Abstract

As a drug advances through the late stages of clinical development, formulation changes are common to meet clinical, manufacturing, and/or business needs. Since some formulation changes may alter in vivo drug absorption, it is critical to understand the impact of these changes on in vivo PK performances to support the transition between pre- and post-change formulations and ensure the drug’s efficacy and safety. While clinical RBA/BE studies are time-consuming and expensive, other formulation bridging approaches that bring opportunities to expedite drug development by waiving clinical formulation bridging studies are summarized. This review discussed the current formulation bridging options based on in vitro dissolution, physiologically-based biopharmaceutics modeling (PBBM), in vitro – in vivo correlation (IVIVC), and risk-based assessment during the early and late stages of clinical development. By increasing the understanding of the opportunities and challenges associated with different formulation bridging approaches, this review helps with the selection/design of formulation bridging studies in a phase appropriate manner for formulation change during product development.

By Murui Han and Jin Xu Yiqing Lin