Regenerative therapies with stem cells

Regenerative medicine has been rapidly developing and drawing increasing attention as an innovative treatment option. However, without ensuring safety and efficacy, the risk to patients increases, and the sound development of medical technologies may be hindered.
Accordingly, proper implementation of regenerative medicine is governed by two key laws in Japan: the Pharmaceuticals and Medical Devices Act (PMD Act) and the Act on the Safety of Regenerative Medicine.
Regenerative medicine in Japan is provided under two main categories: 'regenerative medical products,' which are offered under public health insurance and regulated by the Pharmaceuticals and Medical Devices Act (PMD Act), and 'Specific Processed Cells', which are offered as part of private (uninsured) medical care and regulated under the Act on the Safety of Regenerative Medicine.
TOPs cells fall under the category of 'Specific Processed Cells' as defined by the Act on the Safety of Regenerative Medicine.

Manufacture
and marketing

Pharmaceuticals and Medical Devices Act
(PMD Act): Revised in 2014.

Purpose	To regulate the quality and safety of pharmaceuticals, medical devices, cosmetics, and regenerative medical products, and prevent health hazards caused by their use. To promote the research and development of pharmaceuticals, medical devices, and regenerative medical products that are particularly needed from a medical standpoint, to improve public health.
Content	In addition to pharmaceuticals and medical devices, regenerative medical products have been newly established as a regulated category. A conditional and time-limited approval system has been introduced, under which products may be approved if their efficacy is reasonably expected and their safety is confirmed, subject to certain conditions and a defined period.

Regenerative
Medical Products

Definition	These products are manufactured and marketed under the Pharmaceuticals and Medical Devices Act (PMD Act) in facilities that strictly comply with GMP (Good Manufacturing Practice) or GCTP (Good Gene-, Cellular-, and Tissue-based Product Manufacturing Practice). Their quality, safety, and efficacy have been validated scientifically.
Features	Owing to the high development costs involved, only a limited number of products have reached the market. As of 2022, the domestic market size was 5.4 billion yen, with 20 regenerative medical products approved for marketing. Representative products include Temcell (JCR Pharmaceuticals) and JACE (Japan Tissue Engineering Co., Ltd. (J-TEC).

Uninsured
medical care

Clinical
research

Act on the Safety of Regenerative
Medicine: Enforced in 2014.

Purpose

The purpose is to ensure the prompt and safe provision of regenerative medicine by clarifying the responsibilities and required measures for providers, while also establishing a licensing system for the manufacturing of Specific Processed Cells.

Content

To provide regenerative medicine, submitting a treatment plan to the Minister of Health, Labour and Welfare is mandatory. The required procedures vary depending on the risk classification of the therapy. A Review by a (Certified) Committee for Regenerative Medicine is required. Cell processing can be outsourced to companies or organizations licensed by the Minister of Health, Labour, and Welfare. When a medical institution performs cell processing in-house, it is required to submit a notification to the Minister of Health, Labour, and Welfare.

Specific
Processed Cells

Definition	Cells are manufactured and provided per the Act on the Safety of Regenerative Medicine at cell- processing facilities operated by medical institutions or companies that have been assigned a facility number by the Minister of Health, Labour and Welfare.
Features	Can be promptly used in clinical settings. As this treatment is provided outside the public insurance system, it enables more personalized and patient-centered care. Regulatory requirements are reasonably relaxed, allowing for reduced cost and time to commercialization.

Under the Act on the Safety of Regenerative Medicine, as illustrated in the flowchart below, regenerative medicine practices are classified into three categories (Classes I, II, and III) based on their potential impact on human life and health. Appropriate regulatory measures are applied to each category.

Under the Act on the Safety of Regenerative Medicine, adipose-derived stem cells (ADSCs) are used to treat various diseases.
A large proportion of regenerative medicine using adipose-derived stem cells falls under Category II regenerative medicine provision plans, accounting for approximately 50% of all treatment plans in this category.

Osteoarthritis of the knee Arthritis
Regeneration of jawbone defects, alveolar bone, and periodontal tissues
Regeneration of ligaments, tendons, and muscles (sports-related injuries)