The DIA Regulatory Submissions, Information, and Document Management (RSIDM) Forum, held online and in person from February 14 to 16, was packed with practical information. It was great to catch up with colleagues from across the industry and share our perspectives and practices. As always, the Ask the Regulators Sessions were well-attended and full of practical questions and thoughtful responses. The presentation by US FDA’s Jonathan Resnick, Project Management Officer from the Office of Business Informatics, Center for Drug Evaluation and Research, offered great practical reminders of imminent changes that will impact submissions starting next month.
In his Electronic Submissions Update, Resnick reminded the audience about two significant short-term changes that will become effective March 1, 2022.
eCTD Module 1 Specification
The first change relates to the updated eCTD Module 1 specification. Effective March 1, 2022, the Module 1 DTD v2.01 will no longer be supported at the agency. All US submissions must use DTD v3.3 to pass validation. The new version of the DTD supports grouped submissions and other updates.
eCTD Validation Errors
The second impending change relates to two critical validation errors that will be elevated to a higher severity level.
Effective March 1, 2022, the FDA will reject any submissions that fail validation #1306 and #1323. Error 1306 refers to “no leaf element for file” and error 1323 refers to “no file for leaf element.” Currently, both errors trigger warnings that CDER includes in the electronic submission gateway (ESG) 3rd acknowledgment. Starting March 1, any submission that receives these errors will be rejected.
The 1306 error creates an issue for reviewers because files are not referenced in the eCTD backbone. These files cannot be easily identified or accessed by the FDA’s systems that use the backbone information to present submission content or by FDA reviewers. The errors represent .25% of the total submissions processed. Still, the concern relates to critical data that reviewers won’t know exists because they cannot access it.
The 1323 error represents .49% of the total submissions processed. Again, this may seem like a minor issue, given the number of submissions that generate the error. However, the concern is similar in that it appears that a file is in the submission, but reviewers and the FDA’s systems cannot identify it.
eCTD Compilation and Validation Practices
Sponsors should be transitioning now to the new version of the Module 1 specification. They should be paying close attention to the validation errors. The small percentage of errors noted by the FDA will be of little consolation if your submission is rejected.
If you have any questions or concerns about your company’s regulatory submissions related to these changes, request a meeting with one of our regulatory experts.