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[Toward Regulatory Acceptance of MPS-Cardiac Safety Assessment as an Example]
1National Institute of Health Sciences.
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.
Insights
Microphysiological systems (MPS) offer improved human predictability in drug discovery. This review explores their regulatory approval pathway using cardiac safety evaluation and a novel 3D heart tissue model.
Area of Science:
- Biotechnology and pharmaceutical research.
- In vitro modeling for drug development.
Background:
- Microphysiological systems (MPS) mimic in vivo organ functions for enhanced drug discovery predictability.
- Significant investment in MPS research by NIH (US) and national institutes in Japan (AIST, NIHS).
- Increasing adoption of MPS by pharmaceutical companies, yet regulatory acceptance remains a challenge.
Approach:
- Focuses on cardiac safety evaluation as a case study for MPS regulatory approval.
- Introduces a human 3D heart tissue model developed at NIHS as a cardiac MPS.
- Discusses the necessary steps for MPS data integration into drug approval processes.
Key Points:
- MPS technology is advancing, with global research initiatives and industry adoption.
- Regulatory hurdles exist for incorporating MPS data into drug approval documentation.
- Cardiac safety evaluation serves as a model for demonstrating MPS utility and gaining regulatory trust.
- Novel 3D heart tissue models represent a significant advancement in cardiac MPS.
Conclusions:
- Establishing clear regulatory pathways is crucial for the widespread adoption of MPS in drug discovery.
- The development and validation of specific MPS models, like the 3D heart tissue, are key to overcoming regulatory barriers.
- Successful integration of MPS data requires collaboration between researchers, industry, and regulatory bodies.
