PT - JOURNAL ARTICLE AU - Lorna Ewart AU - Athanasia Apostolou AU - Skyler A. Briggs AU - Christopher V. Carman AU - Jake T. Chaff AU - Anthony R. Heng AU - Sushma Jadalannagari AU - Jeshina Janardhanan AU - Kyung-Jin Jang AU - Sannidhi R. Joshipura AU - Mahika M. Kadam AU - Marianne Kanellias AU - Ville J. Kujala AU - Gauri Kulkarni AU - Christopher Y. Le AU - Carolina Lucchesi AU - Dimitris V. Manatakis AU - Kairav K. Maniar AU - Meaghan E. Quinn AU - Joseph S. Ravan AU - Ann Catherine Rizos AU - John F.K. Sauld AU - Josiah D. Sliz AU - William Tien-Street AU - Dennis Ramos Trinidad AU - James Velez AU - Max Wendell AU - Onyi Irrechukwu AU - Prathap Kumar Mahalingaiah AU - Donald E. Ingber AU - Jack W. Scannell AU - Daniel Levner TI - Qualifying a human Liver-Chip for predictive toxicology: Performance assessment and economic implications AID - 10.1101/2021.12.14.472674 DP - 2022 Jan 01 TA - bioRxiv PG - 2021.12.14.472674 4099 - http://biorxiv.org/content/early/2022/08/02/2021.12.14.472674.short 4100 - http://biorxiv.org/content/early/2022/08/02/2021.12.14.472674.full AB - 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 to confront this challenge has published guidelines that define criteria for qualifying preclinical models, however, systematic and quantitative evaluation of the predictive value of Organ-Chips has not yet been reported. Here, 870 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 87% and a specificity of 100%. A computational economic value analysis suggests that with this performance the Liver-Chip could generate $3 billion annually for the pharmaceutical industry due to increased R&D productivity.Competing Interest StatementL.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., S. R. J., J.F.K.S., M.M.K., 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 or former employees of Emulate Inc. and may hold equity; D.E.I. is a founder, board member, SAB chair, and equity holder in Emulate Inc. J.W.S. is a shareholder and director of JW Scannell Analytics LTD and received payment from Emulate Inc. for contributing to this work.