluminium Vessels 50-100kgs.
Capacity, Gendna, Bhatti.
11. Capsule 100 sq. feet Pulveriser, Powder mixer
(where needed), capsule filling
machine, Air conditioner, De-
humidifier, Balance with weights,
storage containers, glass.
12. Sharbat and Joshanda 100 sq. feet Tinctum Press, exhaust fan fitted,
Bhatti section, Bottle washing
machine, Filter Press Gravity filter,
Liquid filling tank with tap/liquid
filling machine, hot air oven
electrically heated with thermostatic
control, kettle.
13. Qutoor-e- Chashm
and Marham(Eye
drops, eye ointment)
100 sq. feet
Hot air oven electrically heated
with thermostatic control, kettle
14. Each manufacturing
unit will have a
separate area for
Bhatti, furnaces,
boilers, putta,etc.
This will have proper
ventilation,removal
of smoke, prevention
of flies, insects, dust,
etc.
200 sq. feet
Drugs and Cosmetics Rules 1945
565
C. LIST OF EQUIPMENT RECOMMENDED FOR IN-HOUSE QUALITY CONTROL
SECTION
(Alternatively, unit can get testing done from the Government approved laboratory).
(A) CHEMISTRY SECTION (B) PHARMACOGNOSY SECTION
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17
18
19.
20
21.
22
23.
24
25.
Alcohol Determination Apparatus
(complete set)
Volatile Oil Determination
Apparatus.
Boiling Point Determination
Apparatus.
Melting Point Determination
Apparatus.
Refractometer.
Polarimeter.
Viscometer.
Tablet Disintegration Apparatus.
Moisture Meter.
Muffle Furnace.
Electronic Balance.
Magnetic Stirrer.
Hot Air Oven.
Refrigerator.
Glass/Steel Distillation Apparatus.
LPG Gas Cylinders with Burners.
Water Bath (Temperature controlled.)
Heating Mantles/ Hot Plates.
TLC Apparatus with all accessories
(Manual)
Paper Chromatography apparatus
with accessories.
Sieve size 10 to120 with Sieve
shaker.
Centrifuge Machine.
Dehumidifier.
pH Meter.
Limit Test Apparatus.
1.
2.
3.
4.
5.
6.
7.
8.
Microscope Binoculor.
Dissecting Microscope.
Microtome.
Physical Balance.
Aluminium Slide Trays.
Stage Micrometer.
Camera Lucida (Prism and
Mirror Type).
Chemicals, Glassware etc.
Drugs and Cosmetics Rules 1945
566
1
[D. SUPPLEMENTARY GUIDELINES FOR MANUFACTURING OF
RASAUSHADHIES OR RASAMARUNTHUKAL AND KUSHTAJAT (HERBO-
MINERAL-METALLIC COMPOUNDS) OF AYURVEDA, SIDDHA AND UNANI
MEDICINES
These guidelines are intended to complement those provided above and should be
read in conjunction with the parent guidelines. The supplementary guidelines are to
provide general and minimum technical requirements for quality assurance and control in
manufacturing Rasaushadhis or Rasamarunthukal and Kushtajat (Herbo-mineral-metallic
formulations). These supplementary guidelines deal with Bhasmas, Sindura, Pishti, Kajjali,
Khalviya Ras, Kupipakwa, Rasayan, Parpati, Potali Rasa, Satwa (of Metals and Minerals
origin) Druti Parpam, Karpu, and Kushta etc. used in Ayurvedic, Siddha and Unani
Systems of medicine.
The supplementary GMP guidelines for Rasaushadhi or Rasamarunthukal and
Kushtajat are needed to establish the authenticity of raw drug, minerals and metals, in-
process validation and quality control parameters to ensure that these formulations are
processed and prepared in accordance with classical texts and for which safety measures
are complied. Only those manufacturing units which have Good Manufacturing Practices
for ASU drugs and supplementary certificate for Rasaushadhi or Rasamarunthukal and
Kushtajat formulations shall be allowed to manufacture th e same. Supplementary Good
Manufactur ing Pr actices Certificate for Rasaushadhies shall be issued by the State
Licensing Authority only after thorough inspection by an expert team including
Rasashastra experts nominated by the Department of AYUSH.
2. Manufacturing Process Areas :-
For the manufacture of Bhasma and Kupipakawa and Rasaushadhi preparations
made from metals and minerals the following specific areas shall be provided, which
should be completely segregated from the production area used for preparation of plants
and animal by product based formulation to avoid cross contamination. The following
exclusive areas the required for Rasaushadhies or Rasamarunthukal and Kushtajat:-
2.2
(a)
Bhatti or Heating Device Section for Bhasma and Rasaushadhies :- 100 sq.
feet for heating, burning, putta and any heat related work with proper
ventilation, exhaust and chimney. This could be tin shed also.
1. Ins. By G.S.R. 157(E), dated 04-03-2009
Drugs and Cosmetics Rules 1945
567
(b)
Grinding, Drying and Processing Section for Bhasma and Rasaushadhies:-
100 Sq. feet (Manual or Mechanical, oven etc.). Drying
1
[Shall be] done in
a space which is covered by glass or other transparent material to allow
entry of sunrays on the material to keep for the purpose. If drying is being
done in oven the temperature of the same may be selected specific
temperature.
(c)
Rashaushadi Related Store :-100 Sq. feet.
The size and dimensions of each Bhatti Section would be so designed to suit the
batch size or quantity of materials to be processed, keeping in mind the processing is done
as per the conditions of Drug and Cosmetics Act mentioned under Schedule I official
books.
In addition to the fuels prescribed in the schedule books namely coal, fire wood,
cow dung cakes etc., use of other heating devices e.g. electrical heating, oil or gas fired
furnaces and others Shall be] employed so as to provide the required temperature as per
the nature of material and object of heating. Depending on the formulation being
manufactured, manufacturers may adopt aerobic or anaerobic process. Properly baked and
clean earthen pots of other crucibles and glass containers of appropriate design shall be
used.
The manufacturing area should be designed with special attention to process the
products that generate toxic fumes like SO2, arsenic and mercury vapor, etc. When heating
and boiling of the materials is necessary, suitable ventilation and air exhaust flow
mechanism should be provided to prevent accumulation of unintended fumes and vapors.
Such areas may be provided with properly designed chimneys or ducts fitted with exhaust
system and suitable scrubbing system to remove fumes and smoke, so that safety of
personnel and environment is taken care of.
Since processing of Rasaushadhis may introduce heavy metal contamination and
cross contamination etc., therefore, cleaning of equipment is particularly important after
every process by using appropriate cleaning agent which should not react with material of
equipment and must be free from unwanted properties e.g. corrosiveness.
2.3 Records shall be maintained specially for temperatures attained during the entire
process of Bhasmikaran, while employing different kinds of classical puta, furnaces using
oil, gas or electricity. Appropriate temperature measuring instrument should be employed
such as pyrometer and, pyrograph for manual reading or recording by heat sensors,
connected to computer as the case may be.
In order to handle large quantities, appropriate technology like use of hand operated
extruders for making chakrikas or pellets may be adopeted. However, such equipments
made of aluminium or its alloys should not be used.
1. Subs. by G.S.R.Subs. by G.S.R.338(E), dated 15-04-2010.
Drugs and Cosmetics Rules 1945
568
Access to manufacturing areas shall be restricted to minimum number of authorized
personnel only.
3. Quality Control :-
A. Inprocess Quality Control :-
The registers as indicated below should exclusively be maintained for ready reference :-
(a) Shodhan Register with following details :-
1. Sl No.
2. Batch No. and Size
3. Date, time and duration
4. Name of the Raw-material with Quality reference and quantity
5. Quantity of Shodhana Dravya
6. Book Reference followed
7. Methodology
(b) Bhavana and Putta Register with following details :-
1. Sl No.
2. Batch No.
3. Date, time
4. Name of the material and quantity of starting materials
5. Quantity of Nirvapya Dravya
6. Quantity of Bhavana Dravya
7. Date and time of Starting and completion of Bhavana or Mardana and
duration
8. Type and Number of Puttas
9. Time and Date of completion of Puttas
10. Color and texture of the product or standards
11. Inprocess tests followed (Bhasma Pariksha and any other tests)
12. In case heating at a particular temperature is required, record of attainment
of that temperature.
(c) Grinding Record Register:- (Finished Product / Intermediate procedure)
1. Sl. No.
2. Batch No.
3. Date and time
4. Name of the material and quantity
5. Name of the equipment (SS/granite)
6. Duration of grinding
7. Repeat the grinding if required (Number of repetition)
(d) Packing details:-
1. Name of Rasaushadhi
2. Type of Dosage Form (eg. Powder, pill, tablet etc)
3. Weight of Rasaushadhi in each unit
Drugs and Cosmetics Rules 1945
569
B. Product Quality Control:-
The specifications for finished Rasaushadhi are primarily intended to define the
quality rather than to establish full characterization, and should focus on those
characteristics found to be useful in ensuring the quality. Consistent quality for
Rasaushadhi can only be assured if the starting material-metals and minerals are used of
pharmacopoeial standards. In some cases more detailed information may be needed on
aspects of their process. The manufacturer will ensure in-house standards for the uniform
quality of product.
Quality testing will be carried out as per official Pharmaceutica or Schedule books
for texts namely, color, taste, varitaratwa, Rekhapurnatwa, Laghutva, Nirdhumatwa,
Dntagre Kachakacha, Niruttha, Apunarbhava and Nischandratwa.
The Particle size of the product should be tested by adopting microscope fitted with
micrometer or particle size analyzer or any appropriate other techniques. Required physio-
chemical characterization of the product should be undertaken by appropriate analytical
equipment. The Standard Manufacturing Process of the product should be evolved/follow
up. The disintegration time of pills-vati and tablets should also be recorded.
4. Product recalls:- Literature inserted inside the product package should indicate the
name, address of the manufacturing unit
1
[and] telephone number for reporting of any
adverse drug reaction by physicians or patients. On receipt of such Adverse Drug Reaction
report, it will be the responsibility of the manufacturer to ensure the recall of the product
from the market.
Standard Operating Procedures (SOP) should be included for storage of recalled
Rasaushadhies in a secure segregated area, complying with the requirements specified for
storage till their final disposal.
5. Medical examination of the Employees:- Employees engaged in manufacturing should
be medially examined periodically at least once a year for any adverse effect of the drug
during manufacturing process for which necessary investigations
1
[Shall be] carried out
for ensuring that there is no effect of material on the vital organs of the employees. Annual
examination reports of the employees shall be made available to statutory inspectors
during Good Manufacturing Practices inspections.
6. Self-Inspection:- The release of Rasaushadhis should be under the control of a person
who has been trained in the specific features of the processing and quality assurance of
Rasaushadhis. Personnel dealing with the production and quality assurance of
Rasaushadhis manufacturing section should have an adequate training in the specific
subject of Rasaushadhis manufacturing. He will be at least a degree holder in Ayurvedic,
Siddha / Unani medicines or B.Pharma degree holder in Ayurvedic / Siddha / Unani
medicines.
1. Subs. by G.S.R. 338(E) dated 15-04-2010.
Drugs and Cosmetics Rules 1945
570
7. Dosage form of Rasaushadhis:- The Rasaushadhis may be made into an acceptable
dosage forms such as churna, vati, guti, tablet or capsules etc. after adding suitable
permissible fillers or binding agents as permissible under the Ayurvedic Pharmacopoeia
of India or Indian pharmacopoeia as updated from time to time. In such cases the label
must indicate the quantity of Ayurveda, Siddha and Unani medicines in one Tablet or Pill
or Capsule in addition to the filler. The crystalline product may be grinded before packing
in the individual dispensing size. All the Rasaushadhis or Rasamaruthukal or Kushtajat
shall be packed in a dosage form which is ready for use for the consumer. Grinding and
weighing of individual dose of potentially poisonous products will not be permissible in
patient consumer pack. This arrangement may reduce the Adverse Drug Reaction of
Rasaushadhi which takes place due to dose variation. However, for hospital bulk pack, it
will not be applicable and label will clearly indicate the ―Hospital pack.‖
8. Area Specifications/ requirement for an applicant companies only to have GMP of
Rasaushadhis or Rasamarunthukal and Kushtajat (Herbomineral/metallic
compounds) of Ayurveda, Siddha and Unani medicines:-
1. Subs. by G.S.R. 338(E) dated 15-04-2010
Drugs and Cosmetics Rules 1945
571
Sr. No.
Category of Medicine /
Manufacturing area
Minimum
Manufacturing
space required
(1500 sq. ft.)
Machinery equipme recommended
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Pisti / grinding area for
Bhasma, Pishti, Kushtajat
Powdering area for raw drugs
of plant origin giving in
Rasaushadhis (Herbo-metalic
formulations)
Pills / Vati/ Gutika Matrica
and tablets / Habb making area
Kupi pakva / Ksara / Parpati /
Lavana Bhasma Satva /
Sindura Kapu / Uppa / Param /
Qushta / Jawhar
Receiving and storing raw
material
Quality Control Section
Quarantine / observation
Finished goods store
Rejected goods store
Bhatti-putta area
Area for water and washing
etc.
Office
100 sq. ft.
200 sq. ft.
100 sq. ft.
150 sq. ft.
200 sq. ft.
150 sq. ft.
50 sq. ft.
150 sq. ft.
50 sq. ft.
200 sq. ft.
50 sq. ft.
100 sq. ft.
Kharal/mechanized/motorized Kharal,
End runner / Ball-Mill Sieves / Sifter.
Grinder / Distintegrator /Pulverisor / Powder
mixer / Sieves / Sifter
Ball Mills, Mass Mixer/Powder mixer,
Granulator, drier, tablet compressing machine,
pill/ vati cutting machine, stainless steel trays /
container for storage and sugar coating,
polishing pan in case of sugar coated tablets,
mechanized chatoo, (for mixing
of guggulu) where required.
Bhatti, Karahi / stainless steel vessels
/patila flask, Multani Matti / Plaster
of Paris, Copper Rod, Earthen container, Gaj
Put Bhatti, Muffle furnace (electrically
operated) End / Edge Runner, Exhaust Fan,
Wooden, S.S. Spatula.
TOTAL
1500 sq. ft
Note : The above requirements of machinery, equipments, space are made subject to
the modification at the discretion of the Licensing Authority; if he is of the opinion that having
regard to the nature and extent of the manufacturing operations it is necessary to relax or alter
them in the circumstances in a particular case,
1
[he may do so after recording reasons in
writing]].
1. Added by G.S.R.463(E), dated 08-07-2005
Drugs and Cosmetics Rules 1945
572
1
[Schedule TA
(See rule 157 A)
FORM FOR RECORD OF UTILIZATION OF RAW MATERIAL BY AYURVEDA OR
SIDDHA OR UNANI LICENSED MANUFACTURING UNITS DURING THE
FINANCIAL YEAR
Identification Particulars:
Manufacturing License No ...................................
Issued by..................................................................
Name: ............................................
Address: ........................................
State: ............................................. Pin Code: ...................................................................
Telephone:...................................... Fax: .........................................................................
Email: ..................................
1. Quantity of Medicinal Plants/Extracts/Essential Oils/Metals/Animal By-Products
Minerals Used During 1st April, to 31st March of the preceeding year (For Productions at
the identified facility)
(a) Herbs Used
Common Name
as in AFI/API*
Plant’s
Botanical
Name
Quantity
Used/per
annum (in
Kgs.)
Sources of Supply
Part Used
Traders/
Manufacturers
Forest
Collectors
Cultivators
Imported
Total
Whole
plans
Root
Leaf
Others
*Ayurvedic Formulary of India/Ayurvedic Pharmacopoeia of India
(b) Extracts Used
Name of Extracts
Quantity Used/per
annum (in Kgs.)
Sources of Supply
Common Name as in
AFI/API*
Botanical Name
In-House
Export Suppliers
Imported
Total
* Ayurvedic Formulary of India/Ayurvedic Pharmacopoeia of India
(c) Metals/Minerals Used
Name of Mineral
Quantity Used/per
annum (in Kgs.)
Sources of Supply
Common Name
Chemical Name
Manufacturers Traders
(Domestic)
Importers
Total
1. Ins. By G.S.R. 512 (E), dated 09-07-2008
Drugs and Cosmetics Rules 1945
573
(d) Animal By-Products Used
Name of By-Product
Quantity Used/per
annum (in Kgs.)
Sources of Supply
Common Name
Biological/Chemical
Name (if any)
Manufacturers Traders
(Domestic)
Importers
Total
2. Shortage of raw material(s)/inputs during the preceeding year.
If yes, please indicate name(s) of such raw material(s) by level of importance
starting from most important to least important, reason for shortage [availability, quality
or any other (please specify)]
Name of Raw Materials
Appro. Qty of shortage (in
Kgs.)
Reason
Name of the drug and part
used as mentioned in official
formulary / Pharmacopoeial/
Schedue I books
Biological/ Chemical Name (if
any)
1
[SCHEDULE U
(See rules 74, 74A, 74B, 78 and
78A)
I. PARTICULARS TO BE SHOWN IN MANUFACTURING
RECORDS
A. SUBSTANCES, OTHER THAN PARENTERAL PREPARATIONS IN GENERAL.
1. Serial number
2. Name of the product
3. Reference of Master Formula Records.
4. Lot/Batch Size.
5. Lot/Batch Number.
6. Date of commencement of manufacture and date of completion of manufacture and assigned
date of expiry.
7. Name of all ingredients, specifications quantities required for the lot/Batch size and quantities
actually used. All weighings and measurements shall be carried out by a responsible person and
initialled by him and shall be counter-checked and signed by the competent technical staff under whose
personal supervision the ingredients are used for manufacture.
8. Control Numbers of raw materials used in the formulation.
9. Date, time and duration of mixing.
10. Details of environmental controls like room temperature, relative humidity.
11.Date of granulation, wherever applicable.
12. Theoretical weight and actual weight of granules/powder blend.
13. Records of in-processes controls (Periodically whenever necessary):
(a) Uniformity of mixing.
(b) Moisture content of granules/powder in case of Tablet/Capsules.
(c) pH of solution in case of liquid.
(d) Weight
variation.
(e)
Disintegration time.
1. Subs. by G.S.R. 735(E) dated 24-06-1988
N
Y
Drugs and Cosmetics Rules 1945
574
(f) Hardness
(g) Friability test
(h) Leak test in case of strip packing.
(i) Filled volume of liquids.
(j) Quantity of tablets/capsules in the final container.
(k) Content of ointment in the filled containers.
14. Date of compression in case of Tablets/date of filling in case of capsules.
15. Date of sealing/coating /polishing in case of capsules/tablets wherever applicable.
16. Reference to analytical Report number stating the result of test and analysis.
17. Separate records of the disposal of the rejected batches and of batches withdrawn from the
market.
18.The theoretical yield and actual productions yield and packing particulars indicating the size and
quantity of finished packings.
19. Specimen of label/strip, carton with batch coding information like Batch Number, date of
manufacture, date of expiry, retail price as applicable stamped thereon and inserts used in the finished
packings.
20. Signature with date of competent technical staff responsible for the manufacture.
21. Counter-signature of the head of the testing units or other approved person-in-charge of testing
for having verified the batch records and for having released and batch for sale and distribution, the
quantity released and date of release.
22. Date of release of finished packings and quantity released for sale and distribution.
23. Quantity transferred to warehouse.
24. For Hypodermic tablets and ophthalmic preparations, which are required to be manufactured
under aseptic conditions, records shall be maintained indicating the precautions taken during the process
of manufacture to ensure that aseptic conditions are maintained.
B. PARENTERAL PREPARATIONS.
1. Serial number.
2. Name of the product.
3. Reference of the master formula record.
4. Batch /Lot size.
5. Batch No. and/or Lot No.
6. Date of commencement of manufacture and date of completion.
7. Names of all ingredients, specifications and quantity required for the Lot/Batch size
and quantity actually used. All weighings and measurements shall be carried out by a
responsible person and initialled by him and shall be countersigned by the technical staff under
whose personal supervision the stock are issued and by another competent technical staff under
whose supervision the ingredients are used for manufacture.
8. Control numbers of raw materials used in the formulation.
9. Date, time and duration of mixing.
10. Details of environmental controls like temperature, humidity, microbial count in the
sterile working areas.
11. pH of the solution, wherever applicable.
12. Date and method of filtration.
13. Sterility test, reference on bulk batch wherever applicable.
14. Record of check on volume filled.
15. Date of filling.
16. Records of tests employed: -
Drugs and Cosmetics Rules 1945
575
(a) To ensure that sealed ampoules are leak proof
(b) To check the presence of foreign particles.
(c) Pyrogen test, wherever applicable
(d) Toxicity test, wherever applicable.
17. Records of checking of instruments and apparatus of sterilization (indicators).
18. Records of cleaning and sterilization of containers and closures, if necessary.
19. Records of sterilization in case of parenteral preparations which are heat sterilized
including particulars of time, temperature and pressure employed. Such records should be
marked to relate to the batch sterilized.
20. Number and size of containers filled and quantity rejected.
21. The theoretical yield and actual yield and the percentage yield thereof.
22. Reference to Analytical report numbers stating whether of standard quality or otherwise.
23. Specimen of labels, cartons, etc. with Batch coding information like batch number, date
of manufacture, date of expiry, as applicable, stamped thereon, and inserts used in the finished
packings.
24. Signature with date of the component technical staff responsible for manufacture.
25. Particulars regarding the precautions taken during the manufacture to ensure that aseptic
conditions are maintained.
26. Countersignature of head of the testing unit or person in charge of testing for having
verified the documents and for having released the product for sale and distribution, the
quantity released and date of release.
27. Records for having transferred to warehouse giving packings and quantities.
28. Separate records of the disposal of the rejected batches and of all batches withdrawn
from the market.
29. Records of reprocessing if any and particulars of reprocessing.
II. RECORDS OF RAW
MATERIALS
Records in respect of each raw material shall be maintained indicating the date of receipt,
invoice number, name and address of the manufacturer/supplier, batch number, quantity received, pack
size, date of manufacture, date of expiry, if any, date of analysis and release/rejection by quality
control, analytical report number with special remarks, if any, quantity issued, date of issue and the
particulars of the name and batch numbers of products for the manufacture of which issued and the
proper disposal of the stocks.
III. PARTICULARS TO BE RECORDED IN THE ANALYTICAL RECORDS
A. TABLETS AND
CAPSULES.
1. Analytical report number.
2. Name of the sample.
3. Date of receipt of sample.
4. Batch/Lot number.
5. Protocols of tests applied.
(a) Description.
(b) Identification.
(c) Uniformity of weight.
(d) Uniformity of diameter (if applicable).
(e) Disintegration test (time in minutes).
(f) Any other tests.
(g) Results of Assay.
Drugs and Cosmetics Rules 1945
576
Note: Records regarding various tests applied (including readings and calculations) should be
maintained and necessary reference to these records should be entered in Col. 5 above whenever
necessary.
6. Signature of the Analyst.
7. Opinion and signature of the approved Analyst.
B. PARENTERAL PREPARATIONS.
1. Analytical report number.
2. Name of the sample.
3. Batch number.
4. Date of receipt of samples.
5. Number of containers filled.
6. Number of containers received.
7. Protocols of tests applied.
(a) Clarity.
(b) pH wherever applicable.
(c) Identification.
(d) Volume in container.
(e) Sterility –
(i) Bulk sample wherever applicable
(ii) container sample.
(f) Pyrogen test, wherever applicable.
(g) Toxicity test, wherever applicable.
(h) Any other tests.
(i) Results of Assay.
Note: Records regarding various tests applied (including readings and calculations) should be
maintained and necessary reference to these records should be entered in Col. 7 above, wherever
necessary.
8. Signature of the Analyst.
9. Opinion and signature of the approved Analyst.
PYROGEN TEST:
1. Test Report
Number.
2. Name of the
samp
le.
3. Batch Number.
4. Number of rabbits used.
5. Weight of each rabbit.
6. Normal temperature of each rabbit.
7. Mean initial temperature of each rabbit.
8. Dose and volume of solution injected into each rabbit and time of injection.
9. Temperature of each rabbit noted at suitable intervals.
10. Maximum temperature.
11. Response.
12. Summed response.
13. Signature of the Analyst.
14.Opinion and signature of the approved Analyst.
TOXICITY TEST
1. Test Report Number.
2. Name of the sample.
Drugs and Cosmetics Rules 1945
577
3. Batch Number.
4. Number of mice used and weight of each mouse.
5. Strength and volume of the drugs injected.
6. Date of injection.
7. Results and remarks.
8. Signature of Analyst.
9. Opinion and signature of the approved Analyst.
C. FOR OTHER DRUGS
1. Analytical report number.
2. Name of the sample.
3. Batch/Lot number.
4. Date of receipt of sample.
5. Protocol of tests applied.
(a) Description.
(b) Identification.
(c) Any other tests.
(d) Results of Assay.
Note:Particulars regarding various tests applied (including readings and calculations) shall be maintained
and necessary reference to these records shall be entered in Column 5 above, wherever necessary.
6. Signature of Analyst.
7. Opinion and signature of the approved Analyst.
D. RAW MATERIALS
1. Serial number.
2. Name of the materials.
3. Name of the manufacturer/supplier.
4. Quantity received.
5. Invoice/Challan number and date.
6. Protocols of tests applied.
Note: Particulars regarding various tests applied (including readings and calculations) shall be
maintained and necessary reference to these records shall be entered in Column 6 above, wherever
necessary.
E. CONTAINER, PACKING MATERIALS
ETC.
1. Serial number.
2. Name of the item.
3. Name of the manufacturer/supplier.
4. Quantity received.
5. Invoice/Challan number and date
6. Results of tests applied.
Note: Particulars regarding various tests applied shall be maintained and necessary reference to these
records shall be entered in Column 6 above, wherever necessary
7. Remarks.
8. Signature of the examiner.
Notes: 1. The foregoing provisions represent the minimum requirements to be complied with by
the licensee. The Licensing Authority may, however, direct the nature of records to be maintained by the
licensee for such products as are not covered by the categories described above.
2. The Licensing Authority may permit the licensee to maintain records in such manner as
are considered satisfactory, provided the basic requirements laid down above are complied with.
3. The Licensing Authority may at its discretion direct the licensee to maintain records for such
additional particulars as it may consider necessary in the circumstances of a particular case.]
Drugs and Cosmetics Rules 1945
578
1
[SCHEDULE U(I)
(See rules 142 and
142B)
I. PARTICULARS TO BE SHOWN IN THE MANUFACTURING RECORDS:
1. Serial number.
2. Name of the product.
3. Lot/Batch size.
4. Lot/Batch number.
5. Date of commencement of manufacture and date when manufacture was completed.
6. Names of all ingredients, quantities required for the lot/batch size, quantities actually used.
7. Control reference numbers in respect of raw materials used in formulation.
8. Reference to analytical report numbers.
9. Actual production and packing particulars indicating the size and quantity of
finished packings.
10. Date of release of finished packing for distribution or sale.
11. Signature of the expert staff responsible for the manufacture.
II. RECORDS OF RAW MATERIALS:
Records in respect of each raw material shall be maintained indicating the quantity received,
control reference number, the quantity issued from time to time, the names and batch numbers of the
products for the manufacture of which the said quantity of raw material has been issued and the
particulars relating to the proper disposal of the stocks.
Notes: (1) The Licensing Authority may permit the licensee to maintain records in such
manner as is considered satisfactory, provided the basic requirements laid down above are complied
with.
(2) The Licensing Authority may direct the licensee to maintain records for such
additional particulars, as it may consider necessary in the circumstances of a particular case.]
2
[SCHEDULE
V
( See rule
124B)
STANDARDS FOR PATENT OR PROPRIETARY MEDICINES
3
[***]
4
[2. Standards for patent or proprietary medicines, containing vitamins: Patent or proprietary
medicines containing vitamins for prophylactic, therapeutic or paediatric use shall contain the
vitamins in quantities not less than and not more than those specified below in single or in two divided
daily doses, namely: - [see table below].
3
[***]
5
[4. General Standards for Different Categories of Patent or Proprietary Medicines. - In the
case of pharmaceutical products containing several active ingredients, the selection shall be such that
the ingredients do not interact with one another and do not affect the safety and therapeutic efficacy of
the product. The combination shall not also lead to analytical difficulties for the purpose of assaying
the content of such ingredient separately. The substances added as additives shall be innocuous, shall
not affect the safety or therapeutic efficacy of the active ingredients, and shall not affect the assays and
identity tests in the amount present.]
1. Added by G.S.R. 1594, dt. 28-10-1976.
2. Added by G.S.R. 665, dt. 06-05-1977.
3. Omitted. G.S.R. 56(E) ,dt. 22.1.1992.
4. Added by G.S.R. No. 930 ,dt. 13-7-1978.
5. Ins. by. G.S.R. 792(E) ,dt. 17.9.1987.
Drugs and Cosmetics Rules 1945
579
Subject to the provisions of these rules, patent or proprietary medicines shall comply with the
following standards, namely: -
1. Patent or proprietary medicines shall comply with the general requirements of the dosage
form under which it falls as given in the Indian Pharmacopoeia. If the dosage form is not included in
the Indian Pharmacopoeia, but is included in any other pharmacopoeia, prescribed for the purpose of
the Second Schedule to the Act, it shall comply with the general requirements of the dosage of
such pharmacopoeia. Without prejudice to the generality of the foregoing requirements, general
requirements shall include compliance with colour consistency, clarity, stability, freedom from
contamination with foreign matter or fungal growth, defects like chipping and capping of tablets,
cracking of the coating, mottled appearance and other characteristic defects that can be perceived by
visual inspection.
2. Without prejudice to the generality of the following paras, dosage forms of patent or
proprietary medicines shall comply with the following requirements, namely:-
(a) Tablets: Medicines shall comply with requirements for tablets as laid down in the Indian
Pharmacopoeia. The nature of coating shall be indicated on the label. Permitted colours
may, however, be added and declared on the label. Nature of tablets, such as uncoated, sugar
coated or film coated, shall be declared on the label.
1
[***]
(
b) Capsules : Medicines shall comply with the requirements for capsules laid down in the
Indian Pharmacopoeia. However, the capsules shall be free from distortion or shape, dis-
colouration and other physical defects like leakage of powder from joints, pinholes or cracks in
the capsules;
(c) Liquid oral dosage forms: Emulsions and suspensions shall disperse uniformly on shaking.
Homogeneous solutions shall contain no sediments. The volume of the product (net content) in
the container shall be not less than the labelled volume. The limit for ethanol content of
pharmaceutical products shall be not less than 90 per cent and not more than 110 per cent of the
labelled contents.
(d) Injections: Medicines shall comply with the requirements for injections as laid down in the
Indian Pharmacopoeia.
(e) Ointments: Medicines shall comply with the requirements for injections as laid down in the
Indian Pharmacopoeia.
3. The content of active ingredients, other than vitamins, enzymes and antibiotics, in patent or
proprietary medicines shall be not less than 90 per cent and not more than 110 per cent of the labelled
content; however, for enzymes and vitamins, only for lower limit of 90 per cent shall apply. In all dry
formulations containing antibiotics, the limit shall be 90 to 130 per cent of the labelled contents and in
case of liquid antibiotic formulations, the limit shall be 90 to 140 per cent of labelled contents.
Fiducial limits for error for microbiological assay of antibiotics may be estimated depending
upon the design of assay procedure. Methods, used for assaying active ingredients shall employ the
same basic principles and shall use same organisms as given in the latest edition of the Indian
Pharmacopoeia or shall follow any other methods as approved by the authority competent to grant
licence to manufacture.
1. Omitted. by G.S.R. 59(E) ,dt. 22.1.1992.
Drugs and Cosmetics Rules 1945
580
4. All patent or proprietary medicines containing aspirin shall be subjected to ―Free Salicylic
Acid Test‖ and the limit of such acid shall be 0.75 per cent. Except in case of soluble type aspirin in
which case the limit of such acid shall be 3 per cent.
5. Patent or proprietary medicine to be tested under the provisions of rule 121-A for pyrogen
shall be tested by injecting into rabbits not less than the human dose of the medicine based on body
weight of a 60 kg. human being. Methodology and limits shall be based on the method recorded in
the Indian Pharmacopoeia. Dose selected shall be indicated in the protocol but the dose shall be not
greater than 5 times the human dose based on body weight of 60 kg for man.
6. In injectable patent or proprietary medicines, the test for freedom from toxicity, shall be
performed as described in the Indian Pharmacopoeia. Dose selected shall be indicated in the protocol
but the dose shall not be less than five times the human dose based on body weight of 60 kg. human
being.]
Drugs and Cosmetics Rules 1945
581
Drugs and Cosmetics Rules, 1945
Vitamin
Unit
Patent or proprietary
Patent or proprietary
Patent or proprietary medicines containing
Medicines containing
medicines containing
vitamins for paediatric use.
Vitamins for prophylactic
vitamins for therapeutic
Use.
(in single dose or in two divided doses) per daily dose
For adults
For infants less than For children above one
one year. year up to adults
1
2
3
4
5 6
Vitamin A.
I.U
Not less than 1600 and not
more than 2,500
Not less than 5000 and not more
than 10,000
Not less than 750 and not Not less than 1500 and more
more than 3,000 than 5,000
Vitamin D.
I.U
Not less than 100 and not more
than 200.
Not less than 400 and not more
than 1,000
Not less than 200 and not Not less than 100 and more than
more than 400 400
Vitamin B1
mg.
Not less than 1 and not more
than 2
Not less than 4.5 and not more
than 10
Not less than 0.5 and more Not less than 1 and not more
than 1 than 4.5
Vitamin B2
mg
Not less than 1 and not more
than 3
Not less than 5 and not more
than 10
Not less than 0.5 and not Not less than 1 and not more
more than 1.5 than 5.
Vitamin B6
mg
Not less than 0.5 and not more
than 1.5
Not less than 1.5 and not more
than 3
Not less than 0.5 and not Not less than 1 and not more
more than 1.5 than 3
Niacinamide
mg
Not less than 15 and not more
than 26
Not less than 45 and not more
than 100
Not less than 5 and not more Not less than 10 and not more
than 15 than 40.
d-Pantothenic
mg
Not less than 1 and not more
Not less than 5 and not more
Not less than 1 and not more
Not less than 2.5 and not more
acid or its salts
than 5
than 50
than 3
than 10
and panthenol.
Folic acid
mg.
Not less than 50 and not more
Not less than 1000 and not more
Not less than 25 and not
Not less than 100 and not more
than 300
than 1500
more than 100
than 500
Drugs and Cosmetics Rules 1945
582
Drugs and Cosmetics Rules, 1945
1 2 3 4 5 6
Vitamin B12
mcg
Not less than 0.5 and not more
Not less than 5 and not more
Not less than 1 and not more
Not less than 1 and not more
than 1
than 15
than 3
than 5
Vitamin C mg Not less than 25 and not more
than 50
Not less than 75 and not more
than 150
Not less than 20 and not
more than 40
Not less than 30 and not more
than 80
Vitamin E I.U Not less than 5 and not more
than 10
Not less than 15 and not more
than 25
Not less than 2.5 and not
more than 10
Not less than 5 and not more
than 20.
Notes: (1) Patent or proprietary medicines containing vitamins intended for prophylactic, therapeutic or paediatric use shall bear on the label the words ―For
Prophylactic Use‖ ― For Therapeutic Use,‖ or ―For Paediatric Use‖ as the case may be. In the case of paediatric preparations the age of the infant or
the child for whose use it is intended, shall be given in addition to the particulars required to be given under these rules.
(2)The above standards shall not apply to any preparation containing a single vitamin only and also to any preparation containing vitamins intended
for parenteral use.
Provided, however, that in the case of patent or proprietary medicines containing vitamins which are intended for the treatment of certain specific
conditions or diseases, the Licensing Authority specified in clause (b) of rule 21, may permit the addition of vitamins therein in relaxation of the limits
specified above, if satisfactory evidence is produced in justification of such relaxation.
1. Subs. by G.S.R. dated 22-12-2009
Drugs and Cosmetics Rules 1945
583
1
[***]
2
[SCHEDULE X
[See Rules 23, 61, 75, 97 and
105A]
Amobarbital
Glutethimide
Pentobarbital
3
[Ketamine hydrochloride]
Amphetamine
Meprobamate
Phencyclidine
Barbital
Methamphetamine
Phenometrazine
Cyclobarbital
4
[***]
5
[***]
Dexamphetamine
Methylphenidate
Secobarbital
Ethclorvynol
Methylphenobarbital
Note: 1. Any stereoisometric form of the substance specified in this Schedule, any salt of the
substance and preparation containing such substances are also covered by this Schedule.
2. Preparations containing the above substances are also covered by this Schedule.
Provided, however, preparations containing Meprobamate
5
[***] in combination
with
other drugs may be exempted by the Licensing Authority specified in clause (b) of rule
21, from
the provisions of this Schedule, if satisfactory evidence is adduced that these
preparations are not liable to be misused.]
1.Omitted by. G.S.R. 94(E) ,dt. 8.5. 2000
2 Ins. by G.S.R. 462(E) ,dt. 22.6.1982
3. Ins. by G.S.R. 724(E) ,dt. 07.11.2013
4. Omitted by G.S.R. 647(E) ,dt. 28.10.1998.
5.Omitted by. G.S.R. 673(E) ,dt. 27.10.1993.
Drugs and Cosmetics Rules 1945
584
1
[SCHEDULE
Y
(See rules 122A, 122B, 122D, 122DA, 122DAA and
122E)
REQUIREMENTS AND GUIDELINES FOR PERMISSION TO IMPORT AND /
OR
MANUFACTURE OF NEW DRUGS FOR SALE OR TO UNDERTAKE
CLINICAL
TRIALS
1. Application for permission.- (1) Application for permission to import or manufacture
new drugs for sale or to undertake clinical trials shall be made in Form 44 accompanied with
following data in accordance with the appendices, namely:-
(i) chemical and pharmaceutical information as prescribed in item 2 of Appendix I;
(ii) animal pharmacology data as prescribed in item 3 of Appendix I and Appendix IV;
(a) specific pharmacological actions as prescribed in item 3.2 of Appendix I, and
demonstrating, therapeutic potential for humans shall be described according to
the animal models and species used. Wherever possible, dose-response relationships
and ED
50s
shall be submitted. Special studies conducted to elucidate mode of
action shall also be described (Appendix IV);
(b) general pharmacological actions as prescribed in item 3.3 of Appendix I and item
1.2 of Appendix IV;
(c) pharmacokinetic data related to the absorption, distribution, metabolism and
excretion of the test substance as prescribed in item 3.5 of Appendix I. Wherever
possible, the drug effects shall be corelated to the plasma drug concentrations;
(iii) animal toxicology data as prescribed in item 4 of Appendix I and Appendix III;
(iv) human Clinical Pharmacology Data as prescribed in items 5, 6 and 7 of Appendix I
and as stated below:-
(a) for new drug substances discovered in India, clinical trials are required to be carried
out in India right from Phase I and data should be submitted as required under items
1, 2, 3, 4, 5 (data, if any, from other countries), and 9 of Appendix I;
(b) for new drug substances discovered in countries other than India, Phase I data as
required under items 1, 2, 3, 4, 5 (data from other countries) and 9 of Appendix I
should be submitted along with the application. After submission of Phase I
data generated outside India to the Licensing Authority, permission may be granted
to repeat Phase I trials and/or to conduct Phase II trials and subsequently Phase III
trials concurrently with other global trials for that drug. Phase III trials are required
to be conducted in India before permission to market the drug in India is granted;
(c) the data required will depend upon the purpose of the new drug application . The
number of study subjects and sites to be involved in the conduct of clinical trial
will depend upon the nature and objective of the study. Permission to carry out these
trials shall generally be given in stages, considering the data emerging from earlier
Phase(s);
(d) application for permission to initiate specific phase of clinical trial should also
accompany Investigator‘s brochure, proposed protocol (Appendix X), case record
form, study subject‘s informed consent document(s) (Appendix V), investigator‘s
undertaking (Appendix VII) and ethics committee clearance, if available (Appendix
VIII);
1. Subs. G.S.R. 32(E), dt. 20.1.2005.
Drugs and Cosmetics Rules 1945
585
(e) reports of clinical studies submitted under items 5-8 of Appendix I should be in
consonance with the format prescribed in Appendix II of this Schedule. The study
report shall be certified by the Principal Investigator or, if no Principal Investigator is
designated, then by each of the Investigators participating in the study. The certification
should acknowledge the contents of the report, the accurate presentation of the study
as undertaken, and express agreement with the conclusions. Each page should be
numbered;
(v) regulatory status in other countries as prescribed in item 9.2 of Appendix I, including
Information in respect of restrictions imposed, if any, on the use of the drug in other countries,
e.g. dosage limits, exclusion of certain age groups, warning about adverse drug reactions,.etc.
(item 9.2 of Appendix I). Likewise, if the drug has been withdrawn in any country by the
manufacturer or by regulatory authorities, such information should also be furnished along with
the reasons and their relevance, if any, to India. This information must continue to be submitted
by the sponsor to the Licensing Authority during the course of marketing of the drug in India;
(vi) the full prescribing information should be submitted as part of the new drug
application for marketing as prescribed in item 10 of Appendix I. The prescribing information
(package insert) shall comprise the following sections: generic name; composition; dosage
form/s, indications; dose and method of administration; use in special populations (such as
pregnant women, lactating women, paediatric patients, geriatric patients etc.); contra-indications;
warnings; precautions; drug interactions; undesirable effects; overdose; pharmacodynamic and
pharmacokinetic properties; incompatibilities; shelf-life; packaging information; storage and
handling instructions. All package inserts, promotional literature and patient education material
subsequently produced are required to be consistent with the contents of the approved full
prescribing information. The drafts of label and carton texts should comply with provisions of
rules 96 and 97. After submission and approval by the Licensing Authority, no changes in
the package insert shall be effected without such changes being approved by the Licensing
Authority; and
(vii) complete testing protocol/s for quality control testing together with a complete
impurity profile and release specifications for the product as prescribed in item 11 of Appendix I
should be submitted as part of new drug application for marketing. Samples of the pure drug
substance and finished product are to be submitted when desired by the regulatory authority.
(2) If the study drug is intended to be imported for the purposes of examination, test or
analysis, the application for import of small quantities of drugs for such purpose should also be
made in Form 12.
(3) For drugs indicated in life threatening / serious diseases or diseases of special relevance
to the Indian health scenario, the toxicological and clinical data requirements may be
abbreviated, deferred or omitted, as deemed appropriate by the Licensing Authority.
2. Clinical Trial:
(1) Approval for clinical trial
(i) Clinical trial on a new drug shall be initiated only after the permission has been granted
by the Licensing Authority under rule 21 (b), and the approval obtained from the respective
ethics committee (s). The Licensing Authority as defined shall be informed of the approval of the
respective institutional ethics committee(s) as prescribed in Appendix VIII, and the trial initiated
at each respective site only after obtaining such an approval for that site. The trial site(s)
may accept the approval granted to the protocol by the ethics committee of another trial
site or the approval granted by an independent ethics committee (constituted as per Appendix
VIII), provided
that the approving ethics committee(s) is/are willing to accept their responsibilities for the study
at such trial site(s) and the trial site(s) is/are willing to accept such an arrangement and that the
protocol version is same at all trial sites.
(ii) All trial Investigator(s) should possess appropriate qualifications, training and
experience and should have access to such investigational and treatment facilities as are relevant
Drugs and Cosmetics Rules 1945
586
to the proposed trial protocol. A qualified physician (or dentist, when appropriate) who is an
investigator or a sub-investigator for the trial, should be responsible for all trial-related
medical (or dental) decisions. Laboratories used for generating data for clinical trials should
be compliant with Good Laboratory Practices. If services of a laboratory or a facilities outside
the country are to be availed, its/their name(s), address(s) and specific services to be used should
be stated in the protocol to avail Licensing Authority‘s permission to send clinical trial related
samples to such laboratory(ies) and/or facility(ies). In all cases, information about
laboratory(ies) / facilities to be used for the trial, if other than those at the investigation site(s),
should be furnished to the Licensing Authority prior to initiation of trial at such site(s).
(iii) Protocol amendments if become necessary before initiation or during the course
of a clinical trial, all such amendments should be notified to the Licensing Authority in writing
along with the approval by the ethics committee which has granted the approval for the study.
No deviations from or changes to the protocol should be implemented without prior written
approval of the ethics committee and the Licensing Authority except when it is necessary to
eliminate immediate hazards to the trial Subject(s) or when change(s) involve(s) only
logistic or administrative aspects of the trial. All such exceptions must be immediately notified
to the ethics committee as well as to the Licensing Authority. Administrative and/or logistic
changes in the protocol should be notified to the Licensing Authority within 30 days.
(2) Responsibilities of Sponsor:
(i) The clinical trial Sponsor is responsible for implementing and maintaining
quality assurance systems to ensure that the clinical trial is conducted and data generated,
documented and reported in compliance with the protocol and Good Clinical Practice (GCP)
Guidelines issued by the Central Drugs Standard Control Organization, Directorate
General of Health Services, Government of India as well as with all applicable statutory
provisions. Standard operating procedures should be documented to ensure compliance with
GCP and applicable regulations.
(ii) Sponsors are required to submit a status report on the clinical trial to the Licensing
Authority at the prescribed periodicity.
(iii) In case of studies prematurely discontinued for any reason including lack of
commercial interest in pursuing the new drug application, a summary report should be submitted
within 3 months. The summary report should provide a brief description of the study, the number
of patients exposed to the drug, dose and duration of exposure, details of adverse drug
reactions (Appendix XI), if any, and the reason for discontinuation of the study or non-
pursuit of the new drug application;
1
[(iv) Any report of the serious adverse event, after due analysis shall be forwarded by the
sponsor to the Licensing Authority as referred to in clause (b) of rule 21, the Chairman of the
Ethics Committee and the head of the institution where the trial has been conducted, within
fourteen days of the occurrence of the serious adverse event.]
2
[(v) in case of injury or death occurring to the clinical trial subject, the Sponsor (whether
a pharmaceutical company or an Institution) or his representative, whosoever, had obtained
permission from the Licensing Authority for conduct of the clinical trial, shall make payment for
medical management of the subject and also provide financial compensation for the clinical trial
related injury or death in the manner as prescribed in Appendix XII;
2
[(vi) the Sponsor (whether a pharmaceutical company or an Institution) or his
representative, whosoever had obtained permission from the Licensing Authority for conduct of
the clinical trial, shall submit details of compensation provided or paid for clinical trial related
injury or death, to the Licensing Authority within thirty days of the receipt of the order of the
Licensing Authority.]
1. Subs. by G.S.R. 889(E) dated 12-12-2014
2. Ins. By G.S.R. 53(E) dated 30-1-2013
Drugs and Cosmetics Rules 1945
587
1
[(3)(i)] Responsibilities of the Investigator(s):
The Investigator(s) shall be responsible for the conduct of the trial according to the
protocol and the GCP Guidelines and also for compliance as per the undertaking given in
Appendix VII. Standard operating procedures are required to be documented by the
investigators for the tasks performed by them. During and following a subject‘s participation in
a trial, the investigator should ensure that adequate medical care is provided to the
participant for any adverse events. Investigator(s) shall report all serious and unexpected adverse
events to the
2
[Licensing Authority defined under clause (b) of rule 21, the Sponsor or his
repeesentative, whosoever had obtained permission from the Licensing Authority for conduct of
the clinical trial, and the Ethics Committee that accorded approval to the study protocol, within
twenty four hours of their occurance.
3
[In case, the Investigator fails to report any serious adverse
event within the stipulated period, he shall have to furnish the reason for the delay to the
satisfaction of the Licensing Authority along with the report of the serious adverse event. The
report of the serious adverse event, after due analysis, shall be forwarded by the Investigator to
the Licensing Authority as referred to in clause (b) of rule 21, the Chairman of the Ethics
Committee and the Head of the institution where the trial has been conducted within fourteen
days of the occurrence of the serious adverse event.]].
4
[(ii)The Investigator shall provide information to the clinical trial subject through informed
consent process as provided in Appendix V about the essential elements of the clinical trial and
the subject‘s right to claim compensation in case of trial related injury or death. He shall also
inform the subject or his/her nominees(s) of their rights to contact the Sponsor or his
representative whosoever had obtained permission from the Licensing Authority for conduct of
the clinical trial for the purpose of making claims in the case of trial related injury or death.]
(4) Informed Consent:
(i) In all trials, a freely given, informed, written consent is required to be obtained
from each study subject. The Investigator must provide information about the study verbally
as well as using a patient information sheet, in a language that is non-technical and
understandable by the study subject. The Subject‘s consent must be obtained in writing using
an ‗Informed Consent Form‘. Both the patient information sheet as well as the Informed
Consent Form should have been approved by the ethics committee and furnished to the Licensing
Authority. Any changes in the informed consent documents should be approved by the ethics
committee and submitted to the Licensing Authority before such changes are implemented.
(ii) Where a subject is not able to give informed consent (e.g. an unconscious person or a
minor or those suffering from severe mental illness or disability), the same may be obtained
from a legally acceptable representative (a legally acceptable representative is a person who
is able to give consent for or authorize an intervention in the patient as provided by the law(s) of
India). If the Subject or his/her legally acceptable representative is unable to read/write – an
impartial witness should be present during the entire informed consent process who must append
his/her signatures to the consent form.
(iii) A checklist of essential elements to be included in the study subject‘s informed
consent document as well as a format for the Informed Consent Form for study Subjects is given
in Appendix V.
1. Sub-para (3) renumbered as sub-para, (3)(i) thereof by G.S.R 53(E), dated 30-01-2013.
2. Subs. by G.S.R. 53(E), dated 30-01-2013.
3. Subs. by G.S.R. 889(E), dated 12-12-2014.
4. Ins. by G.S.R. 53(E), dated 30-01-2013.
Drugs and Cosmetics Rules 1945
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(5) Responsibilities of the Ethics Committee:
(i) It is the responsibility of the ethics committee that reviews and accords its approval to
a trial protocol to safeguard the rights, safety and well being of all trial subjects. The ethics
committee should exercise particular care to protect the rights, safety and well being of all
vulnerable subjects participating in the study, e.g., members of a group with hierarchical
structure (e.g. prisoners, armed forces personnel, staff and students of medical, nursing and
pharmacy academic institutions), patients with incurable diseases, umemployed or impoverished
persons, patients in emergency situation, ethnic minority groups, homeless persons, nomads,
refugees, minors or others incapable of personally giving consent. Ethics committee(s) should
get document ‗standard operating procedures‘ and should maintain a record of its proceedings.
(ii) Ethics Committee(s) should make, at appropriate intervals, an ongoing review of the
trials for which they review the protocol(s). Such a review may be based on the periodic
study progress reports furnished by the investigators and/or monitoring and internal audit reports
furnished by the Sponsor and/or by visiting the study sites.
(iii) In case an ethics committee revokes its approval accorded to a trial protocol, it must
record the reasons for doing so and at once communicate such a decision to the Investigator as
well as to the Licensing Authority.
1
[(iv) In case of serious adverse event occurring to the clinical trial subject, the Ethics
Committee shall forward its report on the serious adverse event, after due analysis, along with its
opinion on the financial compensation, if any, to be paid by the Sponsor or his representative,
whosoever had obtained permission from the Licensing Authority as referred to in clause (b) of
rule 21 for conducting the clinical trial, to the Licensing Authority within thirty days of the
occurrence of the serious adverse event.
2
[5(A). Serious Adverse Events:
(1) A serious adverse event is an untoward medical occurrence during clinical trial that is
associated with death, in patient hospitalization (in case the study was being conducted on out-
patient), prolongation of hospitalization (in case the study was being conducted on in-patient),
persistent or significant disability or incapacity, a congenital anomaly or birth defect or is
otherwise life threatening.
(2) The Investigator shall report all serious
3
[***] adverse events to the Licensing
Authority as defined under clause (b) of Rule 21, the Sponsor or his representative, whosoever
had obtained permission from the Licensing Authority for conduct of the clinical trial and the
Ethics Committee that accorded approval to the study protocol, within twenty four hours of their
occurrence as per Appendix XI and the said Licensing Authority shall determine the cause of
injury or death as per the procedure prescribed under Appendix XII and pass orders as deemed
necessary.
4
[In case, the Investigator fails to report any serious adverse event within the stipulated
period, he shall have to furnish the reason for the delay to the satisfaction of the Licensing
Authority along with the report of the serious adverse event.
1. Subs. by G.S.R. 889(E) dated 12-12-2014.
2. Ins. by G.S.R. 53(E) dated 30-01-2013.
3. The words ―and unexpected‖omitted by G.S.R. 889(E) dated 12-12-2014.
4. Ins. by G.S.R. 889 (E) dated 12-12-2014.
Drugs and Cosmetics Rules 1945
589
(6) Human Pharmacology (Phase I):
(i) The objective of studies in this Phase is the estimation of safety and tolerability with
the initial administration of an investigational new drug into human(s). Studies in this Phase of
development usually have non-therapeutic objectives and may be conducted in healthy volunteers
subjects or certain types of patients. Drugs with significant potential toxicity e.g. cytotoxic drugs
are usually studied in patients. Phase I trials should preferably be carried out by Investigators
trained in clinical pharmacology with access to the necessary facilities to closely observe and
monitor the Subjects.
(ii) Studies conducted in Phase I, usually intended to involve one or a combination of
the following objectives:-
(a) Maximum tolerated dose: To determine the tolerability of the dose range expected
to be needed for later clinical studies and to determine the nature of adverse reactions that
can be expected. These studies include both single and multiple dose administration.
(b) Pharmacokinetics, i.e., characterization of a drug's absorption, distribution,
metabolism and excretion. Although these studies continue throughout the development plan,
they should be performed to support formulation development and determine pharmacokinetic
parameters in different age groups to support dosing recommendations.
(c) Pharmacodynamics: Depending on the drug and the endpoints studied,
pharmacodynamic studies and studies relating to drug blood levels (pharmacokinetic/
pharmacodynamic studies) may be conducted in healthy volunteer Subjects or in patients with
the target disease. If there are appropriate validated indicators of activity and potential efficacy,
pharmacodynamic data obtained from patients may guide the dosage and dose regimen to be
applied in later studies.
(d) Early Measurement of Drug Activity: Preliminary studies of activity or potential
therapeutic benefit may be conducted in Phase I as a secondary objective. Such studies are
generally performed in later Phases but may be appropriate when drug activity is readily
measurable with a short duration of drug exposure in patients at this early stage.
(7) Therapeutic exploratory trials (Phase II):
(i) The primary objective of Phase II trials is to evaluate the effectiveness of a drug for a
particular indication or indications in patients with the condition under study and to determine the
common short-term side-effects and risks associated with the drug. Studies in Phase II should be
conducted in a group of patients who are selected by relatively narrow criteria leading to a
relatively homogeneous population. These studies should be closely monitored. An important
goal for this Phase is to determine the dose(s) and regimen for Phase III trials. Doses used in
Phase II are usually (but not always) less than the highest doses used in Phase I.
(ii) Additional objectives of Phase II studies can include evaluation of potential study
endpoints, therapeutic regimens (including concomitant medications) and target populations (e.g.
mild versus severe disease) for further studies in Phase II or III. These objectives may be served
by exploratory analyses, examining subsets of data and by including multiple endpoints in trials.
(iii) If the application is for conduct of clinical trials as a part of multi-national clinical
development of the drug, the number of sites and the patients as well as the justification for
undertaking such trials in India shall be provided to the Licensing Authority.
Drugs and Cosmetics Rules 1945
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(8) Therapeutic confirmatory trials (Phase III):
(i) Phase III studies have primary objective of demonstration or confirmation of
therapeutic benefit(s). Studies in Phase III are designed to confirm the preliminary evidence
accumulated in Phase II that a drug is safe and effective for use in the intended indication and
recipient population. These studies should be intended to provide an adequate basis for
marketing approval. Studies in Phase III may also further explore the dose-response relationships
(relationships among dose, drug concentration in blood and clinical response), use of the drug in
wider populations, in different stages of disease, or the safety and efficacy of the drug in
combination with other drug(s).
(ii) For drugs intended to be administered for long periods, trials involving extended
exposure to the drug are ordinarily conducted in Phase III, although they may be initiated in
Phase II. These studies carried out in Phase III complete the information needed to support
adequate instructions for use of the drug (prescribing information).
(iii) For new drugs approved outside India, Phase III studies need to be carried out
primarily to generate evidence of efficacy and safety of the drug in Indian patients when used as
recommended in the prescribing information. Prior to conduct of Phase III studies in Indian
subjects, Licensing Authority may require pharmacokinetic studies to be undertaken to verify that
the data generated in Indian population is in conformity with the data already generated abroad.
(iv) If the application is for the conduct of clinical trials as a part of multi-national
clinical development of the drug, the number of sites and patients as well as the justification for
undertaking such trials in India should be provided to the Licensing Authority along with the
application.
(9) Post Marketing Trials (Phase IV):
Post Marketing trials are studies (other than routine surveillance) performed after drug
approval and related to the approved indication(s). These trials go beyond the prior
demonstration of the drug‘s safety, efficacy and dose definition. These trials may not be
considered necessary at the time of new drug approval but may be required by the Licensing
Authority for optimizing the drug's use. They may be of any type but should have valid
scientific objectives. Phase IV trials include additional drug-drug interaction(s), dose-
response or safety studies and trials designed to support use under the approved indication(s), e.g.
mortality/morbidity studies, epidemiological studies etc.
3. Studies in special populations:
Information supporting the use of the drug in children, pregnant women, nursing women,
elderly patients, patients with renal or other organ systems failure, and those on specific
concomitant medication is required to be submitted if relevant to the clinical profile of the
drug and its anticipated usage pattern. Any claim sought to be made for the drug product that is
not based on data submitted under preceding items of this Schedule should be supported by
studies included under this item of the Schedule (Appendix I, item 8.3).
(1) Geriatrics:
Geriatric patients should be included in Phase III clinical trials (and in Phase II trials, at
the Sponsor's option) in meaningful numbers, if-
(a) the disease intended to be treated is characteristically a disease of aging; or
(b) the population to be treated is known to include substantial numbers of geriatric
patients; or
Drugs and Cosmetics Rules 1945
591
(c) when there is specific reason to expect that conditions common in the elderly are
likely to be encountered; or
(d) when the new drug is likely to alter the geriatric patient's response (with regard to
safety or efficacy) compared with that of the non-geriatric patient.
(2) Paediatrics:
(i) The timing of paediatric studies in the new drug development program will depend on
the medicinal product, the type of disease being treated, safety considerations, and the efficacy
and safety of available treatments. For a drug expected to be used in children, evaluations
should be made in the appropriate age group. When clinical development is to include studies in
children, it is usually appropriate to begin with older children before extending the trial to
younger children and then infants.
(ii) If the new drug is for diseases predominantly or exclusively affecting paediatric
patients, clinical trial data should be generated in the paediatric population except for initial
safety and tolerability data, which will usually be obtained in adults unless such initial safety
studies in adults would yield little useful information or expose them to inappropriate risk.
(iii) If the new drug is intended to treat serious or life-threatening diseases,
occurring in both adults and paediatric patients, for which there are currently no or limited
therapeutic options, paediatric population should be included in the clinical trials early, following
assessment of initial safety data and reasonable evidence of potential benefit. In circumstances
where this is not possible, lack of data should be justified in detail.
(iv) If the new drug has a potential for use in paediatric patients – Paediatric studies
should be conducted. These studies may be initiated at various phases of clinical
development or after post marketing survelliance in adults if a safety concern exists. In cases
where there is limited paediatric data at the time of submission of application – more data in
paediatric patients would be expected after marketing authorisation for use in children is granted.
(v) The paediatric studies should include –
(a) clinical trials,
(b) relative bioequivalence comparisons of the paediatric formulation with the
adult formulation performed in adults, and
(c) definitive pharmacokinetic studies for dose selection across the age ranges of
paediatric patients in whom the drug is likely to be used. These studies
should be conducted in the paediatric patient population with the disease
under study.
(vi) If the new drug is a major therapeutic advance for the paediatric population – the
studies should begin early in the drug development , and this data should be submitted with the
new drug application.
(vii) Paediatric Subjects are legally unable to provide written informed consent, and are
dependent on their parent(s)/ legal guardian to assume responsibility for their participation in
clinical studies. Written informed consent should be obtained from the parent/ legal guardian.
However, all paediatric participants should be informed to the fullest extent possible about the
study in a language and in terms that they are able to understand. Where appropriate,
paediatric participants should additionally assent to enrol in the study. Mature minors and
adolescents should personally sign and date a separately designed written assent form.
Although a participant‘s wish to withdraw from a study must be respected, there may be
circumstances in therapeutic studies for serious or life-threatening diseases in which, in the
opinion of the Investigator and parent(s)/ legal guardian, the welfare of a pediatric patient would
Drugs and Cosmetics Rules 1945
592
be jeopardized by his or her failing to participate in the study. In this situation, continued
parental/ legal guardian consent should be sufficient to allow participation in the study.
(viii) For clinical trials conducted in the paediatric population, the reviewing ethics
committee should include members who are knowledgeable about pediatric, ethical, clinical and
psychosocial issues.
(3) Pregnant or nursing women:
(i) Pregnant or nursing women should be included in clinical trials only when the drug is
intended for use by pregnant/nursing women or foetuses/nursing infants and where the data
generated from women who are not pregnant or nursing, is not suitable.
(ii) For new drugs intended for use during pregnancy, follow-up data (pertaining to a
period appropriate for that drug) on the pregnancy, foetus and child will be required.
Where applicable, excretion of the drug or its metabolites into human milk should be examined
and the infant should be monitored for predicted pharmacological effects of the drug.
1
[(4) Post Marketing Surveillance:
(i) The applicant shall have a pharmacovigilance system in place for collecting,
processing and forwarding the report to the licensing authority for information on
adverse drug reactions emerging from the use of the drug manufactured or marketed by
the applicant in the country.
(ia) The system shall be managed by qualified and trained personnel and the officer in-
charge of collection and processing of data shall be a medical officer or a pharmacist
trained in collection and analysis of adverse drug reaction reports.
(ib) Subsequent to approval of the product, new drug shall be closely monitored for its
clinical safety once it is marketed.
(ic) The applicant shall furnish Periodic Safety Update Reports (PSURs) in order to-
(a) report all the relevant new information from appropriate sources;
(b) relate these data to patient exposure ;
(c) summarize the market authorization status in different countries and
any significant variations related to safety; and
(d) indicate whether changes should be made to product information in order to
optimize the use of the product.
(ii) Ordinarily all dosage forms and formulations as well as indications for new drugs
should be covered in one PSUR. Within the single PSUR separate presentations of data for
different dosage forms, indications or separate population need to be given.
(iii) All relevant clinical and non-clinical safety data should cover only the period of the
report (interval data). The PSURs shall be submitted every six months for the first two years after
approval of the drug is granted to the applicant. For subsequent two years – the PSURs need to
be submitted annually. Licensing authority may extend the total duration of submission of
PSURs if it is considered necessary in the interest of public health. PSURs due for a period must
be submitted within 30 calendar days of the last day of the reporting period.
However, all cases involving serious unexpected adverse reactions must be reported to the
licensing authority within 15 days of initial receipt of the information by the applicant. If
marketing of the new drug is delayed by the applicant after obtaining approval to market, such
data will have to be provided on the deferred basis beginning from the time the new drug is
marketed.
(iv) New studies specifically planned or conducted to examine a safety issue should be
described in the PSURs.
1. Subs. by G.S.R. 287(E) dated 08-03-2016.
Drugs and Cosmetics Rules 1945
593
(v) A PSUR should be structured as follows:
(a) A title page stating: Periodic safety update report for the product, applicant‘s
name, period covered by the report, date of approval of new drug, date of
marketing of new drug and date of reporting;
(b) Introduction,
(c) Current worldwide market authorization status,
(d) Update of actions taken for safety reasons,
(e) Changes to reference safety information,
(f) Estimated patient exposure,
(g) Presentation of individual case histories,
(h) Studies,
(i) Other information,
(j) Overall safety evaluation,
(k) Conclusion,
(l) Appendix providing material relating to indications, dosing, pharmacology
and other related information.
(5) Special studies: Bioavailability / Bioequivalence Studies:
(i) For drugs approved elsewhere in the world and absorbed systemically, bioequivalence
with the reference formulation should be carried out wherever applicable. These studies should
be conducted under the labelled conditions of administration. Data on the extent of systemic
absorption may be required for formulations other than those designed for systemic absorption.
(ii) Evaluation of the effect of food on absorption following oral administration should be
carried out. Data from dissolution studies should also be submitted for all solid oral dosage
forms.
(iii) Dissolution and bioavailability data submitted with the new drug application must
provide information that assures bioequivalence or establishes bioavailability and dosage
correlations between the formulation(s) sought to be marketed and those used for clinical trials
during clinical development of the product. (See items 8.1, 8.2 and 8.3 of Appendix I).
(iv) All bioavailability and bioequivalence studies should be conducted according to the
Guidelines for Bioavailability and Bioequivalence studies as prescribed.
Note.- The data requirements stated in this Schedule are expected to provide
adequate information to evaluate the efficacy, safety and therapeutic rationale of new drugs (as
defined under rule 122-E) prior to the permission for sale. Depending upon the nature of new
drugs and disease(s), additional information may be required by the Licensing Authority. The
applicant shall certify the authencity of the data and documents submitted in support of an
application for new drug. The Licensing Authority reserves the right to reject any data or any
document(s) if such data or contents of such documents are found to be of doubtful integrity.
APPENDIX I
DATA TO BE SUBMITTED ALONG WITH THE APPLICATION TO
CONDUCT
CLINICAL
TRIALS/IMPORT/MANUFACTURE
OF NEW DRUGS
FOR
MARKETING IN
THE
COUNTRY
1. Introduction
A brief description of the drug and the therapeutic class to which it belongs.
2. Chemical and pharmaceutical information
Drugs and Cosmetics Rules 1945
594
2.1. Information on active ingredients
Drug information (Generic Name, Chemical Name or INN)
2.2. Physicochemical Data
(a) Chemical name and Structure
Empirical formula
Molecular weight
(b) Physical properties
Description
Solubility
Rotation
Partition coefficient
Dissociation constant
2.3. Analytical Data
Elemental analysis
Mass spectrum
NMR spectra
IR spectra
UV spectra
Polymorphic identification
2.4. Complete monograph specification including
Identification
Identity/quantification of impurities
Enantiomeric purity
Assay
2.5. Validations
Assay method
Impurity estimation method
Residual solvent/other volatile impurities (OVI) estimation method
2.6. Stability Studies (for details refer Appendix IX)
Final release specification
Reference standard characterization
Material safety data sheet
2.7. Data on Formulation
Dosage form
Composition
Master manufacturing formula
Details of the formulation (including inactive ingredients)
In process quality control check
Finished product specification
Excipient compatibility study
Validation of the analytical method
Comparative evaluation with international brand(s) or approved Indian brands,
if applicable
Pack presentation
Dissolution
Assay
Impurities
Drugs and Cosmetics Rules 1945
595
Content uniformity
pH
Force degradation study
Stability evaluation in market intended pack at proposed storage conditions
Packing specifications
Process validation
When the application is for clinical trials only, the international non-proprietary name
(INN) or generic name, drug category, dosage form and data supporting stability in the
intended container-closure system for the duration of the clinical trial (information covered in
item nos. 2.1, 2.3, 2.6, 2.7) are required.
3. Animal Pharmacology (for details refer Appendix IV)
3.1. Summary
3.2. Specific pharmacological actions
3.3. General pharmacological actions
3.4. Follow-up and Supplemental Safety Pharmacology Studies
3.5. Pharmacokinetics: absorption, distribution; metabolism; excretion
4. Animal Toxicology (for details refer Appendix III)
4.1. General Aspects
4.2. Systemic Toxicity Studies
4.3. Male Fertility Study
4.4. Female Reproduction and Developmental Toxicity Studies
4.5. Local toxicity
4.6. Allergenicity/Hypersensitivity
4.7. Genotoxicity
4.8. Carcinogenicity
1
[Note.- Where the data on animal toxicity as per the specifications of Appendix III has been
submitted and the same has been considered by the regulatory authority of the country which had
earlier approved the drug, the animal toxicity studies shall not be required to be conducted in India
except in cases where there are specific concerns recorded in writing.]
5. Human / Clinical pharmacology (Phase
I)
5.1. Summary
5.2. Specific Pharmacological effects
5.3. General Pharmacological effects
5.4. Pharmacokinetics, absorption, distribution, metabolism, excretion
5.5. Pharmacodynamics / early measurement of drug activity
6. Therapeutic exploratory trials (Phase
II)
6.1. Summary
6.2. Study report(s) as given in Appendix II
7. Therapeutic confirmatory trials (Phase
III)
7.1. Summary
7.2. Individual study reports with listing of sites and Investigators.
8. Special studies
8.1. Summary
8.2. Bio-availability / Bio-equivalence.
8.3. Other studies e.g. geriatrics, paediatrics, pregnant or nursing women
1. Subs. by G.S.R. 313(E) dated 16-03-2016.
Drugs and Cosmetics Rules 1945
596
9. Regulatory status in other
countries
9.1. Countries where the drug is
a. Marketed
b. Approved
c. Approved as IND
d. Withdrawn, if any, with reasons
9.2. Restrictions on use, if any, in countries where marketed /approved
9.3. Free sale certificate or certificate of analysis, as appropriate.
10. Prescribing
information
10.1. Proposed full prescribing information
11. Samples and Testing Protocol/s
11.1. Samples of pure drug substance and finished product (an equivalent of 50 clinical
doses, or more number of clinical doses if prescribed by the Licensing Authority), with
testing protocol/s, full impurity profile and release specifications.
1
[12. New Chemical Entity and Global Clinical Trial:
12.1 Assessment of risk versus benefit to the patients
12.2 Innovation vis-à-vis existing therapeutic option
12.3 Unmet medical need in the country.]
NOTES:
(1) All items may not be applicable to all drugs. For explanation, refer text of Schedule Y.
(2) For requirements of data to be submitted with application for clinical trials refer text
of this Schedule.
APPENDIX
IA
DATA REQUIRED TO BE SUBMITTED BY AN APPLICANT FOR GRANT
OF
PERMISSION TO IMPORT AND / OR MANUFACTURE A NEW DRUG
ALREADY
APPROVED IN THE
COUNTRY
1. Introduction
A brief description of the drug and the therapeutic class
2. Chemical and pharmaceutical information
2.1. Chemical name, code name or number, if any; non-proprietary or generic name, if
any, structure; physico-chemical properties
2.2. Dosage form and its composition
2.3. Test specifications
(a) active ingredients
(b) inactive ingredients
2.4 Tests for identification of the active ingredients and method of its assay
2.5 Outline of the method of manufacture of active ingredients
2.6 Stability data
1. Ins. by G.S.R. 826 (E), dt. 30-10-2015.
Drugs and Cosmetics Rules 1945
597
3. Marketing information
3.1 Proposed package insert / promotional literature
3.2 Draft specimen of the label and carton
4. Special studies conducted with approval of Licensing Authority
4.1 Bioavailability / Bioequivalence and comparative dissolution studies for oral dosage forms
4.2 Sub-acute animal toxicity studies for intravenous infusions and injectables.
1
[APPENDIX I B
DATA TO BE SUBMITTED ALONG WITH APPLICATION TO CONDUCT CLINICAL
TRIAL OR IMPORT OR MANUFACTURE OF A PHYTOPHARMACEUTICAL DRUG IN
THE COUNTRY
PART - I
1. Data to be submitted by the applicant:
1.1. A brief description or summary of the phytopharmaceutical drug giving the botanical name of
the plant (including vernacular or scriptural name, wherever applicable), formulation and route of
administration, dosages, therapeutic class for which it is indicated and the claims to be made for the
phytopharmaceutical product.
1.2. Published literature including information on plant or product or phytopharmaceutical drug, as a
traditional medicine or as an ethno medicine and provide reference to books and other documents,
regarding composition, process prescribed, dose or method of usage, proportion of the active
ingredients in such traditional preparations per dose or per day‘s consumption and uses.
1.3. Information on any contraindications, side effects mentioned in traditional medicine or ethno
medicine literature or reports on current usage of the formulation.
1.4. Published scientific reports in respect of safety and pharmacological studies relevant for the
phytopharmaceutical drug intended to be marketed,-
(a) where the process and usages are similar or same to the product known in traditional medicine or
ethno medicine; and
(b) where process or usage is different from that known in traditional medicine or ethno medicine.
1.5. Information on any contraindications, side effects mentioned or reported in any of the studies,
information on side effects and adverse reactions reported during current usage of the
phytopharmaceutical in the last three years, wherever applicable.
1.6. Present usage of the phytopharmaceutical drug, – to establish history of usages, provide details
of the product, manufacturer, quantum sold, extent of exposure on human population and number of
years for which the product is being sold.
2. Human or clinical pharmacology information:
2.1. Published scientific reports in respect of pharmacological studies including human studies or
clinical studies or epidemiological studies, relevant for the phytopharmaceutical drug intended to be
marketed,-
(a) where the process and usages are similar or same to the product known in traditional medicine or
ethno medicine; and
(b) where process or usage is different from that known in traditional medicine or ethno medicine.
2.2. Pharmacodynamic information (if available).
2.3. Monographs, if any, published on the plant or product or extract or phytopharmaceutical.
(Copies of all publications, along with english translation to be attached.)
1. Ins. by G.S.R. 918 (E), dt. 30-11-2015.
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PART – II
Data generated by applicant
3. Identification, authentication and source of plant used for extraction and fractionation:
3.1. Taxonomical identity of the plant used as a source of the phytopharmaceutical drug giving
botanical name of genus, species and family, followed by the authority citation (taxonomist‘s name
who named the species), the variety or the cultivar (if any) needs to be mentioned.
3.2 Morphological and anatomical description giving diagnostic features and a photograph of the
plant or plant part for further confirmation of identity and authenticity. (Furnish certificate of
confirmation of botanical identity by a qualified taxonomist).
3.3 Natural habitat and geographical distribution of the plant and also mention whether the part of
the plant used is renewable or destructive and the source whether cultivated or wild.
3.4 Season or time of collection.
3.5 Source of the plant including its geographical location and season or time of collection.
3.6 A statement indicating whether the species is any of the following, namely:-
(a) determined to be endangered or threatened under the Endangered Species Act or the Convention
on International Trade in Endangered species (CITES) of wild Fauna and Flora;
(b) entitled to special protection under the Biological Diversity Act, 2002 (18 of 2003); (c) any
known genotypic, chemotypic and ecotypic variability of species.
3.7. A list of grower or supplier (including names and addresses) and information on the following
items for each grower or supplier, if available or identified already, including information of primary
processing, namely:-
(a) harvest location;
(b) growth conditions;
(c) stage of plant growth at harvest;
(d) harvesting time;
(e) collection, washing, drying and storage conditions;
(f) handling, garbling and transportation;
(g) grinding, pulverising of the plant material; and
(h) sieving for getting uniform particle size of powdered plant material.
3.8. Quality specifications, namely:-
(a) foreign matter;
(b) total ash;
(c) acid insoluble ash;
(d) pesticide residue;
(e) heavy metal contamination;
(f) microbial load;
(g) chromatographic finger print profile with phytochemical reference marker;
(h) assay for bio-active or phytochemical compounds; and
(i) chromatographic fingerprint of a sample as per test method given under quality control of the
phytopharmaceutical drug (photo documentation).
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3.9 . An undertaking to supply specimen sample of plant duly labeled and photocopy of the
certificate of identity confirmation issued by a qualified taxonomist along with drawings or
photographs of the diagnostic morphological and histological features of the botanical raw material
used for the confirmation of authenticity.
4. Process for extraction and subsequent fractionation and purification:
4.1. Quality specifications and test methods for starting material.
4.2. Steps involved in processing.
(a) details of solvent used, extractive values, solvent residue tests or limits, physico-chemical tests,
microbial loads, heavy metal contaminants, chromatographic finger print profile with phytochemical
reference markers, assay for active constituents or characteristic markers, if active constituents are
not known;
(b) characterisation of final purified fraction;
(c) data on bio-active constituent of final purified fraction;
(d) information on any excipients or diluents or stabiliser or preservative used, if any.
4.3. Details of packaging of the purified and characterised final product, storage conditions and
labeling.
5. Formulation of phytopharmaceutical drug applied for:
5.1. Details of the composition, proportion of the final purified fraction with defined markers of
phytopharmaceutical drug per unit dose, name and proportions of all excipients, stabilisers and any
other agent used and packaging materials.
5.2. Test for identification for the phytopharmaceutical drug.
5.3. Quality specifications for active and inactive phytopharmaceutical chromatographic finger print
profile with phytochemical reference marker and assay of active constituent or characteristic
chemical marker.
6. Manufacturing process of formulation:
6.1. The outline of the method of manufacture of the dosage form, along with environmental
controls, in-process quality control tests and limits for acceptance.
6.2. Details of all packaging materials used, packing steps and description of the final packs.
6.3. Finished product‘s quality specifications, including tests specific for the dosage form, quality
and chromatographic finger print profile with phytochemical reference marker and assay for active
constituent or characteristic marker, if active constituents are not known.
7. Stability data:
7.1. Stability data of the phytopharmaceutical drug described at 4 above, stored at room temperature
at 40 +/- 2 deg. C and humidity at 75%RH +/- 5%RH for 0, 1, 2, 3 and 6 months.
7.2 Stability data of the phytopharmaceutical drug in dosage form or formulation stored at room
temperature at 40 +/- 2 deg. C and humidity at 75%RH +/- 5%RH for 0, 1, 2, 3 and 6 months, in the
pack intended for marketing.
8. Safety and pharmacological information:
8.1. Data on safety and pharmacological studies to be provided.
8.2. Animal toxicity and safety data:
(a) 28 to 90 days repeat dose oral toxicity on two species of animals;
(b) In-vitro genotoxicity data (Ame‘s test and Chromosomal aberration test as per Schedule Y);
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(c) dermal toxicity tests for topical use products;
(d) teratogenicity study (only if phytopharmaceutical drug is intended for use during pregnancy).
9. Human studies:
9.1. Clinical trials for phytopharmaceutical drugs to be conducted as per applicable rules and
guidelines for new drugs.
9.2. For all phytopharmaceutical drugs data from phase I (to determine maximum tolerated dose and
associated toxicities) and the protocols shall be submitted prior to performing the studies.
9.3. Data of results of dose finding studies performed and the protocols shall be submitted prior to
performing the studies: Provided that in the case of phytopharmaceutical drug already marketed for
more than five years or where there is adequate published evidence regarding the safety of the
phytopharmaceutical drug, the studies may be abbreviated, modified or relaxed.
10. Confirmatory clinical trials:
10.1. Submit protocols for approval for any specific or special safety and efficacy study proposed
specific to the phytopharmaceutical drug.
10.2. Submit proposed protocol for approval for human clinical studies appropriate to generate or
validate safety and efficacy data for the phytopharmaceutical dosage form or product as per
applicable rules and guidelines.
10.3. Submit information on how the quality of the formulation would be maintained during the
above studies.
11. Regulatory status:
11.1. Status of the phytopharmaceutical drug marketed in any country under any category like
functional food or dietary supplement or as traditional medicine or as an approved drug.
12. Marketing information:
12.1. Details of package insert or patient information sheet of the phytopharmaceutical drug to be
marketed.
12.2. Draft of the text for label and carton.
13. Post marketing surveillance (PMS):
13.1. The applicant shall furnish periodic safety update reports every six months for the first two
years after approval the drug is granted.
13.2. For subsequent two years the periodic safety update reports need to be submitted annually.
14. Any other relevant information:
Any other relevant information which the applicant considers that it will help in scientific evaluation
of the application.]
APPENDIX
II
STRUCTURE, CONTENTS AND FORMAT FOR CLINICAL STUDY REPORTS
1. Title Page:
This page should contain information about the title of the study, the protocol code, name of the
investigational product tested, development Phase, indication studied, a brief description of the trial
design, the start and end date of patient accrual and the names of the Sponsor and the participating
Institutes (Investigators).
2. Study Synopsis (1 to 2 pages):
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A brief overview of the study from the protocol development to the trial closure should be given
here. This section will only summarize the important conclusions derived from the study.
3. Statement of compliance with the ‗Guidelines for Clinical Trials on Pharmaceutical
Products in India :
GCP Guidelines‘ issued by the Central Drugs Standard Control Organization, Ministry of
Health, Government of India.
4. List of Abbreviations and Definitions
5. Table of contents
6. Ethics Committee:
This section should document that the study was conducted in accordance with the ethical
principles of Declaration of Helsinki. A detailed description of the Ethics Committee constitution
and date(s) of approvals of trial documents for each of the participating sites should be
provided. A declaration should state that EC notifications as per Good Clinical Practice
Guidelines issued by Central Drugs Standard Control Organization and Ethical Guidelines for
Biomedical Research on Human Subjects, issued by Indian Council of Medical Research have been
followed.
7. Study Team:
Briefly describe the administrative structure of the study (Investigators, site staff, Sponsor/
designates, Central laboratory etc).
8. Introduction:
A brief description of the product development rationale should be given here.
9. Study Objective:
A statement describing the overall purpose of the study and the primary and secondary
objectives to be achieved should be mentioned here.
10. Investigational Plan:
This section should describe the overall trial design, the Subject selection criteria, the treatment
procedures, blinding / randomization techniques if any, allowed/ disallowed concomitant treatment,
the efficacy and safety criteria assessed, the data quality assurance procedures and the statistical
methods planned for the analysis of the data obtained.
11. Trial Subjects:
A clear accounting of all trial Subjects who entered the study will be given here. Mention should
also be made of all cases that were dropouts or protocol deviations. Enumerate the patients
screened, randomised, and prematurely discontinued. State reasons for premature discontinuation of
therapy in each applicable case.
12. Efficacy evaluation
The results of evaluation of all the efficacy variables will be described in this section with
appropriate tabular and graphical representation. A brief description of the demographic
characteristics of the trial patients should also be provided along with a listing of patients and
observations excluded from efficacy analysis.
13. Safety Evaluation:
This section should include the complete list
13.1 All serious adverse events, whether expected or unexpected and
13.2 unexpected advese events whether serious or not (compiled from data received as per Appendix
XI).
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The comparison of adverse events across study groups may be presented in a tabular or
graphical form. This section should also give a brief narrative of all important events considered
related to the investigational product.
14. Discussion and overall Conclusion:
Discussion of the important conclusions derived from the trial and scope for further
development.
15. List of References:
16. Appendices:
List of Appendices to the Clinical Trial Report
(a) Protocol and amendments
(b) Specimen of Case Record Form
(c) Investigators‘ name(s) with contact addresses, phone, e-mail etc. (d) Patient data listings
(e) List of trial participants treated with investigational product
(f) Discontinued participants
(g) Protocol deviations
(h) CRFs of cases involving death and life threatening adverse event cases
(i) Publications from the trial
(j) Important publications referenced in the study
(k) Audit certificate, if available
(l) Investigator‘s certificate that he/she has read the report and that the report accurately
describes the conduct and the results of the study.
APPENDIX
III
ANIMAL TOXICOLOGY (NON-CLINICAL TOXICITY
STUDIES)
1. General Principles:
Toxicity studies should comply with the norms of Good Laboratory Practice (GLP). Briefly,
these studies should be performed by suitably trained and qualified staff employing properly
calibrated and standardized equipment of adequate size and capacity. Studies should be done as per
written protocols with modifications (if any) verifiable retrospectively. Standard operating
procedures (SOPs) should be followed for all managerial and laboratory tasks related to these
studies. Test substances and test systems (in-vitro or in-vivo) should be properly characterized
and standardized. All documents belonging to each study, including its approved protocol, raw
data, draft report, final report, and histology slides and paraffin tissue blocks should be preserved for
a minimum of 5 years after marketing of the drug.
Toxicokinetic studies (generation of pharmacokinetic data either as an integral component of the
conduct of non-clinical toxicity studies or in specially designed studies) should be conducted to
assess the systemic exposure achieved in animals and its relationship to dose level and the time
course of the toxicity study. Other objectives of toxicokinetic studies include obtaining data to
relate the exposure achieved in toxicity studies to toxicological findings and contribute to the
assessment of the relevance of these findings to clinical safety, to support the choice of species and
treatment regimen in nonclinical toxicity studies and to provide information which, in conjunction
with the toxicity findings, contributes to the design of subsequent non-clinical toxicity studies.
1.1 Systemic Toxicity Studies
1.1.1 Single-dose Toxicity Studies: These studies (see Appendix I item 4.2) should be carried out in
2 rodent species (mice and rats) using the same route as intended for humans. In addition,
unless the intended route of administration in humans is only intravenous, at least one more
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route should be used in one of the species to ensure systemic absorption of the drug. This
route should depend on the nature of the drug. A limit of 2g/kg (or 10 times the normal
dose that is intended in humans, whichever is higher) is recommended for oral dosing.
Animals should be observed for 14 days after the drug administration, and minimum lethal
dose (MLD) and maximum tolerated dose (MTD) should be established. If possible, the
target organ of toxicity should also be determined. Mortality should be observed for up to 7
days after parenteral administration and up to 14 days after oral administration. Symptoms,
signs and mode of death should be reported, with appropriate macroscopic and microscopic
findings where necessary. LD10 and LD50 should be reported preferably with 95 percent
confidence limits. If LD50s cannot be determined, reasons for the same should be stated.
The dose causing severe toxic manifestations or death should be defined in the case of
cytotoxic anticancer agents, and the post-dosing observation period should be up to 14 days.
Mice should first be used for determination of MTD. Findings should then be confirmed in rat
for establishing linear relationship between toxicity and body surface area. In case of
nonlinearity, data of the more sensitive species should be used to determine the Phase I
starting dose. Where rodents are known to be poor predictors of human toxicity (e.g.,
antifolates), or where the cytotoxic drug acts by a novel mechanism of action, MTD should be
established in non-rodent species.
1.1.2 Repeated-dose Systemic Toxicity Studies: These studies (see Appendix I, item 4.2) should be
carried out in at least two mammalian species, of which one should be a non- rodent. Dose
ranging studies should precede the 14-, 28-, 90- or 180- day toxicity studies. Duration of the
final systematic toxicity study will depend on the duration, therapeutic indication and scale of
the proposed clinical trial (see item 1.8). If a species is known to metabolize the drug in the
same way as humans, it should be preferred for toxicity studies.
In repeated-dose toxicity studies the drug should be administered 7 days a week by the
route intended for clinical use. The number of animals required for these studies, i.e. the
minimum number of animals on which data should be available, is shown in Item 1.9.
Wherever applicable, a control group of animals given the vehicle alone should be
included, and three other groups should be given graded doses of the drug. The highest dose
should produce observable toxicity; the lowest dose should not cause observable toxicity, but
should be comparable to the intended therapeutic dose in humans or a multiple of it . To make
allowance for the sensitivity of the species the intermediate dose should cause some
symptoms, but not gross toxicity or death, and should be placed logarithmically between the
other two doses.
The parameters to be monitored and recorded in long-term toxicity studies should include
behavioral, physiological, biochemical and microscopic observations. In case of parenteral
drug administration, the sites of injection should be subjected to gross and microscopic
examination. Initial and final electrocardiogram and fundus examination should be carried out
in the non-rodent species.
In the case of cytotoxic anticancer agents dosing and study design should be in
accordance with the proposed clinical schedule in terms of days of exposure and number of
cycles. Two rodent species may be tested for initiating Phase I trials. A non-rodent species
should be added if the drug has a novel mechanism of action, or if permission for Phase II, III
or marketing is being sought.
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For most compounds, it is expected that single dose tissue distribution studies with
sufficient sensitivity and specificity will provide an adequate assessment of tissue
distribution and the potential for accumulation. Thus, repeated dose tissue distribution
studies should not be required uniformly for all compounds and should only be conducted
when appropriate data cannot be derived from other sources. Repeated dose studies may be
appropriate under certain circumstances based on the data from single dose tissue
distribution studies, toxicity and toxicokinetic studies. The studies may be most appropriate
for compounds which have an apparently long half life, incomplete elimination or
unanticipated organ toxicity.
Notes:
(i) Single Dose Toxicity Study: Each group should contain at least 5 animals of either sex. At
least four graded doses should be given. Animals should be exposed to the test substance in a single
bolus or by continuous infusion or several doses within 24 hours. Animals should be observed for 14
days. Signs of intoxication, effect on body weight, gross pathological changes should be reported.
It is desirable to include histo-pathology of grossly affected organs, if any.
(ii) Dose-ranging Study: Objectives of this study include the identification of target organ of
toxicity and establishment of MTD for subsequent studies.
(a) Rodents: Study should be performed in one rodent species (preferably rat) by the
proposed clinical route of administration. At least four graded doses including control
should be given, and each dose group as well as the vehicle control should consist of a
minimum of 5 animals of each sex. Animals should be exposed to the test substance
daily for 10 consecutive days. Highest dose should be the maximum tolerated dose of
single-dose study. Animals should be observed daily for signs of intoxication (general
appearance, activity and behaviour etc), and periodically for the body weight and
laboratory parameters. Gross examination of viscera and microscopic examination of
affected organs should be done.
(b) Non-rodents: One male and one female are to be taken for ascending Phase MTD study.
Dosing should start after initial recording of cage-side and laboratory parameters.
Starting dose may be 3 to 5 times the extrapolated effective dose or MTD (whichever is
less), and dose escalation in suitable steps should be done every third day after
drawing the samples for laboratory parameters. Dose should be lowered appropriately
when clinical or laboratory evidence of toxicity are observed. Administration of test
substance should then continue for 10 days at the well-tolerated dose level following
which, samples for laboratory parameters should be taken. Sacrifice, autopsy and
microscopic examination of affected tissues should be performed as in the case of
rodents.
(iii) 14-28 Day repeated-dose toxicity studies: One rodent (6-10/sex/group) and one non-
rodent (2-3/sex/group) species are needed. Daily dosing by proposed clinical route at
three dose levels should be done with highest dose having observable toxicity, mid- dose
between high and low dose, and low dose. The doses should preferably be multiples of
the effective dose and free from toxicity. Observation parameters should include cage-
side observations, body weight changes, food/water intake, blood biochemistry,
haematology, and gross and microscopic studies of all viscera and tissues.
(iv) 90-Day repeated-dose toxicity studies: One rodent (15-30/sex/group) and one non-
rodent (4-6/sex/group) species are needed. Daily dosing by proposed clinical route at
three graded dose levels should be done. In addition to the control a ―high-dose-reversal‖
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group and its control group should be also included. Parameters should include signs of
intoxication (general appearance, activity and behaviour etc), body weight, food intake,
blood biochemical parameters, haematological values, urine analysis, organ weights,
gross and microscopic study of viscera and tissues. Half the animals in ―reversal‖ groups
(treated and control) should be sacrificed after 14 days of stopping the treatment. The
remaining animals should be sacrificed after 28 days of stopping the treatment or after the
recovery of signs and/or clinical pathological changes – whichever comes later, and
evaluated for the parameters used for the main study.
(v) 180-Day repeated-dose toxicity studies: One rodent (15-30/sex/group) and one non-
rodent (4-6/sex/group) species are needed. At least 4 groups, including control, should
be taken. Daily dosing by proposed clinical route at three graded dose levels should be
done. Parameters should include signs of intoxication, body weight, food intake, blood
biochemistry, hematology, urine analysis, organ weights, gross and microscopic
examination of organs and tissues.
1.2 Male Fertility Study
One rodent species (preferably rat) should be used. Dose selection should be done from the
results of the previous 14 or 28-day toxicity study in rat. Three dose groups, the highest one
showing minimal toxicity in systemic studies, and a control group should be taken. Each
group should consist of 6 adult male animals. Animals should be treated with the test
substance by the intended route of clinical use for minimum 28 days and maximum 70 days
before they are paired with female animals of proven fertility in a ratio of 1:2 for mating.
Drug treatment of the male animals should continue during pairing. Pairing should be
continued till the detection of vaginal plug or 10 days, whichever is earlier. Females getting
thus pregnant should be examined for their fertility index after day 13 of gestation.
All the male animals should be sacrificed at the end of the study. Weights of each testis and
epididymis should be separately recorded. Sperms from one epididymis should be examined
for their motility and morphology. The other epididymis and both testes should be examined
for their histology.
1.3 Female Reproduction and Developmental Toxicity Studies
These studies (see Appendix I, item 4.4) need to be carried out for all drugs proposed to be
studied or used in women of child bearing age. Segment I, II and III studies (see below) are
to be performed in albino mice or rats, and segment II study should include albino rabbits
also as a second test species.
On the occasion, when the test article is not compatible with the rabbit (e.g. antibiotics which
are effective against gram positive, anaerobic organisms and protozoas) the Segment II data
in the mouse may be substituted.
1.3.1 Female Fertility Study (Segment I): The study should be done in one rodent species (rat
preferred). The drug should be administered to both males and females, beginning a
sufficient number of days (28 days in males and 14 days in females) before mating. Drug
treatment should continue during mating and, subsequently, during the gestation period.
Three graded doses should be used, the highest dose (usually the MTD obtained from
previous systemic toxicity studies) should not affect general health of the parent animals. At
least 15 males and 15 females should be used per dose group. Control and the
treated groups should be of similar size. The route of administration should be the
same as intended for therapeutic use
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Dams should be allowed to litter and their medication should be continued till the
weaning of pups. Observations on body weight, food intake, clinical signs
of intoxication, mating behaviour, progress of gestation/ parturition periods,
length of gestation, parturition, post-partum health and gross pathology (and
histopathology of affected organs) of dams should be recorded. The pups from both
treated and control groups should be observed for general signs of intoxication, sex-wise
distribution in different treatment groups, body weight, growth parameters, survival, gross
examination, and autopsy. Histopathology of affected organs should be done.
1.3.2 Teratogenicity Study (Segment II):
One rodent (preferably rat) and one non-rodent (rabbit) species are to be used. The drug
should be administered throughout the period of organogenesis, using three dose levels as
described for segment I. The highest dose should cause minimum maternal toxicity and
the lowest one should be proportional to the proposed dose for clinical use in humans or
a multiple of it. The route of administration should be the same as intended for
human therapeutic use.
The control and the treated groups should consist of at least 20 pregnant rats (or
mice) and 12 rabbits, on each dose level. All foetuses should be subjected to
gross examination, one of the foetuses should be examined for skeletal abnormalities and
the other half for visceral abnormalities. Observation parameters should include: (Dams)
signs of intoxication, effect on body weight, effect on food intake, examination of uterus,
ovaries and uterine contents, number of corpora lutea, implantation sites, resorptions (if
any); and for the foetuses, the total number, gender, body length, weight and gross/ visceral/
skeletal abnormalities, if any.
1.3.3 Perinatal Study (Segment III):
This study is specially recommended if the drug is to be given to pregnant or nursing
mothers for long periods or where there are indications of possible adverse effects on foetal
development. One rodent species (preferably rat) is needed. Dosing at levels comparable
to multiples of human dose should be done by the intended clinical route. At least 4 groups
(including control), each consisting of 15 dams should be used. The drug should
be administered throughout the last trimester of pregnancy (from day 15 of
gestation) and then the dose that causes low foetal loss should be continued
throughout lactation and weaning. Dams should then be sacrificed and examined
as described below.
One male and one female from each litter of F
1
generation (total 15 males and 15
females in each group) should be selected at weaning and treated with vehicle or test
substance (at the dose levels described above) throughout their periods of growth to
sexual maturity, pairing, gestation, parturition and lactation. Mating performance and
fertility of F
1
generation should thus be evaluated to obtain the F
2
generation whose growth
parameters should be monitored till weaning. The criteria of evaluation should be the same
as described earlier (3.4.1).
Animals should be sacrificed at the end of the study and the observation parameters should
include (Dams) body weight, food intake, general signs of intoxication, progress of
gestation/ parturition periods and gross pathology (if any); and for pups, the clinical signs,
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sex-wise distribution in dose groups, body weight, growth parameters, gross
examination, survival and autopsy (if needed) and where necessary, histopathology.
1.4 Local toxicity
These studies (see Appendix I, item 4.5) are required when the new drug is proposed to be
used by some special route (other than oral) in humans. The drug should be applied to an
appropriate site (e.g., skin or vaginal mucous membrane) to determine local effects in a
suitable species. Typical study designs for these studies should include three dose levels
and untreated and/ or vehicle control, preferably use of 2 species, and increasing group size
with increase in duration of treatment. Where dosing is restricted due to anatomical or
humane reasons, or the drug concentration cannot be increased beyond a certain level due to
the problems of solubility, pH or tonicity, a clear statement to this effect should be given. If
the drug is absorbed from the site of application, appropriate systemic toxicity studies will
also be required.
Notes:
(i) Dermal toxicity study: The study should be done in rabbit and rat. Daily topical
(dermal) application of test substance in its clinical dosage form should be done. Test
material should be applied on shaved skin covering not less than 10% of the total body
surface area. Porous gauze dressing should be used to hold liquid material in place.
Formulations with different concentrations (at least 3) of test substance, several fold
higher than the clinical dosage form should be used. Period of application may vary from 7
to 90 days depending on the clinical duration of use. Where skin irritation is grossly visible
in the initial studies, a recovery group should be included in the subsequent repeated-dose
study. Local signs (erythema, oedema and eschar formation) as well as histological
examination of sites of application should be used for evaluation of results.
(ii) Photo-allergy or dermal photo-toxicity: It should be tested by Armstrong/ Harber
Test in guinea pig. This test should be done if the drug or a metabolite is related to an agent
causing photosensitivity or the nature of action suggests such a potential (e.g., drugs to be
used in treatment of leucoderma). Pretest in 8 animals should screen 4
concentrations (patch application for 2 hours ±15 min.) with and without UV exposure (10
J/cm2). Observations recorded at 24 and 48 hours should be used to ascertain highest
nonirritant dose. Main test should be performed with 10 test animals and 5 controls.
Induction with the dose selected from pretest should use 0.3 ml/patch for 2 hour ±15 min.
followed by 10 J/cm2 of UV exposure. This should be repeated on day 0, 2,4,7,9 and 11 of
the test. Animals should be challenged with the same concentration of test substance
between day 20 to 24 of the test with a similar 2-hour application followed by exposure to 10
J/cm2 of UV light. Examination and grading of erythema and oedema formation at the
challenge sites should be done 24 and 48 hours after the challenge. A positive control like
musk ambrett or psoralin should be used.
(iii) Vaginal Toxicity Test: Study is to be done in rabbit or dog. Test substance should
be applied topically (vaginal mucosa) in the form of pessary, cream or ointment. Six to
ten animals per dose group should be taken. Higher concentrations or several daily
applications of test substance should be done to achieve multiples of daily human dose.
The minimum duration of drug treatment is 7 days (more according to clinical use),
subject to a maximum of 30 days. Observation parameters should include swelling, closure
of introitus and histopathology of vaginal wall.
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(iv) Rectal Tolerance Test: For all preparations meant for rectal administration this
test may be performed in rabbits or dogs. Six to ten animals per dose group should be taken.
Formulation in volume comparable to human dose (or the maximum possible volume)
should be applied once or several times daily, per rectally, to achieve administration of
multiples of daily human dose. The minimum duration of application is 7 days (more
according to clinical use), subject to a maximum of 30 days. Size of suppositories may be
smaller, but the drug content should be several fold higher than the proposed human dose.
Observation parameters should include clinical signs (sliding on backside), signs of pain,
blood and/or mucus in faeces, condition of anal region/sphincter, gross and (if required)
histological examination of rectal mucosa.
(v) Parenteral Drugs: For products meant for intravenous or intramuscular or
subcutaneous or intradermal injection the sites of injection in systemic toxicity studies
should be specially examined grossly and microscopically. If needed, reversibility of
adverse effects may be determined on a case to case basis.
(vi) Ocular toxicity studies (for products meant for ocular instillation): These studies
should be carried out in two species, one of which should be the albino rabbit which has a
sufficiently large conjunctival sac. Direct delivery of drug onto the cornea in case of
animals having small conjunctival sacs should be ensured. Liquids, ointments, gels or soft
contact lenses (saturated with drug) should be used. Initial single dose application should be
done to decide the exposure concentrations for repeated-dose studies and the need to
include a recovery group. Duration of the final study will depend on the proposed length of
human exposure subject to a maximum of 90 days. At least two different
concentrations exceeding the human dose should be used for demonstrating the margin of
safety. In acute studies, one eye should be used for drug administration and the other kept as
control. A separate control group should be included in repeated-dose studies.
Slit-lamp examination should be done to detect the changes in cornea, iris and aqueous
humor. Fluorescent dyes (sodium fluorescein, 0.25 to 1.0%) should be used for detecting the
defects in surface epithelium of cornea and conjunctiva. Changes in intra-ocular tension
should be monitored by a tonometer. Histological examination of eyes should be done at the
end of the study after fixation in Davidson‘s or Zenker‘s fluid.
(vii) Inhalation toxicity studies: The studies are to be undertaken in one rodent and one
non-rodent species using the formulation that is to be eventually proposed to be marketed.
Acute, subacute and chronic toxicity studies should be performed according to the intended
duration of human exposure. Standard systemic toxicity study designs (described above)
should be used. Gases and vapours should be given in whole body exposure chambers;
aerosols are to be given by nose-only method. Exposure time and concentrations of test
substance (limit dose of 5mg/l) should be adjusted to ensure exposure at levels
comparable to multiples of intended human exposure. Three dose groups and a control
(plus vehicle control, if needed) are required. Duration of exposure may vary subject to a
maximum of 6 hours per day and five days a week. Food and water should be withdrawn
during the period of exposure to test substance.
Temperature, humidity and flow rate of exposure chamber should be recorded and reported.
Evidence of exposure with test substance of particle size of 4 micron (especially for
aerosols) with not less that 25% being 1 micron should be provided. Effects on
respiratory rate, findings of bronchial lavage fluid examination, histological examination of
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respiratory passages and lung tissue should be included along with the regular parameters of
systemic toxicity studies or assessment of margin of safety.
1.5 Allergenicity/ Hypersensitivity:
Standard tests include guinea pig maximization test (GPMT) and local lymph node assay
(LLNA) in mouse. Any one of the two may be done.
Notes:
(i) Guinea Pig Maximization Test: The test is to be performed in two steps; first,
determination of maximum nonirritant and minimum irritant doses, and second, the main
test. The initial study will also have two components. To determine the intradermal
induction dose, 4 dose levels should be tested by the same route in a batch of 4 male and 4
female animals (2 of each sex should be given Freund‘s adjuvant). The minimum irritant
dose should be used for induction. Similarly, a topical minimum irritant dose should be
determined for challenge. This should be established in 2 males and 2 females. A
minimum of 6 male and 6 female animals per group should be used in the main study.
One test and one control group should be used. It is preferable to have one more positive
control group. Intradermal induction (day 1) coupled with topical challenge (day 21)
should be done. If there is no response, re-challenge should be done 7-30 days after the
primary challenge. Erythema and oedema (individual animal scores as well as
maximization grading) should be used as evaluation criteria.
(ii) Local Lymph Node Assay: Mice used in this test should be of the same sex, either only
males or only females. Drug treatment is to be given on ear skin. Three graded doses,
the highest being maximum nonirritant dose plus vehicle control should be used. A
minimum of 6 mice per group should be used. Test material should be applied on ear skin on
three consecutive days and on day 5, the draining auricular lymph nodes should be dissected
out 5 hours after i.v. H-thymidine or bromo-deoxy-uridine (BrdU). Increase in H-
thymidine or BrdU incorporation should be used as the criterion for evaluation of
results.
1.6 Genotoxicity
Genotoxic compounds, in the absence of other data, shall be presumed to be trans- species
carcinogens, implying a hazard to humans. Such compounds need not be subjected to
long-term carcinogenicity studies. However, if such a drug is intended to be administered
for chronic illnesses or otherwise over a long period of time - a chronic toxicity study (up to
one year) may be necessary to detect early tumorigenic effects.
Genotoxicity tests are in vitro and in vivo tests conducted to detect compounds which induce
genetic damage directly or indirectly. These tests should enable a hazard identification with
respect to damage to DNA and its fixation.
The following standard test battery is generally expected to be conducted:
(i) A test for gene mutation in bacteria.
(ii) An in vitro test with cytogenetic evaluation of chromosomal damage with mammalian
cells or an in vitro mouse lymphoma tic assay.
(iii) An in vivo test for chromosomal damage using rodent haematopoietic cells.
Other
genotoxicity tests e.g. tests for measurement of DNA adducts, DNA strand
breaks, DNA repair or recombination serve as options in addition to the standard battery
for further investigation of genotoxicity test results obtained in the standard battery. Only
under extreme conditions in which one or more tests comprising the standard battery cannot
Drugs and Cosmetics Rules 1945
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be employed for technical reasons, alternative validated tests can serve as substitutes
provided sufficient scientific justification should be provided to support the argument that a
given standard battery test is not appropriate.
Both in-vitro and in-vivo studies should be done. In-vitro studies should include Ames‘
Salmonella assay and chromosomal aberrations (CA) in cultured cells. In-vivo studies
should include micronucleus assay (MNA) or CA in rodent bone marrow. Data analysis of
CA should include analysis of ‗gaps.‘
Cytotoxic anticancer agents: Genotoxicity data are not required before Phase I and
II trials. But these studies should be completed before applying for Phase III trials.
Notes:
Ames‘ Test (Reverse mutation assay in Salmonella): S. typhimurium tester strains
such as TA98, TA100, TA102, TA1535, TA97 or Escherichia coli WP2 uvrA or
Escherichia coli WP2 uvrA (pKM101) should be used.
(i) In-vitro exposure (with and without metabolic activation, S9 mix) should be done at a
minimum of 5 log dose levels. ―Solvent‖ and ―positive‖ control should be used. Positive
control may include 9-amino-acridine, 2-nitrofluorine, sodium azide and mitomycin C,
respectively, in the tester strains mentioned above. Each set should consist of at least three
replicates. A 2.5 fold (or more) increase in number of revertants in comparison to
spontaneous revertants would be considered positive.
(ii) In-vitro cytogenetic assay : The desired level of toxicity for in vitro cytogenetic tests
using cell lines should be greater than 50% reduction in cell number or culture confluency.
For lymphocyte cultures, an inhibition of mitotic index by greater than 50% is considered
sufficient. It should be performed in CHO cells or on human lymphocyte in culture. In-vitro
exposure (with and without metabolic activation, S9 mix) should be done using a minimum
of 3 log doses. ―Solvent‖ and ―positive‖ control should be included. A positive control like
Cyclophosphamide with metabolic activation and Mitomycin C for without metabolic
activation should be used to give a reproducible and detectable increase clastogenic effect
over the background which demonstrates the sensitivity of the test system. Each set should
consist of at least three replicates. Increased number of aberrations in metaphase
chromosomes should be used as the criteria for evaluation.
(iii) In-vivo micronucleus assay: One rodent species (preferably mouse) is needed. Route
of administration of test substance should be the same as intended for humans. Five animals
per sex per dose groups should be used. At least three dose levels, plus ―solvent‖ and
―positive‖ control should be tested. A positive control like mitomycin C or
cyclophosphamide should be used. Dosing should be done on day 1 and 2 of study
followed by sacrifice of animals 6 hours after the last injection. Bone marrow from both the
femora should be taken out, flushed with fetal bovine serum (20 min.), pelletted and
smeared on glass slides. Giemsa-MayGruenwald staining should be done and increased
number of micronuclei in polychromatic erythrocytes (minimum 1000) should be used as
the evaluation criteria.
(iv) In-vivo cytogenetic assay: One rodent species (preferably rat) is to be used. Route of
administration of test substance should be the same as intended for humans. Five
animals/sex/dose groups should be used. At least three dose levels, plus ―solvent‖ and
―positive‖ control should be tested. Positive control may include cyclophosphamide.
Dosing should be done on day 1 followed by intra-peritoneal colchicine administration at
22 hours. Animals should be sacrificed 2 hours after colchicine administration. Bone
marrow from both the femora should be taken out, flushed with hypotonic saline (20 min.),
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pelletted and resuspended in Carnoy‘s fluid. Once again the cells should be pelletted and
dropped on clean glass slides with a Pasteur pipette. Giemsa staining should be done and
increased number of aberrations in metaphase chromosomes (minimum 100) should be used
as the evaluation criteria.
1.7 Carcinogenicity (see Appendix I, item 4.8)
Carcinogenicity studies should be performed for all drugs that are expected to be
clinically used for more than 6 months as well as for drugs used frequently in an intermittent
manner in the treatment of chronic or recurrent conditions. Carcinogenicity studies are also
to be performed for drugs if there is concern about their carcinogenic potential emanating
from previous demonstration of carcinogenic potential in the product class that is considered
relevant to humans or where structure-activity relationship suggests carcinogenic risk or
when there is evidence of preneoplastic lesions in repeated dose toxicity studies or when
long-term tissue retention of parent compound or metabolite(s) results in local tissue
reactions or other pathophysiological responses. For pharmaceuticals developed to treat
certain serious diseases, Licensing Authority may allow carcinogenicity testing to be
conducted after marketing permission has been granted.
In instances where the life-expectancy in the indicated population is short (i.e., less than
2-3 years)- no long-term carcinogenicity studies may be required. In cases where the
therapeutic agent for cancer is generally successful and life is significantly prolonged
there may be later concerns regarding secondary cancers. When such drugs are
intended for adjuvant therapy in tumour free patients or for prolonged use in non-cancer
indications, carcinogenicity studies may be / are needed. Completed rodent carcinogenicity
studies are not needed in advance of the conduct of large scale clinical trials, unless there is
special concern for the patient population.
Carcinogenicity studies should be done in a rodent species (preferably rat). Mouse may be
employed only with proper scientific justification. The selected strain of animals should not
have a very high or very low incidence of spontaneous tumors.
At least three dose levels should be used. The highest dose should be sub-lethal, and it
should not reduce the life span of animals by more than 10% of expected normal. The
lowest dose should be comparable to the intended human therapeutic dose or a multiple of it,
e.g.
2.5x; to make allowance for the sensitivity of the species. The intermediate dose to be
placed logarithmically between the other two doses. An untreated control and (if indicated) a
vehicle control group should be included. The drug should be administered 7 days a week for
a fraction of the life span comparable to the fraction of human life span over which the drug
is likely to be used therapeutically. Generally, the period of dosing should be 24 months for
rats and 18 months for mice.
Observations should include macroscopic changes observed at autopsy and detailed
histopathology of organs and tissues. Additional tests for carcinogenicity (short-term
bioassays, neonatal mouse assay or tests employing transgenic animals) may also be done
depending on their applicability on a case to case basis.
Note:
Each dose group and concurrent control group not intended to be sacrificed early should contain
atleast 50 animals of each sex. A high dose sattelite group for evaluation of pathology other than
neoplasia should contain 20 animals of each sex while the sattelite control group should contain 10
animals of each sex. Observation parameters should include signs of intoxication, effect on body
weight, food intake, clinical chemistry parameters, hematology parameters, urine analysis, organ
weights, gross pathology and detailed histopathology. Comprehensive descriptions of benign and
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malignant tumour development, time of their detection, site, dimensions, histological typing etc.
should be given.
1.8
Animal
toxicity
requirements for
clinic
al trials and marketing of a new drug.
Systemic Toxicity Studies
Route of administration
Duration of
proposed human
administration
Human Phase(s)
for which study is
proposed to be
conducted
Long term toxicity
requirements
1
[Oral or Parenteral or
Transdermal
Single dose or
several doses in one
day, Upto 1wk
I,II,III
2sp,2wks
> 1 wk but upto 2wks
I,II,III
2sp;4wks
Upto 2 wks
Marketing permission
2sp;4wks
> 2 wk but upto 4wks
I,II,III
2 sp; equal to duration of human
exposure
Marketing permission
2 sp; 12 wks
> 4 wks but upto 12 wks
I,II,III
2 sp; equal to duration of human
exposure
Marketing permission
2sp;24wks
> 12 wks but upto 24
wks
I,II,III
2 sp; equal to duration of human
exposure
Marketing permission
2 sp; Rodent 24 wks, non-rodent
36 wks
> 24 wks
I,II,III
2 sp; Rodent 24 wks, non-rodent
36 wks
Marketing permission
2 sp; Rodent 24 wks, non-rodent
36 wks]
Inhalation (general
anaesthetics, aerosols)
Upto 2 wk
I,II,III
2sp;1mo;
(Exposure time 3h/d,
5d/wk)
Upto 4wk
I,II,III
2sp;12wk,
(Exposure time
6h/d, 5d/wk)
> 1 4wk
I,II,III
2sp;24wk,
(Exposure time
6h/d, 5d/wk)
Local Toxicity Studies
Dermal
Upto 2 wk
I,II,
1sp;4wk
III
2sp;4wk
> 2 wk
I,II,III
2sp;12wk
Ocular or Otic or
Nasal
Upto 2 wk
I,II
1sp;4wk
III
2sp;4wk
> 2 wk
I,II,III
2sp;12wk
Vaginal or Rectal
Upto 2 wk
I,II
1sp;4wk
III
2sp;4wk
> 2 wk
I,II,III
2sp;12wk
1. Subs. by G.S.R. 287(E), dt. 08.3.2016.
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Special Toxicity Studies
Male Fertility Study:
1
[
Phase III in m
ale
volunteers/patients
]
Female Reproduction and Developmental Toxicity Studies:
Segment II studies in 2 species; Phase II, III involving female patients of child- bearing
age.
Segment I study; Phase III involving female patients of child-bearing age.
Segment III study; Phase III for drugs to be given to pregnant or nursing mothers for long
periods or where there are indications of possible adverse effects on foetal development.
Allergenicity/Hypersensitivity: Phase I, II, III - when there is a cause of concern or for parenteral
drugs (including derrmal application).
Photo-allergy or dermal photo-toxicity:
Phase I, II, III - if the drug or a metabolite is related to an agent causing
photosensitivity or the nature of action suggests such a potential.
Genotoxicity
:
In-vitro studies - Phase I
Both in-vitro and in-vivo - Phase II, III
Arcinogenicity:
Phase III - when there is a cause for concern, or when the drug is to be used for more
than 6
months.
Abbreviations: sp-species; mo-month; wk-week; d -day; h-hour; I, II, III - Phases of clinical trial;
Note:
1. Animal toxicity data generated in other countries may be accepted and may not be asked to be
repeated/duplicated in India on a case to case basis depending upon the quality of data and the
credentials of the laboratory(ies) where such data has been generated.
2. Requirements for fixed dose combinations are given in Appendix VI.
1.9 Number of animals required for repeated-dose toxicity studies
14-28 days 84-182 days
Group Rodent (Rat) Non-rodent
(Dog
or
Rodent (Rat) Non-rodent
(Dog
or
Monkey)
Monkey)
M
F
M
F
M
F
M
F
Control 6-10
6-10 2-3 2-3 15-30
15-30
4-6 4-6
Low dose 6-10
6-10 2-3 2-3 15-30
15-30
4-6 4-6
Intermediate 6-10
6-10 2-3 2-3 15-30
15-30
4-6 4-6
dose
High dose 6-10
6-10 2-3 2-3 15-30
15-30
4-6 4-6
1. Subs. by G.S.R. 287(E), dt. 08.3.2016.
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2.0 Laboratory parameters to be included in toxicity studies.
Haematological parameters
•
Haemoglobin
•
Total RBC
Count
•
Haematocrit
•
Reticulocyte Count
•
Total WBC Count
•
Differential WBC
Count
•
Platelet
Count
•
Terminal Bone
Marrow Examination
•
ESR (Non-
rodents only)
•
General Blood Picture: A special mention of abnormal and immature
cells should be made.
•
Coagulation Parameters (Non-rodents only): Bleeding Time, Coagulation Time, Prothrombin Time,
Activated
Partial
Thromboplastin Tim
e
Urinalysis Parameters:
•
Colour
•
Appearance
•
Specific
•
24-hour urinary
Gravity
output
• Reaction (pH) • Albumin •Sugar
•
Acetone
Bile pigments Urobilinogen
•
Occult
Blood
•
Microscopic examination of urinary sediment.
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Blood Biochemical Parameters
•
Glucose
•
Cholesterol
•
Triglycerides
•
HDL
Cholesterol
(Non-
rodents
only)
•
LDL
Cholesterol
(Non-rodents
•
Bilirubin
•
SGPT (ALT)
• SGOT
(AST)
only)
•
Alkaline
•
GGT
•
Blood Urea
•
Ceatinine
Phosphatase
(Non-rodents only)
(ALP)
• Total Proteins
•
Albumin
Nitrogen
•
Globulin
•
(Calculated
Sodium
values)
• • •
Potassium
Phosphorus
Calciu
m
Gross and Microscopic Pathology
•
Brain*:
Cerebrum,
cerebellum,
•
(Spinal Cord)
•
Eye
•
(Middle Ear)
Midbrain
•
Thyroid
•
Parathyroid)
•
Spleen
•
Thymus
•
Adrenal*
•
(Pancreas)
•
(Trachea)
•
Lung*
•
Heart*
•
Aorta
•
Oesophagus
•
Stomach
•
Duodenum
•
Jejunum
•
Terminal
•
Colon
ileum
•
(Rectum)
•
Liver*
•
Kidney*
•
Urinary bladder
•
Epididymis
•
Testis*
•
Ovary
•
Uterus*
•
Skin
•
Mammary
•
Mesenteric
• Skeletal muscle
gland
lymph node
* Organs marked with an asterisk should be weighed.
() Organs listed in parenthesis should be examined if indicated by the nature of the drug or
observed effects.
Non-clinical toxicity testing and safety evaluation data of an IND needed for the conduct of
different phases of clinical trials.
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Note: Refer Appendix III (Points 1.1 through 1.7 and tables 1.8 and 1.9) for essential
features of study designs of the non-clinical toxicity studies listed below.
For Phase I Clinical Trials
Systemic Toxicity studies
(i) Single dose toxicity studies
(ii) Dose Ranging Studies
(iii) Repeat-dose systemic toxicity studies of appropriate duration to support the
duration of proposed human exposure.
Male fertility study
In-vitro genotoxicity tests
Relevant local toxicity studies with proposed route of clinical application (duration
depending on proposed length of clinical exposure)
Allergenicity/Hypersensitivity tests (when there is a cause for concern or for
parenteral drugs, including dermal application)
Photo-allergy or dermal photo-toxicity test (if the drug or a metabolite is related to
an agent causing photosensitivity or the nature of action suggests such a potential)
For Phase II Clinical Trials
Provide a summary of all the non-clinical safety data (listed above) already submitted
while obtaining the permissions for Phase I trial, with appropriate references.
In case of an application for directly starting a Phase II trial - complete details of the
non- clinical safety data needed for obtaining the permission for Phase I trial, as per
the list provided above must be submitted.
Repeat-dose systemic toxicity studies of appropriate duration to support the duration
of proposed human exposure
In-vivo genotoxicity tests-
Segment II reproductive/developmental toxicity study (if female patients of child
bearing age are going to be involved)
For Phase III Clinical Trials
Provide a summary of all the non-clinical safety data (listed above) already
submitted while obtaining the permissions for Phase I and II trials, with appropriate
references.
In case of an application for directly initiating a Phase III trial - complete details
of the non-clinical safety data needed for obtaining the permissions for Phase I and II
trials, as per the list provided above must be provided.
Repeat-dose systemic toxicity studies of appropriate duration to support the duration
of proposed human exposure
Reproductive/developmental toxicity studies
Segment I (if female patients of child bearing age are going to be involved), and
Segment III (for drugs to be given to pregnant or nursing mothers or where there are
indications of possible adverse effects on foetal development).
Carcinogenicity studies (when there is a cause for concern or when the drug is to be
used for more than 6 months).
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For Phase IV Clinical Trials
Provide a summary of all the non-clinical safety data (listed above) already
submitted while obtaining the permissions for Phase I, II and III trials, with appropriate
references.
In case an application is made for initiating the Phase IV trial, complete details of the
non-clinical safety data needed for obtaining the permissions for Phase I, II and III trials, as
per the list provided above must be submitted.
Application Of Good Laboratory Practices (GLP)
The animal studies be conducted in an accredited laboratory. Where the safety
pharmacology studies are part of toxicology studies, these studies should also be conducted
in an accredited laboratory.
1. General Principles
APPENDIX IV
ANIMAL PHARMACOLOGY
Specific and general pharmacological studies should be conducted to support use of
therapeutics in humans. In the early stages of drug development enough information may
not be available to rationally select study design for safety assessment. In such a
situation, a general approach to safety pharmacology studies can be applied. Safety
pharmacology studies are studies that investigate potential undesirable pharmacodynamic
effects of a substance on physiological functions in relation to exposure within the
therapeutic range or above.
1.1 Specific Pharmacological Actions
Specific pharmacological actions are those which demonstrate the therapeutic potential
for humans.
The specific studies that should be conducted and their design will be different based on
the individual properties and intended uses of investigational drug. Scientifically validated
methods should be used. The use of new technologies and methodologies in accordance
with sound scientific principles should be preferred.
1.2 General Pharmacological Actions
1.2.1 Essential Safety Pharmacology
Safety pharmacology studies need to be conducted to investigate the potential
undesirable pharmacodynamic effects of a substance on physiological functions in relation
to exposure within the therapeutic range and above. These studies should be designed to
identify undesirable pharmacodynamic properties of a substance that may have relevance
to its human safety; to evaluate adverse pharmacodynamic and/or pathophysiological
effects observed in toxicology and/or clinical studies; and to investigate the mechanism of
the adverse pharmacodynamic effects observed and/or suspected.
The aim of the essential safety pharmacology is to study the effects of the test drug on
vital functions. Vital organ systems such as cardiovascular, respiratory and central nervous
systems should be studied. Essential safety pharmacology studies may be excluded or
supplemented based on scientific rationale. Also, the exclusion of certain
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test(s) or exploration(s) of certain organs, systems or functions should be scientifically
justified.
1.2.1.1 Cardiovascular System
Effects of the investigational drug should be studied on blood pressure, heart rate, and
the electrocardiogram. If possible in vitro, in vivo and/or ex vivo methods including
electrophysiology should also be considered.
1.2.1.2 Central Nervous System
Effects of the investigational drug should be studied on motor activity, behavioral
changes, coordination, sensory and motor reflex responses and body temperature.
1.2.1.3 Respiratory System
Effects of the investigational drug on respiratory rate and other functions such as tidal
volume and hemoglobin oxygen saturation should be studied.
1.3 Follow-up and Supplemental Safety Pharmacology Studies
In addition to the essential safety pharmacological studies, additional supplemental and
follow-up safety pharmacology studies may need to be conducted as appropriate. These
depend on the pharmacological properties or chemical class of the test substance, and the
data generated from safety pharmacology studies, clinical trials, pharmacovigilance,
experimental in vitro or in vivo studies, or from literature reports.
1.3.1 Follow-up Studies For Essential Safety Pharmacology
Follow-up studies provide additional information or a better understanding than
that provided by the essential safety pharmacology.
1.3.1.1 Cardiovascular System
These include ventricular contractility, vascular resistance and the effects of chemical
mediators, their agonists and antagonists on the cardiovascular system.
1.3.1.2 Central Nervous
System
These include behavioral studies , learning and memory, electrophysiology studies ,
neurochemistry and ligand binding studies.
1.3.1.3 Respiratory
System
These include airway resistance, compliance, pulmonary arterial pressure, blood gases
and blood pH.
1.3.2 Supplemental Safety Pharmacology Studies
These studies are required to investigate the possible adverse pharmacological effects
that are not assessed in the essential safety pharmacological studies and are a cause for
concern.
Drugs and Cosmetics Rules 1945
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1.3.2.1 Urinary System
These include urine volume, specific gravity, osmolality, pH, proteins, cytology and
blood urea nitrogen, creatinine and plasma proteins estimation.
1.3.2.2 Autonomic Nervous System
These include binding to receptors relevant for the autonomic nervous system, and
functional response to agonist or antagonist responses in vivo or in vitro, and effects of direct
stimulation of autonomic nerves and their effects on cardiovascular responses.
1.3.2.3 Gastrointestinal System
These include studies on gastric secretion, gastric pH measurement, gastric mucosal
examination, bile secretion, gastric emptying time in vivo and ileocaecal contraction in
vitro.
1.3.2.4 Other Organ Systems
Effects of the investigational drug on organ systems not investigated elsewhere
should be assessed when there is a cause for concern. For example dependency potential,
skeletal muscle, immune and endocrine functions may be investigated.
1.4 Conditions Under Which Safety Pharmacology Studies Are Not Necessary
Safety pharmacology studies are usually not required for locally applied agents e.g.
dermal or ocular, in cases when the pharmacology of the investigational drug is well known,
and/or when systemic absorption from the site of application is low. Safety pharmacology
testing is also not necessary, in the case of a new derivative having similar pharmacokinetics
and pharmacodynamics.
1.5 Timing Of Safety Pharmacology Studies In Relation To Clinical Development
1.5.1 Prior To First Administration In Humans
The effects of an investigational drug on the vital functions listed in the essential safety
pharmacology should be studied prior to first administration in humans. Any follow-up or
supplemental studies identified, should be conducted if necessary, based on a cause for
concern.
1.5.2 During Clinical Development
Additional investigations may be warranted to clarify observed or suspected
adverse effects in animals and humans during clinical development
1.5.3 Before applying for marketing
Approval
Follow-up and supplemental safety pharmacology studies should be assessed prior to
approval unless not required, in which case this should be justified. Available
information from toxicology studies addressing safety pharmacology endpoints or
information from clinical studies can replace such studies.
1.6 Application Of Good Laboratory Practices
(GLP)
The animal studies be conducted in an accredited laboratory. Where the safety
pharmacology studies are part of toxicology studies, these studies should also be conducted
in an accredited laboratory.
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APPENDIX
V
INFORMED
CONSENT
1. Checklist for study Subject‘s informed consent
documents
1.1 Essential Elements:
1. Statement that the study involves research and explanation of the purpose of the research
2. Expected duration of the Subject's
participation.
3. Description of the procedures to be followed, including all invasive procedures and
4. Description of any reasonably foreseeable risks or discomforts to the Subject
5. Description of any benefits to the Subject or others reasonably expected from research. If no
benefit is expected Subject should be made aware of this.
6. Disclosure of specific appropriate alternative procedures or therapies available to the
Subject.
7. Statement describing the extent to which confidentiality of records identifying the Subject
will be maintained and who will have access to Subject‘s medical records
8. Trial treatment schedule(s) and the probability for random assignment to each treatment (for
randomized trials)
9.
1
[Statement describing the financial compensation and medical management as under:
2
[(a) In case of any injury occurring to the subject during the clinical trial, free medical
management shall be given as long as required or till such time it is established that the
injury is not related to the clinical trial, whichever is earlier.]
(b) In the event of a trial related injury or death, the Sponsor or his representative,
whosoever has obtained permission from the Licensing Authority for conduct of the clinical
trial, shall provide financial compensation for the injury or death].
10. An explanation about whom to contact for trial related queries, rights of Subjects and in the
event of any injury
11. The anticipated prorated payment, if any, to the Subject for participating in the trial
12. Subject's responsibilities on participation in the trial
13. Statement that participation is voluntary, that the subject can withdraw from the study at any
time and that refusal to participate will not involve any penalty or loss of benefits to which
the Subject is otherwise entitled.
3
[14. Statement that there is a possibility of failure of investigational product to provide
intended therapeutic effect.
15. Statement that in the case of placebo controlled trial, the placebo administered to the
subjects shall not have any therapeutic effect.
16.Any other pertinent information.]
1.2 Additional elements, which may be required
(a) Statement of foreseeable circumstances under which the Subject's participation may be
terminated by the Investigator without the Subject's consent.
(b) Additional costs to the Subject that may result from participation in the study.
(c) The consequences of a Subject‘s decision to withdraw from the research and
procedures for orderly termination of participation by Subject.
(d) Statement that the Subject or Subject's representative will be notified in a timely manner
if significant new findings develop during the course of the research which may affect the Subject's
willingness to continue participation will be provided.
(e) A statement that the particular treatment or procedure may involve risks to the Subject (or
to the embryo or fetus, if the Subject is or may become pregnant), which are currently
unforeseeable
(f) Approximate number of Subjects enrolled in the study.
1. Subs. by G.S.R. 53(E), dt. 30-01-2013. 3. G.S.R. 611(E), dt. 31-7-2015.
2. Subs. by G.S.R. 889(E), dt. 12-12-2014.
Drugs and Cosmetics Rules 1945
621
2. Format of informed consent form for Subjects participating in a clinical trial
Informed Consent form to participate in a clinical trial
Study Title:
Study Number:
Subject‘s Initials: _________ Subject‘s Name: ______________
Date of Birth / Age: _______
1
[Address of the Subject______________
Qualification ______________________
Occupation: Student/Self-Employed/ Service/Housewife/Others (Please tick as appropriate)
Annual Income of the subject __________________
Name and address of the nominee(s) and his relation to the subject ________ (for the purpose of
compensation in case of trial related death).]
Please initial
box
(Subject)
(i) I confirm that I have read and understood the information sheet dated [ ]
for the above study and have had the opportunity to ask questions.
(ii) I understand that my participation in the study is voluntary and that I am [ ]
free to withdraw at any time, without giving any reason, without my
medical care or legal rights being affected.
(iii) I understand that the Sponsor of the clinical trial, others working on the [ ]
Sponsor‘s behalf, the Ethics Committee and the regulatory authorities
will not need my permission to look at my health records both in respect
of the current study and any further research that may be conducted in
relation to it, even if I withdraw from the trial. I agree to this access.
However, I understand that my identity will not be revealed in any
information released to third parties or published.
(iv) I agree not to restrict the use of any data or results that arise from this [ ]
study provided such a use is only for scientific purpose(s)
(v) I agree to take part in the above study. [ ]
Signature (or Thumb impression) of the Subject/Legally Acceptable
Representativ
e:
_________________________________________________________________
Date: /
_/
Signatory‘s
Name:
Signature
of
t
h
e
Investigator:
_______________________________________________
Date:
Study
Investigator‘s
Name:
Signature
of
t
h
e
Witness
Date:
/
/
Name
of
the
Witness:
1
[Copy of the Patient Information Sheet and duly filled Informed Consent Form shall be
handled over to the subject or his/her attendant.]
1. Ins. by G.S.R 53(E), dt. 30-01-2013
Drugs and Cosmetics Rules, 1945
622
APPENDIX
VI
FIXED DOSE COMBINATIONS
(FDCs)
Fixed Dose Combinations refer to products containing one or more active ingredients used for a
particular indication(s). FDCs can be divided into the following groups and data required for approval
for marketing is described below:
(a) The first group of FDCs includes those in which one or more of the active ingredients is a
new drug. For such FDCs to be approved for marketing data to be submitted will be similar to data
required for any new drug (including clinical trials) [see rule 122E, item (a)].
(b)(i) The second group FDCs includes those in which active ingredients already
approved/marketed individually are combined for the first time, for a particular claim and where the
ingredients are likely to have significant interaction of a pharmacodynamic or pharmacokinetic nature
[see rule 122E, item (c)]. If clinical trials have been carried out with the FDC in other countries, reports
of such trials should be submitted. If the FDC is marketed abroad, the regulatory status in other
countries should be stated. (see Appendix I, item 9).
(ii) For marketing permission, appropriate chemical and pharmaceutical data will be submitted.
In case such a combination is not marketed anywhere in the world but these drugs are already in use
concomitantly (not as an FDC but individually) for the said claim, marketing permission may be
granted based on chemical and pharmaceutical data. Data showing the stability of the proposed dosage
form will also have to be submitted.
(iii) For any other such FDCs, clinical trials may be required. For obtaining permission to
carry out clinical trials with such FDCs a summary of available pharmacological, toxicological and
clinical data on the individual ingredients should be submitted, along with the rationale for combining
them in the proposed ratio. In addition, acute toxicity data (LD 50) and pharmacological data should be
submitted on the individual ingredients as well as their combination in the proposed ratio.
(c) The third group of FDCs includes those which are already marketed, but in which it is
proposed either to change the ratio of active ingredients or to make a new therapeutic claim. For such
FDCs, the appropriate rationale including published reports (if any) should be submitted to obtain
marketing permission. Permission will be granted depending upon the nature of the claim and data
submitted.
(d) The fourth group of FDC includes those whose individual active ingredients (or drugs from
the same class) have been widely used in a particular indication(s) for years, their concomitant use is
often necessary and no claim is proposed to be made other than convenience. It will have to be
demonstrated that the proposed dosage form is stable and the ingredients are unlikely to have significant
interaction of a pharmacodynamic or pharmacokinetic nature.
No additional animal or human data are generally required for these FDCs, and marketing permission may
be granted if the FDC has an acceptable rationale.
APPENDIX VII
UNDERTAKING BY
THE
INVESTIGATOR
1. Full name, address and title of the Principal Investigator (or Investigator(s) when there is no
Principal Investigator)
2. Name and address of the medical college, hospital or other facility where the clinical trial will be
conducted: Education, training & experience that qualify the Investigator for the clinical trial (Attach
details including Medical Council registration number, and / or any other statement(s) of qualification(s))
3. Name and address of all clinical laboratory facilities to be used in the study.
Drugs and Cosmetics Rules, 1945
623
4. Name and address of the Ethics Committee that is responsible for approval and continuing
review of the study.
5. Names of the other members of the research team (Co- or sub-Investigators) who will be
assisting the Investigator in the conduct of the investigation (s).
6. Protocol Title and Study number (if any) of the clinical trial to be conducted by the
Investigator.
7. Commitments:
(i) I have reviewed the clinical protocol and agree that it contains all the necessary
information to conduct the study. I will not begin the study until all necessary Ethics
Committee and regulatory approvals have been obtained.
(ii) I agree to conduct the study in accordance with the current protocol. I will not
implement any deviation from or changes of the protocol without agreement by the Sponsor
and prior review and documented approval / favorable opinion from the Ethics Committee of the
amendment, except where necessary to eliminate an immediate hazard(s) to the trial
Subjects or when the change(s) involved are only logistical or administrative in nature.
(iii) I agree to personally conduct and/or supervise the clinical trial at my site.
(iv) I agree to inform all Subjects, that the drugs are being used for investigational purposes
and I will ensure that the requirements relating to obtaining informed consent and ethics
committee review and approval specified in the GCP guidelines are met.
(v) I agree to report to the Sponsor all adverse experiences that occur in the course of the
investigation(s) in accordance with the regulatory and GCP guidelines.
(vi) I have read and understood the information in the Investigator's brochure, including the
potential risks and side effects of the drug.
(vii) I agree to ensure that all associates, colleagues and employees assisting in the conduct
of the study are suitably qualified and experienced and they have been informed about their
obligations in meeting their commitments in the trial.
(viii) I agree to maintain adequate and accurate records and to make those records available
for audit / inspection by the Sponsor, Ethics Committee, Licensing Authority or their authorized
representatives, in accordance with regulatory and GCP provisions. I will fully cooperate with
any study related audit conducted by regulatory officials or authorized representatives of the
Sponsor.
(ix) I agree to promptly report to the Ethics Committee all changes in the clinical trial
activities and all unanticipated problems involving risks to human Subjects or others.
(x) I agree to inform all unexpected serious adverse events to the Sponsor as well as the
Ethics Committee within seven days of their occurence.
(xi) I will maintain confidentiality of the identification of all participating study patients and
assure security and confidentiality of study data.
(xii) I agree to comply with all other requirements, guidelines and statutory obligations as
applicable to clinical Investigators participating in clinical trials
8. Signature of Investigator with Date
Drugs and Cosmetics Rules, 1945
624
APPENDIX
VIII
ETHICS
COMMITTEE
1
[I. Requirements and guidelines for registration of Ethics Committee
1. Scope:
Ethics Committee shall review every clinical trial proposal and evaluate the possible
risks to the subjects, expected benefits and adequacy of documentation for ensuring privacy,
confidentiality and justice. In the case of any serious adverse event occurring to the clinical trial
subjects during the clinical trial, the Ethics Committee shall analyze and forward its opinion as
per procedures specified in APPENDIX XII of Schedule Y.
2. Composition of Ethics Committee:
(a) Ethics Committee shall consist of not less than seven members and one among its
members, who is from outside the institute, shall be appointed as Chairman; one member as a
Member Secretary and rest of the members shall be from Medical, Scientific, Non-medical and
Non-scientific fields including lay public.
(b) The committee shall include at least one member whose primary area of interest or
specialization is Non-scientific and at least one member who is independent of the institution.
Besides, there should be appropriate gender representation on the Ethics Committee.
(c) The Ethics Committee can have as its members, individuals from other
Institutions or Communities, if required.
(d) Members should be conversant with the provisions of clinical trials under this Schedule,
Good Clinical Practice Guidelines for clinical trials in India and other regulatory requirements
to safeguard the rights, safety and well- being of the trial subjects.
(e) For review of each protocol the quorum of Ethics Committee shall be at least five
members with the following representations:
(i) Basic medical scientist (preferably one pharmacologist)
(ii) Clinician;
(iii) Legal expert;
(iv) Social scientist or representative of non-governmental voluntary agency or
philosopher or ethicist or theologian or a similar person;
(v) Lay person from community.
(f) The members representing medical scientists and clinicians should have post graduate
qualification and adequate experience in their respective fields and aware of their
role and responsibilities as committee members.
(g) As far as possible, based on the requirement of research area such as HIV, Genetic
disorder etc., specific patient group may also be represented in the Ethics
Committee.
(h) There should be no conflict of interest. The members shall voluntarily withdraw
from the Ethics Committee meeting while making a decision on an application
which evokes a conflict of interest which may be indicated in writing to the
Chairman prior to the review and be recorded so in the minutes. All members shall
sign a declaration on conflict of interest.
(i) Subject experts or other experts may be invited to the meetings for their advice. But
no such expert shall have voting rights.
3. Information required to be submitted by the applicant for registration of Ethics
Committee:
(a) Name of the Ethics Committee
(b) Authority under which the Ethics Committee has been constituted, membership
requirements, the term of reference, conditions of appointment and the quorum
required.
1. Subs. by G.S.R. 72(E), dt. 8-2-2013.
Drugs and Cosmetics Rules, 1945
625
(c) The procedure for resignation, replacement or removal of members.
(d) Address of the office of the Ethics Committee.
(e) Name, address, qualification, organizational title, telephone number, fax number,
email, mailing address and brief profile of the Chairman.
(f) Names, qualifications, organizational title, telephone number, fax number, e-mail and
mailing address of the members of the Ethics Committee. The information shall also
in clude member ‘s specialty (pr imary, scientific or non -scientific), member ‘s
affiliation with institutions and patient group representation, if any.
(g) Details of the supporting staff.
(h) In the case of Ethics Committees existing before the publication of the Drugs and
Cosmetics (Third Amendment) Rules, 2013,-
(i) Type of clinical research reviewed by the committee (e.g. pharmaceuticals,
devices, epidemiological, retrospective, herbals, etc.)
(ii) Documents reviewed for every clinical trial protocol including Informed
Consent documents.
(iii) In for mation in respect of number of meetings of the committee and
documentation of the minutes of meetings of these committees concerning
clinical trials.
(iv) Information regarding review of serious adverse events reported during the
conduct of the trial.
(i) The Standard Operating Procedures to be followed by the committee in general.
(j) Standard Operating Procedures to be followed by the committee for vulnerable
population.
(k) Policy regarding training for new and existing committee members along with
Standard Operating Procedures.
(l) Policy to monitor or prevent the conflict of interest along with Standard Operating
Procedures.
(m) If the committee has been audited or inspected before, give details.
4. Maintenance of record:
All documentation and communication of an Ethics Committee are to be dated, filed and
preserved according to the Standard Operating Procedures. Strict confidentiality shall
be maintained during access and retrieval procedures. Records should be maintained
for the following, namely:-
(a) The constitution and composition of the Ethics Committee; (b) The curriculum vitae
of all the committee members;
(c) Standard Operating Procedures followed by the committee; (d) National and
international guidelines;
(e) Copies of the protocol, data collection formats, Case Report Forms, Investigator‘s
brochures, etc, submitted for review;
(f) All correspondence with committee members and Investigators regarding
application, decision and follow up;
(g) Agenda of all Ethics Committee meetings;
(h) Minutes of all Ethics Committee meetings with signature of the Chairman; (i)
Copies of decisions communicated to the applicants;
(j) Record of all notification issued for premature termination of a study with a
summary of the reasons;
(k) Final report of the study including microfilms, compact disks or video-recordings.
All records shall be safely maintained after the completion or termination of the
study for not less than five years from the date of completion or termination of the
trial (Both in hard and soft copies).
5. The Ethics Committee shall be open to inspection by the officers authorized by the Central
Drugs Standard Control Organization, who may include an officer of the State Drug Control
Authority concerned, to verify compliance to the requirements of Schedule Y, Good Clinical
Drugs and Cosmetics Rules, 1945
626
Practice guidelines and other applicable regulation for safeguarding the rights, safety and
well-being of the trial subjects.]
III. Format for According Approval to clinical trial protocol by the Ethics Committee.]
To
Dr.
Dear
Dr.
The Institutional Ethics Committee / Independent Ethics Committee (state name of the
committee, as appropriate) reviewed and discussed your application to conduct the clinical trial
entitled ―……‖ on …….(date).
The following documents were reviewed:
(a) Trial Protocol (including protocol amendments), dated Version no
(s).
(b) Patient Information Sheet and Informed Consent Form (including updates if any) in English and/or
vernacular language.
(c)
Investigator‘s
Brochure,
dated
,
Version
no.
(d) Proposed methods for patient accrual including advertisement (s) etc. proposed to be used for
the purpose.
(e) Principal Investigator‘s current CV.
(f) Insurance Policy / Compensation for participation and for serious adverse events occurring during
the study participation.
(g) Investigator‘s Agreement with the Sponsor.
(h) Investigator‘s Undertaking (Appendix VII).
The following members of the ethics committee were present at the meeting held on (date, time,
place).
Chairman of the Ethics Committee
Member secretary of the Ethics Committee
Name of each member with designation
We approve the trial to be conducted in its presented form.
The Institutional Ethics Committee / Independent Ethics Committee expects to be informed about the
progress of the study, any SAE occurring in the course of the study, any changes in the protocol and
patient information/informed consent and asks to be provided a copy of the final report.
Yours sincerely,
Member Secretary, Ethics Committee.
Drugs and Cosmetics Rules, 1945
627
APPENDIX
IX
STABILITY TESTING OF NEW
DRUGS
Stability testing is to be performed to provide evidence on how the quality of a drug substance or
formulation varies with time under the influence of various environmental factors such as temperature,
humidity and light, and to establish shelf life for the formulation and recommended storage conditions.
Stability studies should include testing of those attributes of the drug substance that are susceptible
to change during storage and are likely to influence quality, safety, and/or efficacy. In case of
formulations the testing should cover, as appropriate, the physical, chemical, biological, and
microbiological attributes, preservative content (e.g., antioxidant, antimicrobial preservative), and
functionality tests (e.g., for a dose delivery system).
Validated stability-indicating analytical procedures should be applied. For long term studies,
frequency of testing should be sufficient to establish the stability profile of the drug substance.
In general, a drug substance should be evaluated under storage conditions that test its thermal
stability and, if applicable, its sensitivity to moisture. The storage conditions and the length of studies
chosen should be sufficient to cover storage, shipment and subsequent use.
Stress testing of the drug substance should be conducted to identify the likely degradation products,
which in turn establish the degradation pathways, evaluate the intrinsic stability of the molecule and
validate the stability indicating power of the analytical procedures used. The nature of the stress testing
will depend on the individual drug substance and the type of formulation involved.
Stress testing may generally be carried out on a single batch of the drug substance. It should
include the effect of temperatures ), humidity where appropriate, oxidation, and photolysis on the
drug substance.
Data should be provided for (a) Photostability on at least one primary batch of the drug substance
as well as the formulation, as the case may be and (b) the susceptibility of the drug substance to
hydrolysis across a wide range of pH values when in solution or suspension.
Long-term testing should cover a minimum of 12 months‘ duration on at least three primary
batches of the drug substance or the formulation at the time of submission and should be continued for a
period of time sufficient to cover the proposed shelf life. Accelerated testing should cover a
minimum of 6 months duration at the time of submission.
In case of drug substances, the batches should be manufactured to a minimum of pilot scale by the
same synthetic route and using a method of manufacture that simulates the final process to be used for
production batches. In case of formulations, two of the three batches should be at least pilot scale and
the third one may be smaller. The manufacturing process(es) used for primary batches should simulate
that to be applied to production batches and should provide products of the same quality and meeting the
same specifications as that intended for marketing.
The stability studies for drug substances should be conducted either in the same container - closure
system as proposed for storage and distribution or in a container - closure system that simulates the
proposed final packaging. In case of formulations, the stability studies should be conducted in the final
container - closure system proposed for marketing.
Stability Testing of new drug substances and formulations:
(i) Study conditions for drug substances and formulations intended to be stored under
general conditions
Drugs and Cosmetics Rules, 1945
628
Study
Study conditions
Duration of study
Long term
30°C ± 2°C/65% RH ± 5% RH
12 months
Accelerated
40°C ± 2°C/75% RH ± 5% RH
6 months
If at any time during 6 months‘ testing under the accelerated storage condition, such changes occur that
cause the product to fail in complying with the prescribed standards, additional testing under an
intermediate storage condition should be conducted and evaluated against significant change criteria.
(ii) Study conditions for drug substances and formulations intended to be stored in a refrigerator
Study
Study conditions
Duration of study
Long term
5°C ± 3°C
12 months
Accelerated
25°C ± 2°C/60% RH ± 5% RH
6 months
(iii) Study conditions for drug substances and formulations intended to be stored
in
a freezer
Study Study conditions Duration of
study____________________
Long term - 20°C ± 5°C 12 months
(iv) Drug substances intended for storage below -20°C shall be treated on a case-by-
case basis.
(v) Stability testing of the formulation after constitution or dilution, if applicable,
should be conducted to provide information for the labelling on the preparation, storage
condition, and in-use period of the constituted or diluted product. This testing should be
performed on the constituted or diluted product through the proposed in-use period.
APPENDIX
X
CONTENTS OF THE PROPOSED PROTOCOL FOR CONDUCTING
CLINICAL
TRIALS
1. Title Page
(a) Full title of the clinical study,
(b) Protocol / Study number, and protocol version number with date
(c) The IND name/number of the investigational drug
(d) Complete name and address of the Sponsor and contract research organization if any
(e) List of the Investigators who are conducting the study, their respective institutional
affiliations and site locations
(f) Name(s) of clinical laboratories and other departments and/or facilities participating in
the study.
2. Table of Contents
A complete Table of Contents including a list of all
Appendices.
1. Background and Introduction
(a) Preclinical experience.
(b) Clinical experience.
Previous clinical work with the new drug should be reviewed here and a description of how the
current protocol extends existing data should be provided. If this is an entirely new indication, how this
drug was considered for this should be discussed. Relevant information regarding pharmacological,
toxicological and other biological properties of the drug/biologic/medical device, and previous efficacy
and safety experience should be described.
Drugs and Cosmetics Rules, 1945
629
2. Study Rationale
This section should describe a brief summary of the background information relevant to the study
design and protocol methodology. The reasons for performing this study in the particular population
included by the protocol should be provided.
3. Study Objective(s) (primary as well as secondray) and their logical relation to the study design.
4. Study Design
(a) Overview of the Study Design: Including a description of the type of study (i.e., double-blind,
multicentre, placebo controlled, etc.), a detail of the specific treatment groups and number of study
Subjects in each group and investigative site, Subject number assignment, and the type, sequence
and duration of study periods.
(b) Flow chart of the study
(c) A brief description of the methods and procedures to be used during the study.
(d) Discussion of Study Design: This discussion details the rationale for the design chosen for this
study.
5. Study Population: the number of Subjects required to be enrolled in the study at the investigative site
and by all sites along with a brief description of the nature of the Subject population required is also
mentioned.
6. Subject Eligibility
(a) Inclusion Criteria
(b) Exclusion Criteria
7. Study Assessments – plan, procedures and methods to be described in detail
8. Study Conduct stating the types of study activities that would be included in this section
would be: medical history, type of physical examination, blood or urine testing, electrocardiogram
(ECG), diagnostic testing such as pulmonary function tests, symptom measurement, dispensation and
retrieval of medication, Subject cohort assignment, adverse event review, etc.
Each visit should be described separately as Visit 1, Visit 2, etc.
Discontinued Subjects: Describes the circumstances for Subject withdrawal, dropouts, or other
reasons for discontinuation of Subjects . State how dropouts would be managed and if they would be
replaced, describe the method of handling of protocol waivers, if any. The person(s) who approves all
such waivers should be identified and the criteria used for specific waivers should be provided.
Describes how protocol violations will be treated, including conditions where the study will be
terminated for non-compliance with the protocol.
9. Study Treatment
(a) Dosing schedule (dose, frequency, and duration of the experimental treatment) Describe the
administration of placebos and/or dummy medications if they are part of the treatment plan. If
applicable, concomitant drug(s), their doses, frequency, and duration of concomitant treatment should be
stated.
(b) Study drug supplies and administration: A statement about who is going to provide the study
medication and that the investigational drug formulation has been manufactured following all
regulations Details of the product stability, storage requirements and dispensing requirements
should be provided.
(c) Dose modification for study drug toxicity: Rules for changing the dose or stopping the study drug
should be provided.
(d) Possible drug interactions.
(e) Concomitant therapy: The drugs that are permitted during the study and the conditions under
which they may be used are detailed here. Describe the drugs that a Subject is not allowed to use during
Drugs and Cosmetics Rules, 1945
630
parts of or the entire study. If any washout periods for prohibited medications are needed prior to
enrolment, these should be described here.
(f) Blinding procedures: A detailed description of the blinding procedure if the study employs a blind
on the Investigator and/or the Subject.
(g) Unblinding procedures: If the study is blinded, the circumstances in which unblinding may be
done and the mechanism to be used for unblinding should be given.
10. Adverse Events (See Appendix XI): Description of expected adverse events should be given.
Procedures used to evaluate an adverse event should be described.
11. Ethical Considerations: Give the summary of:
(a) Risk/benefit assessment:
(b) Ethics Committee review and communications.
(c) Informed consent process.
(d) Statement of Subject confidentiality including ownership of data and coding procedures.
12. Study Monitoring and Supervision: A description of study monitoring policies and procedures
should be provided along with the proposed frequency of site monitoring visits, and who is expected to
perform monitoring.
Case Record Form (CRF) completion requirements, including who gets which copies of the forms
and any specifics required in filling out the forms CRF correction requirements, including who is
authorized to make corrections on the CRF and how queries about study data are handled and how
errors, if any, are to be corrected should be stated.
Investigator study files, including what needs to be stored following study completion should be
described.
13. Investigational Product Management
(a) Give Investigational product description and packaging (stating all Ingredients and the
formulation of the investigational drug and any placebos used in the study)
(b) The precise dosing required during the study.
(c) Method of packaging, labelling, and blinding of study substances.
(d) Method of assigning treatments to Subjects and the Subject identification code numbering
system.
(e) Storage conditions for study substances.
(f) Investigational product accountability: Describe instructions for the receipt, storage, dispensation,
and return of the investigational products to ensure a complete accounting of all investigational
products received, dispensed, and returned/destroyed.
(g.) Describe policy and procedure for handling unused investigational products.
14. Data Analysis:
Provide details of the statistical approach to be followed including sample size, how the
sample size was determined, including assumptions made in making this determination, efficacy
endpoints (primary as well as secondary) and safety endpoints.
Statistical analysis: Give complete details of how the results will be analyzed and reported along
with the description of statistical tests to be used to analyze the primary and secondary endpoints
defined above. Describe the level of significance, statistical tests to be used, and the methods used for
missing data; method of evaluation of the data for treatment failures, non-compliance, and Subject
withdrawals; rationale and conditions for any interim analysis if planned.
Describe statistical considerations for Pharmacokinetic (PK) analysis, if applicable.
15. Undertaking by the Investigator (see Appendix VII).
Drugs and Cosmetics Rules, 1945
631
16. Appendices: Provide a study synopsis, copies of the informed consent documents (patient
information sheet, informed consent form etc.); CRF and other data collection forms; a summary of
relevant pre-clinical safety information and any other documents referenced in the clinical protocol.
APPENDIX
XI
Data Elements for reporting serious adverse events occuring in a clinical trial
1. Patient Details
Initials & other relevant identifier (hospital/OPD record number etc.)* Gender
Age and/or date of birth
Weight
Height
2. Suspected Drug(s)
Generic name of the drug*.
Indication(s) for which suspect drug was prescribed or tested. Dosage form and strength.
Daily dose and regimen (specify units - e.g., mg, ml, mg/kg).
Route of administration.
Starting date and time of day.
Stopping date and time, or duration of treatment
3. Other Treatment(s)
Provide the same information for concomitant drugs (including non prescription/OTC
drugs) and non-drug therapies, as for the suspected drug(s).
4. Details of Suspected Adverse Drug Reaction(s)
Full description of reaction(s) including body site and severity, as well as the criterion (or criteria)
for regarding the report as serious. In addition to a description of the reported signs and
symptoms, whenever possible, describe a specific diagnosis for the reaction.*
Start date (and time) of onset of reaction.
Stop date (and time) or duration of reaction.
Dechallenge and rechallenge information.
Setting (e.g., hospital, out-patient clinic, home, nursing home).
5. Outcome
Information on recovery and any sequelae; results of specific tests and/or treatment that may
have been conducted.
For a fatal outcome, cause of death and a comment on its possible relationship to the suspected
reaction; any post-mortem findings.
Other information: anything relevant to facilitate assessment of the case, such as medical history
including allergy, drug or alcohol abuse; family history; findings from special investigations etc.
6. Details about the Investigator*
Name
Address
Telephone number
Profession (speciality)
Date of reporting the event to Licensing Authority:
Date of reporting the event to Ethics Committee overseeing the site:
Signature of the Investigator
Note: Information marked * must be provided.‖]
Drugs and Cosmetics Rules, 1945
632
1
[APPENDIX
XII
Compensation in case of injury or death during clinical trial
2
[(1) In case of an injury occurring to the subject during the clinical trial, free medical
management shall be given as long as required or till such time it is established that
the injury is not related to the clinical trial, whichever is earlier.]
(2) In case the injury occurring to the trial subject is related to the clinical trial, such
subject shall also be entitled for financial compensation as per order of the
Licensing Authority defined under clause (b) of Rule 21 and the financial
compensation will be over and above any expenses incurred on the medical
management of the subject.
3
[In case, there is no permanent injury, the quantum of
compensation shall be commensurate with the nature of the non-permanent injury
and loss of wages.]
(3) In the case of clinical trial related death of the subject, his/her nominee(s) would be
entitled for financial compensation as per the order of the Licensing Authority
defined under clause (b) of Rule 21, and the financial compensation will be over
and above any expenses incurred on the medical management of the subject.
(4) The financial compensation for clinical trial related injury or death could be in the
form of:-
(a) Payment for medical management;
(b) Financial compensation for trail related injury;
(c) Financial compensation to nominee(s) of the trial subject in case of death;
(d) Financial compensation for the child injured in–utero because of the
participation of parent in clinical trial.
(5) The Sponsor or his representative, whosoever had obtained permission from the
Licensing Authority for conduct of the clinical trial shall provide financial
compensation, if the injury or death has occurred because of any or the following
reasons, namely:-
(a) Adverse effect of investigational product(s);
(b) Any clinical trial procedures involved in the study;
(c) Violation of the approved protocol, scientific misconduct or negligence by the
Sponsor or his representative or the Investigator;
(d) Failure of investigational product to provide intended therapeutic effect; where,
the standard care, though available, was not provided to the subject as per the
clinical trial protocol.
(e) Use of placebo in a placebo-controlled trial, where, the standard care, though
available, was not provided to the subject as per the clinical trial protocol;
1. Ins. by G.S.R. 53(E), dt. 30.1.2013.
2. Subs. by G.S.R. 889(E), dt. 12.12.2014.
3. Ins. by G.S.R. 889(E), dt. 12.12.2014.
Drugs and Cosmetics Rules, 1945
633
(f) Adverse effects due to concomitant medication excluding standard care,
necessitated as part of approved protocol;
(g) Injury to the child in-utero because of the participation of parent in clinical trial.
(6) Procedure for payment of financial compensation.
(a) The Investigator shall report all serious
1
[***] adverse events to the Licensing
Authority as defined under clause (b) of Rule 21, the Sponsor or his representative
whosoever had obtained permission from the Licensing Authority for conduct of
the clinical trial and the Ethics Committee that accorded approval to the study
protocol, within twenty four hours of their occurrence as per Appendix XI.
2
[In
case, the Investigator fails to report any serious adverse event within the stipulated
period, he shall have to furnish the reason for the delay to the satisfaction of the
Licensing Authority along with the report of the serious adverse event.]
(b) (i) The cases of serious adverse events of death shall be examined as under:
(A) An independent Expert Committee shall be constituted by the Licensing
Authority as defined under Rule 21(b) to examine the cases and recommend to
the Licensing Authority for the purpose of arriving at the cause of death and
quantum of compensation in case of clinical trial related death.
(B)The Sponsor or his representative, whosoever had obtained permission from
the Licensing Authority for conducting the clinical trial and the Investigator
shall forward their reports on serious adverse event of death after due analysis
to
3
[***] the Licensing Authority as defined under Rule 21(b) and the head of
the Institution where the trial has been conducted within
4
[fourteen days] of
occurrence of the serious adverse event of death.
(C) The Ethics Committee shall forward its report on serious adverse event of
death after due analysis along with its opinion on the financial compensation, if
any, to be paid by the Sponsor or his representative, whosoever had obtained
permission from the Licensing Authority as defined under Rule 21(b) for
conducting the clinical trial,
5
[***] to the Licensing Authority within
6
[thirty
days] of the occurrence of the serious adverse event of death.
2
[(CA) The Licensing Authority shall forward the report of the Investigator,
Sponsor or his representative whosoever had obtained permission from the
Licensing Authority for conducting clinical trial and the Ethics Committee to
the Chairman of the Expert Committee.]
1. The word ―and unexpected‖ omitted by G.S.R. 889(E), dt. 12.12.2014.
2. Ins. by G.S.R. 889(E), dt. 12.12.2014.
3. The word ―Chairman of the Expert Committee with a copy of the report to‖ omitted by
G.S.R. 889(E), dt. 12.12.2014.
4. Subs. by G.S.R. 889(E), dt. 12.12.2014.
5. The word ―to the Chairman of the Expert Committee with a copy of the report‖ omitted by
G.S.R. 889(E), dt. 12.12.2014.
6. Subs. by G.S.R. 889(E), dt. 12.12.2014.
Drugs and Cosmetics Rules, 1945
634
(D) The Expert Committee shall examine the report of serious adverse event of
death and give its recommendations to the Licensing Authority for the
purpose of arriving at the cause of the adverse event with in
1
[one hundred
and five days of the occurrence of the adverse event,] and the expert
committee while examining the event, may take into consideration, the
reports of the Investigator, Sponsor or his representative whosoever had
obtained permission from the Licensing Authority for conducting the
clinical trial and the Ethics Committee.
(E) In the case of clinical trial related death, the Expert Committee shall also
recommend the quantum of compensation to be paid by the Sponsor or his
representative, whosoever had obtained permission from the Licensing
Authority as defined under Rule 21(b) for conducting the clinical trial.
(F) The Licensing Authority shall consider the recommendations of the Expert
Committee and shall determine the cause of death and pass orders as
deemed necessary.
(G) In case of clinical trial related death, the Licensing Authority, after
considering the recommendations of the Expert Committee, shall decide
the quantum of compensation to be paid by the Sponsor or his
representative, whosoever had obtained permission from the Licensing
Authority for conducting the clinical trial and shall pass orders as deemed
necessary within
1
[one hundred and fifty days of the occurrence of the
adverse event]
.
(ii) Cases of serious adverse events, other than deaths, shall be examined as under:
(A) The Sponsor or his representative, whosoever had obtained permission
from the Licensing Authority for conducting the clinical trial, and the
Investigator shall forward their reports on serious adverse event, after
due analysis, to the Licensing Authority as defined under Rule 21(b),
Chairman of the Ethics Committee and the head of the Institution where
the trial has been conducted within
1
[fourteen days] of occurrence of the
serious adverse event.
(B) The Ethics Committee shall forward its report on the serious adverse
event, after due analysis along with its opinion regarding the financial
compensation, if any, to be paid by the Sponsor or his representative,
whosoever had obtained permission from the Licensing Authority as
defined under Rule 21(b) for conducting the clinical trial, to the
Licensing Authority within
1
[thirty days] of occurrence of the serious
adverse event.
(C) The Licensing Authority shall determine the cause of injury and pass
order as deemed necessary. The Licensing Authority shall have the
option to constitute an independent Expert Committee, wherever
considered necessary, to examine such serious adverse events of injury,
which will recommend to the Licensing Authority for arriving at the
1. Subs. by G.S.R. 889(E), dt. 12.12.2014.
Drugs and Cosmetics Rules, 1945
635
cause considered necessary, to examine such serious adverse events of
injury, which will recommend to the Licensing Authority for arriving at the
cause of the injury and also the quantum of compensation in case of clinical
trial related injury, to be paid by the Sponsor or his representative
whosoever had obtained permission from the Licensing Authority as
defined under Rule 21(b) for conducting the clinical trial.
(D) In case of clinical trial related injury, the Licensing Authority, shall decide
the quantum of compensation to be paid by the Sponsor or his
representative whosoever had obtained permission from the Licensing
Authority for conducting the clinical trial and shall pass orders as deemed
necessary within
1
[one hundred and fifty days of the occurrence of the
adverse event]
.
(c) The sponsor or his representative, whosoever had obtained permission from the
Licensing Authority for conducting the clinical trial shall pay the compensation
in case of clinical trial related injury or death as per the order of the Licensing
Authority as defined under Rule 21(b) within thirty days of the receipt of such
order.]
1. Subs. by G.S.R. 889(E), dt. 12.12.2014.
