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
research and utilities have been shared in the SAS community on how to combine PDFs properly and
efficiently in a submission-ready format. This paper will address the gap here by introducing a novel
approach that implements both a SAS macro and two third-party utilities (a Visual Basic application and a
Java application) to make the PDF combination quick, easy, and submission-ready.
KEYWORDS
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
hyperlinks for documents of more than five pages. In the combined PDF, FDA and ICH also require
bookmarks for each table, figure, or listing (TFL) listed in the TOCs. Even for the TFL outputs in
submission package that are produced in non-PDF file formats, FDA instructs that those files “should also
be provided in PDF format” (U. S. Food and Drug Administration, 2013, p. 2).
To convert and combine TFL outputs into one PDF file, conventional methods generally come in two
approaches. The first common approach is to directly combine in SAS. One frequently used method is to
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
PDF file at the end. The other common approach is to utilize third-party applications. For instance, Adobe
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
files using Adobe Acrobat, it is not only time-consuming but also very often unstable in processing due to
exhaustion of computing resources. The second challenge is in compliance with the regulatory guidelines.
For instance, when using third-party applications such as Adobe Acrobat, the final combined PDFs are