New approach methodologies (NAMs) for drug-induced liver injury (DILI): Where are we now?

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.