New guidance for industry: M13A Bioequivalence for Immediate-Release Solid Oral Dosage Forms

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On January 31, 2023, FDA published draft guidance for industry, “M13A Bioequivalence for Immediate- Release Solid Oral Dosage Forms,” which provides recommendations for conducting bioequivalence (BE) studies during development and post-approval phases for orally administered immediate-release (IR) solid oral dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules/powders for oral suspension.

BE for IR solid oral dosage forms with systemic action is largely established via clinical pharmacokinetic (PK) BE studies or comparative in vitro dissolution studies. BE assessment for these oral dosage forms is important for establishing therapeutic equivalence for generic drug products to their respective comparator products. Demonstration of BE may be critical for approval decisions in certain new (innovator) drug development situations and BE studies are also used by innovator and generic product developers for supporting post-approval formulation and/or manufacturing process changes.

This draft guidance (M13A) was prepared with the support of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) by the ICH M13 Expert Working Group. The draft guidance is intended to provide harmonized, global, scientific recommendations for conducting BE studies during both development and post approval phases that can increase the efficiency of drug development and accelerate the availability of safe and effective orally administered IR solid oral dosage forms.

M13 is the first ICH guidance developed on harmonizing BE standards for generic drugs following the publication of the ICH reflection paper, “Further Opportunities for Harmonisation of Standards for Generic Drugs” (November 2018). M13A serves as the first in the series to describe the scientific and technical aspects of study design and data analysis to support BE assessment for orally administered IR solid oral dosage forms or oral suspensions. The second in the series, M13B, will describe biowaiver considerations for additional strengths not investigated in BE studies. The third in the series, M13C, will include data analysis and BE assessment for 1) highly variable drugs, 2) drugs with narrow therapeutic index, and 3) complex BE study design and data analysis considerations, e.g., adaptive BE study design.

In December 2022, the ICH Assembly endorsed the draft titled “M13A Bioequivalence for Immediate-Release Solid Oral Dosage Forms” and agreed that the guidance should be made available for public comment. Comments about this draft will be considered by FDA and the ICH M13 Expert Working Group. For information on how to comment, please see the Federal Register Notice.