Japan’s Drugs and Medical Devices Law revision involves changes which affect regenerative medical products. These changes are intended to facilitate timely approval of the products so patients can benefit from the products. Regenerative medical products are controlled by two laws in Japan: Act on Safety of Regenerative Medicine and Drugs and Medical Devices Law. Act on Safety of Regenerative Medicine applies to all medical technologies using processed cells whose safety and efficacy have not yet been established. Drugs and Medical Devices Law applies to production and marketing of regenerative and cellular therapeutic products by firms.
Because of the biological characteristics attributable to heterogeneous source cells of regenerative medical products, precise statistical analyses of clinical trial data are more difficult compared to drugs. In addition, regenerative medical products are often intended to treat rare diseases/conditions where other treatment options are not available and number of patients with the condition is low. These factors render implementation of clinical trials of regenerative medical products difficult.
Definition and an independent chapter for regenerative medical products have been introduced into the Act on Safety of Regenerative Medicine with the recent revision. Introduction of conditional approval (requirement for additional clinical trials and/or approved for use at limited medical institutions)/time-limited (less than 7 years) approval system is expected to result in prompt approval of regenerative medical products and expedited availability of the products to patients.
Definition of “Processing”
Regenerative medical products are defined by Drugs and Medical Devices Law as processed cells that are intended to be used for either (1) reconstruction, repair, or formation of structures or functions of the human body or animals; or (2) treatment or prevention of human or animal diseases. Processed cells for gene therapy are also included in this category.
The following processing or manipulation methodologies are regulated:
- Artificial proliferation and differentiation of cells and tissues
- Creation of cell lines
- Drug treatment for the purpose of cell activation
- Chemical treatment
- Biological properties modification
- Combination with non-cellular components
- Genetic engineering modification
- Isolation/separation of specific cells by biological and chemical treatment with agents
- Cells for non-homologous use
This represents a slightly wider scope compared to “more than minimal manipulation” defined by FDA. However, the term “processing” does not apply to instances where cells are utilized to generate structure/function which differ from those of original cells.
Good Gene Cell & Tissue Practice (GCTP)
Considering the fact that cells and other related materials from which regenerative medicine products are derived are difficult to sterilize, good gene cell & tissue (manufacturing) practice (GCTP) was introduced to indicate essential elements of quality management system to be utilized in regenerative medicine products.
- Quality risk management
- Production control (sterility assurance, cross contamination prevention, etc.)
- Quality control (validation & verification, quality reference)
- Structural facility
PMDA has established a system to inspect manufacturing sites of cellular and tissue-based products located in Japan or overseas in order to determine whether their manufacturing facilities as well as manufacturing process and quality management system comply with GCTP.