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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
24,99 € / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
209,00 € per year
only 17,42 € per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Log in
Learn about institutional subscriptions
Read our FAQs
Contact customer support
References
Golchin, A. & Farahany, T. Z. Stem Cell Rev. Rep.15, 166–175 (2019).
Article
PubMed
Google Scholar
Eder, C. & Wild, C. J. Mark. Access Health Policy7, 1600939 (2019).
Article
PubMed
PubMed Central
Google Scholar
Nagai, S. Int. J. Mol. Sci.20, 3801 (2019).
Article
CAS
PubMed
PubMed Central
Google Scholar
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).
Jokura, Y., Yano, K. & Yamato, M. J. Tissue Eng. Regen. Med.12, e1056–e1062 (2018).
CAS
PubMed
Google Scholar
Konomi, K., Tobita, M., Kimura, K. & Sato, D. Cell Stem Cell16, 350–352 (2015).
Article
CAS
PubMed
Google Scholar
Yano, K. et al. Regen. Ther.1, 45–56 (2014).
Article
PubMed
PubMed Central
Google Scholar
MHLW. Report on the deliberation results: JACC. https://www.pmda.go.jp/files/000229937.pdf (2012).
MHLW. Report on the deliberation results: Nepic. https://www.pmda.go.jp/files/000237511.pdf (2020).
MHLW. Report on the deliberation results: Ocural. https://www.pmda.go.jp/files/000246286.pdf (2021).
MHLW. Report on the deliberation results: Sakracy. https://www.pmda.go.jp/files/000247920.pdf (2021).
Nguyen, P. K., Rhee, J. W. & Wu, J. C. JAMA Cardiol.1, 831–841 (2016).
Article
PubMed
PubMed Central
Google Scholar
Cyranoski, D. Nature565, 544–545 (2019).
Article
CAS
PubMed
Google Scholar
Nature528, 163–164 (2015).
Nature557, 611–612 (2018).
Nature565, 535–536 (2019).
Sato, D., Arakawa, Y. & Isobe, S. Regen. Ther.4, 103–104 (2016).
Article
PubMed
PubMed Central
Google Scholar
Miyamoto, S. Nature569, 40 (2019).
Article
CAS
PubMed
Google Scholar
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).
Belch, J. et al. Lancet377, 1929–1937 (2011).
Article
CAS
PubMed
Google Scholar
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).
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).
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).
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
Hokkaido University Hospital, Clinical Research and Medical Innovation Center, Sapporo, Japan
Teruyo Arato
Hokkaido University Graduate School of Medicine, Department of Regulatory Science, Sapporo, Japan
Teruyo Arato
Teikyo Heisei University, Faculty of Pharmaceutical Sciences, Tokyo, Japan
Kaori Nomura
Fukushima Medical University, Advanced Clinical Research Center, Fukushima, Japan
Kaori Nomura
Contributions
Both authors contributed equally to conception and writing of the paper.
Corresponding author
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
About this article
Cite this article
Arato, T., Nomura, K. Cell and gene therapy approvals in Japan and the need for international harmonization.
Nat Biotechnol (2024). https://doi.org/10.1038/s41587-023-02053-7
Download citation
Published: 08 January 2024
DOI: https://doi.org/10.1038/s41587-023-02053-7
>>> Read full article>>>
Copyright for syndicated content belongs to the linked Source : Nature.com – https://www.nature.com/articles/s41587-023-02053-7