In Vitro Biopredictive Methods: A Workshop Summary Report

Xavier J H Pepin; Jennifer Dressman; Neil Parrott; Poonam Delvadia; Amitava Mitra; Xinyuan Zhang; Andrew Babiskin; Vidula Kolhatkar; Paul Seo; Lynne S Taylor; Erik Sjögren; James M Butler; Edmund Kostewicz; Christer Tannergren; Mirko Koziolek; Filippos Kesisoglou; André Dallmann; Yang Zhao; Sandra Suarez-Sharp

doi:10.1016/j.xphs.2020.09.021

In Vitro Biopredictive Methods: A Workshop Summary Report

J Pharm Sci. 2021 Feb;110(2):567-583. doi: 10.1016/j.xphs.2020.09.021. Epub 2020 Sep 19.

Authors

Xavier J H Pepin¹, Jennifer Dressman², Neil Parrott³, Poonam Delvadia⁴, Amitava Mitra⁵, Xinyuan Zhang⁶, Andrew Babiskin⁷, Vidula Kolhatkar⁴, Paul Seo⁴, Lynne S Taylor⁸, Erik Sjögren⁹, James M Butler¹⁰, Edmund Kostewicz¹¹, Christer Tannergren¹², Mirko Koziolek¹³, Filippos Kesisoglou¹⁴, André Dallmann¹⁵, Yang Zhao⁴, Sandra Suarez-Sharp¹⁶

Affiliations

¹ New Modalities and Parenteral Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield, UK. Electronic address: Xavier.pepin@astrazeneca.com.
² Fraunhofer Institute for Molecular Biology and Applied Ecology and Goethe University, Frankfurt, Germany.
³ Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
⁴ Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁵ Clinical Pharmacology and Pharmacometrics, Janssen Research & Development, Spring House, PA, USA.
⁶ Division of Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁷ 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.
⁸ Purdue University, College of Pharmacy, West Lafayette, IN, USA.
⁹ Pharmetheus, Uppsala, Sweden.
¹⁰ Biopharmaceutics, Drug Product Design & Dev, GlaxoSmithKline R&D, Ware, UK.
¹¹ Institute of Pharmaceutical Technology, Goethe University, Frankfurt, Germany.
¹² Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Gothenburg, Sweden.
¹³ University of Greifswald, Institute of Pharmacy, Greifswald, Germany; Current: NCE Formulation Sciences, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
¹⁴ Pharmaceutical Sciences, Merck & Co., Inc., Kenilworth, NJ, USA.
¹⁵ Clinical Pharmacometrics, Research & Development, Pharmaceuticals, Bayer AG, Leverkusen, Germany.
¹⁶ Regulatory Affairs, Simulations Plus Inc., 42505 10th Street West, Lancaster, CA 93534, USA.

PMID: 32956678
DOI: 10.1016/j.xphs.2020.09.021

Abstract

This workshop report summarizes the proceedings of Day 1 of a three-day workshop on "Current State and Future Expectations of Translational Modeling Strategies to Support Drug Product Development, Manufacturing Changes and Controls". Physiologically based biopharmaceutics models (PBBM) are tools which enable the drug product quality attributes to be linked to the in vivo performance. These tools rely on key quality inputs in order to provide reliable predictions. After introducing the objectives of the workshop and the expectations from the breakout sessions, Day 1 of the workshop focused on the best practices and challenges in measuring in vitro inputs needed for modeling, such as the drug solubility, the dissolution rate of the drug product, potential precipitation of the drug and drug permeability. This paper reports the podium presentations and summarizes breakout session discussions related to A) the best strategies for determining solubility, supersaturation and critical supersaturation; B) the best strategies for the development of biopredictive (clinically relevant) dissolution methods; C) the challenges associated with describing gastro-intestinal systems parameters such as mucus, liquid volume and motility; and D) the challenges with translating biopharmaceutical measures of drug permeability along the gastrointestinal tract to a meaningful model parameter.

Keywords: Bioequivalence; Biopredictive dissolution; CQAs; IVIVC; IVIVR; Modeling; PBBM; PBPK; Permeability; Precipitation; Solubility.

Publication types

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

MeSH terms

Administration, Oral
Biopharmaceutics
Drug Development
Intestinal Absorption
Models, Biological*
Research Report*
Solubility

Grants and funding

U01 FD005946/FD/FDA HHS/United States