Abstract
Human organ-on-a-chip (Organ-Chip) technology has the potential to disrupt preclinical drug discovery and improve success in drug development pipelines as it can recapitulate organ-level pathophysiology and clinical responses. The Innovation and Quality (IQ) consortium formed by multiple pharmaceutical and biotechnology companies, however, systematic and quantitative evaluation of the predictive value of Organ-Chips has not yet been reported. Here, 780 Liver-Chips were analyzed to determine their ability to predict drug-induced liver injury (DILI) caused by small molecules identified as benchmarks by the IQ consortium. The Liver-Chip met the qualification guidelines across a blinded set of 27 known hepatotoxic and non-toxic drugs with a sensitivity of 80% and a specificity of 100%. With this performance, a computational economic value analysis suggests that the Liver-Chip could generate $3 billion annually for the pharmaceutical industry due to increased R&D productivity.
Competing Interest Statement
L.E., D.L., D.V.M., J.D.S., A.A., S.A.B., J.T.C., C.V.C., A.R.H., J.J., S.J., M.K., K.K.M., M.E.Q., A.C.R., W.T., M.W., G.K., V.J.K., C.Y.L., C. L., J.S.R., D.R.T., J.V., K-J.J. are employees of Emulate and may hold equity; D.E.I. is a founder, board member, SAB chair, and equity holder in Emulate Inc.