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

Abstract

Summary 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-five 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.

The need for strategic development of safety sciences

“…CAAT has started a number of collaborative programs to advance safety sciences, which include the Human Toxome Collaboration (see above), the Evidence-based Toxicology Collaboration (see below), the Good Cell Culture Practice Collaboration (Pamies et al, 2017) building on earlier work steered by ECVAM (Coecke et al, 2005), the Good ReadAcross Practice Collaboration (Patlewicz et al, 2014, Ball et al, 2016Zhu et al, 2016), the Refinement Collaboration (Zurlo and Hutchinson, 2014) and others. CAAT's transatlantic think tank for toxicology (t 4 ) has organized more than 30 workshops to advance concepts of toxicology such as integrated testing strategies (Hartung et al, 2013b;Rovida et al, 2015b), epithelial barrier models (Gordon et al, 2015), 3D cell cultures (Alépée et al, 2014), microphysiological systems (Marx et al, 2016), high-content imaging (van Vliet et al, 2014), and has commissioned a number of white papers. (Andersen et al, 2011.…”

Fetal bovine serum (FBS): Past – present – future

“…In spring 2013, a severe case of fraudulent blending of FBS batches came to public attention (Gstraunthaler et al, , 2014. Also, successful serum-free applications that had been developed for primary neuronal cell systems to approximate cerebrospinal fluid (CSF) (Schaffner et al, 1995) were extended to other cell types for microphysiological systems and organon-chip technologies (Marx et al, 2016;Sung et al, 2013), one of which is completely serum-free (Oleaga et al, 2016). These promising developments gave reason to organize a 3 rd workshop on FBS, Serum Alternatives and Serum-free Media.…”

Opinion versus evidence for the need to move away from animal testing

“…Human tissues and their reconstruction in vitro (Alépée et al, 2014), including bioprinting and organ-on-chip bioengineering, represent the next line of opportunities (Andersen et al, 2014;Marx et al, 2016). The current paradigm shift toward organotypic cultures with organ architectures and organ functionalities presents avenues to more meaningful models.…”