In vivo and In vitro Bioequivalence Testing

For approval of generic drug products, bioequivalence testing is considered as a surrogate for clinical evaluation of the therapeutic equivalence of drug products based on the Fundamental Bioequivalence Assumption that when two drug products (e.g., a brand-name drug and its generic copy) are equivalent in bioavailability, they will reach the same therapeutic effect. Although bioavailability for in vivo bioequivalence studies is usually assessed through the measures of the rate and extent to which the drug product is absorbed into the bloodstream of human subjects, for some locally acting drug products such as nasal aerosols (e.g., etered-dose inhalers) and nasal sprays (e.g., metered-dose spray pumps) that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action. For those local delivery drug products, the United States Food and Drug Administration (FDA) indicates that bioequivalence may be assessed, with suitable justification, by in vitro bioequivalence studies alone (e.g., Part 21 Codes of Federal Regulations Section 320.24).