title: Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing.
abstract: 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.
authors.affiliation: TissUse GmbH, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Marx
authors.affiliation: AstraZeneca, Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, Mölndal, Sweden.|Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tommy B
authors.initials: TB
authors.lastname: Andersson
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University Boston, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bahinski
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Non-clinical Drug Safety, Biberach, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Beilmann
authors.affiliation: Federal Agency for Medicines and Health Products, Brussels, Belgium.
authors.forename: Sonja
authors.initials: S
authors.lastname: Beken
authors.affiliation: National Institute for Public Health & the Environment, Bilthoven, The Netherlands.|Institute for Risc Assessment Science, Utrecht University, The Netherlands.
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
authors.affiliation: Massachusetts Institute of Technology, Cambridge, USA.
authors.forename: Murat
authors.initials: M
authors.lastname: Cirit
authors.affiliation: Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Mardas
authors.initials: M
authors.lastname: Daneshian
authors.affiliation: US Food and Drugs Administration, Center for Food Safety and Applied Nutrition, College Park, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Fitzpatrick
authors.affiliation: ETH Zurich, Dept. Biosystems Science and Engineering, Bio Engineering Laboratory, Basel, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Frey
authors.affiliation: microfluidic ChipShop GmbH, Jena, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gaertner
authors.affiliation: ProBioGen AG, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Giese
authors.affiliation: Massachusetts Institute of Technology, Cambridge, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Griffith
authors.affiliation: Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.|Center for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.affiliation: National Institute for Public Health & the Environment, Bilthoven, The Netherlands.
authors.forename: Minne B
authors.initials: MB
authors.lastname: Heringa
authors.affiliation: Philip Morris International R&D, Neuchatal, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.affiliation: National Institute for Public Health & the Environment, Bilthoven, The Netherlands.
authors.forename: Wim H
authors.initials: WH
authors.lastname: de Jong
authors.affiliation: Japanese Center for Validation of Animal Methods, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kojima
authors.affiliation: Beiersdorf, Hamburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kuehnl
authors.affiliation: Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.affiliation: German Federal Institute for Risk Assessment, Department of Chemicals and Product Safety, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Luch
authors.affiliation: TissUse GmbH, Berlin, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Maschmeyer
authors.affiliation: Scientific Research Centre Bioclinicum, Moscow, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Sakharov
authors.affiliation: National Institute for Public Health & the Environment, Bilthoven, The Netherlands.
authors.forename: Adrienne J A M
authors.initials: AJ
authors.lastname: Sips
authors.affiliation: Bayer, Investigational Toxicology, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Steger-Hartmann
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
authors.forename: Danilo A
authors.initials: DA
authors.lastname: Tagle
authors.affiliation: National Center of Medical Radiological Research, Moscow, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tonevitsky
authors.affiliation: German Federal Institute for Risk Assessment, Department of Chemicals and Product Safety, Berlin, Germany.
authors.forename: Tewes
authors.initials: T
authors.lastname: Tralau
authors.affiliation: Russian Ministry of Production and Trade, Moscow, Russia.
authors.forename: Sergej
authors.initials: S
authors.lastname: Tsyb
authors.affiliation: The Institute for Human Organ and Disease Model Technologies, Leiden, The Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: van de Stolpe
authors.affiliation: National Institute for Public Health & the Environment, Bilthoven, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Vandebriel
authors.affiliation: MIMETAS BV, Leiden, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Vulto
authors.affiliation: Chinese National Center for Safety Evaluation for Drugs, Beijing, China.
authors.forename: Jufeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: cellasys GmbH, Kronburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Wiest
authors.affiliation: National Institute for Public Health & the Environment, Bilthoven, The Netherlands.
authors.forename: Marleen
authors.initials: M
authors.lastname: Rodenburg
authors.affiliation: F. Hoffmann-La Roche Ltd, Roche Innovation Centre Basel, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Roth
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D002460:Cell Line; D015386:Hazardous Substances / Q000633:toxicity*; D056656:Lab-On-A-Chip Devices; D013234:Stem Cells / Q000502:physiology*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D015386:Hazardous Substances
keywords: drug testing; in vitro models; microphysiological systems; organ-on-a-chip; predictive toxicology