Complete Response Letter BLA 125806 (Jun 14, 2024)

Summary

This is a Complete Response Letter from the FDA to Rocket Pharmaceuticals, Inc. regarding their Biologics License Application (BLA) for marnetegragene autotemcel. The FDA has concluded that they cannot grant final approval due to deficiencies, primarily in Chemistry, Manufacturing, and Controls (CMC), and also reserves comment on labeling until the application is otherwise acceptable. The letter outlines requirements for resubmission and options for discussion.

Key points

• Address all Chemistry, Manufacturing, and Controls (CMC) deficiencies.
• Formally update all revisions and corrections discussed during the interactive review within the BLA submission.
• Document revisions to documents or data with red-lined versions included in tandem.
• Submit all updated, corrected, or revised information discussed during the review cycle with the resubmission.
• Provide a tabulated summary of all changes made, including the affected document or module, nature of the updated information, the information request and amendment number, and any other pertinent information.
• Resubmit or withdraw the application within one year after the date of this letter.
• Fully address all listed deficiencies in any resubmission.
• Submit meeting requests as described in the guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products and CBER’s SOPP 8101.1 Scheduling and Conduct of Regulatory Review Meetings with Sponsors and Applicants if a meeting or teleconference is desired.

Cited reasons

• Inconsistent Documentation of CMC Changes and Data
• Labeling Review Reserved Pending CMC Resolution
• The Biologics License Application (BLA) for marnetegragene autotemcel received a Complete Response Letter due to significant Chemistry, Manufacturing, and Controls (CMC) deficiencies, primarily related to inconsistent documentation and failure to formally update the BLA with revisions discussed during the review cycle. Labeling review is reserved until these CMC issues are resolved.

Recommended actions

• Address all Chemistry, Manufacturing, and Controls (CMC) deficiencies.
• Formally update all revisions and corrections discussed during the interactive review within the BLA submission.
• Document revisions to documents or data with red-lined versions included in tandem.
• Submit all updated, corrected, or revised information discussed during the review cycle with the resubmission.
• Provide a tabulated summary of all changes made, including the affected document or module, nature of the updated information, the information request and amendment number, and any other pertinent information.
• Resubmit or withdraw the application within one year after the date of this letter.
• Fully address all listed deficiencies in any resubmission.
• Submit meeting requests as described in the guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products and CBER’s SOPP 8101.1 Scheduling and Conduct of Regulatory Review Meetings with Sponsors and Applicants if a meeting or teleconference is desired.

Deficiency summary

The Biologics License Application (BLA) for marnetegragene autotemcel received a Complete Response Letter due to significant Chemistry, Manufacturing, and Controls (CMC) deficiencies, primarily related to inconsistent documentation and failure to formally update the BLA with revisions discussed during the review cycle. Labeling review is reserved until these CMC issues are resolved.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

BLA

Impact

Impact score

0.75

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary theme is a lack of robust document control and data integrity within the CMC section of the BLA, leading to inconsistencies between submitted information and agreed-upon changes during the review cycle. This fundamental issue prevents final approval and delays the review of other sections like labeling.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%