Equivalence Testing and FDA Regulations

From a “historical” perspective (the first journal article on an equivalence test appeared as late as in the sixties of the twentieth century), the interest of statistical researchers in equivalence assessment was almost exclusively triggered by the introduction of special approval regulations for so-called generic drugs by the Food and Drug Administration (FDA) of the U.S. as well as the drug regulation authorities of many other industrial countries. Essentially, these regulations provide that the positive result of a test, which enables one to demonstrate with the data obtained from a so-called comparative bioavailability trial the equivalence of the new generic version of a drug to the primary manufacturer’s formulation, shall be accepted as a sufficient condition for approval of the generic formulation to the market. The overwhelming practi- cal importance of the entailed problems of bioequivalence assessment (drugs whose equivalence with respect to the measured bioavailabilities can be taken for granted, are termed “bioequivalent” in clinical pharmacology literature), arises mainly out of quantity: Nowadays, at least half of the prescription drug units sold in the leading industrial countries are generic drugs that have been approved to be marketed on the basis of some bioequivalence trial.