FDA Publishes Guidance on Bioavailability and Bioequivalence Samples

FDA published guidance on August 18, 2020 that describes the requirements for retaining reserve samples of test articles and reference standards used in an in-vivo bioavailability (BA) and in-vivo or in-vitro bioequivalence (BE) study. The guidance discusses the requirement in 21 Code of Federal Regulations (CFR) 320.38(c) to retain sufficient quantity of reserve samples so that FDA may perform “five times all the release tests required in an application or supplemental application.”

The guidance states, “Since the final rule was issued in 1993, technological advances in FDA’s ability to test these products have led to test methods that are less destructive and more sensitive, allowing FDA to detect the identity and composition of the test article and reference standard with smaller volumes of samples. As such, under current physicochemical testing, the Agency generally needs, for products manufactured in single-dose units, 30 units each of the test article and reference standard from each shipment or, for products manufactured in multi-dose units, 3 units each of the test article and reference standard from each shipment, to conduct the necessarytesting of the samples. Consistent with these developments, FDA has received communications from applicants and CROs requesting to retain a lower quantity of the reserve samples. In light of these technological advances, FDA finds it appropriate for applicants (or their CROs) to retain a quantity of samples less than what is specified in 21 CFR 320.38(c) when FDA has determined that the lower quantity of reserve samples is sufficient for FDA to conduct the necessary ‘chemical and physical examination of the samples to assure the identity and composition of the test article and reference standard’ intended by the regulation. Accordingly, at this time and based on our current understanding of the risks involved, FDA does not intend to enforce the requirement to retain a sufficient quantity to perform five times all the release tests required in the application or supplemental application, so long as the identified lower quantities are retained.”

The guidance also describes circumstances where FDA may not take enforcement actions against an applicant or contract research organization for not retaining enough reserve samples of the test article or reference standard used in the BA or BE study.