Compliance Policy for the Quantity of Bioavailability (BA) and Bioequivalence (BE) Samples Retained Under 21 CFR 320.38(c)
As of August 18, 2020, the FDA is changing its stance on the number of samples considered sufficient for testing and reference standards used in BA or BE studies. The last update to this code was implemented in 1993. At the time, it was required that New Drug Application (NDA) and Abbreviated New Drug Application (ANDA) applicants “retain reserve samples of the test product and reference standard used in an in vivo bioavailability (BA) and in vivo or in vitro bioequivalence (BE) study that consists of a sufficient quantity to perform five times all the release tests required in the application or supplemental application.” This meant that applicants were required to retain as many as 300 units of each test article.
Due to technological advances in testing capabilities, and requests from applicants and CROs, smaller samples may be retained by applicants; as few as 30 units of each test article or 3 units of multi-dose units.
Applicants also have the ability to request an even smaller sample size if deemed appropriate by the FDA for 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.
In conclusion, the FDA will not take action against violations of the current 320.38(c) standards as long as the samples are large enough to perform proper testing. They have also included an appendix (Appendix 1 available in the link below) for companies to reference moving forward.
Applicants should also note that generic drug product development should be submitted as controlled correspondence and should seek guidance from the Controlled Correspondence Related to Generic Drug Development.
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