Next-Generation Toxicity Testing: A Comparative Review of Organ-on-a-Chip versus Traditional In Vivo Models

Abstract

Objective: To compare organ-on-a-chip (OoC) microphysiological systems with conventional in vivo animal models for preclinical toxicity testing across predictive validity, cost and throughput, moral and regulatory standing, and systemic physiological intricacy.

Methods: This is a narrative, non-systematic comparative review. Sources were identified by directed searches of PubMed, Google Scholar, and the websites of the FDA, EMA and CDSCO, supplemented by hand-searching essential reference lists, focusing on primary validation studies, regulatory announcements, and significant evaluations released 2007–2026; official systematic-review methodology (search strings, date limits, PRISMA option) was not applied.

Results: Standard animal panels predict human toxicity with concordance of approximately 71% overall (63% non-rodents exclusively, 43% rodents solely). A blinded validation study of a human Liver-Chip reported 87% sensitivity and 100% specificity for drug-induced liver injury (DILI) across 870 chips, three donors and 27 drugs. As of September 2024, the FDA’s ISTAND Pilot Program had accepted a Letter of Intent for this Liver-Chip; qualification remains in progress. OoC platforms otherwise continue to be limited by unfinished standardisation, the absence of immune/endocrine crosstalk, and reduced throughput compared with traditional assays.

Conclusion: OoC platforms already outperform conventional and customary animal models for explicit and well-defined endpoints, most distinctly hepatotoxicity, but continue to be constrained for systemic and persistent toxicity. The domain is converging on a hybrid testing paradigm in which OoC technology increasingly displaces select in vivo studies while animal models retain a narrowing but still vital and indispensable role, at least over the following decade.