Toward Regulatory Acceptance of MPS-Cardiac Safety Assessment as an Example

Abstract

Microphysiological system (MPS) are "Cell/tissue culture systems that reproduce in vivo organ functions in vitro by placing organ compartments that mimic the physiological environment of various organs such as the liver, small intestine, and lungs in micro-spaces." The MPS are attracting attention around the world as tools to improve human predictability in drug discovery research. In the U.S., in 2012, the NIH (National Institutes of Health) allocated a large budget to academia for research development of MPS. In Japan, the National Institute of Advanced Industrial Science and Technology and the NIHS (National Institute of Health Sciences) have been playing a central role in commercialization, performance evaluation, and standardization of MPS devices developed by academia for the liver, small intestine, kidney, and BBB as target organs/tissues in the AMED-MPS project that started in 2017. Pharmaceutical companies are beginning to utilize MPS in drug discovery research. However, MPS have only just been raised as a topic of discussion between regulatory authorities and pharmaceutical companies, and it will be necessary to overcome many barriers before data obtained by MPS can be included in drug approval documents and be widely accepted administratively. In this review, I would like to introduce cardiac safety evaluation as a concrete example to show what paths MPS should take to gain regulatory approval. In addition, I would like also to introduce human 3D heart tissue, which was developed in NIHS, as a cardiac MPS.