In mid-December 2020, the United States Food and Drug Administration finalized updated guidance to generic drug manufacturers. The final guidance updates a 2017 draft, Controlled Correspondence Related to Generic Drug Development Guidance for Industry, and replaces the September 2015 guidance for industry Controlled Correspondence Related to Generic Drug Development.
The updated guidance is issued to incorporate program enhancements related to the review of controlled correspondence as part of the reauthorization of GDUFA (GDUFA II). It provides information to manufacturers on how they or their representatives can submit to the FDA controlled correspondence requesting information related to generic drug development and describes the agency’s process for providing communications related to such correspondence.
Revisions to the guidance include clarification about how the agency handles controlled correspondence related to a pending petition, what information should be submitted for requests related to an inactive ingredient, and criteria the agency may use to determine that an inquiry is a “complex” controlled correspondence.
Pending Petitions
If a request is submitted that is related to a pending petition, the FDA will not start its response to the controlled correspondence until it has responded to the pending petition and no notice will be given when the FDA starts its review of the controlled correspondence. Therefore, the FDA suggests requestors monitor the status of petitions here.
If a controlled correspondence request is related to a matter the FDA is actively considering, the request will stay open until the FDA issues a response.
If a requestor is seeking clarification on an existing controlled correspondence response that they find ambiguous, that clarification request must be submitted within seven calendar days of the original FDA response. If it is not submitted in that time frame, the FDA will consider it to be a new controlled correspondence.
Inactive Ingredient Requests
When seeking information on inactive ingredients in a drug product, the FDA recommends that requestors submit no more than three inactive ingredients for evaluation and no more than three proposed levels for a drug product. FDA also recommends that the request should identify the reference listed drug (RLD) and the specific drug product strength.
Controlled Correspondence Scope
There are some requests for information that are not going to be appropriate for the controlled correspondence process, such as methods of characterization for complex products or clinically critical BE considerations, which may be better suited for a pre-ANDA meeting. The FDA also noted that topics that are general in nature would be more appropriately considered as part of the Regulatory Science Initiative, such as the proposed use of in vitro data to support demonstration of BE for a class of [RLD] products for which no ANDAs have been submitted.
FDA Response Timeline
Under GDUFA II, the FDA agreed to review and respond to 90% of standard controlled correspondence within 60 calendar days of submission, 90% of complex controlled correspondence within 120 calendar days of submission, and 90% of requests for clarifications within 14 calendar days of submission.