The US FDA has published the guidance for industry entitled “Compliance Policy for the Quantity of Bioavailability and Bioequivalence Samples Retained Under 21 CFR 320.38(c).” This guidance describes FDA’s compliance policy related to the retention of reserve samples of the test article and reference standard used in an in vivo bioavailability (BA) and in vivo or in vitro bioequivalence (BE) study. This guidance applies only to the requirements for retention of reserve samples contained in 21 CFR 320.38(c).
FDA has determined that, with technological advances, generally, a reduced quantity of reserve samples than the quantity set forth in the regulation is now sufficient for FDA testing provided that the applicant retains the minimum quantity deemed by FDA to be sufficient for conducting the necessary chemical and physical examination of the samples to assure the identity and composition of the test article and reference standard as intended by the regulation. Accordingly, at this time and based on the 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.
Specifically, this guidance:
- Addresses the requirement at 21 CFR 320.38(c) to retain reserve samples of sufficient quantity to permit FDA to perform five times all the release tests required in an application or supplemental application; and
- Describes the conditions under which the Agency does not generally intend to take regulatory action against an applicant or contract research organization (CRO) for retaining less than the quantity of reserve samples of the test article and reference standard that were used in the BA or BE study specified in 21 CFR 320.38(c)
This guidance does not apply to the other requirements for retention of reserve samples contained in 21 CFR 320.38, such as how testing facilities must select samples for testing, how the reserve samples must be retained, and whether reserve samples are in fact representative of the test article and reference standard used in the BA or BE study. Additionally, this guidance does not affect the requirement in 21 CFR 211.170 to retain samples under current good manufacturing practices.
Although this guidance document is immediately in effect, it remains subject to comment in accordance with FDA’s good guidance practices regulation and FDA will consider all comments received and revise the guidance document as appropriate (see 21 CFR 10.115(g)(3)). Electronic or written comments on this guidance can be submitted at any time via www.regulations.gov.