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How Are Class I, II, and III Regenerative Medicine Decided in Japan?
Committees, the 90-Day Rule, and Penalties by Class

“Is this treatment Class II, or Class III?” — the class is not, in fact, something the medical institution chooses. Under Japan’s Act on the Safety of Regenerative Medicine, Class I, II, and III follow automatically from fitting the technology to the categories set out in ordinances of the Ministry of Health, Labour and Welfare (MHLW), and the same cells can change class depending on whose they are and where they are put. This article walks through how the class is decided, and how the committee, the procedures, and the penalties change with it, following the text of the Act, the Cabinet Order, and the MHLW ordinances.

This article in 30 seconds

  • The class is not chosen; it is decided by fitting the technology to the categories in MHLW ordinance. The test runs in the order Class I → Class II → Class III, and the same cells can change class depending on whose cells they are and where they are put.
  • What changes with the class is the reviewing committee, when provision may begin, and how heavy the penalties are. Class I alone may not be provided, as a rule, for 90 days from submission of the plan.
  • Cell-free culture supernatant and secretome are outside the scope of the Act at present. The condition, however, is that “it is clear that no cells are contained,” and a review clause requires this treatment to be reconsidered roughly two years after enforcement.

This article explains the law of Japan. The classifications and procedures described here apply to regenerative medicine provided within Japan, and do not describe the rules of any other country. Article numbers refer to Japanese statutes.

The sections below follow the same order as the actual determination. Every point can be confirmed in the text of the Act, the Cabinet Order, or the MHLW ordinances.

1. Is it “regenerative medicine” in the first place?

Before thinking about the class, you first need to confirm whether the technology is covered by this law at all. If it is not, the question of Class I, II, or III never arises.

The law at issue is Japan’s Act on the Safety of Regenerative Medicine (Act No. 85 of 2013; hereinafter the “Act”). It came into force on 25 November 2014 and sets out the procedures that apply when a medical institution provides regenerative medicine to patients on its own responsibility. Class I, Class II, and Class III are categories placed inside this Act.

Two things are covered by the Act.

In this Act, “regenerative medicine technology” means a medical technology that is intended for use in the reconstruction, repair, or formation of the structure or function of the human body, or in the treatment or prevention of human disease, and that is specified by Cabinet Order from among the following (omitted).
(i) medical technologies using processed cell products (omitted)
(ii) medical technologies using nucleic acids, etc. (omitted)

Article 2(2) of the Act

A “processed cell product” is defined as something obtained by culturing or otherwise processing human or animal cells (Article 2(4) of the Act). Whether the cells themselves are present is the first dividing line.

The “nucleic acids, etc.” of item (ii) was added by the 2024 amendment (Act No. 51 of 2024, promulgated on 14 June 2024) and has been in force since 31 May 2025. The amendment brings within scope treatments that introduce genes directly inside the body without processing cells outside it (in vivo gene therapy). Until then, gene therapy that does not involve processing cells sat outside this Act.

There is one more important exclusion, set out in a parenthetical clause of the provision. Using an approved regenerative medicine product in accordance with the dosage and administration covered by its approval is excluded from “medical technologies using processed cell products” as the term is used here (Article 2(2)(i) of the Act). Where a product has already cleared review under Japan’s Pharmaceuticals and Medical Devices Act and is used as stated in its package insert, the medical institution need not separately follow the procedures of this Act. An exclusion of the same structure is provided for nucleic acids, etc. (item (ii) of the same paragraph).

Blood transfusion and hematopoietic stem cell transplantation also fall outside the scope, so long as no processing that alters their properties has been applied (Article 1(i) of the Enforcement Order of the Act). In addition, carrying out a procedure as a clinical trial (chiken) aimed at approval is excluded from “regenerative medicine” (Article 2(1) of the Act), because clinical trials are governed by the Pharmaceuticals and Medical Devices Act and GCP.

2. The three classes are divided by degree of risk

Once the technology is known to be covered, the next step is the class. In a word, the criterion is how unpredictable the technology is. Setting the wording of the provisions side by side makes that plain.

Class I regenerative medicine technology…whose effect on human life and health is not clear, or which, even when considerable care is exercised, may have a serious effect on human life and health, and, on that basis, (…) regenerative medicine technology specified by Order of the Ministry of Health, Labour and Welfare

Class II regenerative medicine technology…which, even when considerable care is exercised, may have an effect on human life and health, and, on that basis, (…) regenerative medicine technology specified by Order of the Ministry of Health, Labour and Welfare (excluding technology falling under Class I regenerative medicine technology)

Class III regenerative medicine technology…regenerative medicine technology other than Class I regenerative medicine technology and Class II regenerative medicine technology

Article 2(7), (8), and (9) of the Act

Comparing the three, the differences are whether the word “serious” appears, and the fact that Class I also takes in cases where the effect is “not clear.” The less track record a technology has and the less predictable its outcome, the higher the class it is placed in — that is the thinking.

The statutory text alone, however, is not enough to apply the rules to a real case. The concrete lines are drawn by the Enforcement Regulation of Japan’s Act on the Safety of Regenerative Medicine (Ordinance of the Ministry of Health, Labour and Welfare No. 110 of 2014; hereinafter the “Enforcement Regulation”), which enumerates Class I in Article 2 and Class II in Article 3. There is no list for Class III: whatever does not fall under the two above becomes Class III as it stands.

The key point

The class is not something you apply for. Picture a set of sieves worked through from the top: first the Class I sieve, then the Class II sieve, and whatever is caught by neither is Class III.

The determination proceeds in the following order.

  1. Does it fall under one of the five categories in Article 2 of the Enforcement Regulation? If so, it is Class I.
  2. If not, does it fall under one of the three categories in Article 3 of the Enforcement Regulation? If so, it is Class II.
  3. If neither applies, it is Class III.
Order for determining Class I, II, and III First, confirm whether the medical technology uses a processed cell product or nucleic acids, etc.; if it does not, it is outside the scope of this Act. If it is within scope, check whether it falls under one of the five categories in Article 2 of the Enforcement Regulation; if it does, it is Class I. If it does not, check whether it falls under one of the three categories in Article 3 of the Enforcement Regulation; if it does, it is Class II. If neither applies, it is Class III. Apply in order Uses processed cells or nucleic acids? Act Art. 2(2); Order Art. 1 Not used Outside this Act Reg. Art. 2: one of 5 types? ES/iPS, gene edit, animal, donor cells, in vivo NA Yes Class I Reg. Art. 3: one of 3 types? Cultured stem cells, reconstruction, non-homologous Yes Class II Neither applies Act Art. 2(9) Class III The class is not chosen; it follows from this test.
Figure 1: The determination runs from the top down. Class III is the leftover box for whatever fell under neither Class I nor Class II.

3. What falls under Class I — Article 2 of the Enforcement Regulation

Class I consists of five categories in which the unknowns are greatest: ES and iPS cells, genetic manipulation, animal cells, and cells from another person. They are enumerated in Article 2 of the Enforcement Regulation, and item (v) was added on 31 May 2025.

The five categories of Class I regenerative medicine technology (Article 2 of the Enforcement Regulation)
ItemText of the provisionExamples
Item (i)Uses human embryonic stem cells, induced pluripotent stem cells, or induced pluripotent stem cell-like cells that have been cultured or otherwise processedTransplanting cells made from ES cells or iPS cells
Item (ii)Uses cells into which a gene has been introduced or in which a gene has been modified, or products processed from such cellsIntroducing a gene into harvested cells and returning them to the patient (where a medical institution itself performs the same technique used in CAR-T)
Item (iii)Uses animal cells that have been cultured or otherwise processedUsing cells derived from non-human animals such as pigs
Item (iv)Cells from a person other than the recipient, cultured or otherwise processed, are usedCulturing and administering mesenchymal stem cells derived from another person (a donor)
Item (v)Introducing nucleic acids, etc. into a person’s cells inside that person’s bodyDelivering a gene directly into the body with a viral vector or the like

“Induced pluripotent stem cells” in item (i) are defined as stem cells in which pluripotency has been artificially induced (Article 1(ii) of the Enforcement Regulation). Item (v) was added by the amendment that took effect on 31 May 2025, and under the text of the provision, substances containing cell secretions are excluded.

The key point

Look at item (iv). The class rises according to whose cells they are, not the type of cell. The same mesenchymal stem cells are Class II if taken from the patient’s own body, and Class I if taken from another person. Risks such as immune rejection and transmission of infection are harder to read when the cells come from someone else.

4. What falls under Class II — Article 3 of the Enforcement Regulation

Among the technologies that pass through the Class I sieve, three categories are Class II: cultured stem cells, uses aimed at reconstruction and the like, and non-homologous use. They are set out in Article 3 of the Enforcement Regulation.

The three categories of Class II regenerative medicine technology (Article 3 of the Enforcement Regulation)
ItemText of the provisionExamples
Item (i)Uses cultured stem cells, or products processed from themCulturing and administering mesenchymal stem cells taken from the patient’s own fat
Item (ii)Uses cultured cells, or products processed from them, for the purpose of the reconstruction, repair, or formation of the structure or function of the human body (excluding item (i))Culturing the patient’s own chondrocytes or fibroblasts and using them to repair tissue
Item (iii)Use of cells that is not homologous use (excluding items (i) and (ii))Using cells taken from one site at another site with a different function

The term “homologous use”

“Homologous use” in item (iii) means, put plainly, having the cells do the same job they did in their original workplace. The Enforcement Regulation defines it as follows.

“Homologous use” means a method of administering cells in which the harvested cells have a function similar to that of the cells at the site of the person receiving the regenerative medicine that is the target of that regenerative medicine.

Article 1(iv) of the Enforcement Regulation

The enforcement notice of the Ministry of Health, Labour and Welfare gives concrete examples of this determination. Administering adipose tissue-derived stem cells harvested from the abdomen to the affected area after breast cancer surgery for the purpose of breast reconstruction is homologous use. However, administering the same cells intravenously to treat diabetes is not homologous use, because it is not aimed at reconstructing adipose tissue.

The same reasoning applies where nothing is cultured. Where peripheral blood is centrifuged and used without culturing, administration to the skin or the oral cavity is homologous use, while administration to tissue with poor blood flow, such as inside a joint cavity, is treated as not being homologous use.

The key point

The same cells fall into a different class depending on where they are put and for what purpose. If the use is not homologous, the technology moves up to Class II under Article 3(iii) of the Enforcement Regulation. The class is settled only once “what cells” is joined by “from whom, to where, and for what purpose.”

5. Class III is “everything else”

Anything that falls under neither Class I nor Class II is Class III (Article 2(9) of the Act). There is no enumerated list; Class III is the leftover box that catches whatever fell through the two sieves.

Restated along the lines of the provisions, a technology is Class III when it meets all of the following conditions. It uses neither ES or iPS cells, nor genetically manipulated cells, nor animal cells, but the patient’s own cells (so Article 2 of the Enforcement Regulation does not apply); it does not use cultured stem cells; it is not aimed at the reconstruction, repair, or formation of the structure or function of the body; and it is homologous use (so Article 3 of the Enforcement Regulation does not apply).

For example, a treatment that cultures the patient’s own immune cells and returns them to the body for that same immune function meets these conditions. In the same treatment, if the cells came from another person, Article 2(iv) of the Enforcement Regulation applies and the technology jumps all the way up to Class I.

6. What changes with the class

Here the practical substance begins. A different class changes which committee gives its opinion, where the plan is submitted, when provision may begin, and how heavy the penalties are. The table below sets them side by side.

Procedural differences by class
Class IClass IIClass III
Committee whose opinion must be soughtSpecial Certified Regenerative Medicine Committee
Article 7 of the Act
Special Certified Regenerative Medicine Committee
Article 11 of the Act
Certified Regenerative Medicine Committee
Article 4(2) of the Act
Where the plan is submittedMinister of Health, Labour and Welfare
handled by MHLW headquarters
Addressed to the Minister of Health, Labour and Welfare, but the authority is delegated to the Director-General of the Regional Bureau of Health and Welfare
Article 118(1)(i) of the Enforcement Regulation
When provision may beginAfter 90 days have passed from submission, as a rule
Article 9 of the Act
No waiting period prescribedNo waiting period prescribed
Health Sciences CouncilIts opinion is heard before a change order is issued
Article 55(iv) of the Act
Matters covered by the provision standardsIncludes matters concerning facilities and personnel (Article 3(2)(i) of the Act)Matters concerning facilities and personnel are excluded
Providing treatment without submitting a planImprisonment for up to 1 year
or a fine of up to 1,000,000 yen
Article 60(1)(i) of the Act
A fine of up to 500,000 yen
Article 62(i) of the Act

In every class, the committee must be asked for its opinion before submission, and a document setting out that opinion must be attached to the plan (Article 4(2) and (3) of the Act). Both Class I and Class II require the opinion of a Special Certified Regenerative Medicine Committee. On this point, Class I is not special. What is special about Class I is the waiting period before provision may begin and the severity of the penalties.

How the two types of committee differ

The two committees are not separately created systems. A committee certified under Article 26(1) of the Act is a Certified Regenerative Medicine Committee, and among these, one that meets all of the requirements in the items of paragraph (4) of the same Article is a Special Certified Regenerative Medicine Committee (Article 7 of the Act).

For a committee that handles only Class III plans, some of the requirements on review capability are relaxed (parenthetical clause in Article 26(1) of the Act). The difference shows in who sits on the committee.

  • Committees that review Class I and Class II: experts in molecular biology and related fields, persons with scientific knowledge of regenerative medicine, clinicians, persons with expertise in the manufacture of specified processed cell products, etc., legal experts, persons with expertise in bioethics, persons with expertise in biostatistics and related fields, and lay members — these eight categories must each be filled by a different member, with no concurrent service. Where nucleic acids, etc. are handled, two further categories are added (Article 44 of the Enforcement Regulation). There are also criteria requiring at least two members of each sex, at least two members with no interest in the establishing entity, and fewer than half of the members belonging to the same medical institution (Article 46 of the Enforcement Regulation).
  • Committees that review Class III only: three categories suffice, with at least five members, at least one member of each sex, and at least two members with no interest in the establishing entity (Articles 45 and 47 of the Enforcement Regulation).

7. The 90-day rule that applies only to Class I

For Class I, the greatest practical impact comes from the wait before provision may begin. Submitting the plan does not mean you can start. Two articles govern this.

The first is Article 8(1) of the Act: the Minister of Health, Labour and Welfare may, on finding that a plan does not conform to the regenerative medicine provision standards, order changes or other measures only within 90 days counting from the date of submission. The second is Article 9 of the Act, which provides that the administrator of the medical institution may not provide the treatment until that period has elapsed.

The key point

The 90 days are not the time the review takes; they are the government’s allotted time for calling a halt. During this period, the government hears the opinion of the Health Sciences Council and then decides whether to order changes (Article 55(iv) of the Act).

Steps before Class I regenerative medicine can begin First, the plan is reviewed by a Special Certified Regenerative Medicine Committee, and the provision plan is then submitted to the Minister of Health, Labour and Welfare together with the committee’s opinion. Provision is not allowed during the 90 days counting from the date of submission, and the Minister may issue a change order only within that period. Before issuing an order, the Minister hears the opinion of the Health Sciences Council. The period is shortened if the plan is found to conform to the standards, and extended if there is a reasonable ground for being unable to issue an order within 90 days. Class II and Class III have no such waiting period. Special committee review Article 7 Submit provision plan Day 0 / Art. 4(1) Provision may begin Article 9 90 days (Art. 8(1)) No provision allowed Submission to start Class II/III: no wait - Shortened if found compliant (Art. 8(3)) - Extended for cause if no order within 90 days (Art. 8(2)) - Council heard before an order (Art. 55(iv))
Figure 2: For Class I, the 90 days are not a review period but the period in which the government can order changes. The period is shortened once the plan is found to conform, and extended when no determination can be reached.

Providing treatment without observing this period violates Article 9 of the Act and is punishable by imprisonment for up to 1 year or a fine of up to 1,000,000 yen (Article 60(1)(iv) of the Act). Physicians and dentists are also under their own duty to confirm that the period has elapsed before performing the procedure (Article 13(ii) of the Act).

8. The place where cells are processed is regulated separately

This is a frequently misunderstood point. Facilities that culture and process cells (cell processing facilities) are regulated as well, but the dividing line is not Class I, Class II, or Class III. It turns on whether the facility is located inside a medical institution.

Procedures for facilities that manufacture specified processed cell products, etc.
ProcedureWho it applies toLegal basis
NotificationFacilities established within a hospital or clinic, and the like (including manufacturing sites licensed under the Pharmaceuticals and Medical Devices Act and facilities of cord blood supply operations)Article 40(1) of the Act
LicenseAnyone else who intends to manufacture. Businesses that take on manufacturing under contract from outside fall hereArticle 35(1) of the Act
AccreditationPersons who intend to manufacture, outside Japan, specified processed cell products, etc. for use in regenerative medicine within JapanArticle 39(1) of the Act

The structure of the statute confirms this. Chapter IV of the Act (Articles 35 to 54), which governs manufacturing, and Chapter IV of the Enforcement Regulation never once use the words Class I, Class II, or Class III. The idea of dividing by class simply is not there to begin with.

A license has a term of validity and must be renewed every 5 years (Article 36(1) of the Act and Article 5 of the Enforcement Order of the Act). At the time of application, an investigation is conducted into whether the structure and equipment conform to the standards (Article 35(5) of the Act), and this investigation may be carried out by the Pharmaceuticals and Medical Devices Agency (PMDA) (Article 38(1) of the Act). Each facility must also appoint an administrator with knowledge of biology (Article 43 of the Act).

Where a medical institution outsources manufacturing, the contractor must be a business that has obtained one of the notifications, licenses, or accreditations above (Article 12 of the Act).

9. Obligations that continue after provision begins

Submitting the plan is not the end of it. The following reports and records continue while treatment is being provided.

  • Reporting of diseases, etc.: When a disease, disability, death, or infection suspected to be caused by the provision comes to the institution’s knowledge, it must be reported both to the Certified Regenerative Medicine Committee (Article 17(1) of the Act) and to the Minister of Health, Labour and Welfare (Article 18 of the Act). The deadline depends on the content: cases of death, or that may lead to death, must be reported within 7 days, while hospitalization, prolongation of hospitalization, disability, risk of disability, serious cases, and congenital anomalies in later generations must be reported within 15 days (Article 35(1) of the Enforcement Regulation). Anything else falls outside ministerial reporting and is reported only to the committee, every 60 days.
  • Periodic reporting: The status of provision is reported to the committee (Article 20(1) of the Act) and to the Minister of Health, Labour and Welfare (Article 21(1) of the Act). It is due every year counting from the date the provision plan was submitted, within 90 days after the end of that period (Articles 37 and 38 of the Enforcement Regulation). A report must be submitted even if there were 0 cases of provision in that period. The Minister of Health, Labour and Welfare compiles the reports and publishes a summary (Article 21(2) of the Act).
  • Creating and retaining records: The date and time, place, and content of what was carried out are recorded, and the administrator retains them (Article 16 of the Act).
  • Notification of discontinuation: If provision is discontinued, the institution must notify the committee within 10 days and report to the Minister of Health, Labour and Welfare (Article 6 of the Act).

If a problem arises, the Minister of Health, Labour and Welfare may issue an emergency order (Article 22 of the Act) or an improvement order (Article 23(1) of the Act), for example ordering a temporary suspension. If an order is not complied with, provision may be restricted by order (paragraph (2) of the same Article). The Act also provides for on-site inspections (Article 24 of the Act).

10. Penalties for noncompliance

The penalty depends on the combination of class and conduct. The heaviest is failure to comply with an emergency order, followed by providing Class I without a plan or within the 90-day period.

Principal penalties
ViolationPenaltyBasis
Failure to comply with an emergency orderImprisonment for up to 3 years or a fine of up to 3,000,000 yen (both may be imposed)Article 59 of the Act
Providing Class I regenerative medicine without submitting a plan / providing it within the 90-day periodImprisonment for up to 1 year or a fine of up to 1,000,000 yenArticle 60(1)(i) and (iv) of the Act
Manufacturing specified processed cell products, etc. without a licenseImprisonment for up to 6 months or a fine of up to 300,000 yenArticle 61(i) of the Act
Providing Class II or Class III regenerative medicine without submitting a planA fine of up to 500,000 yenArticle 62(i) of the Act
Manufacturing specified processed cell products, etc. without filing a notificationA fine of up to 200,000 yenArticle 63(i) of the Act

Where an employee of a corporation commits a violation in connection with its business, a fine is imposed on the corporation as well as on the individual offender (Article 64 of the Act; dual liability provision).

11. Which class do culture supernatant and exosomes fall into?

This is the question we are asked most often. To state the conclusion first, administering cell-free culture supernatant or exosomes falls into none of the classes under this Act at present. It drops out one stage before classification: it is outside the scope of the Act itself.

The reason lies in the definitions. The Act covers two things: medical technologies that use processed cell products and medical technologies that use nucleic acids, etc. (Article 2(2) of the Act). Culture supernatant is a liquid from which the cells have been removed, so it is not a processed cell product (something produced by processing human or animal cells). On the nucleic acids, etc. side as well, Article 2(v) of the Enforcement Regulation, added in 2025, states expressly that the substances covered “exclude cell secretions”.

On this point there is no need to rely on inference. In its 2025 Q&A, the Ministry of Health, Labour and Welfare answered naming the term “secretome” explicitly.

Q. Are medical technologies that use culture supernatant or secretome subject to the Act?
A. Where it is clear that the culture supernatant contains no cells, it is outside the scope of the Act. As for secretome, the term is a general designation for proteins secreted by cells into the extracellular space. Where it is clear that the substance in question contains no cells, it is outside the scope of the Act. Note that the supplementary provisions of the amending Act provide that, with respect to medical technologies using cell secretions, consideration is to be given to how the Act should apply, and to related matters, with a target of two years after the amending Act comes into force.

Research and Development Policy Division, Health Policy Bureau, Ministry of Health, Labour and Welfare, administrative notice “Q&A on the Act on the Safety of Regenerative Medicine (Japan) and Related Regulations” (30 May 2025), A.1-1-08

The key point

What must not be overlooked is the condition “where it is clear that no cells are contained.” The answer is not written so that anything named “culture supernatant” is automatically excluded. Only where the manufacturing process and testing can demonstrate that no cells remain does a product come under this interpretation.

The same Q&A also marks out the boundaries. A medical technology that administers only cytokines (including growth factors) is outside the scope (A.1-1-09). On the other hand, mitochondria obtained by processing cells are a specified processed cell product and are subject to the Act (A.1-1-10). Not everything derived from cells is excluded across the board.

Nor does this mean “there is no regulation, so there is no problem.” In 2024 the Ministry of Health, Labour and Welfare issued the following administrative notice addressed to the administrators of providing institutions.

With respect to medical care using culture supernatant of human stem cells and cell secretions such as extracellular vesicles that may be contained in that supernatant (hereinafter “exosomes, etc.”) (omitted), at present there is no pharmaceutical product among the exosomes, etc. used whose efficacy and safety have been demonstrated, including in other countries, and which has obtained regulatory approval and is manufactured and marketed. For this reason, where such medical care is provided, it is considered necessary for the physician or dentist performing it to pay particular attention to its safety, under his or her own responsibility.

Research and Development Policy Division, Health Policy Bureau, Ministry of Health, Labour and Welfare, administrative notice “Concerning Medical Care Using Stem Cell Culture Supernatant and Exosomes, etc. (Notification)” (31 July 2024)

That notice asks providers to refer to the Japanese Society for Regenerative Medicine’s “Guidance on the Clinical Application of Extracellular Vesicles, etc.” Being outside the scope of the Act is one matter; being relieved of quality and risk management is another.

This treatment is under review

“Outside the scope” is not a permanent settlement. The 2024 amending Act contains the following review clause.

The government shall, with a target of two years after this Act comes into force, and with respect to advanced medical technologies that use cell secretions (omitted) and other substances, take into account research and development on such medical technologies, the provision of medical care using them, the state of regulation of such medical technologies in other countries and other circumstances, review how (omitted) the Act should apply to such medical technologies and related matters, and, based on the results, take legislative measures and any other necessary measures.

Act No. 51 of 2024, Supplementary Provisions, Article 2(1)

Because the enforcement date is 31 May 2025, that target falls around May 2027. The current position that these products are “outside the scope” is best treated as one that holds as of today only.

Our stem cell secretome is supplied as a research reagent and is not represented as having an effect on any particular disease. Our approach to manufacturing and quality control is explained in What Is a Secretome, and the testing is described in Safety Testing of Culture Supernatant.

12. Where to file

Provision plans are submitted, and applications concerning Certified Regenerative Medicine Committees are made, through the Ministry of Health, Labour and Welfare’s online filing site “e-再生医療” (e-Regenerative Medicine). The site also publishes a list of the provision plans already filed and a list of Certified Regenerative Medicine Committees, so anyone can check which medical institution has filed what, and under which class.

If you are unsure how the classification applies, the surest course is to consult in advance with the Certified Regenerative Medicine Committee whose opinion you will be seeking and with the regenerative medicine desk of the Regional Bureau of Health and Welfare.

Frequently asked questions

Can we choose Class I, II, or III ourselves?

No. It is determined by whether the technology falls within the categories set out in MHLW ordinance. If it falls within one of the five categories in Article 2 of the Enforcement Regulation, it is Class I; if it does not and falls within one of the three categories in Article 3, it is Class II; if neither applies, it is Class III. The determination is made in that order.

If we use the patient’s own cells, is it always Class II or lower?

No. Even with autologous cells, if genes are introduced or modified, the technology falls under Article 2(ii) of the Enforcement Regulation and is Class I. Conversely, administering cultured stem cells back to the same person is Class II under Article 3(i) of the Enforcement Regulation, while administering the same cells to another person is Class I under Article 2(iv) of the Enforcement Regulation.

Must the 90 days for Class I always be observed?

Not always. If the Minister of Health, Labour and Welfare finds that the plan conforms to the regenerative medicine provision standards, the period can be shortened (Article 8(3) of the Act), and it is extended where there is a reasonable ground for being unable to issue an order within 90 days (paragraph (2) of the same Article). Both shortening and extension are notified to the administrator.

Do the license and notification requirements for cell processing facilities differ by class?

No. The dividing line is not Class I, II, or III but whether the facility is inside a medical institution. Facilities established within a hospital or clinic file a notification (Article 40(1) of the Act), while other businesses that manufacture under contract require a license (Article 35(1) of the Act).

Is a provision plan required for administering stem cell culture supernatant or exosomes?

Not at present. A.1-1-08 of the Ministry of Health, Labour and Welfare Q&A (administrative notice of 30 May 2025) answers, with respect to culture supernatant and secretome, that “where it is clear that no cells are contained, it is outside the scope of the Act.” Note, however, that the condition “where it is clear” is attached: the determination turns not on the name but on whether you can demonstrate that no cells remain. The administrative notice of 31 July 2024 also calls for attention to safety, and Article 2 of the Supplementary Provisions of the amending Act states that the treatment of these products is to be reviewed with a target of two years after enforcement.

This article is a general explanation based on the provisions in force as of 4 September 2026 and is not legal advice on any individual case. For the actual classification and the procedures, please confirm with the Certified Regenerative Medicine Committee, the Regional Bureau of Health and Welfare, and the Ministry of Health, Labour and Welfare. Our stem cell secretome (the totality of components secreted by the cells during culture) is supplied as a research reagent and is not represented as having an effect on any particular disease.

Sources

  • Act on the Safety of Regenerative Medicine (Japan) (Act No. 85 of 2013) / e-Gov Law Search https://laws.e-gov.go.jp/law/425AC0000000085
  • Enforcement Order of the Act on the Safety of Regenerative Medicine (Japan) (Cabinet Order No. 278 of 2014) / e-Gov Law Search https://laws.e-gov.go.jp/law/426CO0000000278
  • Enforcement Regulation of the Act on the Safety of Regenerative Medicine (Japan) (Ordinance of the Ministry of Health, Labour and Welfare No. 110 of 2014) / e-Gov Law Search https://laws.e-gov.go.jp/law/426M60000100110
  • Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (Japan) (Pharmaceuticals and Medical Devices Act; Act No. 145 of 1960) / e-Gov Law Search https://laws.e-gov.go.jp/law/335AC0000000145
  • Research and Development Policy Division, Health Policy Bureau, Ministry of Health, Labour and Welfare, “Q&A on the Act on the Safety of Regenerative Medicine (Japan) and Related Regulations” (administrative notice of 30 May 2025) https://www.mhlw.go.jp/content/10800000/001498987.pdf
  • Ministry of Health, Labour and Welfare, “Enforcement of the Act on the Safety of Regenerative Medicine (Japan) and Related Regulations” (15 May 2025, Iseiken-hatsu No. 0515-18) https://www.mhlw.go.jp/content/10800000/001512549.pdf
  • Research and Development Policy Division, Health Policy Bureau, Ministry of Health, Labour and Welfare, “Concerning Medical Care Using Stem Cell Culture Supernatant and Exosomes, etc. (Notification)” (administrative notice of 31 July 2024) https://www.mhlw.go.jp/content/001281987.pdf
  • Ministry of Health, Labour and Welfare, “Submission of Regenerative Medicine Provision Plans (Overview)” https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/iryou/saisei_iryou/plan.html
  • Ministry of Health, Labour and Welfare, “e-再生医療” (e-Regenerative Medicine), the online site for regenerative medicine applications and filings https://saiseiiryo.mhlw.go.jp/
  • Japanese Society for Regenerative Medicine, “Guidance on the Clinical Application of Extracellular Vesicles, etc. (First Edition)” https://www.jsrm.jp/cms/uploads/2024/05/news14993-2.pdf

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