Savaryn, John P., Coe, Kevin, Cerny, Matthew A., Colizza, Kevin X., Moliner, Patricia, King, Lloyd, Ma, Bin, Atherton, Jim, Auclair, Adam, Cancilla, Markt T., Eno, Marsha, Jurva, Ulrik, Yue, Qin, Zhu, Sean, Freiberger, Elyse, Zhong, Guo, Barlock, Ben, Nachtigall, Jonny, Laboureur, Laurent, Pusalkar, Sandeepraj, Guo, Runcong, Niehues, Michael, Hauri, Simon, Tor Carreras, Ester, Maurer, Christine, Prakash, Chandra and Jenkins, Gary (2024) The Current State of Biotransformation Science – Industry Survey of In Vitro and In Vivo Practices, Clinical Translation, and Future Trends. Pharmaceutical Research. ISSN 1573-904X

Abstract

Embedded within the field of drug metabolism and pharmacokinetics (DMPK), biotransformation is a discipline that studies
the origins, disposition, and structural identity of metabolites to provide a comprehensive safety assessment, including the
assessment of exposure coverage in toxicological species. Spanning discovery and development, metabolite identification
(metID) scientists employ various strategies and tools to address stage-specific questions aimed at guiding the maturation
of early chemical matter into drug candidates. During this process, the identity of major (and minor) circulating human
metabolites is ascertained to comply with the regulatory requirements such as the Metabolites in Safety Testing (MIST)
guidance. Through the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the
“Translatability of MetID In Vitro Systems Working Group” was created within the Translational and ADME Sciences
Leadership Group. The remit of this group was to objectively determine how accurate commonly employed in vitro systems
have been with respect to prediction of circulating human metabolites, both qualitatively and quantitatively. A survey
composed of 34 questions was conducted across 26 pharmaceutical companies to obtain a foundational understanding of
current metID practices, preclinically and clinically, as well as to provide perspective on how successful these practices
have been at predicting circulating human metabolites. The results of this survey are presented as an initial snapshot of
current industry-based metID practices, including our perspective on how a harmonized framework for the conduct of in
vitro metID studies could be established. Future perspectives from current practices to emerging advances with greater
translational capability are also provided.

Item Type:	Article
Keywords:	ADME - biotransformation - IVIVC - MetID
Date Deposited:	30 Nov 2024 00:45
Last Modified:	30 Nov 2024 00:45
URI:	https://oak.novartis.com/id/eprint/53705