FDA draft guidance on controlled correspondence reflects GDUFA III commitments

The US Food and Drug Administration (FDA) on Wednesday issued a draft guidance to assist generic drug manufacturers in requesting information from the agency through the controlled correspondence process. The guidance reflects the changes that were part of the reauthorization of the Generic Drug User Fee Amendments (GDUFA III) and expands the topics that are eligible for controlled correspondence as compared to previous iterations of the program.
 
The GDUFA III commitment letter, issued in November 2021, reflected the performance goals and program enhancements that will guide the program over the next five years (RELATED: GDUFA III commitment letter details coming changes to FDA’s generic review program, Regulatory Focus, 2 November 2021).
 
The GDUFA III program will affect all controlled correspondence submitted to the agency on or after 1 October 2022.
 
When finalized, the update will replace a final guidance issued in December 2020, which reflected the commitment made to industry under GDUFA II (RELATED: Generics: FDA finalizes guidance on controlled correspondence, Regulatory Focus, 17 December 2020).
 
Some of the changes compared to the GDUFA II program are the inclusion of two new categories for submitting controlled correspondence requests—level 1 and level 2.
 
The draft guidance “provides additional details and recommendations concerning what inquiries FDA considers controlled correspondence for the purposes of meeting the Agency’s performance goals under the GDUFA III commitment letter,” according to an announcement from the agency.
 
A level 1 controlled correspondence would be for situations where a new or revised product-specific guidance (PSG) may conflict with a sponsor’s drug development program and where an applicant has already conducted an in vivo bioequivalence study. In these situations, applicants can request a teleconference to obtain FDA’s feedback on the potential impact of the new or revised PSG on its development program.
 
A level 2 controlled correspondence would be for requests that involve the evaluation of clinical content by different review divisions. FDA states that “consistent with FDA’s past and current practices, FDA will continue to consider controlled correspondence that requires evaluation of clinical content (and is therefore level 2 controlled correspondence) to include requests that require input from OGD’s [Office of Generic Drugs] Office of Safety and Clinical Evaluation and OGD’s Office of Research and Standard Clinical Safety and Human Subject Research Team.”
 
FDA also will consider level 2 controlled correspondence for requests that require input from offices or centers outside of OGD such as the Center for Devices and Radiological Health (CDRH).
 
“The evaluation of clinical content includes, but is not limited to, clear, specific questions related to the planning of a BE [bioequivalence] study with comparative clinical endpoints and questions related to adverse event that occur during the conduct of a BE study,” the guidance states.
 
The guidance also provides more detail on the information that should be submitted in a controlled correspondence compared to previous iterations of the program. For example, if the controlled corresponded is related to a deficiency identified in a complete response letter (CRL), sponsors should reference that specific deficiency in a controlled correspondence.
 
The guidance also expands the topics subject to a controlled correspondence. For example, the revision addresses requests for feedback for drug-device combination products. These can include discussions on the differences between the user interface of a proposed generic drug-device combination product compared to the reference-listed drug (RLD). It also expands the topics under which sponsors can obtain information on requests related to inactive ingredients.
 
The public has 60 days to comment on the guidance.
 
Guidance
 
Notice