Physiologically Based Biopharmaceutics Models (PBBMs) are new tools which can be used to aid in formulation selection and drug product quality specifications as part of successful drug development. PBBMs have gained increased regulatory interest and acceptance over the past 5 years and FDA as well as ANVISA have recently provided PBBM draft guidances, and PMDA has shown interest in PBBM in MIDD. PBBM has been used for several applications: a) calculation of a bioequivalence safe space, where similar dissolution profiles are expected to lead to bioequivalent pharmacokinetics of e.g. an early capsule formulation and final market image tablet, b) formulation selection and PK bioanalysis for bioequivalence studies, c) setting of clinically relevant drug product specifications.
Five publications in Molecular Pharmaceutics Special PBBM Edition have highlighted the recent advances in PBBM:
1) PBBM credibility assessment framework and level of validation, 2) Use of disposition parameters in PBBM and points to consider when iv data are not available, 3) Application of PBBMs for establishing safe space and failure edges. 4) PBBM for internal decision making and regulatory expectations
Publications include: 1.Mackie, C., et al., Physiologically Based Biopharmaceutics Modeling (PBBM): Best Practices for Drug Product Quality, Regulatory and Industry Perspectives: 2023 Workshop Summary Report. Molecular Pharmaceutics, 2024. 21(5): p. 2065-2080. 2. Pepin, X., et al., Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report. Molecular Pharmaceutics, 2024. 21(8): p. 3697-3731. 3. Heimbach, T., et al., PBBM Considerations for Base Models, Model Validation, and Application Steps: Workshop Summary Report. Molecular Pharmaceutics, 2024. 21(11): p. 5353-5372. 4.Tannergren, C., et al., Current State and New Horizons in Applications of Physiologically Based Biopharmaceutics Modeling (PBBM): A Workshop Report. Molecular Pharmaceutics, 2025. 22(1): p. 5-27. 5.Arora, S., et al., Development of a Physiologically Based Biopharmaceutics Model Template: Considerations for Improved Quality in View of Regulatory Submissions, https://doi.org/10.1021/acs.molpharmaceut.5c00225.
Learning Objectives:
This session teaches:
1a) PBBM credibility assessment framework
1b) PBBM input parameters, model validation, model acceptance criteria
2a) Conducting virtual bioequivalence trials
2b) Bioequivalence safe space and failure edges.
3a) Published PBBM Template use in regulatory filings and company internal decision making
3b) Familiarity with recent draft guidances by ANVISA, FDA and PBBM workflows by PMDA
