Pharmaceutically equivalent multisource pharmaceutical products must be shown to be therapeutically equivalent to one another in order to be considered interchangeable. Several test methods are available to assess equivalence, including:
(a) Comparative bioavailability (bioequivalence) studies, in which the active drug substance or one or more metabolites is measured in an accessible biologic fluid such as plasma, blood or urine.
(b) Comparative pharmacodynamic studies in humans.
Comparative clinical trials.
(d) In vitro dissolution tests.
Applicability of each of these four modalities is discussed in subsequent sections of this guideline and special guidance is provided to conduct an assessment of bioequivalence studies. Other modalities have been used to assess bioequivalence, such as bioequivalence studies in animals, but are not discussed in this guideline because this approach is not accepted worldwide.
Acceptance of any test procedure in the documentation of equivalence between two pharmaceutical products by a drug regulatory authority depends on many factors, including characteristics of the active drug substance and the drug product and availability of resources for the conduct of a specific type of study. Where a drug produces meaningful concentrations in an accessible biologic fluid, such as plasma, bioequivalence studies are preferred. Where a drug does not produce measurable concentrations in an accessible biologic fluid, comparative clinical trials or pharmacodynamic studies may be necessary to document equivalence. In vitro testing, preferably based on a documented in vitro/in vivo correlation, may sometimes provide some indication of equivalence between two pharmaceutical products (see section 3).
Additional criteria that indicate when equivalence studies are necessary are discussed in the following two sections of the guideline (8 and 9).