Pharmaceutical industry perspective on the utility of animal cell-based microphysiological systems to support human...

Microphysiological systems (MPS) are envisioned to improve drug approval success rates. Yet, integration of MPS into drug development processes has been hampered in part by uncertainties in data translation. To speed adoption, development of animal cell-based MPS is advocated by the pharmaceutical industry. In our view, animal MPS availability would fill a key gap in the ability to examine in vitro to in vivo translatability. Since in vivo animal data will be available and guide decision making in regulatory activities for the foreseeable future, there is significant opportunity for translational assessments. In vivo animal study findings that are recapitulated using in vitro models generated from the corresponding animal species provide validation that those models possess the relevant and necessary attributes, e.g., species-specific pharmacodynamics, metabolism, transport, susceptibility to toxicity, etc. Results from the corresponding human models can then be interpreted with greater confidence for the relevant context of use (COU). Some drugs do not get to the clinic due to adverse findings in animals, so there is considerably more data to directly compare to animal in vitro models than human systems. Another benefit of animal MPS is that drug candidates exhibiting animal safety findings might be easier to derisk, for example if the finding was observed in animal but not the corresponding human in vitro model. This paper reviews considerations and recommendations for adopting animal MPS models in drug discovery and development and describes how their deployment is consistent with 3Rs principles.