AAM seeks clarity, leeway in BA/BE studies guidance

The Association for Accessible Medicines (AAM) wants the US Food and Drug Administration (FDA) to clarify what its expectations of sponsors of bioavailability (BA) and bioequivalence (BE) studies in the agency’s recently updated guidance on the topic. It also wants regulators to waive a five-year sample retention requirement if the facility has passed agency inspection.

FDA published a guidance in March that is mostly in draft form but with a key finalized section that outlines procedures for handling reserve samples from BA/BE studies. It details the different responsibilities of each party involved in such studies, including sponsors of new drug applications (NDAs) and abbreviated new drug applications (ANDAs), and contract research organizations (CROs).

The guidance states that the parties involved must keep sufficient quantities of test article (T) and reference standard (RS) samples from BA/BE studies for the FDA to perform chemical and physical analyses of those samples and verify the outcomes reported by the sponsors. However, it also noted that due to technological advancements fewer samples may need to be kept for the agency to conduct its analysis. Furthermore, the guidance stated that generally, reserve samples need to be kept for at least five years after an application or supplemental application has been approved. If the application hasn’t been approved, the samples should be kept for five years after completing the BA/BE study.

Section IV.B, the finalized portion of the guidance, lays out when FDA won't take enforcement action against the various parties for keeping less of the sample quantities than the guidance in general asks for.

“AAM also appreciates that FDA designates as final and for immediate implementation section IV.B in which FDA describes the conditions under which it does not intend to take enforcement action against an applicant or CRO for retaining less than the quantity of reserve samples of the test article (“T”) and reference standard (“RS”) that were used in the BA or BE study,” said AAMI in their comments to FDA on the guidance.

“The Guidance notes that this policy applies to all reserve samples held to date, including reserve samples from previously completed BA or BE studies,” the group added. “This immediate implementation of a less burdensome approach to retention of samples will reduce costs associated with testing, freeing up resources that can be used for additional generic drug development, increasing patient access to more safe and effective and cost-effective medicines.”

AAM also asked for additional clarity in the guidance, including what the agency expects if a study needs to be redone or if it fails, and whether the sponsor needs to submit data from a failed study in a new submission. AAM specifically laid out three scenarios related to failed studies, including where it may be necessary to conduct a single dose study at the same clinical site as the original study, use the same batch of reference listed drug (RLD), and when sponsors should use 30 single dose (SD) units of each of the T and RS samples from the first study.

“If a new shipment from the pharmacy to the clinic site of the RS product is required to conduct the new study, how many additional samples must the site retain (a minimum of 1 additional SD unit or 30 SD units) from the new shipment?” AAM asked.

AAM also asked FDA to clarify whether it is necessary to keep samples from a failed BE study and for how long that sample should be kept if the sponsor no longer wants to submit a new application. It also asked what should happen if the sponsor doesn’t plan on using the data from the failed study for their application because the formulation or manufacturing method has changed and if they don't plan on submitting an application but do plan to submit a complete or summary report.

AAM also recommended that sponsors be allowed to discard samples sooner if their storage sites meet FDA requirements.

“We recommend that the Guidance state that if, before the 5-year mark, the site where samples are collected and stored has been inspected and is found to be in good compliance standing, the samples can be discarded,” the group said. “There are administrative costs and burdens associated with retaining samples, which would not be warranted if the site has passed an inspection.”

Guidance comments

AAM seeks clarity, leeway in BA/BE studies guidance

Related topics

Recommended content

Welcome to the new RAPS Digital Experience