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Cited by 38Biomedical Ethics and RegulationHealthcare RegulationTissue Engineering and Regenerative Medicine

Brief summary of the regulatory frameworks of regenerative medicine therapies

Open access
Yoon, Jinah, Lee, Sukhyang, Kim, Min Jung, Kim, Jung-Hyun·2025·Frontiers in Pharmacology
DOI 10.3389/fphar.2024.1486812PMC PMC11794276
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Abstract

The rapid advancements in regenerative medicine (RM), including cell therapies, gene therapies, tissue-engineered products, and combined RM advanced therapies, require the development of regulatory frameworks. The global landscape of regulatory frameworks presents diverse approaches to the oversight of these therapies, posing challenges in the global application of RM. This paper reviews the regulatory frameworks for RM across the United States, European Union, Japan, Canada, Australia, Taiwan, and South Korea and compares the unique features of the respective legislations.

AI snapshot

Written from the paper’s full text.

TL;DR

This review compares regenerative medicine regulatory frameworks in the US, EU, UK, Canada, Japan, South Korea, and Taiwan, focusing on legislation, regulatory bodies, review committees, and approval pathways. It finds diverse approaches—such as US RMAT, EU ATMP centralized authorization, and Asian conditional/time-limited and dual-track systems—and argues for global harmonization.

Key findings

  • As of June 2024, 32 gene therapies (including genetically modified cell therapies) had been approved, along with 28 RNA therapies and 68 non-genetically modified cell therapies; 4,002 gene, cell, and RNA therapies were in development, including 2,093 gene therapies (52%) and 885 non-genetically modified cell therapies (22%).
  • The US uses the 21st Century Cures Act and RMAT designation with CBER oversight; the EU regulates ATMPs under Regulation (EC) No 1394/2007 with CAT and CHMP; Canada regulates RM products as biologics under the Food and Drugs Act via Health Canada/BRDD; the UK continues ATMP regulation through MHRA.
  • Japan, South Korea, and Taiwan feature dual-track, risk-based systems and conditional/time-limited approval: Japan’s ASRM and PMD Act with CRMC and PMDA; Korea’s ARMAB with MOHW/MFDS; Taiwan’s Regenerative Medicine Act with TFDA and CTL approval similar to Japan’s PMD Act.
  • The paper reports that inconsistent regulatory requirements remain a major hurdle, citing Tisagenlecleucel (Kymriah) as approved by the US FDA and in 34 other countries but not in Scotland, and calls for global harmonization.

Methods

  • Narrative review comparing RM legislation, regulatory authorities, review boards, and key features across countries, summarized in Table 2.
  • Sources include legal/regulatory documents and prior literature; Table 1 lists approved RMs in the US from 2020 to April 2024.
  • No systematic search strategy, inclusion criteria, or quantitative synthesis is described.

Limitations

  • The authors state this is a brief overview and that a more thorough, comprehensive analysis of specific provisions within each legislative framework is necessary for practical guidelines grounded in international consensus.
  • The abstract says the review covers Australia, but the full text has no dedicated Australia section; the main comparison covers the US, Canada, EU, UK, Japan, South Korea, and Taiwan (evident from the text).
  • The review does not describe a systematic literature search or empirical validation, so coverage may be selective (evident from the text).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fphar.2024.1486812

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

3 of 25 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    In September 2014, the Japanese Diet enacted laws and amendments intended to improve and simplify the regulation of regenerative medicine in Japan.

    “In September 2014, the Japanese Diet, or legislature, enacted a set of laws and amendments intended to improve and simplify the regulation of regenerative medicine in Japan”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites Konomi et al., 2015 source

      The Abstract (page not provided) says two laws creating a new framework for regenerative medicine came into effect on November 25, 2014. The Introduction describes a revised pharmaceutical law and the aim of delivering treatments promptly while ensuring safety. Our copy does not say that the Japanese Diet enacted the laws in September 2014; the November effective date does not establish their enactment date. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Azuma and Yamanaka, 2016 source

      The sections on conditional approval and alternative clinical research describe revisions to Japan’s regenerative-medicine regulations, including a new product category and changes to the rules for clinical research. They say the revised PMD Act became effective in November 2014 and the RM Act applied from November 2014; they do not establish that the Japanese Diet enacted the laws in September 2014. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites Sipp and Okano, 2018 source

      No passage from our copy was provided, and searches for “September 2014,” the Japanese Diet, regulation, and the Act on the Safety of Regenerative Medicine returned no matches. Our copy therefore does not verify the attributed date, legislative action, or stated purpose. (LLM, conf=0.70)

      Experimental — accuracy not yet measured
  • Findingnone given

    The development of legislation in each country affects each other's regulatory pathway structures and contents.

    “We found that the development of legislation in each country affects each other’s regulatory pathway structures and contents.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    The 21st Century Cures Act introduced the Regenerative Medicine Advanced Therapy (RMAT) designation to expedite development and review of regenerative medicine products.

    “Specifically, it introduced the Regenerative Medicine Advanced Therapy (RMAT) designation to expedite the development and review of regenerative medicine products”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites ADMINISTRATION USFD, 2023

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisecitation

    Regulation (EC) No 1394/2007 covers gene therapy products, cell therapy products, tissue-engineered products, and some combined ATMPs which may contain one or more medical devices as an integral part of the medicine.

    “This regulation covers a range of ATMPs, including gene therapy products, cell therapy products, tissue-engineered products and, some combined ATMPs which may contain one or more medical devices as an integral part of the medicine”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Agency EM, 2016

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisenone given

    The UK continues to regulate ATMPs under guidelines in place during its EU membership, managed by the MHRA.

    “The UK is establishing its regulatory pathways, continuing to regulate advanced therapy medicinal products (ATMPs) under the guidelines that were in place during its membership in the EU, managed by the Medicines and Healthcare products Regulatory Agency (MHRA).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 16
  • Classified as probably not a substantial claim. 4

  • May combine two claims.

    Findingcitation

    Tisagenlecleucel (Kymriah®) was the first cell-based gene therapy approved by the US FDA and in 34 other countries, yet it is not approved in Scotland.

    “For example, Tisagenlecleucel (Kymriah®) was the first cell-based gene therapy approved by the US FDA and in 34 other countries (Awasthi et al., 2023), yet it is not approved in Scotland.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Awasthi et al., 2023 source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    Following Japan, other countries in Asia, including South Korea and Taiwan, established legal frameworks and regulatory guidelines for regenerative medicine.

    “Following this, other countries in Asia, including South Korea and Taiwan, have established legal frameworks and regulatory guidelines for regenerative medicine, reflecting the rapid advancements in this field.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Only clinical studies for regenerative medicine can be applied to the ARMAB track, except for clinical trials, and clinical trials can be applied to the MFDS track only.

    “In fact, only clinical studies for regenerative medicine can be applied to the ARMAB track, except for clinical trials. Clinical trials can be applied to the MFDS track only.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Although regenerative medicine is not specifically listed in Canada's Food & Drug Act, the Act provides legal authority to Health Canada to regulate and oversee development and marketing of regenerative medicine.

    “Although regenerative medicine is not specifically listed in the Food & Drug Act in Canada 2 , Food & Drug Act provide legal authority to Health Canada to regulate and oversee development and marketing of RM”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chisholm et al., 2019 source

  • May combine two claims.

    Premisecitation

    Canada's Food and Drugs Act and associated regulations classify regenerative medicine products under biologic drugs, requiring rigorous clinical trials and evaluations for market authorization.

    “the Food and Drugs Act and its associated regulations classify regenerative medicine products under biologic drugs, requiring rigorous clinical trials and evaluations for market authorization”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Chisholm et al., 2019 source
    • cites Don Husereau SRA et al., 2021

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The PMD Act introduces a conditional and time-limited approval system for regenerative medical products, allowing these therapies to reach the market more quickly, with products conditionally approved based on preliminary safety and efficacy data and full approval contingent upon further validation.

    “The PMD Act introduces a conditional and time-limited approval system for regenerative medical products, allowing these therapies to reach the market more quickly”
    • Also stated in: § Legislations and regulations for RM world-wide · plain
      “Products can be conditionally approved based on preliminary safety and efficacy data, with full approval contingent upon further validation”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Articles 23–26, The Pharmaceutical and Medical Devices Act

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Matsushita et al., 2020 source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Premisecitation

    The ASRM applies to medical treatments that intend to use cell-processed products, and applicable clinical trials are reviewed by certified committees for RM or the Certified Special Committee for Regenerative Medicine accredited by MHLW.

    “The ASRM applies to medical treatments that intend to use cell-processed products (Article 2).”
    • Also stated in: § Legislations and regulations for RM world-wide · plain
      “The applicable clinical trials are reviewed by certified committees for RM (Certified Regenerative Medicine Committee, CRMC) or the Certified Special Committee for Regenerative Medicine accredited by the Ministry of Health, Labour, and Welfare (MHLW)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Article 2

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Ikka et al., 2023 source
    • cites Tobita et al., 2016 source

      Checked before — its earlier verdict is held back until a new check runs.

  • May combine two claims.

    Premisenone given

    RM is regulated by the Taiwan Food and Drug Administration (TFDA), established in 2010, as medicinal products under the Pharmaceutical Affairs Act, and Taiwan's Legislative Yuan passed the Regenerative Medicine Act (RMA) and the Regenerative Medicine Product Regulations in June 2024.

    “RM is regulated by the Taiwan Food and Drug Administration (TFDA), established in 2010, as “medicinal products” under the Pharmaceutical Affairs Act.”
    • Also stated in: § Legislations and regulations for RM world-wide · plain
      “on 4 June 2024, Taiwan’s Legislative Yuan passed two drafts of regenerative medicine legislation proposed by the Ministry of Health and Welfare, Taiwan. The Regenerative Medicine Act (RMA) 12 ” and the Regenerative Medicine Product Regulations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Under Regulation (EC) No 1394/2007, a Committee for Advanced Therapies within the EMA was established, and it prepares a draft opinion on the quality, safety and efficacy of each ATMP before the CHMP adopts a final opinion on marketing authorization.

    “Under the Regulation (EC) No 1394/2007 3 , a Committee for Advanced Therapies (CAT) within the EMA was established”
    • Also stated in: § Legislations and regulations for RM world-wide · plain
      “CAT is responsible for preparing a draft opinion on the quality, safety and efficacy of each ATMP (Article 215, Regulation (EC) No 1394/2007) before the Committee for Medicinal Products for Human Use (CHMP) in EMA adopts a final opinion on the marketing authorization of the medicine concerned”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites AGENCY, 2000

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites AGENCY EM, 2015

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationnone given

    The global landscape of regulatory frameworks presents diverse approaches to the oversight of regenerative medicine therapies, posing challenges in the global application of regenerative medicine.

    “The global landscape of regulatory frameworks presents diverse approaches to the oversight of these therapies, posing challenges in the global application of RM.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ARMAB establishes Advanced Regenerative Medicine Safety Management Institutions under MOHW and an Advanced Regenerative Medicine and Advanced Biopharmaceuticals Review Committee that approves clinical studies by MOHW.

    “South Korea’s ARMAB typically establishes Advanced Regenerative Medicine Safety Management Institutions under MOHW to ensure the safety of RM and is responsible for the management and supervision of RM institutes, and the establishment of a follow-up system to investigate the causes of adverse reactions after clinical research of advanced regenerative medicine (Article 19).”
    • Also stated in: § Legislations and regulations for RM world-wide · plain
      “ARMAB also established the Advanced Regenerative Medicine and Advanced Biopharmaceuticals Review Committee, which approves clinical studies by MOHW.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Article 19

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) is the regulatory body for regenerative medicine product approval, and for marketing authorization it evaluates quality, safety, and efficacy and recommends approval through either full or conditional time-limited pathways.

    “In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) is the regulatory body for regenerative medicine product approval.”
    • Also stated in: § Legislations and regulations for RM world-wide · plain
      “For marketing authorization, PMDA receives the applications and evaluates the product’s quality, safety, and efficacy, performs a risk assessment, and recommends approval through either the full approval pathway or the conditional time-limited approval pathway”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites PMD Act

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The 21st Century Cures Act of 2016 brought significant changes to regenerative medicine regulation in the US and aimed to improve FDA regulation, support, and accelerate innovation of medical technology to the market.

    “In 2016, 21st Century Cures Act 1 brought significant changes to RM regulation. It aimed to improve The U.S. Food and Drug Administration (FDA) regulation, support, and accelerate the innovation of medical technology to the market”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Barlas, 2018

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Cellular therapy and tissue engineering products are regulated under FDA regulations, specifically outlined in 21 CFR Part 1,271.

    “Cellular therapy and tissue engineering products are regulated under FDA regulations, specifically outlined in 21 CFR Part 1,271”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    In November 2014, Japan enacted the Regenerative Medicine Promotion Act, followed by the Act on the Safety of Regenerative Medicine (ASRM) and the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act).

    “In November 2014, Japan enacted the Regenerative Medicine Promotion Act. Then, two other pieces of legislation for RM were enacted. The first one was The Act on the Safety of Regenerative Medicine (ASRM) 7 , and the second one was the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act) 8 .”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    CBER regulates cellular therapy products, human gene therapy products, and certain devices related to cell and gene therapy, and uses the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act as foundational legislation.

    “The Center for Biologics Evaluation and Research (CBER) regulates cellular therapy products, human gene therapy products, and certain devices related to cell and gene therapy. CBER utilizes the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act as the foundational legislation for its oversight functions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The long-term safety study is a part of regulatory requirements in Japan, South Korea, and Taiwan.

    “The long-term safety study is a part of regulatory requirements in Japan, South Korea, and Taiwan.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    The definition of RM products in the three Asian countries follows the EU, where RM products are classified into four categories: gene therapy products, cell therapy products, tissue-engineered products, and composite products, rather than RMAT.

    “Third, the definition of RM products in the three Asian countries follows the EU, where RM products are classified into four categories: gene therapy products, cell therapy products, tissue-engineered products, and composite products, rather than RMAT”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    The law implements a risk-based classification system for cell-based interventions and provides for a review of research and therapeutic plans for regenerative medical procedures by authorized committees.

    “Second, the law implements a risk-based classification system for cell-based interventions and provides for a review of research and therapeutic plans for regenerative medical procedures by authorized committees.”
    Quote in the paperNot a substantial claim
19 of 19

  • The paper relies on this without support.

    Rapid advancements in regenerative medicine require the development of regulatory frameworks.

    “The rapid advancements in regenerative medicine (RM), including cell therapies, gene therapies, tissue-engineered products, and combined RM advanced therapies, require the development of regulatory frameworks.”

  • The paper relies on this without support.

    Global harmonization of regenerative medicine regulations is desirable or needed.

    “Therefore, we need a global consensus on scientific disciplines, so-called regulatory science, for better decision-making throughout the quality, safety, and efficacy assessment of RM globally.”
2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Pfizer therapy has two names

    Minor

    The introduction calls Pfizer's hemophilia B therapy "Beqvez," but Table 1 calls a Pfizer hemophilia B gene therapy "Beqbez."

  • The stated countries reviewed differ

    Minor

    The abstract lists Australia among the seven places reviewed, while the discussion's list of seven substitutes the United Kingdom for Australia.

2 of 2

Cites

Flagged first, then by citations

1 of the 20 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. AsoGCTAa, 2024, American Society of Gene and Cell Therapy, Gene, cell, & RNA therapy landscape report: Q1 2024 quarterly data report
  2. Atala, 2019, Principles of regenerative medicine book • third edition • 2019
  3. 2018, Licensed biological products regulated by the center for biologics evaluation and research
  4. 2004, 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004
  5. Seida, 2021, Stem cell/regenerative medicine in Canada: current state and future prospects/research report and summary from national roundtable conducted for the stem cell network of Canada, Inst. Health Econ. Alta. Can
  6. Safety MoHaWAMoFaD

Cited by

Sorted by citations

Related

Authors
Yoon, J., Lee, S., Kim, M. J., & Kim, J.-H.
Affiliations
  • Hanyang Cyber University (KR)
  • Ajou University (KR)
Corresponding author
Kim, Jung-Hyun
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2025-01-22
Volume
15
Pages
1486812-1486812
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2024.1486812
PMC
PMC11794276
OpenAlex
W4406717522
Cited by
38
References
20
Citations by year
2026: 28 · 2025: 10
FWCI
4.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation
  • Ministry of Food and Drug Safety (21153MFDS602)
  • National Research Foundation of Korea
Topics
  • Health Sciences › Medicine › Physiology › Biomedical Ethics and Regulation
  • Health Sciences › Health Professions › Health Information Management › Healthcare Regulation
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
regenerative medicine, regulatory framework, cell therapy regulation, gene therapy regulation, tissue-engineered products, advanced therapies, regulatory comparison, regulatory oversight, biotechnology law

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