I'm honored to have been referenced on a new Italian eCTD web site, the eCTD.it User Group. The site references a post of mine about Gary Gensinger's remarks at DIA on a page called eCTD: The Quality of the Dossier:
http://www.ectd.it/knowledge/introduzioni/77-ectd-la-qualita-del-dossier Fortunately, my ability to read and speak Italian like a native served me well here... Just kidding ;-)
But seriously, there are some interesting articles on this site. You can access a translated version by googling "ectd.it" and clicking on the Translate this Page link (for some reason this only seems to work from www.google.com and not from my google toolbar). With this approach, Google will continue to translage the pages as you follow the links.
Tuesday, November 25, 2008
Common eCTD Mistakes - as Described by FDA (Part 2)
Continued from last time... Notes from my discussion with Virginia Ventura.
Virginia mentioned lack of a cover letter, or lack of a useful cover letter, as a significant issue. Although the cover letter is not a regulatory requirement, it serves as the reviewers' "Road Map" to the submission, and Virginia can't understand why a sponsor would not take advantage of the opportunity to provide clarity on the structure and contents of the submission. Her recommendations here:
• When you reference documents in your cover letter, provide hyperlinks to those documents.
• Review your cover letter closely for accuracy. Mistakes in the cover letter can cause significant confusion.
We discussed the concept of providing more detailed reviewer guides as well. Again, these are not a regulatory requirement, but some companies consistently provide well-structured guides that make reviewing much easier. These should not just reproduce the TOC, but might included details and discussions such as the following:
• How the eCTD was constructed (for example, using which software package) and how it was submitted (via the gateway, etc.)
• Version of specs used
• Brief description of pivotal studies, with mention of where they are located and hyperlinks to key documents and summary sections
• Discussion of how study reports were constructed (ICH granularity, etc.)
You also may wish to discuss placement issues (for example, when a study could legitimately be placed in more than one section), instances when the same document was submitted in more than one section, etc.
As a reminder, FDA has organized documents related to electronic submissions on http://www.fda.gov/cder/regulatory/ersr/. This is a great collection of resources, and Virginia mentioned that not all sponsors are aware that this page exists before they contact her.
Specifically pertinent to this post, FDA has a posted presentation, eCTD Validation, available on their website. This was presented by Don Duggan in February at DIA EDM in Philadelphia.
Virginia mentioned lack of a cover letter, or lack of a useful cover letter, as a significant issue. Although the cover letter is not a regulatory requirement, it serves as the reviewers' "Road Map" to the submission, and Virginia can't understand why a sponsor would not take advantage of the opportunity to provide clarity on the structure and contents of the submission. Her recommendations here:
• When you reference documents in your cover letter, provide hyperlinks to those documents.
• Review your cover letter closely for accuracy. Mistakes in the cover letter can cause significant confusion.
We discussed the concept of providing more detailed reviewer guides as well. Again, these are not a regulatory requirement, but some companies consistently provide well-structured guides that make reviewing much easier. These should not just reproduce the TOC, but might included details and discussions such as the following:
• How the eCTD was constructed (for example, using which software package) and how it was submitted (via the gateway, etc.)
• Version of specs used
• Brief description of pivotal studies, with mention of where they are located and hyperlinks to key documents and summary sections
• Discussion of how study reports were constructed (ICH granularity, etc.)
You also may wish to discuss placement issues (for example, when a study could legitimately be placed in more than one section), instances when the same document was submitted in more than one section, etc.
As a reminder, FDA has organized documents related to electronic submissions on http://www.fda.gov/cder/regulatory/ersr/. This is a great collection of resources, and Virginia mentioned that not all sponsors are aware that this page exists before they contact her.
Specifically pertinent to this post, FDA has a posted presentation, eCTD Validation, available on their website. This was presented by Don Duggan in February at DIA EDM in Philadelphia.
Friday, November 7, 2008
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...
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:
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...
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