The Japanese laws on regenerative medicine: a controversial example of regulatory innovation?
In 2014 Japan updated its regulation of medicinal products by enacting two new laws; the Pharmaceuticals and Medical Devices Act (PMDA) and the Act on the Safety of Regenerative Medicine (ASRM). Both laws were prompted by the need to overhaul Japanese regulation in response to the emerging field of regenerative medicine (RM).
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Regenerative medicine involves the use of human cells, tissues and genes for the ‘repair, replacement or regeneration’ of bodily damage resulting from disease or injury. As they often involve the use of living tissues as the basis for therapeutic effect, regenerative therapies pose some significant differences compared to conventional pharmaceutical drugs or medical devices. Indeed, it can be argued that RM sits somewhat uneasily between medical products like drugs and devices, and medical procedures, such as organ transplants and surgery.
Japan’s regulatory reforms reflect the ‘liminal’ or ‘in-between’ nature of RM. The PMD Act is the more conventional of the two laws.
It represents an updating of Japan’s existing Pharmaceutical Affairs Law (1960) to make specific provision for RM products, introducing a new ‘conditional marketing approval’ scheme for regenerative therapies.2 The PMD Act covers all medicinal products being developed for market approval in Japan, and is roughly analogous to the regulatory pathways for medicinal products in other jurisdictions such as the EU, USA, UK, Australia and Canada.
The ASRM is more unusual as it covers the use of regenerative therapies in both medical research and clinical care. This specifically excludes RM products being developed by companies for marketing in Japan. The Japanese Constitution stakes out a broad commitment to individual rights and freedoms, including access to health care in Article 13, and protects freedom of occupation (associated with physicians’ discretion) and academic freedom in Articles 22 and 23. This has traditionally been interpreted as allowing physicians considerable discretion to use approved medicinal products for new purposes other than that for which they received regulatory approval
(so-called ‘off-label use’) and also to devise and apply new bespoke treatments without prior regulatory approval.
The ARSM is partly an attempt to curtail the practice of physicians offering unproven RM treatments to patients, by requiring novel bespoke RM treatments to be subject to the same oversight as clinical research (including prior review by an ethics committee). However, it also recognises the potential for hospital-led clinical innovation— as seen in the history of organ and bone-marrow transplants, and virtually all surgical procedures, as something distinct from industry-led medicinal product development— by creating separate regulatory pathways for both types of activity in the ASRM and PMDA respectively.
This can be considered an example of ‘governation’ – innovation in governance and regulation that emerges in response to innovations in science and technology.3 Promoting, and ideally accelerating, the responsible translation of regenerative medicine, whilst protecting vulnerable patients from exploitation by unscrupulous practitioners, remains one of the major challenges for regulatory agencies around the world. As the ASRM approaches its first decade of implementation, when it is due for review by Japan’s Ministry of Health, Labour and Welfare, it is an appropriate time to reflect on where it has achieved its aims and what further measures might be warranted to improve its effectiveness.
A more detailed account of the history of the ASRM and a review of its strength and limitations can be found in Takashima, Morrison and Minari (2021) ‘Reflection on the enactment and impact of safety laws for regenerative medicine in Japan’ which is now published in Stem Cell Reports and is available here.
1. Sethi N. Regulating for uncertainty: Bridging blurred boundaries in medical innovation, research and treatment. Law, Innov Technol. 2019; 11: 112–133. doi:10.1080/17579961.2019.1573400
2. Azuma K. Regulatory Landscape of Regenerative Medicine in Japan. Curr Stem Cell Reports. 2015; 1: 118–128. doi:10.1007/s40778-015-0012-6
3. Faulkner A. Chapter 9: Device or Drug? Governation of Tissue Engineering. In ‘Medical technology into healthcare and society: A sociology of devices, innovation and governance’. Hampshire: Palgrave Macmillan UK; 2009. pp. 159–187
4. Takashima, K., Morrison, M. and Minari, J. (2021) Reflection on the enactment and impact of safety laws for regenerative medicine in Japan. Stem Cell Reports (epub ahead of print) DOI:https://doi.org/10.1016/j.stemcr.2021.04.017