This publication summarizes the proceedings of day 2 of a 3-day workshop on “Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development.” Patient-centric drug product development from a drug product quality perspective necessitates the establishment of clinically relevant drug product specifications via an in vitro-in vivo link. Modeling and simulation offer a path to establish this link; in this regard, physiologically based modeling has been implemented successfully to support regulatory decision-making and drug product labeling. In this manuscript, case studies of physiologically based biopharmaceutics modeling (PBBM) applied to drug product quality are presented and summarized. These case studies exemplify a possible path to achieve an in vitro-in vivo link and encompass (a) development of biopredictive dissolution methods to support biowaivers, (b) model-informed formulation selection, (c) predicting clinical formulation performance, and (d) defining a safe space for regulatory flexibility via virtual bioequivalence (BE). Workflows for the development and verification of absorption models/PBBM and for the establishment of a safe space using dissolution as an input are described with examples. Breakout session discussions on topics, such as current challenges and some best practices in model development and verification, are included as part of the Supplementary material.
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The meeting organizers are indefinitely grateful to Drs. James Polli (University of Maryland, School of Pharmacy, Baltimore, MD), Tzuchi (Rob) Ju (AbbVie, Inc.), and Ms. Ann Anonson (UM) for their tremendous efforts in helping with the organization of this workshop. The authors wish to thank the following colleagues who have made significant contributions to for providing the material from their case studies that were highlighted in this presentation. Sanofi: Sylvie Fabre-Decourt, Anne Lanotte, Victor Ariel; in Ardea Biosciences: Colin Rowlings, Anna Eidelman, Don Treacy; in AstraZeneca: Talia Flanagan, David Holt, Simon Hartas; Novartis: Marc Laisney, Handan He; Roche: Neil John Parrott and Cordula Stillhart and their co-workers; Janssen: Christophe Tistaert.
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Heimbach, T., Suarez-Sharp, S., Kakhi, M. et al. Dissolution and Translational Modeling Strategies Toward Establishing an In Vitro-In Vivo Link—a Workshop Summary Report. AAPS J 21, 29 (2019). https://doi.org/10.1208/s12248-019-0298-x
- clinically relevant dissolution specifications
- physiologically based biopharmaceutics modeling (PBBM)
- safe space
- virtual bioequivalence