Bioequivalence

Bioequivalence is the property that two pharmaceutical products, typically a test product and a reference product, exhibit similar bioavailability in humans, resulting in comparable systemic drug exposure. It is evaluated by pharmacokinetic measures of rate and extent of absorption, primarily the area under the plasma concentration–time curve (AUC) and the maximum plasma concentration (Cmax). Tmax may be reported but is not always used as a formal criterion for equivalence.

Most assessments are in vivo, using randomized crossover studies in healthy volunteers under controlled conditions. After administration, plasma concentrations are measured, and non-compartmental analysis is used to compute geometric mean ratios of test to reference for AUC and Cmax. Equivalence is declared if the 90% confidence intervals for these ratios lie within predefined acceptance limits, commonly 80% to 125% in many jurisdictions; some drugs or regions employ different or tighter criteria, particularly for highly variable medicines.

Regulatory agencies such as the U.S. FDA, the European Medicines Agency, and other authorities require demonstration of bioequivalence for generic products seeking approval. In certain cases, in vitro dissolution testing or in vitro–in vivo correlation (IVIVC) may supplement or, for some products, substitute in vivo studies. For narrow therapeutic index drugs, additional constraints or studies may be imposed.

Bioequivalence implies similar therapeutic effects under standard conditions but does not guarantee identical clinical outcomes in every patient, as pharmacodynamics and formulation excipients can influence local or individual responses. It is less applicable to biologics, where biosimilarity criteria apply, and to complex locally acting products, where different evidence may be required.