New approach methodologies (NAMs) for drug-induced liver injury (DILI): Where are we now?
Shivangi Shrimali, Minjun Chen, Dongying Li, Weida Tong
Abstract
• Conducted a comparative analysis of overlapping drugs across in vitro NAMs, animal studies, and MPS for DILI prediction. • Observed considerable variability among in vitro NAMs and in the extent of their potential advantages over animal models. • Noted that the relative performance of MPS compared to in vitro NAMs for DILI prediction could be better assessed as more MPS data become available. • Proposed DILIference , a benchmark list to facilitate the development and systematic evaluation of NAMs for DILI. 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.