Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

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

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

Subjects

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
Full size table
Table 2 Clinical trials of gene therapy products approved through 2022 in Japan
Full size table

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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).

References

  1. Golchin, A. & Farahany, T. Z. Stem Cell Rev. Rep. 15, 166–175 (2019).

    Article  PubMed  Google Scholar 

  2. Eder, C. & Wild, C. J. Mark. Access Health Policy 7, 1600939 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Nagai, S. Int. J. Mol. Sci. 20, 3801 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pharmaceuticals and Medical Devices Agency. Review reports: regenerative medical products. https://www.pmda.go.jp/english/review-services/reviews/approved-information/0004.html (accessed 19 September 2023).

  5. Jokura, Y., Yano, K. & Yamato, M. J. Tissue Eng. Regen. Med. 12, e1056–e1062 (2018).

    CAS  PubMed  Google Scholar 

  6. Konomi, K., Tobita, M., Kimura, K. & Sato, D. Cell Stem Cell 16, 350–352 (2015).

    Article  CAS  PubMed  Google Scholar 

  7. Yano, K. et al. Regen. Ther. 1, 45–56 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  8. MHLW. Report on the deliberation results: JACC. https://www.pmda.go.jp/files/000229937.pdf (2012).

  9. MHLW. Report on the deliberation results: Nepic. https://www.pmda.go.jp/files/000237511.pdf (2020).

  10. MHLW. Report on the deliberation results: Ocural. https://www.pmda.go.jp/files/000246286.pdf (2021).

  11. MHLW. Report on the deliberation results: Sakracy. https://www.pmda.go.jp/files/000247920.pdf (2021).

  12. Nguyen, P. K., Rhee, J. W. & Wu, J. C. JAMA Cardiol. 1, 831–841 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cyranoski, D. Nature 565, 544–545 (2019).

    Article  CAS  PubMed  Google Scholar 

  14. Nature 528, 163–164 (2015).

  15. Nature 557, 611–612 (2018).

  16. Nature 565, 535–536 (2019).

  17. Sato, D., Arakawa, Y. & Isobe, S. Regen. Ther. 4, 103–104 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Miyamoto, S. Nature 569, 40 (2019).

    Article  CAS  PubMed  Google Scholar 

  19. MHLW. Minutes of the Committee on Regenerative Medicine and Biotechnology of Pharmaceutical Affairs and Food Sanitation Council, 20 February 2019 [in Japanese]. https://www.mhlw.go.jp/stf/newpage_04743.html (2019).

  20. Belch, J. et al. Lancet 377, 1929–1937 (2011).

    Article  CAS  PubMed  Google Scholar 

  21. European Medicines Agency. CAT quarterly highlights and approved ATMPs: January 2023. https://www.ema.europa.eu/en/documents/report/cat-quarterly-highlights-approved-atmps-january-2023_en.pdf (2023).

  22. Food and Drug Administration. Approved cellular and gene therapy products https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products (accessed 30 June 2023).

  23. European Medicines Agency. Conditional marketing authorisation: report on ten years of experience at the European Medicines Agency. https://www.ema.europa.eu/en/documents/report/conditional-marketing-authorisation-report-ten-years-experience-european-medicines-agency_en.pdf (2017).

  24. International Society for Stem Cell Research. ISSCR guidelines for stem cell research and clinical translation, version 1.0, May 2021. https://www.isscr.org/guidelines (accessed 15 September 2023).

Download references

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

Authors
  1. Teruyo Arato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaori Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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

Corresponding author

Correspondence to Teruyo Arato.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

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

Supplementary information

Supplementary Information

Supplementary Tables 1 and 2

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41587-023-02053-7

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research