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FDA publishes two final guidances for industry: “Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA” and “Statistical Approaches to Establishing Bioequivalence”
On May 28, 2026, FDA published two final guidances for industry related to establishing bioequivalence.
The guidance for industry entitled “Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA” provides recommendations to applicants planning abbreviated new drug application (ANDA) submissions on how to meet the bioequivalence (BE) requirements set forth in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and FDA regulations. This final guidance is generally applicable to dosage forms intended for oral administration and to non-orally administered drug products in which reliance on systemic exposure measures is suitable for establishing BE (e.g., transdermal delivery systems and certain rectal and nasal drug products). This final guidance will also be useful to applicants planning BE studies to be conducted during the postapproval period for changes to a drug product approved under an ANDA.
This guidance finalizes the draft guidance of the same title that was issued in August 2021. It aligns the recommendations with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) recommendations as reflected in the guidance for industry entitled “M13A Bioequivalence for Immediate-Release Solid Oral Dosage Forms” (October 2024) and includes clarifications about study population and study design and updates to the in vitro dissolution testing information.
In addition to this guidance, FDA also recommends that ANDA applicants routinely consult published product specific guidances (PSGs) when considering the appropriate BE study and/or other studies for a proposed generic product. For more information about FDA’s PSG publications and to search for the most recent version of a PSG, see the Product Specific Guidances for Generic Drug Development web page.
The guidance for industry entitled “Statistical Approaches to Establishing Bioequivalence” provides recommendations to sponsors and applicants who intend to use equivalence criteria in analyzing in vivo or in vitro BE studies for investigational new drugs (INDs), new drug applications (NDAs), ANDAs, and their amendments and supplements. This guidance discusses statistical approaches for BE comparisons and focuses on how to use these approaches generally and in specific situations.
This guidance finalizes the draft guidance of the same title issued in December 2022 and replaces the guidance of the same title issued in February 2001. This guidance includes clarifying information on estimands and intercurrent events, sample size determinations, and outlier data, additional information on statistical analysis using population bioequivalence and statistical analysis using modified population bioequivalence, which was previously included in PSGs, and additional information on statistical analysis for the reference scaled average bioequivalence for narrow therapeutic index drugs and highly variable drugs, which was previously included in the draft guidance for industry “Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA” (August 2021).
These guidances are intended to help applicants more effectively plan their BE studies and use equivalence criteria in analyzing these BE studies. By providing clear information to applicants, these guidances will help generate savings by reducing duplicative efforts, regulatory delays, development costs, and process uncertainties for industry, as well as time spent by FDA assessing applications.
FDA is issuing these guidances as part of its Drug Competition Action Plan, which seeks to improve the efficiency of the generic drug development, review, and approval process. An efficient generic drug review process helps to expand access to safe, high-quality, effective generic medicines that can, in turn, help consumers lower their health care costs.
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