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

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Uwe Marx 1, Tommy B. Andersson 2,3, Anthony Bahinski 4, Mario Beilmann 5, Sonja Beken 6, Flemming R. Cassee 7,8, Murat Cirit 9, Mardas Daneshian 10, Susan Fitzpatrick 11, Olivier Frey 12, Claudia Gaertner 13, Christoph Giese 14, Linda Griffith 9, Thomas Hartung 10,15, Minne B. Heringa 7, Julia Hoeng 16, Wim H. de Jong 7, Hajime Kojima 17, Jochen Kuehnl 18, Marcel Leist 10, Andreas Luch 19, Ilka Maschmeyer 1, Dmitry Sakharov 20, Adrienne J. A. M. Sips 7, Thomas Steger-Hartmann 21, Danilo A. Tagle 22, Alexander Tonevitsky 23, Tewes Tralau 19, Sergej Tsyb 24, Anja van de Stolpe 25, Rob Vandebriel 7, Paul Vulto 26, Jufeng Wang 27, Joachim Wiest 28, Marleen Rodenburg 7 and Adrian Roth 29
1 TissUse GmbH, Berlin, Germany
2 AstraZeneca, Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, Mölndal, Sweden
3 Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
4 Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA
5 Boehringer Ingelheim Pharma GmbH & Co. KG, Non-clinical Drug Safety, Biberach, Germany
6 Federal Agency for Medicines and Health Products, Brussels, Belgium
7 National Institute for Public Health & the Environment, Bilthoven, The Netherlands
8 Institute for Risk Assessment Science, Utrecht University, The Netherlands
9 Massachusetts Institute of Technology, Cambridge, MA, USA
10 Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany
11 US Food and Drug Administration, Center for Food Safety and Applied Nutrition, College Park, MD, USA
12 ETH Zurich, Dept. Biosystems Science and Engineering, Bio Engineering Laboratory, Basel, Switzerland
13 microfluidic ChipShop GmbH, Jena, Germany
14 ProBioGen AG, Berlin, Germany
15 Center for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
16 Philip Morris International R&D, Neuchâtel, Switzerland
17 Japanese Center for Validation of Animal Methods, Tokyo, Japan
18 Beiersdorf, Hamburg, Germany
19German Federal Institute for Risk Assessment, Department of Chemicals and Product Safety, Berlin, Germany
20 Scientific Research Centre Bioclinicum, Moscow, Russia
21 Bayer, Investigational Toxicology, Berlin, Germany
22 National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA
23 National Center of Medical Radiological Research, Moscow, Russia
24 Russian Ministry of Production and Trade, Moscow, Russia
25 The Institute for Human Organ and Disease Model Technologies, Leiden, The Netherlands
26 MIMETAS BV, Leiden, The Netherlands
27 Chinese National Center for Safety Evaluation of Drugs, Beijing, China
28 cellasys GmbH, Kronburg, Germany
29 F. Hoffmann-La Roche Ltd, Roche Innovation Centre Basel, Switzerland

Summary
 

The recent advent of microphysiological systems – microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro – promises to enable a global paradigm shift in drug development. An extraordinary US government initiative and various dedicated research programs in Europe and Asia recently have led 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 will 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 the use of laboratory animal models. Here, thirty-six experts from academia, industry and regulatory bodies present 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 towards more predictive and regulatory-accepted substance testing on a global scale is outlined.

 

Keywords: microphysiological systems, organ-on-a-chip, in vitro models, predictive toxicology, drug testing

 


ALTEX 33(3), 272-321

doi: 10.14573/altex.1603161



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