Leveraging Biopharmaceutics Bridging Risk Assessment and In Vivo Predictive Tools to Accelerate Immediate Release Drug Product Development by Minimized Need for Clinical Bridging Studies.

Accelerated development of oral solid dosage forms necessitates effective strategies to link clinical data across development stages. Emerging predictive tools present a viable alternative, ensuring targeted clinical performance with a significantly reduced dependence on traditional clinical bridging studies. This paper introduces a biopharmaceutics bridging risk assessment (BBRA) tool that extends opportunities to avoid clinical bridging studies beyond the biopharmaceutics classification system (BCS) classes 1 and 3, utilizing physiologically based biopharmaceutics modeling (PBBM) and advanced in vitro tools (such as the TNO (Netherlands Organisation for Applied Scientific Research) transit intestinal model, TIM). PBBM uses experimental solubility, dissolution, and permeability input, validated by clinical data, to enhance risk assessment granularity and understanding, while TIM uniquely simulates physiological gastrointestinal conditions, complementary to traditional dissolution tests. The decision-tree framework, aligned with ICH M9 principles, supports iterative decision-making across the drug development life cycle, from preclinical to postapproval phases. An analysis of 32 AstraZeneca bridging cases showed that application of BBRA could reduce the number of clinical studies by 70%. By leveraging in vivo predictions and comprehensive clinical insights, our strategic approach mitigates late-stage BE failure risks, expedites market introduction, and ensures effective patient treatments.