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Cell and gene therapy approvals in Japan and the need for international harmonization

Nature Biotechnology volume 42, pages 13–17 (2024)Cite this article

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The positions of regulatory agencies on new classes of biomedical products such as cell and gene therapies1,2,3 have a strong influence on product development but have not been clearly defined. We examined all 17 cell and gene therapies approved as of December 2022 in Japan4 and compared them to the fates of similar candidate therapies in other countries. This analysis identified notable differences with respect to the use of randomized clinical trials (RCTs), the numbers of participants enrolled, and approaches for evaluating trial results. These differences can be influenced by the use of various accelerated-approval pathways, such as Conditional Early Approval in Japan, the Regenerative Medicine Advance Therapy Designation in the United States, and Priority Medicines in the European Union5,6. We conclude that the nascent field of cell and gene therapies would benefit from a concerted effort toward international harmonization with respect to clinical study designs and product approval criteria.

As of December 2022, Japan’s Ministry of Health, Labor, and Welfare (MHLW) had approved 9 cell-based products (Table 1) and 8 gene-therapy products (Table 2)4. Two of these 17 initial approvals involved an RCT, whereas the other 15 relied on single-arm studies only. In contrast, 7 out of 19 of the US and 14 out of 24 of the EU cell and gene therapy approvals we reviewed used RCTs.

Table 1 Clinical trials of cell-based medical products approved through 2022 in Japan
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Table 2 Clinical trials of gene therapy products approved through 2022 in Japan
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Data availability

The product approval information shown in this paper is available from the websites of the regulatory authorities (https://www.pmda.go.jp/english/search_index.html, https://www.ema.europa.eu/en/medicines, https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products).

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Acknowledgements

We would like to thank Saki Yokoshiki for help in compiling product lists.

Author information

Authors and Affiliations

  1. Hokkaido University Hospital, Clinical Research and Medical Innovation Center, Sapporo, Japan

    Teruyo Arato

  2. Hokkaido University Graduate School of Medicine, Department of Regulatory Science, Sapporo, Japan

    Teruyo Arato

  3. Teikyo Heisei University, Faculty of Pharmaceutical Sciences, Tokyo, Japan

    Kaori Nomura

  4. Fukushima Medical University, Advanced Clinical Research Center, Fukushima, Japan

    Kaori Nomura

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  1. Teruyo Arato
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Both authors contributed equally to conception and writing of the paper.

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Correspondence to Teruyo Arato.

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Nature Biotechnology thanks Megan Munsie and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Arato, T., Nomura, K. Cell and gene therapy approvals in Japan and the need for international harmonization. Nat Biotechnol 42, 13–17 (2024). https://doi.org/10.1038/s41587-023-02053-7

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