Combine PDFs in Submission-ready Format Quick and Easy

Robin Wu, Lili Li, and Steven Huang, PTC Therapeutics

ABSTRACT

Portable Document Format (PDF) is an essential component in the regulatory submission package (U. S.

Food and Drug Administration, 2013; International Council for Harmonisation of Technical Requirements

for Pharmaceuticals for Human Use, 2017). The conventional approaches of combining PDFs include

using a SAS macro or utilizing a third-party stand-alone tool. Both approaches are usually time-

consuming, unstable, and technically challenging in real practices. In the meantime, however, very limited

Combine PDFs, Submission-Ready

INTRODUCTION

U. S. Food and Drug Administration (FDA) and International Council for Harmonisation of Technical

Requirements for Pharmaceuticals for Human Use (ICH) have very specific requirements for the

combined PDF files in submission packages (U. S. Food and Drug Administration, 2005; U. S. Food and

Drug Administration, 2013; International Council for Harmonisation of Technical Requirements for

Pharmaceuticals for Human Use, 2015; International Council for Harmonisation of Technical

Requirements for Pharmaceuticals for Human Use, 2017). For instance, both FDA and ICH request that

the combined PDF file needs to include a Table of Contents (TOCs) page where there are proper

produce SAS Item Store catalogs using the ODS Document statement while producing the TFLs. Then a

stand-alone SAS macro would be called to read in the SAS Item Store catalogs to be combined into one

Acrobat is one of the most popular applications that allow the users to manually select, convert, and

combine individual files from WORD documents format into combined files in PDF format.

However, both conventional approaches pose significant challenges in practical uses. One most

outstanding challenge is that both approaches are time-consuming and resource-consuming, especially

when combining a large number of TFL outputs. It is not unusual for the SAS Item Store catalogs method

to take hours in converting and combining a couple of hundreds of TFL outputs. Similarly in combining

while there are many challenges in conventional approaches as discussed above, not much attention has

been shed on PDF creation for submission packages, especially on the combined PDF files (Poppe,

2005; Shao & Zhang, 2023; Xin & Wang, 2016). This paper introduces a SAS macro that utilizes a Visual

with regulatory requirements for submission purpose.

Compared to conventional methods, the new SAS macro is 1) highly efficient by significantly reducing the

processing time by at least 60% to 90%. The larger of combined file’s size, the more in reduction of the

processing time; 2) very easy to use as it removes all complex macro set-ups; 3) is resource-effective

where the processing does not require much computing resource, thus make it smooth and stable to

execute even with large number of TFL outputs to be converted and combined.

FRONT-END COMPONENT: SAS MACRO

The SAS macro is the front-end component in this application. As the first step of the process, it retrieves

document format have corresponding PDF files. If no corresponding PDF file to a particular WORD output

(in rft format) is found, the macro will report such case into a temporary data set (topdf) where all the TLF

input fname $ char100.;

file=input(scan(fname, 1, ' '), ?? $char100.);

filex=tranwrd(file, '.rtf', '');

/*if ^missing(file);*/

if substr(fname, 1, 1)^='' ;

keep file filex ;

run;

proc sort; by filex; run;

data dirpdf;

keep file filex;

run;

proc sort; by filex; run;

data topdf;

merge dirrtf(in=a keep=filex file) dirpdf(in=b keep=filex);

by filex;

if a=1 and b=0;

run;

Note, trtf is path of the output’s location defined by the libname statement; Using pathname

scope of PDF to be combined. This is achieved by a simple SAS macro to utilize an external excel

spreadsheet (TOC file) and generate a text file to be fed into the back-end Java API tool which will be

presented with more details below.

As shown in the codes below, only two macro parameters are needed. The tocfile denotes the file

name of the external excel spreadsheet where it contains all the outputs’ proper table number, table title,

and output names. The subset macro variable is optional only when a separate PDF file for a subset of

the outputs is needed.

can be found below.

⊂

run;

data _null_;

set temp;

file "%sysfunc(pathname(trtf))\&tocfile..txt" lrecl=3000;

if _n_=1 then do;

put "File Name, TFL No., TFL Title";

end;

%sysfunc(quote(P:\Macro_Library_Development\Combine_PDF\MergePdf.exe -

s="%sysfunc(pathname(trtf))\&tocfile..txt" -

d="%sysfunc(pathname(trtf))\&tocfile._%sysfunc(today(), yymmdd10.).pdf"

-toc-title="%str(PTC Therapeutics, Inc. - &protocol)" -toc-fontsize=8 -

toc-fontfamily=%str(cour.ttf) %str(-toc -b) -add-toc-page=0));

data _null_;

infile cmppdf pad;

length fname $130;

input fname $char130.;

'Open the file

Set objDocument = objWord.Documents.Open(p_strFilePath)

'Save the PDF

objDocument.SaveAs PathOfPDF(p_strFilePath, p_strPdfFolderPath),

WORD_PDF

'Close the file and exit the application

objDocument.Close FALSE

objWord.Quit