Bioavailability and Bioequivalence Studies

Introduction & definitions

• Drug-product performance in vivo — bioavailability (BA) and bioequivalence (BE) are the two in-vivo measures — the release of drug substance from the product leading to its availability at the site of action.
• Bioavailability (BA) — the rate and extent to which the active moiety is absorbed and becomes available at the site of action (US-FDA); equivalently the fraction F of a dose that reaches the systemic circulation unchanged — F = 1 for IV, and F < 1 orally from incomplete absorption plus presystemic (first-pass) metabolism.
• Bioequivalence (BE) — the absence of a significant difference in the rate and extent to which the active moiety becomes available from a test versus a reference product given at the same molar dose under similar conditions; a BE study is a special case of a relative-BA study (during development such comparisons are called relative bioavailability, and "bioequivalence" is reserved for the formal test-vs-reference comparison that supports marketing).
• Chemical vs biological equivalence — different brands or batches may be chemically equivalent (same drug content) yet biologically inequivalent (different blood levels); they are bioequivalent only when rate and extent of BA do not differ significantly.
• Why it matters — BA characterises a new product’s in-vivo performance; BE links the marketed product to the pivotal-trial formulation and underpins generic (ANDA) approval — critical for narrow-margin drugs (digoxin, warfarin, oral hypoglycaemics).