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DIA RSIDM Recap: FDA’s Top 10 eCTD Validation Errors and Top 5 Reasons for Rejected Submissions

April 14, 2016 | B J. Witkin, Senior Manager | Regulatory Operations

Jonathan Resnick from FDA’s Electronic Submission Support Team spoke at the recent DIA RSIDM conference and told us the top 10 validation errors the FDA is seeing in electronic submissions. He also presented a table of the top 12 reasons for rejection. I thought I’d share these with you and discuss some of them.

The Top 10 eCTD Validation Errors

The top 10 validation errors the FDA is seeing in eCTD submissions are as follows:



Notice that all of these errors are of medium severity. Medium severity errors aren’t automatically a reason for rejection, but they can (and usually will) make it harder for your reviewer to properly review your submission. I think that’ll be clear as I go through some of these below.

One more note: I’m honestly surprised that any of these ever came up, for the following reasons:

  • First, unless the errors occurred during transmission through the ESG, these should have been caught by the validator (see my post on validators here). Did the publisher not validate the submission?
  • Second, nearly all of these errors are things a publishing tool should have prevented.

Errors #7, 9 and 10

Every document in the submission should have a leaf title—this, not the file name, is what the reviewer sees in the eCTD viewer, so think of it as the user-friendly name. Errors #7, 9, and 10 all relate to leaf titles.

Error #10 says a file was submitted but for some reason it doesn’t have a leaf title. Error #9 is similar: there’s a file but it’s not associated with a leaf. Error #7 is the opposite of 9: there’s a leaf placeholder and info but no file associated with it.

Error #5

Module 4 and module 5 submissions (like protocols, study reports, and nonclinical reports) to FDA are required to have a Study Tagging File (called an STF). Error #5 says a file was submitted to module 4 or module 5 but there wasn’t a related STF. This could have happened because the documents were copied from a non-FDA submission (maybe an MAA being converted to an NDA).

Errors #3 and 8

Most submission types are required to have a “related sequence”—essentially this is a way to group related submissions. However, some submissions can’t have related sequences (annual reports are the most common example). Error #8 says that the submission you related to was one which doesn’t allow related sequences. Conversely, the third most common eCTD validation error means your submission must have a related sequence (like an IND amendment) and doesn’t.

Error #4

I think this one (invalid file extension) is self-explanatory, but let me explain how it could happen: one publishing tool I used would occasionally convert file extensions, like .pdf, to all upper case (.PDF). Since Windows expects extensions to be all lower case, these will be flagged as being invalid file extensions.

Error #2

The second most common eCTD validation error was that the PDF contents could not be processed. I can only think this is caused by a corrupt file or possibly a file is password-protected.

Error #1

filesThe most common of all eCTD validation errors is that a required attribute value was omitted from module 2 to module 5.

In an earlier post, I talked about submission metadata. Error #1 happens when the publisher doesn’t enter some of the required metadata. In the example at right, the publisher didn’t include the name of the drug product or the dosage form.

The 5 Most Common Reasons for Rejection

Mr. Resnick also presented the 5 most common reasons for a technical rejection of a submission:

  1. Duplicate/incorrect sequence
  2. Submitted to the wrong center
  3. Mismatched application/sequence type
  4. Invalid file type
  5. Not in standard eCTD format

Here again, I’m surprised at 4 of the 5. Other than “Submitted to the wrong center” (that’s user error with the ESG), all of these should be prevented by the publishing tool.

If you need help to make sure you don’t encounter these eCTD validation errors or reasons for rejection, don’t forget to contact us – we’re more than happy to help!

Category: Regulatory Operations
Keywords: DIA RSIDM, eCTD validation errors, eCTD rejections, eCTD metadata errors, FDA reasons for rejection

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