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Updated: Sep 11, 2025

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
New approach methodologies (NAMs) for drug-induced liver injury (DILI): Where are we now?
Shivangi Shrimali1, Minjun Chen1, Dongying Li1
1National Center for Toxicological Research, U.S. Food and Drug Administration (FDA), 3900 NCTR Road, Jefferson, AR 72079, USA.
Abstract:
The FDA's 'Roadmap to Reducing Animal Testing in Preclinical Safety Studies' supports the regulatory advancement of new approach methodologies (NAMs). Focusing on overlapping drugs, this review compared the performance of in vitro NAMs, animal studies, and microphysiological systems (MPS) in predicting drug-induced liver injury (DILI). We observed considerable variability among in vitro NAMs and their potential advantages over animal models. Moreover, limited MPS data hindered meaningful comparison. To enable objective and systematic assessment of NAMs, we propose DILIference, a curated reference drug list compiled from the literature to guide the development and benchmarking of DILI-predictive NAMs.
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