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Bioequivalence

A regulatory standard proving that a generic drug delivers the same amount of active ingredient to the bloodstream at the same rate as the brand-name drug.

How It Works

Bioequivalence (BE) is the scientific foundation of generic drug approval under Hatch-Waxman. FDA defines BE in 21 CFR 320.1 as "the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents... becomes available at the site of drug action." BE is typically demonstrated through in vivo pharmacokinetic (PK) studies in healthy volunteers: a two-period, two-sequence crossover design with 24-36 subjects, where each subject receives both the generic and the reference listed drug (RLD) with a washout period in between. Blood samples measure drug concentration over time, and FDA evaluates three parameters: Cmax (maximum concentration), AUC0-t (area under the curve to last measurable concentration), and AUC0-inf (extrapolated total AUC). FDA requires the 90% confidence interval of the generic-to-reference ratio for Cmax and AUC to fall within 80.00-125.00%. In practice, actual BE study results cluster tightly around 100%, a 2019 FDA analysis of 2,070 ANDA BE studies found a mean Cmax ratio of 1.00 with 4% standard deviation. For narrow therapeutic index drugs (warfarin, lithium, cyclosporine, levothyroxine), FDA uses tightened BE criteria of 90-111%. BE is assessed on the active moiety only; inactive ingredients (excipients) can differ, which occasionally causes differences in patient tolerability (coloring dyes, lactose, gluten). Biosimilar BE requirements under BPCIA are more extensive, including comparative PK/PD plus usually one confirmatory clinical efficacy study rather than just PK.

Related Terms

  • Generic Drug, A medication that contains the same active ingredient, dosage, and form as a brand-name drug, approved after the original's patent expires, typically costing 80-95% less.
  • Abbreviated New Drug Application (ANDA), The FDA application pathway for generic drugs, which requires proving bioequivalence to the brand-name drug rather than repeating full clinical trials.
  • FDA Approval, The process by which the U.S. Food and Drug Administration evaluates a drug's safety and efficacy through clinical trial data before allowing it to be marketed.

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About This Definition

This definition is part of the DrugPrice Drug Pricing Glossary, 49 terms explaining how prescription drug pricing works in the United States. All definitions are written in plain language for patients, caregivers, journalists, and healthcare professionals.

this entity is one of the U.S. Medicare prescription-drug pricing concepts that recurs across this site. The definition above is the technical answer; the paragraphs below add the practical context for how the concept connects to the CMS Medicare Part D Drug Spending data data behind every per-entity page on the site.

In the CMS Medicare Part D Drug Spending data data, this concept shapes one or more of the fields that drive the per-entity grades and rankings on this site. The methodology page describes which fields feed into which output; this glossary entry documents the underlying term.

Source: CMS Medicare Part D Spending, 2026.