IPI - Editorial

IPI
Providing regulatory submissions
in electronic format – US and
EMEA actions
The United States Food and Drug
Administration (FDA) is taking concrete
steps to require the submission of all types
of regulatory communication in electronic
format. Regulatory authorities globally are
all moving to require electronic submission
of regulatory communication. The reasons
are many but the public safety
responsibilities of the regulators require
significantly faster access to content than
can be supported by paper format.
The cost of preparing the content to be
reviewable in electronic format forms the
bulk of the time and human resources
needed to prepare electronic submissions.
Failing to prepare the electronic content in
compliant format can result in the regulatory
authority refusing to conduct the review until
the lack of compliance is corrected – this
could have a profound impact on a
company’s viability if a competitor drug is
approved while the first sponsor is
correcting non-compliant content.
Compliance of electronic documents can
be easily and inexpensively achieved
through the proper use of Microsoft Word to
author documents, combined with the use of
templates with electronic submission
compliance features built into the template
design.
1 HISTORY OF ELECTRONIC
SUBMISSION REQUIREMENTS
1.1 US FDA
• FDA Centers for Drug Evaluation and
Research (CDER) and Biologic Evaluation
and Research (CBER) have required
submission of electronic case report
tabulations (CRTs) and case report forms
(CRFs) in electronic format for new drug
and new biologic license applications
(NDAs and BLAs) since 1999 , .
• FDA CDER has required package inserts
to be submitted in electronic Structured
Product Labeling (SPL) format since
October 1, 2005 .
• FDA CDER has required electronic
submissions to be presented in the
electronic Common Technical Document
(eCTD) format since January 1, 2008 .
• FDA is requiring the content of the Drug
Establishment and Drug Registration
forms to be submitted in electronic format
beginning June 1, 2009 .
• FDA has published the proposed rule that
retired previous electronic submission
formats, and set the stage to require all
submissions be in electronic format using
the eCTD organisation structure and
electronic navigation aids .
1.2 EMEA
The electronic submission juggernaut is
not limited to the US market:
• The European Medicines Evaluation
Agency has announced a timeline which
requires all agencies participating in the
centralised procedure for marketing
authorisation applications (MAA) to begin
submitting in electronic format on January
1, 2009 , and in the eCTD format on
January 10, 2010.
Finally, there is an international effort
underway with involvement by regulatory
authorities and industry to define the next
generation of bi-directional communication
of regulatory submission content in a
messaging format called Regulated Product
Submission that is intended to address
electronic submission requirements for all
products regulated by FDA – drugs,
biologics, devices, veterinary medicine, food
additives, and cosmetics.
2 TECHNICAL REQUIREMENTS
Since 1999, the fundamental building block
of electronic submissions has been the
Adobe Acrobat Portable Document Format
(PDF). However, this is not ordinary run-ofthe-mill
PDFs created by scanning or
printing to Adobe PDF. All regulatory
authorities who accept electronic
submissions have very strict requirements
for the format and electronic navigation aids
within PDF files, Regulatory authorities
globally have refused to review electronic
submissions whose PDF files lacked
required navigation aids.
All of these requirements can be met by
implementing MS Word templates and
configuring PDF conversion to support
these requirements. PDF conversion can be
done via PDFMaker, a plug-in to the
Microsoft Office suite that is automatically
implemented when the Microsoft Office
applications are installed first, and Adobe
Acrobat Standard or Professional are
installed second. These properties can also
be assured by correct configuration of
Acrobat Distiller. Further, companies with
MasterControl electronic document
management systems (EDMS) configured
for life sciences applications frequently have
a PDF rendition server or generator in the
EDMS suite that can be configured to
support the requirements that are identified
below.
FDA has published guidance that
describes the requirements for PDF files for
eCTD submissions, Portable Document
Format Specifications, version 2.0, dated
2008-0604,www.fda.gov/cder/
regulatory/ersr/ PDF_specification_v2.pdf.
Other regulatory authorities have published
requirements that are virtually identical to
the guidance supplied by FDA.
2.1 Fundamental PDF Requirements
One of the strongest directives from the
regulatory authorities’ requirements is that
PDF files conform to predefined page sizes,
have adequate margins on all sides and
have adequate font sizes for legibility.
These translate into the following
specifications:
• US letter page size for the FDA
• A4 page size for rest of the world
• Margins of at least one inch on all four
borders, with larger margins on the
binding edge in the event that paper
volumes will be required
• Times New Roman or Arial font, with the
body text in 12 point and tables no smaller
than 10 point
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