PBBM Considerations for Base Models, Model Validation,\nand Application Steps: Workshop Summary Report

The\nproceedings from the 30th August 2023 (Day 2) of the workshop\n“Physiologically Based Biopharmaceutics Models (PBBM) Best\nPractices for Drug Product Quality: Regulatory and Industry Perspectives”\nare provided herein. Day 2 covered PBBM case studies from six regulatory\nauthorities which provided considerations for model verification,\nvalidation, and application based on the context of use (COU) of the\nmodel. PBBM case studies to define critical material attribute (CMA)\nspecification settings, such as active pharmaceutical ingredient (API)\nparticle size distributions (PSDs) were shared. PBBM case studies\nto define critical quality attributes (CQAs) such as the dissolution\nspecification setting or to define the bioequivalence safe space were\nalso discussed. Examples of PBBM using the credibility assessment\nframework, COU and model risk assessment, as well as scientific learnings\nfrom PBBM case studies are provided. Breakout session discussions\nhighlighted current trends and barriers to application of PBBMs including:\n(a) PBBM credibility assessment framework and level of validation,\n(b) use of disposition parameters in PBBM and points to consider when\niv data are not available, (c) conducting virtual bioequivalence trials\nand dealing with variability, (d) model acceptance criteria, and (e)\napplication of PBBMs for establishing safe space and failure edges.