Considerations from an International Regulatory and Pharmaceutical Industry (IQ MPS Affiliate) Workshop on the Standardization of Complex In Vitro Models in Drug Development

Lindsay Tomlinson; Diane Ramsden; Sofia Batista Leite; Sonja Beken; Jessica A Bonzo; Paul Brown; Pelin L Candarlioglu; Tom S Chan; Eugene Chen; Colin K Choi; Rhiannon David; Nathalie Delrue; Patrick J Devine; Kevin Ford; Martha Iveth Garcia; James R Gosset; Philip Hewitt; Kimberly Homan; Onyi Irrechukwu; Anna K Kopec; Jennifer L Liras; Sandhya Mandlekar; Arek Raczynski; Nakissa Sadrieh; Melanie Z Sakatis; Jeffrey Siegel; Kyung Sung; Ilona Sunyovszki; Terry R Van Vleet; Jason E Ekert; Rhiannon N Hardwick

doi:10.1002/adbi.202300131

Considerations from an International Regulatory and Pharmaceutical Industry (IQ MPS Affiliate) Workshop on the Standardization of Complex In Vitro Models in Drug Development

Adv Biol (Weinh). 2023 Oct 9:e2300131. doi: 10.1002/adbi.202300131. Online ahead of print.

Authors

Lindsay Tomlinson¹, Diane Ramsden², Sofia Batista Leite³, Sonja Beken⁴, Jessica A Bonzo⁵, Paul Brown⁵, Pelin L Candarlioglu⁶, Tom S Chan⁷, Eugene Chen⁸, Colin K Choi⁹, Rhiannon David¹⁰, Nathalie Delrue¹¹, Patrick J Devine¹², Kevin Ford¹³, Martha Iveth Garcia¹³, James R Gosset¹⁴, Philip Hewitt¹⁵, Kimberly Homan¹⁶, Onyi Irrechukwu¹⁷, Anna K Kopec¹⁸, Jennifer L Liras¹⁹, Sandhya Mandlekar²⁰, Arek Raczynski²¹, Nakissa Sadrieh⁵, Melanie Z Sakatis²², Jeffrey Siegel⁵, Kyung Sung²³, Ilona Sunyovszki²⁴, Terry R Van Vleet²⁵, Jason E Ekert²⁶, Rhiannon N Hardwick¹²

Affiliations

¹ Global Pathology, Pfizer Inc., Cambridge, MA, 02140, USA.
² DMPK Oncology, AstraZeneca, Boston, MA, 02451, USA.
³ European Commission Joint Research Centre, Ispra, 21027, Italy.
⁴ Federal Agency for Medicines and Health Products, Brussels, 1210, Belgium.
⁵ Center for Drug Evaluation and Research, Office of New Drugs, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
⁶ Complex In Vitro Models, GSK, Stevenage, SG1 2NY, UK.
⁷ Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 06877, USA.
⁸ DMPK, Genentech, South San Francisco, CA, 94080, USA.
⁹ Preclinical Safety, Biogen, Cambridge, MA, 02142, USA.
¹⁰ Clinical Pharmacology & Safety Sciences, AstraZeneca, Cambridge, CB2 0AA, UK.
¹¹ Organisation for Economic Co-operation and Development, Paris, 75016, France.
¹² Discovery Toxicology, Bristol Myers Squibb, San Diego, CA, 09130, USA.
¹³ Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
¹⁴ DMPK, Pfizer Inc., Cambridge, MA, 02139, USA.
¹⁵ Chemical and Preclinical Safety, Merck Healthcare KGaA, 64293, Darmstadt, Germany.
¹⁶ Complex in Vitro Systems Group, Genentech, South San Francisco, CA, 94080, USA.
¹⁷ Preclinical Sciences and Translational Safety, Johnson and Johnson Innovation Medicine, Spring House, PA, 19002, USA.
¹⁸ Drug Safety Research & Development, Pfizer Inc., Groton, CT, 06340, USA.
¹⁹ Pharmacokinetics, Dynamics & Metabolism-Medicine Design, Pfizer, Cambridge, MA, 02139, USA.
²⁰ Clinical Pharmacology, Genentech, South San Francisco, CA, 94080, USA.
²¹ Preclinical Safety Assessment, Vertex Pharmaceuticals Inc., Boston, MA, 02210, USA.
²² Non-Clinical Safety, In Vitro/In Vivo Translation, GSK R&D, Ware, SG12 9TJ, UK.
²³ Center for Biologics Evaluation and Research, Office of Cellular Therapy and Human Tissue, Cellular and Tissue Therapy Branch, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
²⁴ Translational Cellular Sciences, Biogen, Cambridge, MA, 02142, USA.
²⁵ AbbVie, Inc., North Chicago, IL, 60064, USA.
²⁶ UCB Pharma, Cambridge, MA, 02140, USA.

PMID: 37814378
DOI: 10.1002/adbi.202300131

Abstract

In May 2022, there is an International Regulatory and Pharmaceutical Industry (Innovation and Quality [IQ] Microphysiological Systems [MPS] Affiliate) Workshop on the standardization of complex in vitro models (CIVMs) in drug development. This manuscript summarizes the discussions and conclusions of this joint workshop organized and executed by the IQ MPS Affiliate and the United States Food and Drug Administration (FDA). A key objective of the workshop is to facilitate discussions around opportunities and/or needs for standardization of MPS and chart potential pathways to increase model utilization in the context of regulatory decision making. Participation in the workshop included 200 attendees from the FDA, IQ MPS Affiliate, and 26 global regulatory organizations and affiliated parties representing Europe, Japan, and Canada. It is agreed that understanding global perspectives regarding the readiness of CIVM/MPS models for regulatory decision making and potential pathways to gaining acceptance is useful to align on globally. The obstacles are currently too great to develop standards for every context of use (COU). Instead, it is suggested that a more tractable approach may be to think of broadly applicable standards that can be applied regardless of COU and/or organ system. Considerations and next steps for this effort are described.

Keywords: complex in vitro models; drug development; microphysiological systems; standardization.