In September 2016, the FDA published new deadlines on electronic submissions:
May 5, 2017: NDA, BLA, ANDA and DMFs must be in eCTD format
After these key dates, companies will not be permitted to send paper and/or non-eCTD submissions. In some cases, an exemption may apply and further information regarding exemptions can be found >>here<<
The FDA update also described modifications for all electronic formats including the requirement for PDF forms will need to be fillable and electronic signatures must be used. Emphasis was placed on the correct use of lifecycle management to ensure that content such as study data is not submitted repeatedly.
Submission delivery is changing as well. After May 5th, CD-based submissions will not be accepted. Submissions less than 10GB will need to be transmitted using the online gateway. Larger submissions can be sent using a USB drive (physical electronic media) or the gateway.
The deadlines for standardized study data is the 17th of December 2016 (NDA, BLA and ANDA submissions) except for the IND submissions. Here the deadline is a year later – December 17, 2017. The Study Data Technical Conformance Guide can be viewed >>here<<
The technical rejection criteria for study data documentation is also available >>here<<
Finally, the CDER gateway third acknowledgement is now in place since the end of May and applies only to NDA, ANDA, BLA, IND or DMF submissions. The CDER acknowledgement is added to the ESG Message Delivery Notification acknowledgement (first acknowledgement) and the Official Center acknowledgement (second acknowledgement) and will be sent when a submission is ready for review and has successfully passed the validation and processing. The third message may be delayed if there are difficulties with the validation process and may also communicate the rejection of the submission.
eCTD Observations from the FDA
Reasons for eCTD failures
With the eCTD being in use for quite some time, the FDA has – as well as industry – has been learning about what makes an eCTD submission succeed as well as fail. In terms of problems with eCTD submissions, the FDA observed the following:
- Most eCTD submissions get rejected because the sequence number was used more than once.
- The submissions do not reach the correct destination because they were sent to the wrong centre (e.g. CDER instead of CBER).
- The submissions which made it to the right centre often fail because of a wrong format (.zip or .exe) or a mismatch between application and sequence type.
- Many submissions are missing files and/or do not fit the standard eCTD format.
Top 3 errors with the new M1 (DTD v3.3)
- Providing a submission-ID when starting a new regulatory activity, which does not match the sequence number
- Choosing a Submission Subtype of Amendment and specifying an incorrect Submission-ID
- Transitioning from paper to eCTD and choosing a submission type of original application and submission subtype of amendment
eCTD tips and helpful ideas
- PDFs longer than 5 pages should have a correct TOC, bookmarks and links.
- PDFs are readable and can be viewed in the proper orientation.
- If you must submit scanned documents, be sure to perform OCR and verify the text so reviewers can easily copy and paste content.
- Only hyperlinks should be in blue.