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MAPPing out the timing of a Complete Response submission

A type of FDA document which sometimes slides past under the radar is  MAPP, that is, Manual of Policies and Procedures.  These are actually internal FDA documents which are generally analogous to the SOPs FDA requires that industry have and follow.  However, by virtue of the various requirements for transparency placed on FDA, they are regularly published and can be found online.

They aren’t something you can typically leverage FDA with, but they do provide some insight into FDA operations and often provide useful information.

FDA recently published MAPP  6020.4 Rev.2, titled, “Classifying Resubmissions of Original NDAs, BLAs, and Efficacy Supplements in Response to Complete Response Letters”  This revision is an update connected with some of the commitments required of FDA commensurate with the most recent PDUFA renewal.  It goes toward the answer to the main burning question connected to every application under review: WHEN?

The process described in the MAPP is pretty straightforward:

  • Applicant submits a response to a Complete Response Letter (CRL)
  • FDA determines whether or not the response is complete and responds in a letter to the applicant within 30  calendar days
    • If FDA determines the response is NOT complete CDER so informs the applicant and the review clock does not start until a complete response is received.
    • If FDA determines that the response is complete, it will be classified as Class 1 or Class 2
  • If the CRL is classified as a Class 1, CDER will complete the review and act on the application within 2 months of the receipt date
    • A Class 1 classification includes
      • Final printed labeling
      • Draft labeling
      • Safety updates submitted in the same format, including tabulations, as the original safety submission with new data and changes highlighted (except when large amounts of new information, including important new adverse experiences, not previously reported with the product are presented in the resubmission)
      • Stability updates to support provisional or final dating periods
      • Discussions of postmarketing requirements/commitments, including proposals or protocols for such requirements/commitments
      • Assay validation data
      • Final release testing on the last 1 to 2 lots used to support approval
      • A minor re-analysis of data previously submitted to the application (determined by CDER as fitting the Class 1 category)
      • Other minor clarifying information (determined by CDER as fitting the Class 1 category)
  • If the CRL is classified as a Class 2, CDER will complete the review and act on the application within 6 months of the receipt date
    • A Class 2 resubmission includes any item not specified as a Class 1 item, including any item that would require a presentation to an advisory committee. A resubmission that requires a reinspection also would be a Class 2 resubmission.