Scientific Publications by FDA Staff

ALTEX 2016;33(3):272-321

Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing.

Marx U, Andersson TB, Bahinski A, Beilmann M, Beken S, Cassee FR, Cirit M, Daneshian M, Fitzpatrick S, Frey O, Gaertner C, Giese C, Griffith L, Hartung T, Heringa MB, Hoeng J, de Jong WH, Kojima H, Kuehnl J, Leist M, Luch A, Maschmeyer I, Sakharov D, Sips AJ, Steger-Hartmann T, Tagle DA, Tonevitsky A, Tralau T, Tsyb S, van de Stolpe A, Vandebriel R, Vulto P, Wang J, Wiest J, Rodenburg M, Roth A

The recent advent of microphysiological systems - microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro - is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-six experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale.