Does average bioequivalence equal therapeutic equivalence?
The critical question is whether assessment of bioequivalence assures therapeutic equivalence. Pharmacokinetic bioequivalence studies are a surrogate for clinical outcomes. Clinical studies comparing pioneer and generic drugs are rarely performed, and studies comparing one generic product with another are almost never performed. However, in the 1970s it was recognized that differences in the formulation of products containing the same amount of active ingredient could result in significant differences in bioavailability, and several cases of therapeutic inequivalence involving generic products were reported.30,31 These involved products that were never judged by the FDA to be bioequivalent, leading to development of the clinical and statistical approaches noted above to establish bioequivalence among pharmaceutically equivalent products. Similarly, several more recent reports involving clinical differences or serious bioequivalence problems with generic products have involved “B”-rated
