Abstract
This Article shares the proceedings from the August 29th, 2023 (day 1) workshop “Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives”. The focus of the day was on model parametrization; regulatory authorities from Canada, the USA, Sweden, Belgium, and Norway presented their views on PBBM case studies submitted by industry members of the IQ consortium. The presentations shared key questions raised by regulators during the mock exercise, regarding the PBBM input parameters and their justification. These presentations also shed light on the regulatory assessment processes, content, and format requirements for future PBBM regulatory submissions. In addition, the day 1 breakout presentations and discussions gave the opportunity to share best practices around key questions faced by scientists when parametrizing PBBMs. Key questions included measurement and integration of drug substance solubility for crystalline vs amorphous drugs; impact of excipients on apparent drug solubility/supersaturation; modeling of acid-base reactions at the surface of the dissolving drug; choice of dissolution methods according to the formulation and drug properties with a view to predict the in vivo performance; mechanistic modeling of in vitro product dissolution data to predict in vivo dissolution for various patient populations/species; best practices for characterization of drug precipitation from simple or complex formulations and integration of the data in PBBM; incorporation of drug permeability into PBBM for various routes of uptake and prediction of permeability along the GI tract.
| Original language | English |
|---|---|
| Pages (from-to) | 3697-3731 |
| Number of pages | 35 |
| Journal | Molecular Pharmaceutics |
| Volume | 21 |
| Issue number | 8 |
| Early online date | 30 Jun 2024 |
| DOIs | |
| Publication status | Published - 5 Aug 2024 |
Funding
The meeting organizers are extremely grateful to Keiasia Robinson and Dana Hammell (University of Maryland, Baltimore) and the FDA Office of Regulatory Science and Innovation (ORSI) for significantly contributing to the success of the workshop. This research was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award 5U01FD005946 totaling $5,000 with 100% funded by FDA/HHS. The collaboration work was supported by the IQ consortium. The authors would like to acknowledge the collaborative effort of regulators who participated in the PBBM case studies discussions and the open and constructive way they shared their views on the scientific approach and data submitted. In parallel, the authors would like to thank the IQ consortium company members and for this day Amgen, AstraZeneca, and Pfizer for taking the time to develop PBBMs around relevant biopharmaceutical questions, prepare the submissions, and make this exercise possible. Finally, the authors would like to thank Simulations Plus, Inc. and Certara for sharing their advice and training when requested to use their respective modeling platforms.
| Funders | Funder number |
|---|---|
| U.S Food and Drug Administration | |
| U.S. Department of Health and Human Services | |
| Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) |
Keywords
- bioequivalence
- biopredictive dissolution
- CQAs
- IVIVC
- IVIVR
- modeling
- PBBM
- permeability
- precipitation
- solubility
ASJC Scopus subject areas
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery