Authorisation of multi-origin (generic) drugs is based on the argument of equivalence vs. the originator. To this purpose. clinical therapeutic equivalence studies can be waived if pharmacokinetic equivalence can be evidenced (“bioequivalence” [BE]). BE is an adjusted format of comparative bioavailability (BA) based on two one-sided tests (TOST) each at 5% relative to a predefine tolerance zone. BE favours mere copies and penalises improved (‘supra’) bioavailability.
There is no top limit on sample size; also, regulators allow for reference scaling (with replicate designs) when within-subject data variability is high.
Although poor evidence of therapeutic switchability, average BE is a well-established quality mark of in vivo biopharmaceutical performance that is accepted to suffice for regulatory authorisation of generics, provided regulatory standards for BE-testing are complied with. The latter argument is categorical: requirements met, yes or no!? The related rulings are BE-specific (for BA they ought to be different); also, they differ across jurisdictions. Therefore it is important to know these rulings and/or to have ready access to them.
Therefore in our Library (Topics in Applied Clinical Pharmacology) we have set a section (Applied Clinical Pharmacokinetics – Guidelines | Library_BABE-Guidelines) on BABE-Testing that may be helpful in this regard; also under this topic you will find a useful calculator (see Library – Topics in Applied Clinical Pharmacology | Calculators | Biostatistical Calculators | FARTSSIE) for a preliminary estimate of the sample size you may need (depending on residual variance and trial design | replicate or not).