The U.S. Food and Drug Administration, FDA, recently revised the questions and answers (Q&As) on the development of Abbreviated New Drug Applications (ANDAs) during the COVID-19 pandemic. The guidance - originally published in April 2021 - provides general recommendations related to generic drug product development and regulatory submissions.
The Q&As are presented in the following categories:
Generic drug product development;
Submission and assessment of ANDAs;
Marketing and exclusivity.
Generic Drug Product Development
The Q&As in this section generally assume that bioequivalence (BE) studies being conducted have been delayed, interrupted or have not started due to the COVID-19 pandemic. As a result, applicants are faced with difficulty obtaining reference products. What can be done when a test or reference product batch used in the conduct of a BE study expires while the study is interrupted due to the COVID-19 pandemic?
Test product batch: A test product batch that is beyond the expiration date may be used to resupply the BE study as long as sufficient evidence can be provided to demonstrate the acceptability of the test product batch. Data should be submitted to ensure the test samples stored at the long-term stability conditions beyond the current expiration date are in compliance with the shelf-life specifications at the time of conducting the BE study. The test batch may be considered acceptable if the submitted stability data meet the drug product shelf-life specifications (alternatively, an applicant generally would be permitted to manufacture additional test product to resupply its BE studies).
Reference product batch: The use of an expired reference product batch to complete BE studies is not acceptable. A drug product’s expiration date, as determined by appropriate stability testing, provides assurance that the drug product meets the applicable standards of identity, strength, quality, and purity at the time of use. However, it may be acceptable to utilize a different batch of unexpired reference product to complete a BE study, so long as the applicant provides adequate scientific justifications for the use of different reference product batches.
As a general matter, the agency recommends that applicants take adequate precautions and have written procedures in place to ensure the safety of study subjects and staff involved in the conduct of a BE study during the COVID-19 pandemic.