Japan’s Stem Cell Regulation in 2025: ASRM, PMD Act, and What Patients Can Realistically Expect
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Table of Contents
Why Japan Matters in Regenerative Medicine
Japan is widely regarded as one of the most structured and safety-focused jurisdictions for regenerative medicine. Rather than allowing stem cell therapies to evolve in a regulatory gray zone, Japan has developed a clear legal architecture built on two primary pillars.
• ASRM – Act on the Safety of Regenerative Medicine (2014)
• PMD Act – Pharmaceuticals and Medical Devices Act (amended 2014)
Together, these laws establish a dual system that distinguishes between:
Clinical Practice
Commercial Products
The result is a system that is:
- Highly regulated, with stringent safety standards
- Limited in access, with relatively few fully approved regenerative products
- Designed to support innovation, but only within clearly defined regulatory boundaries
Beyond the legal architecture itself, Japan’s approach is rooted in specific historical and policy concerns. In the early phase of global stem cell commercialization, regulators observed a rapid rise in clinics promoting unproven interventions for complex diseases such as neurodegenerative disorders, autoimmune conditions, and advanced cancers.
Rather than responding case by case, Japanese policymakers opted to build a dedicated framework that could distinguish rigorously designed regenerative medicine from opportunistic, poorly documented “stem cell” services. ASRM and the PMD Act were therefore conceived not only as technical regulations, but as a signal that regenerative medicine would be treated as a serious, long-term healthcare domain rather than a short-lived trend.
Core Legal Framework: ASRM and PMD Act
ASRM – Regulating Clinical Use of Cell Therapies
The Act on the Safety of Regenerative Medicine (ASRM) governs how regenerative treatments are provided in clinical settings, whether they are:
- Conducted as formal clinical research, or
- Offered as self-funded medical procedures outside of conventional insurance coverage.
1. Mandatory Regenerative Medicine Provision Plan
2. Risk-Based Classification (Class I–III)
- Class I covers high-risk therapies such as iPSC/ES or gene-modified cells.
- Class II includes culture-expanded autologous or certain allogeneic MSC uses.
- Class III applies to minimally manipulated autologous cells.
3. Facility and Process Requirements
4. Safety Monitoring and Reporting
In practice, ASRM ensures that even “private” stem cell treatments cannot be offered as informal or unregulated experimental services. They must be embedded within a documented, reviewed, and monitored plan.
PMD Act – Regulating Commercial Regenerative Products
The PMD Act regulates regenerative products as marketable medical products, analogous to pharmaceuticals and medical devices, with a specifically tailored category for:
- Processed cells intended to repair, reconstruct, or regenerate human tissues and functions.
1. Standard Approval
2. Conditional and Time-Limited Approval
- Permits limited market entry prior to full Phase III evidence.
- Requires extensive post-marketing studies, long-term follow-up, and real-world data collection.
- Companies must demonstrate sustained clinical benefit within a defined period or risk losing approval.
3. GCTP Standards (Manufacturing Requirements)
- Identity: Ensuring the correct cellular product is manufactured.
- Purity: Minimizing contaminants and impurities.
- Potency: Confirming the intended biological activity.
- Sterility: Preventing microbial contamination.
- Stability: Ensuring the product maintains quality throughout storage/transport.
ASRM and the PMD Act operate in parallel: A product may receive approval under the PMD Act, but it can only be used in clinical settings that also comply with ASRM and other relevant clinical practice regulations.
Who Actually Regulates: MHLW, PMDA, and Review Committees
In practice, Japan’s stem cell regulation is not driven by a single agency but by a coordinated network of authorities. Each body plays a distinct role in the life cycle of a regenerative therapy—from early clinical planning to commercial approval and long-term safety monitoring. Understanding how these institutions interact is essential for interpreting why access is tightly controlled, and why certain procedures can only be performed in specific settings.
1. MHLW (Ministry of Health, Labour and Welfare)
- Implements ASRM across hospitals and clinics
- Certifies review committees responsible for approving clinical plans
- Oversees adverse event and safety reporting nationwide
- Issues guidance that shapes clinical practice boundaries
2. PMDA (Pharmaceuticals and Medical Devices Agency)
- Reviews commercial regenerative product submissions
- Evaluates preclinical and clinical evidence
- Inspects domestic and international manufacturing sites
- Oversees conditional approval and post-market safety studies
3. Certified Review Boards / Committees
- Evaluate regenerative medicine plans submitted by clinics
- Confirm Class I–III risk classification
- Assess patient safety and ethical compliance
- Monitor ongoing protocols approved under ASRM
Together, they form a multi-layered, documentation-driven system in which no significant regenerative procedure or product can proceed legally without passing through one or more regulatory gatekeepers.
MHLW — Ministry of Health, Labour and Welfare
Key Responsibilities:
• Certifies review committees
• Approves Class I procedures
• Issues regulatory guidance
• Coordinates safety reporting
Oversight Focus: Clinical practice regulation
PMDA — Pharmaceuticals and Medical Devices Agency
Key Responsibilities:
• Evaluates product applications
• Inspects manufacturing facilities
• Manages conditional/time-limited approvals
• Conducts post-market surveillance
Oversight Focus: Commercial regenerative products
Certified Review Boards / Committees
Key Responsibilities:
• Evaluate treatment plans
• Verify risk classification
• Monitor patient protection & consent
• Oversee approved ASRM plans
Oversight Focus: Independent ethical governance
Risk-Based Classification: What Class I–III Really Mean
Under ASRM, risk classification determines the intensity of regulatory oversight:
- Class I – Highest Risk
- iPSC/ES cell–derived products
- Gene-modified cell therapies
- High-risk allogeneic therapies or novel cell types
- Require the strictest review, detailed preclinical safety data, and close MHLW oversight.
- Class II – Medium Risk
- Many autologous MSC therapies involving culture expansion
- Certain allogeneic MSC uses in non-standard indications
- Require Certified Review Board approval, notification to MHLW, and CPC-based manufacturing.
- Class III – Lowest Risk
- Minimally manipulated autologous cells and same-surgical-procedure uses
- Lower documentation burden than Class I/II, but still require review and defined safety and quality controls.
ASRM Risk Classification System
Under Japan’s ASRM framework, regenerative medicine procedures are classified into three risk tiers. The higher the class, the greater the regulatory scrutiny, data requirements, and facility obligations.
High-risk / Novel Cell Therapies
- iPSC/ES cell therapies
- Gene-modified cell therapies
- High-risk allogeneic therapies
- Special committee review
- MHLW approval required
- Detailed preclinical safety data
- Extensive protocol documentation
Culture-Expanded / Selected Allogeneic Uses
- Culture-expanded autologous MSCs
- Some allogeneic MSC indications
- Other non-standard cell applications
- Certified Review Board approval
- Notification to MHLW
- CPC-based manufacturing
- Standard safety monitoring
Minimally Manipulated Autologous Uses
- Minimally manipulated autologous cells
- Same-surgical-procedure uses
- Low-risk somatic applications
- Review board approval
- Simplified documentation
- Basic quality controls
- Reduced reporting burden
In practice, the same cell type can fall into different ASRM classes depending on how it is processed and used. A same-day autologous procedure involving minimal handling generally falls under Class III.
When those cells undergo culture expansion for non-standard indications, the intervention typically shifts to Class II, requiring greater documentation, controlled manufacturing conditions, and additional oversight.
If the cells are allogeneic or genetically modified, the same therapeutic concept may move into Class I. This illustrates that ASRM classification is influenced not only by cell origin, but also by processing complexity, intended use, and the risk profile associated with each step.
Approved Products: TEMCELL, Stemirac, HeartSheet Withdrawal and Others
Despite Japan’s reputation as a global frontrunner in regenerative medicine, the number of fully approved or currently active conditionally approved regenerative medical products remains small.
The 2024-2025 period has become a turning point, as two conditionally approved products—HeartSheet and Collategene—were withdrawn after failing to demonstrate sufficient efficacy during post-marketing surveillance. This shift marks a more stringent enforcement of Japan’s conditional and time-limited approval system.
Approved & Conditionally Approved Regenerative Products in Japan (Updated to late 2025)
The following table highlights regenerative products that have secured full or conditional approval in Japan.
| Product | Type & Indication | 2025 Regulatory Status | Access & Coverage |
|---|---|---|---|
| TEMCELL (JCR Pharma) | Allogeneic bone marrow–derived MSCs Steroid-refractory acute GVHD | Full approval | NHI-covered; available nationwide. |
| Stemirac (Nipro) | Autologous bone marrow–derived MSCs Subacute spinal cord injury | Conditionally approved | Limited coverage; restricted access. |
| Autologous Cultured Chondrocytes | Cultured cartilage cells Orthopedic cartilage repair | Fully approved | Coverage varies by indication. |
Approved & Conditionally Approved Products in Japan
Key regenerative products with full or conditional marketing approval in Japan.
Steroid-refractory acute GVHD
Subacute spinal cord injury
Orthopedic cartilage repair
Withdrawn Regenerative Products: Evidence Gap Case Studies
Two regenerative products were withdrawn after insufficient confirmatory evidence. These cases illustrate
how Japan’s conditional approval pathway responds when clinical benefit is not demonstrated.
HeartSheet (Terumo) — Autologous skeletal myoblast sheet
● Withdrawn (July 2024)
Withdrawn after failure to confirm efficacy in post-approval studies. Often referenced as an example of the
conditional approval pathway discontinuing products that do not demonstrate sufficient benefit.
Collategene (AnGes) — Plasmid HGF gene therapy
● Withdrawn (June 2024)
Withdrawn after the sponsor chose not to pursue renewal due to insufficient confirmatory benefit—
demonstrating the higher evidentiary bar expected for gene-based regenerative interventions.
TEMCELL
Type: Allogeneic bone-marrow mesenchymal stem cell (MSC) product
Indication: Steroid-refractory acute graft-versus-host disease (aGVHD)
Status:
- First granted conditional approval
- Successfully converted to full approval after confirmatory data demonstrated safety and clinical benefit
Access:
- Provided at hematopoietic stem cell transplant centers
- Covered by Japan’s National Health Insurance (NHI) for approved indications
Why it matters:
TEMCELL remains the definitive example of how Japan’s conditional approval pathway should work—early access followed by rigorous real-world data that ultimately supports full authorization.
Stemirac
Type: Autologous bone-marrow–derived MSC therapy
Indication: Subacute spinal cord injury (AIS grades A–C)
Status (as of late 2025):
- Conditionally approved in 2018 based on single-arm study
- Seven-year conditional period ending December 2025
- Expected to submit full approval application before deadline
- Outcome pending PMDA review
Access:
- Restricted to government-authorized hospitals
- Costs typically borne out-of-pocket
Why it matters:
Stemirac now sits at a critical regulatory junction. The PMDA/MHLW must determine whether observational, non-controlled post-marketing data are sufficient for full approval—especially after the withdrawal of HeartSheet and Collategene. This decision will strongly influence the future viability of Japan’s single-arm-trial-based conditional approval model.
Other Regenerative Products and Recent Withdrawals
HeartSheet (Withdrawn 2024)
- World’s first conditionally approved cell-sheet therapy (2015)
- Failed to demonstrate confirmatory efficacy despite multiple extensions
- Officially withdrawn July 2024
- Becomes the first PMDA-approved regenerative product ever revoked
This was a pivotal moment demonstrating that conditional approval is not a regulatory shortcut—products must prove real-world benefit to remain on the market.
Collategene (Withdrawn 2024)
- Plasmid-based HGF gene therapy for critical limb ischemia
- Approved under conditional pathway in 2019
- Sponsor withdrew its application for full approval in June 2024
- Second major example of conditional approval not converting to full approval
Autologous Cultured Chondrocytes
Still fully approved for certain orthopedic indications. These therapies represent some of the earliest regenerative medical products authorized in Japan and continue to be used for cartilage regeneration in specialized orthopedic centers.
MSC and WJ-MSC Therapies: Where They Fit
Mesenchymal stem cells (MSCs) and Wharton’s Jelly–derived MSCs (WJ-MSCs) are important components of Japan’s regenerative medicine pipeline, but their use is carefully segmented:
Approved MSC Products
- Examples: TEMCELL, Stemirac.
- May only be used for approved indications.
- Strict adherence to authorized protocols.
- No off-label use allowed.
Investigational MSC Uses
Includes orthopedics, neurology, immunology:
- Formal PMD Act clinical trials, or
- ASRM-approved regenerative medicine plans.
- Must be conducted in accredited institutions.
Allogeneic MSCs & WJ-MSCs
- Higher-risk due to donor origin.
- Require donor screening + CPC manufacturing.
- Often Class I or high-end Class II.
- As of 2025: No full-approval WJ-MSC products.
Manufacturing and Facility Standards: CPC and GCTP
A defining characteristic of Japan’s system is the tight regulation of cell manufacturing.
Cell Processing Centers (CPCs)
- Any substantial manipulation (culture, expansion, or complex processing) must be performed in a certified CPC.
- CPCs must demonstrate:
- Appropriate cleanroom design and environmental controls
- Validated processes and equipment
- Robust documentation, traceability, and batch records
- Qualified personnel and quality management systems
GCTP Compliance
- For commercial products, manufacturing must comply with GCTP standards, which address identity, purity, potency, sterility, and stability.
These infrastructure and quality requirements significantly contribute to the higher cost of therapies in Japan but also to their comparatively high reliability when contrasted with offerings in less regulated environments.
Costs, Insurance, and Accessibility
Japan occupies a high-cost, high-compliance segment of the global stem cell market. Access is shaped by how therapies are funded, whether they are reimbursed under the National Health Insurance (NHI), and where services are physically concentrated.
Private, Self-Funded Therapies
- Typically involve substantial out-of-pocket costs.
- Pricing varies by cell type, protocol, number of administrations, and CPC-related expenses.
- Generally not covered by NHI; patients pay directly.
Approved Products Under NHI
- Examples include products such as TEMCELL.
- Available to eligible Japanese residents meeting defined clinical criteria.
- NHI coverage can substantially reduce individual financial burden.
Availability and Concentration of Services
- Access is concentrated in major medical centers and specialized institutions in large cities.
- Foreign patients face additional barriers: language, travel logistics, and eligibility screening.
Overall, Japan is not positioned as a low-cost “stem cell tourism” destination.
Enforcement, Advertising Restrictions, and Patient Protection
Japan actively enforces regulations in the regenerative medicine field to limit misleading or unsafe practices.
Key Regulatory Mechanisms
- Mandatory approvals and notifications for ASRM plans
- CPC certification and periodic inspections
- Adverse event reporting to MHLW and PMDA
- Strict advertising regulations under medical and consumer laws:
- Prohibition of exaggerated cure claims
- Ban on promoting unapproved indications
- Mandatory disclosure for investigational or conditional therapies
Administrative Actions & Sanctions
- Warnings and corrective orders
- Suspension or revocation of treatment plans
- Withdrawal of product authorization
- Administrative penalties and — in severe cases — criminal sanctions
Overall, these enforcement mechanisms create a highly controlled environment for regenerative medicine in Japan, particularly in comparison with regions where advertising and treatment practices are less tightly regulated.
Key Regulatory Mechanisms
- Mandatory approvals and notifications for ASRM plans
- CPC certification and periodic inspections
- Adverse event reporting to MHLW and PMDA
- Strict advertising regulations under medical and consumer laws:
- Prohibition of exaggerated cure claims
- Ban on promoting unapproved indications
- Mandatory disclosure for investigational or conditional therapies
Administrative Actions & Sanctions
- Warnings and corrective orders
- Suspension or revocation of treatment plans
- Withdrawal of product authorization
- Administrative penalties and — in severe cases — criminal sanctions
Strengths, Limitations, and Ideal Patient Profile
Strengths
- High safety and manufacturing standards (CPCs and GCTP compliance)
- Clear national legal framework (ASRM + PMD Act), reducing regional inconsistency
- Structured innovation pathways via conditional approval and clinical trials
- Active regulatory oversight, especially in safety and advertising practices
Limitations
- Relatively few fully approved regenerative products compared with the field size
- Limited clinical freedom; physicians must adhere to strict plan-based protocols
- High treatment costs for self-funded interventions
- Language and access barriers for non-Japanese speakers
Who Japan Is Best Suited For
Japan is generally most appropriate for:
- Patients who are eligible for NHI-covered, fully approved products (e.g., aGVHD patients receiving TEMCELL), particularly residents.
- Domestic or international patients with sufficient financial resources who:
- Prioritize regulatory oversight and safety over cost,
- Seek clearly defined, protocol-driven MSC or regenerative treatments under ASRM or within clinical trials, and
- Understand that many potential uses of stem cells remain investigational rather than established standard care.
For individuals primarily seeking broad, low-cost, or highly speculative stem cell interventions, Japan is not a natural fit.
Outlook to 2030: Gradual Expansion, Not Deregulation
Japan’s regenerative medicine landscape is expected to expand gradually through 2030, driven by maturing clinical evidence rather than regulatory relaxation.
1. Growth in Approved Products
Steady increases in approved regenerative products are anticipated, particularly in immunology, orthopedics, and neurology, as more robust clinical data accumulates.
2. Advancement of iPSC and Gene-Edited Therapies
iPSC-derived and selectively gene-edited cell therapies may progress from early-phase studies toward conditional approvals as manufacturing and safety standards evolve.
3. Refinement of the Conditional Approval Framework
• Clearer criteria for conversion to full approval
• More structured post-marketing evidence requirements
• Greater predictability for developers
Japan’s Global Influence
Japan’s risk-based framework is increasingly referenced by jurisdictions seeking to regulate unproven stem cell clinics or accelerate access to advanced therapies. Its conditional approval outcomes—both successful conversions and debated cases—serve as case studies for policymakers designing their own pathways.
Overall, Japan’s trajectory points toward controlled innovation rather than deregulation, strengthening its role as a reference model for integrating regenerative medicine into a mature healthcare system.
Summary
By 2025, Japan has established one of the most structured and mature national frameworks for regenerative medicine worldwide—linking clinical governance, product oversight, and manufacturing standards into a unified system that prioritizes safety, traceability, and regulatory clarity.
Regulatory Snapshot: Core Pillars of Japan’s System
ASRM – Clinical Governance
Governs who may perform regenerative procedures through risk-based classification and mandatory plan review.
PMD Act – Marketed Products
Defines which cell and gene products may be marketed, including the conditional approval pathway and post-market evidence requirements.
CPC & GCTP – Manufacturing Standards
Ensures validated, quality-controlled, and traceable cell manufacturing and processing.
Costs & Accessibility
High costs and limited insurance coverage keep most interventions within specialized centers.
Regulatory Snapshot: Core Pillars of Japan’s System
ASRM – Clinical GovernanceGoverns who may perform regenerative procedures through risk-based classification, mandatory plan review, and institutional accreditation. | PMD Act – Marketed ProductsDefines which cell and gene products may be marketed, including Japan’s |
CPC & GCTP – Manufacturing StandardsEnsures validated, quality-controlled, and traceable cell manipulation | Costs & AccessibilityCosts and accessibility remain limiting factors, with most interventions |
For stakeholders—including patients, clinicians, researchers, and industry—Japan offers:
- A high-trust, high-barrier regulatory environment
- Predictable governance across clinical, product, and manufacturing domains
- Best suited to stakeholders who value structured, evidence-based access
Overall, Japan’s approach reflects a commitment to innovation tempered by rigorous oversight, positioning the country as a reference model for jurisdictions seeking to advance regenerative medicine within a mature and ethically grounded healthcare framework.
Scientific References
Official Government Sources
- PMDA – Pharmaceuticals and Medical Devices Agency Link
- MHLW – Ministry of Health, Labour and Welfare (Japan) Link
- PMDA – Regenerative Medicine (ASRM / PMD Act Summaries) Link
- PMDA – Review Reports: Regenerative Medical Products (incl. TEMCELL, Stemirac, HeartSheet, Collategene) Link
- PMDA – Report on the Deliberation Results: TEMCELL Link
- PMDA – Report on the Deliberation Results: HeartSheet (full approval rejected, July 24, 2024) Link
Academic & Peer-Reviewed Sources
- Pursuing cell therapy approvals in APAC (ScienceDirect – 2025) Link
- Revisions to the Act on the Safety of Regenerative Medicine in Japan (PMC) Link
- New Governmental Regulatory System for Stem Cell-Based Therapies in Japan (ResearchGate) Link
- Stem Cell Therapies: Ensuring Quality & Safety (NCBI) Link
- Clinical Trials of Stem Cell Therapy in Japan (PMC) Link
- Perspectives on Stem Cell-Based Regenerative Medicine (PMC) Link
- Mesenchymal Stem Cells: Japan’s First Approved Cell Therapy (JSTAGE) Link
- Stem Cell Therapy: Revolutionary Cure or Pandora’s Box? (StemCell Research & Therapy) Link
Media & Ethical Guidelines
- Ethical Limits on Embryo Research – Nikkei Link
ℹ Disclaimer
This guide provides an overview of Japan’s stem cell regulatory framework as of December 2025 to help patients, clinicians, and researchers understand the current landscape. Individual medical decisions should be made in consultation with qualified healthcare providers who can assess your specific situation and verify current regulatory requirements.
Stem cell regulations evolve continuously. For the most current information, please refer to:
- Ministry of Health, Labour and Welfare (MHLW) Japan
- Pharmaceuticals and Medical Devices Agency (PMDA)
- Certified medical institutions and review boards
We recommend verifying facility certification, practitioner credentials, product approval status, and clinical trial authorization before pursuing treatment.
Last Updated: December 2025
