Tab. 3:

Proposed end points and data of a shared MPS-based assay evaluation library

Parameter	Explanation
Compounds	Commercially available compounds
Context of use	A clear definition of the relevance of the test method, where relevance describes the relationship of the test method to the effect of interest and whether it is meaningful and useful for a particular purpose (https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-principles-regulatory-acceptance-3rs-replacement-reduction-refinement-testing-approaches_en.pdf). This includes the endpoints which are to be investigated with reference to the conventional animal or human endpoint, e.g. if the MPS is used to detect DILI, it needs to be specified whether it covers all kinds of liver damage (cholestasis, steatosis, inflammation, fibrosis, …) and how these are specified (biomarkers, morphology, histopathology, …).
Historical reference data	Data describing morphological and physiological outcome (e.g., histopathology, clinical chemistry) in MPS for defined reference compounds (positive and negative controls). Concentration ranges tested should be included. Endpoints measured in the MPS might include genomics markers, biomarker changes, etc.
Cell material & quality	Description of cell or tissue source, including potential quality checks (e.g., viability, functional performance tests, metabolic activity)
Specification of materials & media	Detailed description of materials with regard to biocompatibility, potential leachables, surface adsorption (drug binding), composition of media (protein content and source, growth factors included in the medium or added, flow rates, etc.)
Exposure	Drug stability data and determination of exposure (total/unbound, ideally also intracellular)
Exposure modeling	Description of the model that was used to compare exposure in the MPS with the in vivo situation (animal or human)
General documentation	Will Good Laboratory Practice (GLP) need to be met for such studies? A workshop on this topic, perhaps in partnership with the OECD, would be advisable as it will inform any decisions on performance standards. Alternatively, the regulatory agencies could brainstorm on what context of use situation would require these systems to be performed under GLP.
Robustness	Intra-assay (repeatability) and inter-laboratory comparative result data. The need for the latter may be decided on a case-by-case basis.