Bioequivalence and Bioavailability Forum

Dear all,

the FDA published a list¹ of 826 Product-Specific Guidances which are planned to be updated in October 2024:

Planned Revised PSGs for Complex and Non-Complex Generic Drug
Products to Align with ICH M13A
In addition to removing the BE recommendations for BE studies under either fasting
or fed conditions as indicated in the table, these PSGs may also include editorial
revisions to language and formatting as deemed appropriate by the Agency.

For 118 products (14.3%) the recommendation of performing the studies in fasting condition will be removed. For 708 products (85.7%) the recommendation of performing the studies in fed condition will be removed. For the latter there are two products (pimavanserin tartrate, tablet and capsule), where a BCS-based biowaiver will be added as an option.

The current PSGs state ‘Bioequivalence based on 90% CI’ but not which PK metrics have to be assessed. According to the overarching guidance² C_max, AUC_0–t (or AUC_0–72 if t_½ > 24 h), and AUC_0–∞ but according to ICH M13A AUC_0–∞ is not recommended – and for a reason.
Will the FDA’s guidance be updated as well or will we still have to deal with the superfluous AUC_0–∞?

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1. FDA. Upcoming Product-Specific Guidances for Generic Drug Product Development. Silver Spring, MD. 09/13/2024. Online.
   
2. FDA (CDER). Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA. Draft Guidance for Industry. Silver Spring, MD. August 2012. Download.