(W1230-02-10) Post-Complete Response Letter Scientific Meeting Requests: Key Takeaways from Case Studies

Purpose: Many new enhancements within the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years 2023-2027 (GDUFA III) have been made with the intent to reduce the number of assessment cycles for a timely approval of abbreviated new drug applications (ANDAs). One of the new enhancements is a post-complete response letter (CRL) scientific meeting. The purpose of this meeting is to provide scientific advice on possible approaches to address deficiencies identified in a CRL related to establishing equivalence. The meeting request (MR) is granted if (1) it is for a complex product or in FDA’s judgment, the request raises issues that are best addressed via this meeting process and (2) it must include one or more of the following: (i) a new equivalence study needed to address the deficiencies identified in the CRL, (ii) an approach that is different from that submitted in the ANDA, (iii) a new comparative use human factors study, (iv) a new approach to demonstrate sameness of a complex active pharmaceutical ingredient. The present work was aimed to provide an overview of post-CRL scientific MRs under GDUFA III with case studies about the effective utilization of these MRs submitted to the Agency between October 2022 and January 2024.

Methods: The recommendations (including eligibility/qualification criteria), and the timelines were compiled along with different scenarios of granted and denied MRs using this new pathway. Analysis of post-CRL scientific MRs submitted to the Agency was carried out to identify the effective and efficient utilization of this new enhancement by generic drug product applicants.

Results: Twenty-five post-CRL scientific MRs (from 18 different applicants) were received by the Agency between Oct. 2022 and Jan. 2024. Twenty MRs were for complex products, and five MRs were for non-complex products. A total of seventeen MRs were granted. This avenue has been utilized for wide range of dosage forms with different routes of administration for generic drug products, as shown in the figure. The MRs were granted as face to face (18%), videoconference (35%), teleconference (12%), and written response (35%). Out of all granted meetings, some of the MRs are further classified based on the type and complexity of the drug product along with qualification criteria as case studies in the table below. The most common observations for the denial of MRs include (i) the drug products were non-complex and the questions were outside the scope of a post CRL scientific MR or were more appropriate to be addressed through controlled correspondence pathway, (ii) the same question(s) were asked at different avenues at/around the same time, (iii) the request was related to disputes regarding the relevance of deficiency comment(s), and (iv) the request was to evaluate/re-consider previously submitted data.

Conclusion: The purpose of post-CRL scientific MRs is to provide scientific advice on possible approaches to address communicated deficiencies in a CRL related to establishing equivalence. The Agency will not pre-review any specific scientific data submitted in the meeting package within the scope of post-CRL scientific MR. However, it is encouraged to provide supporting data for the proposed approach, as applicable. In general, the acceptability of any proposed new approach along with study data is assessed upon submission of an ANDA amendment with relevant data and information. Applicants may proactively consider above-mentioned observations to efficiently utilize this enhancement feature added in GDUFA III. This in turn will help the Agency and Industry to better achieve the goals and benefits of GDUFA to make high quality generic drug products available on time to the American people.

Acknowledgements: Disclaimer: The present work reflects the views of the author(s) and should not be construed to represent U.S. FDA’s views or policies.