A day or so ago, the FDA released Manual of Policy and Procedure (MaPP) 5021.5 titled Assessment of Facility‑Based Deficiency Major‑to‑Minor Reclassification Requests.  A MaPP is a document that informs how the FDA will handle, manage, and prosecute a particular issue internally.  In this case, it describes how the FDA will adjudicate a request to reclassify a Complete Response Letter (CRL) from a major amendment to a minor amendment if the facility’s inspectional status of Official Action Indicated (OAI) is the only major amendment issue.  Once the OAI compliance status is resolved and if the CRL may or may not have other minor issues, the classification to a minor amendment can be granted but with several conditions.

The document is twelve‑pages long and reading it will provide some good advice to applicants making such a request.  It is heavy on detail as to when and what to do and how to do it, down to the finest level of minutiae.  Have you ever submitted a well‑written controlled correspondence only to have it bounced back from the FDA because you left out a minor issue or provided a piece of information in the wrong place?  Well, be certain to tighten your seat belt if you expect to get a ride in this fast‑moving car.  The MaPP can be found here and you’d better pay attention.  There is a lot in the MaPP and I am covering only some major highlights in this post.

First, if you received a CRL that was issued prior to October 1, 2022 (the implementation date of the Generic Drug User Fee Amendments of 2022 program (GDUFA III)), you can’t make a request unless:

  • The CRL is more than one‑year old from issuance and one of the following applies:
  • The product is on the drug shortage list or is a public health emergency product.
  • The facility deficiency is the only deficiency in the CRL (i.e., the facility issue is the only (i.e., single) major deficiency and there are no minor deficiencies).

The FDA will accept a request if:

  • The CRL was issued on or after October 1, 2022 (the implementation date of GDUFA III).
  • The reclassification request is submitted with a CRL response amendment in a single submission.
  • The facility issue is the only major deficiency.
  • The CRL’s major amendment classification is based on observations from a surveillance inspection (e.g., OAI classification of a facility from a surveillance inspection). This includes surveillance inspections conducted by foreign regulatory authorities where information is shared under mutual recognition agreements.
  • The reclassification request is easily identified in the cover letter for the amendment submitted in response to the CR letter.
  • The FDA determines that the words “Facility‑Only Reclassification Request” are included in the submission and verifies that the submission includes the Voluntary Action Indicated (VAI) or No Action Indicated (NAI) Current Good Manufacturing Practice (CGMP) classification letter issued by the FDA to the facility or facilities subsequent to the OAI classification referenced in the CRL.

The FDA will deny the request if:

  • The facility CRL deficiency was issued based on an inspection other than a surveillance inspection or assessment (e.g., a withhold recommendation based on a Pre‑Approval Inspection (PAI) or the use of alternative tools).
  • The facility deficiency has not been adequately resolved for the subject drug (e.g., the FDA intends to conduct additional follow‑up to verify that a corrective and preventive action(s) plan(s) was appropriate and fully implemented).
  • The submission does not include the VAI or the NAI CGMP classification letter issued by the FDA.

The MaPP also includes a table describing how GDUFA goal dates will be assigned if the OGD grants or denies a reclassification request.

How the FDA handles the request gets more complicated and introduces some additional watch‑outs and hurdles that must be jumped before the Agency will even make a decision.  The bottom line here is to read this MaPP several times and make a chart or template that includes all of the various required elements to ensure that you don’t miss anything!  Detail can and will make a big difference towards success!  Good luck!