On November 25, 2014, the Japanese government revised the Pharmaceutical Affairs Law (PAL) and implemented the new PMD Act (“Act on Securing Quality Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics”). The new PMD Act was based on previous ordinances implemented in the summer of 2014. Two of the main points of this revision are to increase safety measures for medical devices and introduce new cellular and tissue therapeutic product regulations.
To register a medical device in Japan, a foreign manufacturer needs to submit a complete dossier that includes an application with attachments and a Summary Technical Document (STED). In addition to this dossier, a Quality Management System (QMS), and Foreign Manufacturer Accreditation (FMA) are required.
In the past, Class I and some Class II products in Japan could be approved by an independent third party via certification, while other Class II products and all Class III and IV products would need to get PMDA approval (equivalent to the FDA). In general, the process to get many Class II, III, and IV products registered via the PMDA can be long and difficult. With the new PMD Act, however, Japan is going to increase the number of products that can receive third party certification (i.e. do not require PMDA approval). Thus, going forward, all Class II and some Class III medical devices can also be registered via an independent third party via certification. Some Class III and all Class IV products will still need to go through the PMDA approval route.
In allowing more third party certifications for additional Class II and some Class III products, the PMDA will require more stringent requirements for third party certification; the quality of the reviewers will be improved, more information on QMS will be reported to the PMDA, and the overall supervision of third parties will be increased.
Quality Management Systems (QMS)
In the past, device manufacturers trying to get an approval in Japan needed to file a very detailed QMS document. The old QMS requirements regarding audits for compliance were product-specific, meaning they were based on a comprehensive evaluation of the risks associated with the product, the complexity of the manufacturing process, and previous inspection results. Additional requirements included the product standard code, retention periods of documents and records, and infrastructure requirements.
However, going forward, the QMS inspection will be simplified and changed to a QMS certification system that will be conducted according to product groups, not individual products. Also, rather than requiring an application for every facility that has to be inspected, the new system only requires a single application that covers the entire process from product design and development to release of the product to the Japanese market. The PMDA or a registered certification body will conduct inspections of all relevant manufacturing site facilities submitted with one single application. Upon receiving approval, device manufacturers will not have to do additional inspections for five years if the product group name, facilities, and MAH remain the same.
Foreign Manufacturer Accreditation (FMA)
Similar to the QMS, FMA documentation is also required to get device approval in Japan. In the past, the FMA approval was a license and accreditation process that was based primarily on document review. The required documents included a product and process list, an outline of the facility building, an executive organization chart, forms related to the health and personal history of the person responsible for the manufacturing operations, and various licenses and certificates for the product.
With the new PMD Act, FMA approval has been changed from a license and accreditation process to a registration process. The manufacturing site will now consist of only the facilities which are responsible for manufacturing. Under the old system for license and accreditation, additional facilities that were involved with cell tissue, sterilization, labeling/storage, etc. were also required. Going forward, the required materials for FMA approval have been simplified, so the manufacturer will need to submit the resume of the person who is responsible for the manufacturing operations, a document confirming that the applicant is not under the influence of illegal substances such as cannabis or narcotics, and a map depicting the areas surrounding the manufacturing site.
Changes in Cellular and Tissue Therapeutic Products Regulations
With the new PMD Act, cellular and tissue therapeutic products will be allocated their own classification category. The old classification system included the cellular and tissue therapeutic products as part of the medical device classification, but this will no longer be the case.
The main change with respect to cellular and tissue products will be the approval system. Under the past approval system for these types of products, the foreign manufacturer would need to do a lengthy clinical trial in Japan confirming the efficacy and safety to receive approval in Japan. With the new PMD Act, a foreign manufacturer can do a significantly smaller initial clinical trial in Japan, which leads to a temporary approval. The product can then be marketed, and there will be a significant analysis of post-market data to determine the efficacy and safety of the product. Once additional data is collected during the post-market period, the foreign applicant will need to submit another dossier to get final approval. With this new system, foreign companies with cellular and tissue products will be able to get their products on the market significantly earlier in Japan.
A registry system for patients that are treated with cellular and tissue therapeutic products is also being considered.
Software as a standalone medical device
In the past, medical software was always approved as a component of an approved medical device. In other words, if you were trying to register a computerized tomography (CT) scanner, the software within the device would be approved as part of the device approval. Going forward, software will be registered independently from the hardware.
Software classified as Class I will not be regulated in Japan, and the JMD codes for other software products is still being developed. Thus, it is still unclear how medical software products will be registered independently and what documentation will be needed to do so. The PMDA has indicated that they will have more definition on what requirements independent software registration will have in the near future.
Reduced review time at the PMDA
Over the last 10 years, the Japanese government has continually said they would approve products on a more timely basis. In the new PMD Act, there are additional measures to shorten and standardize the review time for medical device approval. Again, the government promises an increase of reviewers with better background knowledge. The shortening of the review time will also be applied to in vitro diagnostics (IVDs).
Many of the changes discussed above will help more foreign medical device companies get their products on the Japanese market sooner. It is important that foreign medical device manufacturers study these new regulations so they can use them to their advantage to succeed in the Japanese marketplace.