Purpose: As described in the Generic Drug User Fee Amendments Reauthorization Performance Goals and Program Enhancements Fiscal Years 2018-2022 (GDUFA II Goals or Commitment Letter) and the draft guidance for industry Post-Complete Response Letter Meetings Between FDA and ANDA Applicants Under GDUFA, post-complete response letter (CRL) meeting requests (MRs) are used by applicants “to seek clarification concerning deficiencies identified in a CRL.” The analysis described herein provides a snapshot of the post-CRL meeting process implementation in the Divisions of Bioequivalence (DBs) since the start of the GDUFA II program. Specifically, we examined how the DBs have addressed these MRs and how applicants have used the post-CRL meeting request mechanism to seek clarification concerning bioequivalence (BE)-related deficiencies. This information will assist the generic pharmaceutical industry in making the most efficient use of the post-CRL communication process with the ultimate aim being a reduction in the number of review cycles.
Methods: We conducted a retrospective survey of post-CRL MRs which were triaged to the DBs between October 1, 2017 and April 30, 2018. To assess the nature of granted MRs, the clarification questions posed by industry were analyzed based on the drug product dosage form and deficiency categories such as analytical method, study design, formulation, statistical analysis, dissolution testing, and reference standard/reference listed drug (RLD).
Results: Among all MRs received during the above-mentioned time-frame, the most common reason for denying the MR was that the request was not seeking clarification of the identified deficiencies.
Accepted MRs pertained to various dosage forms including tablets, capsules, injections, oral solutions/suspensions, nasal spray/inhalation aerosols, creams, gels, transdermal systems, and ophthalmic emulsions. Among these MRs, common questions concerned formulation proportionality, reference standard selection for the BE study, method validation, dissolution testing, and Office of Study Integrity and Surveillance (OSIS) inspectional conclusions.
Conclusion: Applicants may improve post-CRL MRs by submitting complete MR packages within 10 calendar days of CRL issuance and posing clarification questions within the scope defined in the aforementioned Guidance. The efficient use of post-CRL MRs can assist generic drug applicants in improving the quality of subsequent amendment submissions, thereby reducing review cycles, accelerating the generic drug application approval process and ultimately, facilitating timely access to quality, affordable generic medicines for the American public.