Bioequivalence for Drug Products Acting Locally Within Gastrointestinal Tract

The assessment of bioequivalence (BE) of drug products acting locally within gastrointestinal (GI) tract is one of the biggest challenges generally in generic product development and approval process. In recent years, considerable progress has been made by the FDA in developing alternative bioequivalence approaches to in vivo clinical endpoint studies for locally acting GI products. These BE approaches include in vitro tests, in vivo BE studies with pharmacokinetic (PK) endpoints and in vivo BE studies with pharmacodynamics (PD) endpoints. The selection of the appropriate product-specific BE recommendations depend on a number of factors including biopharmaceutical properties of the drug substance, formulation design, and drug product safety and efficacy profiles. In this chapter, the newly developed BE approaches for a number of locally acting GI products are reviewed. It is expected that the information provided in this chapter will help the industry and regulatory scientists understand the scientific principles for identification of the most appropriate BE methods and thus accelerate the new as well as the generic product development and life-cycle management for locally acting GI products.