Considerations from the pharmaceutical industry (IQ MPS affiliate) workshop on animal microphysiological systems and 3Rs in drug development

Most complex in vitro models (CIVM) and microphysiological systems (MPS) are composed of human cells, with the goal of evaluating diseases, efficacy, safety, and pharmacokinetic questions specifically for humans. The hope with CIVM/MPS is that they will eventually improve our predictivity for clinical responses and reduce or replace animal use in research, supporting the 3Rs concept of only using animals in research when necessary. Given the potential of animal-based models to advance this field by comparing existing in vivo animal data with new animal-based MPS responses, there are currently few CIVM and MPS utilizing animal tissues. Animal-based MPS may also have specific utility for cross-species comparisons or species-specific mechanistic questions on zoonotic diseases, and therapies for animals. Animal-based MPS may help expand in vitro-to in vivo correlations, advance the field and establish confidence in the predictive nature of such platforms. The IQ MPS-FDA workshop provided an interactive venue for pharmaceutical companies and regulatory agencies such as the U.S. Food and Drug Administration (FDA), NC3Rs (UK), Health Canada, NIH/NCATS, NIHS and PMDA (Japan), Danish Medicines Agency, European Commission, NIEHS/ICEATM, HHS, NIST, EURL ECVAM, and the IQ MPS Affiliate, a collaboration of pharmaceutical companies to jointly discuss considerations of animal-based MPS and applications where animal-based MPS are of potential value. Plain language summaryMicrophysiological systems are complex in vitro models that recapitulate human or animal physiology by mimicking their key biological processes and disease states. These models need extensive validation to be utilized routinely as drug discovery tools. The IQ MPS Affiliate comprised of 26 pharmaceutical companies held a joint workshop with the FDA, other regulators and the NC3Rs to address current challenges in the MPS field and discuss context of use for animal-cell based MPS in drug discovery.