Best Practices in the Development and Validation of Physiologically Based Biopharmaceutics Modeling. A Workshop Summary Report

Neil Parrott; Sandra Suarez-Sharp; Filippos Kesisoglou; Shriram M Pathak; David Good; Christian Wagner; André Dallmann; James Mullin; Nikunjkumar Patel; Arian Emami Riedmaier; Amitava Mitra; Kimberly Raines; James Butler; Maziar Kakhi; Min Li; Yang Zhao; Eleftheria Tsakalozou; Talia Flanagan; Jennifer Dressman; Xavier Pepin

doi:10.1016/j.xphs.2020.09.058

Best Practices in the Development and Validation of Physiologically Based Biopharmaceutics Modeling. A Workshop Summary Report

J Pharm Sci. 2021 Feb;110(2):584-593. doi: 10.1016/j.xphs.2020.09.058. Epub 2020 Oct 13.

Authors

Neil Parrott¹, Sandra Suarez-Sharp², Filippos Kesisoglou³, Shriram M Pathak⁴, David Good⁵, Christian Wagner⁶, André Dallmann⁷, James Mullin², Nikunjkumar Patel⁸, Arian Emami Riedmaier⁹, Amitava Mitra¹⁰, Kimberly Raines¹¹, James Butler¹², Maziar Kakhi¹³, Min Li¹¹, Yang Zhao¹¹, Eleftheria Tsakalozou¹⁴, Talia Flanagan¹⁵, Jennifer Dressman¹⁶, Xavier Pepin¹⁷

Affiliations

¹ Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, CH-4070 Basel, Switzerland. Electronic address: [email protected].
² Simulations Plus Inc., 42505 10th Street West, Lancaster, CA 93534, USA.
³ Pharmaceutical Sciences, Merck & Co., Inc., Kenilworth, NJ, USA.
⁴ Quotient Sciences, Nottingham, United Kingdom.
⁵ Biopharmaceutics, Bristol-Myers Squibb, New Brunswick, NJ, USA.
⁶ Pharmaceutical Technologies, Chemical and Pharmaceutical Development, Merck KGaA, Darmstadt, Germany.
⁷ Clinical Pharmacometrics, Research & Development, Pharmaceuticals, Bayer AG, Leverkusen, Germany.
⁸ Certara UK Limited, Simcyp Division, Sheffield, UK.
⁹ DMPK and Translational Modeling, AbbVie Inc., North Chicago, IL, USA.
¹⁰ Clinical Pharmacology and Pharmacometrics, Janssen Research & Development, Spring House, PA, USA.
¹¹ Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality (OPQ), Center for Drug Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, MD, USA.
¹² Biopharmaceutics, Drug Product Design & Dev, GlaxoSmithKline R&D, Ware, UK.
¹³ Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
¹⁴ Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
¹⁵ Pharmaceutical Development, UCB Pharma SA, Braine l'Alleud, Belgium.
¹⁶ Fraunhofer Institute of Translational Medicine and Pharmacology, Carl-von-Noorden-Platz 9, 60596 Frankfurt am Main, Germany.
¹⁷ New Modalities and Parenteral Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield, UK.

PMID: 33058891
DOI: 10.1016/j.xphs.2020.09.058

Abstract

This workshop report summarizes the proceedings of Day 2 of a three-day workshop on "Current State and Future Expectations of Translational Modeling Strategies toSupportDrug Product Development, Manufacturing Changes and Controls". From a drug product quality perspective, physiologically based biopharmaceutics modeling (PBBM) is a tool to link variations in the drug product quality attributes to in vivo outcomes enabling the establishment of clinically relevant drug product specifications (CRDPS). Day 2 of the workshop focused on best practices in developing, verifying and validating PBBM. This manuscript gives an overview of podium presentations and summarizes breakout (BO) session discussions related to (1) challenges and opportunities for using PBBM to assess the clinical impact of formulation and manufacturing changes on the in vivo performance of a drug product, (2) best practices to account for parameter uncertainty and variability during model development, (3) best practices in the development, verification and validation of PBBM and (4) opportunities and knowledge gaps related to leveraging PBBM for virtual bioequivalence simulations.

Keywords: Biopharmaceutical characterization; Clinical pharmacokinetics; In vitro/In vivo (IVIVC) correlation(s); Oral absorption; Pharmacokinetics; Physiologically based pharmacokinetic (PBPK) modeling; Quality by design (QBD); Taken from the JPS dictionary.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Biopharmaceutics*
Models, Biological
Research Report*
Solubility
Therapeutic Equivalency

Grants and funding

U01 FD005946/FD/FDA HHS/United States