Update to FDA Guidance

On June 11th, 2008, FDA issued a Revision 2 of "Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications" (http://www.fda.gov/cder/guidance/7087rev2.pdf). The previous version, Revision 1, dated from April 2006.

So what's new? Very little.

The updates are all administrative in nature, and basically consist of:

• Revisions to title page for FDA's new address
• Minor revisions in language to remove references to hybrid submissions and eNDAs, which are no longer accepted without a waiver
• Updated reference to ICSR guidance in the Periodic safety update reports section

The latter update is merely the replacement of the previous text:

"You should provide bookmarks for each of the sections and subsections of this report. ICSR and ICSR attachments should be provided as described in the guidance for industry Providing Regulatory Submissions in Electronic Format — Postmarketing Periodic Adverse Drug Experience Reports. "

with:

"ICSR and ICSR attachments should be provided as described in FDA’s guidance for industry on electronic submission of postmarketing ICSRs (Available under the topic "Electronic Submission" on CDER and CBER’s guidance Web pages)."

One anticipated change that did not appear in this document was the decrease of the maximum recommended path length. ICH/FDA guidance currently states that the path length can be up to 230 characters. However, for those using the gateway to submit, the gateway adds characters to the path. FDA said at DIA in June that they recommend limiting the path to 150 characters, and reminded the audience that FDA reviewers do not see the folder names so their significance in the US is minimal. Path length problems can result in documents not being seen in the agency's viewer because it is not given all of the necessary information.

ANDA Checklist

Another fairly recent CTD/eCTD related update was the revision of the ANDA checklist on May 28th. (the previous version was dated October 17, 2007). It is posted as PDF (http://www.fda.gov/cder/ogd/anda_checklist.pdf) and MS Word (http://www.fda.gov/cder/ogd/anda_checklist.doc). The Word version is more useful as the PDF is not a fillable form. Changes here include:

• Addition of the Model Bioequivalence Data Summary Tables in 2.7
• Removal of the requirement for MS Word for 5.2 Tabular Listing of Clinical Studies

This brings up a topic that not everyone is aware of - the OGD wants MS Word versions submitted for the QOS and Clinical Summary (Bioequivalence). In presentations, their reviewers have also said that they prefer the QOS submitted as a single document, rather than in modular components.