The use of BDDCS in classifying the permeability of marketed drugs

We recommend that regulatory agencies add the extent of drug metabolism (i.e., >= 90% metabolized) as an alternate method in defining Class 1 marketed drugs suitable for a waiver of in vivo studies of bioequivalence. That is, >= 90% metabolized is an additional methodology that may be substituted for >= 90% absorbed. We propose that the following criteria be used to define >= 90% metabolized for marketed drugs: Following a single oral dose to humans, administered at the highest dose strength, mass balance of the Phase 1 oxidative and Phase 2 conjugative drug metabolites in the urine and feces, measured either as unlabeled, radioactive labeled or nonradioactive labeled substances, account for >= 90% of the drug dosed. This is the strictest definition for a waiver based on metabolism. For an orally administered drug to be >= 90% metabolized by Phase 1 oxidative and Phase 2 conjugative processes, it is obvious that the drug must be absorbed. This proposal, which strictly conforms to the present >= 90% criteria, is a suggested modification to facilitate a number of marketed drugs being appropriately assigned to Class 1.