FDA at DIA RSIDM 2019 – Presentations Highlights

As part of the DIA RSIDM conference in Bethesda, ML in February 2019, the following comprehensive list summarizes our notes from FDA representative presentations during the event.

• The number of submission to the FDA has significantly increased. CDER receives approx.. 200,000 electronic submissions.  Nearly 192,000 were in eCTD format in 2018.
• eCTD guidance became binding:
  • May 5, 2017: NDA, BLA, and ANDA
  • May 5, 2018: Commercial IND and Master Files* (*Type III Master Files effective May 5, 2020)
• Currently, FDA Document Room staff has to read the cover page of every submission (nearly 850 per day) to categorize (submission type/subtype) and route to the correct Review Division.  Data submitted in the eCTD backbone (regional.xml) and Regulatory form are not always consistent. Soon, FDA will automate the process to identify Submission Category based on structured data in the eCTD sequence and route the submission to the appropriate Division.
• Top 3 Rejections:
  • Duplicate sequence number received (Most common rejection reason, nearly 50% of all errors)
  • eCTD Validation Error (Most common validation error – Error #2022 – You have used a submission type-sub-type which is not allowed for the submission type and/or type of application)  For additional information about submission type-sub-type, please refer to Table 2 of the Module 1 specifications.
  • Sequence sent to the wrong Center.
• Frequently asked questions of FDA:
  • Where do I place my content?  See FDA Comprehensive Table of Contents.
  • What file formats are acceptable? See Specifications for File Format Types Using eCTD Specifications
  • Does the 3^rd ESG Acknowledgement mean the Review office finds the submission complete? The 3^rd acknowledgement means the sequence has passed technical validation and is now available to the Review division for processing (filing review).
  • How to get started with eCTD, how to request an application number, how to get a gateway account, etc. Visit the FDA Electronic Submissions to CDER page and the Submit using eCTD page for additional information.
• Sequences out of order will not be rejected.
• Size of the submission should be in the cover letter, but it is not a requirement. ESG provides FDA with size information as well as information on the number of files.  Providing this information in the cover letter allows FDA to compare the information to ensure no files are missing.
• ESG individual file size issue has been resolved.  There does not appear to be a size limitation.
• eCTD v. 4 implementation date – FDA plans to transition to the new viewer first, then potentially do a v.4 pilot.  Hopefully they will begin accepting v.4 in 2021.
• The new FDA viewer is scheduled to be implemented mmid-2019.
• CBER – getting an early application number seems to take time and causes delays.
• Issue with ESG 3^rd acknowledgement taking a long time (eg, 6 hours or overnight) to arrive has been resolved.
• Sequence numbers in batch – some companies assign sequence numbers in batch to be used for specific submission types or by specific groups (eg, sequence numbers in the 5000’s and 6000’s), and this has not caused an issue.  Sponsors need to carefully track sequence numbers.
• Promotional submissions will not be required in eCTD format until 24 months after the issuance of a final guidance.  Currently the guidance is in draft format.
• Cross application linking – FDA’s preferred way is via the XML backbone.
• CBER issues a pre-IND #.  However, when ready to submit, ask for a new IND # and start the sequence at 0001.
• FDA is working on a DMF Application Form.  Has to go through the OMB process before available.
• eCTD is not required for medical devices.

 

DIA RSIDM 2019, Sessions:

1. DIA Electronic Submissions by Jonathan Resnick
2. Ask the Regulators by Ethan Chen, Jonathan Resnick, LaMisha Fields, Mark Gray, Valerie Gooding, Wei Lin.