Common eCTD Mistakes - as Described by FDA

I recently had a great chance to talk to Virginia Ventura of FDA's Electronic Submission Support Team about the common mistakes made by sponsors in preparing eCTDs. Virginia told me that mistakes are not confined to small or inexperienced companies. In many cases, these errors result from a lack of basic QC. Here are some examples:

Not updating documents that were created based on templates intended for paper.

Of course, adding hyperlinks is a big part of this. In some cases, sponsors have not only failed to add hyperlinks, but have retained references to paper volumes, which are of course useless in the eCTD environment.

My colleague Shannon Strom, Director of Regulatory Operations at Cato Research, gave a great example of the need to change practices at a recent presentation: consider the previous practices of using a sentence such as:

Tables 1-3 Indicate The Significant SAEs Reported For Each Clinical Study.

This was fine in the paper world, but in the eCTD world, it gives the publisher no way to hyperlink to Table 2! Thus a better structure is:

All Significant SAEs Reported For Each Clinical Study Are Indicated In Table 1, Table 2, And Table 3.

Bottom line: make sure your documents have been updated for proper presentation in an electronic environment, and as always, keep the reviewer in mind! Virginia says that the FDA has received a number of submissions that were essentially "un-reviewable" due to lack of hyperlinking.

Lack of consistency in the Application Number
The application number appears in four places in an eCTD:

The regional backbone (us-regional.xml in the US)

The root folder of the eCTD content

The application form

The cover letter

It's really important that the application number matches in all four places. (By the way, if it does not match, the FDA will consult your cover letter for arbitration - so heaven help you if it's wrong!)

That also brings up the topic of using the PDF Fillable Form provided by FDA for your application form. They really want you to do this!! Virginia says that lack of a fillable form is the #2 error that the FDA sees for eCTDs. (Interestingly, the #1 error is clicking twice when submitting via the gateway - this causes your submission to be submitted twice, resulting in a number of errors, as you would expect.)

More on my talk with Virgina next time...