The Pharmaceuticals and Medical Devices Agency (PMDA) is the regulatory authority responsible for assuring the safety, efficacy, and quality of pharmaceuticals (including biological products) and medical devices in Japan. PMDA conducts scientific reviews of marketing authorization applications (MAA) for medicinal products and monitors post-marketing safety data. PMDA works with the Ministry of Health, Labour, and Welfare (MHLW) to protect the public health safety of Japan. Within PMDA, the Office of Cellular and Tissue-based Products is responsible for regulating cellular therapy products. Brief overviews of the legal framework and definition of regenerative medicine products in Japan are provided.
Regenerative Medicine Legal Framework
The Regenerative Medicine Promotion Law passed in 2013 detailed the development of two additional acts, Safety and Regenerative Medicine Act (RM Act) and Pharmaceuticals, Medical Devices and Other Therapeutic Products Act (PMD Act), which provide two regulatory pathways for regenerative medicine products, including cell therapy products. The RM Act regulates a clinical research pathway for regenerative medicine products intended for academic research. Data collected from this pathway cannot be used for a marketing authorization procedure. The PMD Act regulates the marketing authorization pathway for regenerative medicine products. This Act provides marketing authorization specific to regenerative medicine product that is conditional and time controlled. After 7 years, a benefit-risk profile is assessed for a second final marketing approval procedure.
Regenerative Medicine Products
For the purposes of marketing authorization, cell therapy products are regulated as regenerative medicine products under the Pharmaceuticals, Medical Devices and Other Therapeutics Act (PMD Act). The Act defines regenerative medicine products as:
Processed human or animal cells intended for either:
the reconstruction, repair, or formation of the structure or function
of the human (or animal) body (i.e., tissue-engineered products);
the treatment or prevention of human (or animal) diseases (i.e.,
cellular therapy products).
Articles intended for the treatment of disease in humans (or animals) and
are transgened to express in human (or animal) cells (i.e., gene therapy
The above definition can include processed, human somatic cells, somatic stem cells, embryonic stem cells and artificial pluripotent cell products.
A key component to the definition of regenerative medicine products regulated under the PMD Act is the term “processed.” As defined in the Act, and ministerial ordinances, processing includes cell line establishment, combination with components other than cells or tissues, artificial expansion or differentiation, modification of biological characteristics, genetic modification, isolation of cells with biological or chemical treatment, and non-homologous use. Processing does not include washing, freezing, thawing, isolation of cell without the use of biological or chemical treatment, gamma ray sterilization, and antibiotic treatment. Therefore, regenerative medicine products that are unprocessed and for homologous use would be free from regulatory oversight under this definition. Unprocessed cell therapies that are intended for nonhomologous use are regulated as regenerative medicine products.