@article {Ewart2021.12.14.472674, author = {Lorna Ewart and Athanasia Apostolou and Skyler A. Briggs and Christopher V. Carman and Jake T. Chaff and Anthony R. Heng and Sushma Jadalannagari and Jeshina Janardhanan and Kyung-Jin Jang and Sannidhi R. Joshipura and Mahika Kadam and Marianne Kanellias and Ville J. Kujala and Gauri Kulkarni and Christopher Y. Le and Carolina Lucchesi and Dimitris V. Manatakis and Kairav K. Maniar and Meaghan E. Quinn and Joseph S. Ravan and Ann Catherine Rizos and John F.K. Sauld and Josiah Sliz and William Tien-Street and Dennis Ramos Trinidad and James Velez and Max Wendell and Onyi Irrechukwu and Prathap Kumar Mahalingaiah and Donald E. Ingber and Daniel Levner}, title = {Qualifying a human Liver-Chip for predictive toxicology: Performance assessment and economic implications}, elocation-id = {2021.12.14.472674}, year = {2021}, doi = {10.1101/2021.12.14.472674}, publisher = {Cold Spring Harbor Laboratory}, 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, 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, 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\%. 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., 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.}, URL = {https://www.biorxiv.org/content/early/2021/12/17/2021.12.14.472674}, eprint = {https://www.biorxiv.org/content/early/2021/12/17/2021.12.14.472674.full.pdf}, journal = {bioRxiv} }