Do today's complex formulation strategies for poorly soluble drugs require a new way of thinking about bioequivalence assessment?

The current concept of bioequivalence testing has mainly been developed on the basis of active pharmaceutical ingredients (APIs) with high water solubility (BCS classes I and III). In the meantime, the majority of the modern APIs show very poor water solubility. In addition, many of the current APIs are weak bases whose solubility is strongly dependent on the pH value. Therefore, the conditions of ingestion may be very important, especially regarding prandial status, fluid intake, and drug therapies that affect gastric pH. As a consequence, oral bioavailability is also heavily influenced by formulation design. Overall, this raises the question of whether the established procedures for bioequivalence assessment are still up to date. The Committee for Human Medicinal Products (CHMP) has recently addressed some of these upcoming questions in the ICH guideline M13A. The presentation will highlight the problems and present and discuss the proposed solutions in the draft ICH guideline.