Medical Devices in Japan: Regulatory Outlook for 2017

Regulatory Landscape

Medical devices are regulated in Japan by the so-called Pharmaceutical and Medical Device Act. The revised Pharmaceutical Affairs Law enforced on November 25, 2014 brought five main changes to secure a safe and expedited supply of medicinal products and medical devices:

1. A charter for Marketing Authorization License and Manufacturing License of medical devices stated separately from that of pharmaceutical products, quasi-drugs and cosmetics
2. The certification system by the private third party was extended to the Specially Controlled Medical Devices, establishing standards for it
3. Monolithic program for diagnoses is handled as medical devices so it can be subject to approval or certification of the Marketing Authorization License (previously, it was not considered for approval or certification)
4. The permission system for Manufacturing License of medical devices was simplified to a registration system
5. Standards compliance investigation into manufacturing and quality control of medical devices was rationalized.

More recently, in June 2016, the Medical Device Evaluation and Licensing Division was established in the Pharmaceutical Safety and Environmental Health Bureau (PSEHB) to strengthen the organization that handles medical devices, in-vitro diagnostic products and regenerative medicine products. The three product areas are now the Pharmaceutical Evaluation and Licensing Division which focuses on medicinal products, quasi drugs and cosmetic products.

The MHLW also introduced an expanded access use of medicinal products under development (the so-called “compassionate use”) on 25 January, 2016. As of July 2016, GCP Ordinances for medical devices and regenerative medicine products have also been revised with the goal of reducing the burden on sponsors or investigators who initiate clinical trials, in order to increase the feasibility of conducting the expanded trials.

Devices Classification

The definition of medical devices is stipulated in Article 2, Paragraph 4 of the Pharmaceutical and Medical Device Act as “Devices and equipment which are used for the purpose of diagnosis, treatment or prevention of diseases of human or animal, or affecting the structure or function of the human or animal body, and designated by the Enforcement Ordinance of the Pharmaceutical and Medical Device Act.”

Medical devices are classified by the level of their risk into four categories (see Table 1), and the requirements for marketing approval vary depending on the category. Japan does not accept CE marking and/or an FDA certificate although European and US approval does help to expedite the review process.

Clinical Research

The clinical research of medical devices is regulated in the same way it is for pharmaceuticals. Review and inspection on the conformity with notification of 30 days before starting of the clinical trial and reporting of adverse events during the trial are required. Note that in vitro diagnostics are categorized as medicines in Japan, while in most Western countries they are considered devices.

Approval Pathway

The marketing authorization for medical devices in Japan also resembles the system established for pharmaceuticals. Regulation of the manufacture of medical devices was transferred in 2014 from a “licensing system” to a “registering system.” In the same way, regulation of medical devices manufactured outside of Japan was transferred from an “accreditation system” to a “registration system.”

The Pharmaceutical and Medical Devices Agency (PMDA) offers consultations to give guidance and advice on clinical trials and data for regulatory submissions. The agency also reviews regulatory documents once they have been submitted.

Marketing applications for medical devices are split into three main categories with sub-categories in order for reviewers to facilitate the review: new, generic and improved medical devices. Those who apply for the marketing approval should carefully check the category before submission.The applicant of the marketing approval of a medical device should submit documents prepared in accordance with the Global Harmonization Task Force (GHTF)-based Summary Technical Documentation (STED), along with the application form and Data Set with Declaration of Conformity with Essential Principles (EP).

For controlled medical devices, a certification system by a third-party certification body is necessary, and the third party must be accredited by the MHLW as an impartial and fair body. The applicant for the certification of a controlled medical device should submit documents on the conformity to the standards.

The approval is granted to a foreign manufacturer provided that the foreign manufacturer has appointed a license holder of marketing authorization (selected marketing authorization license holder). Lists of new and improved approved medical devices are available on the PMDA website as well as review reports.

Post-marketing requirements for medical devices are almost the same as those for pharmaceuticals.

Reimbursement

Once regulatory approval is obtained, a request for reimbursement of a new device must be made to MHLW. Reimbursement decisions for medical devices and in vitro diagnostics are driven by two independent bodies: the Medical Equipment Organization and the Central Social Insurance Medical Council (Chuikyo).

There are four main reimbursement categories: A, B, C, and F (see Figure 1). A and B are for already categorized medical devices while C and F are relatively new medical device reimbursement categories.

To be recognized by the universal health insurance system (A1, A2 or B) applicants must ensure the availability of the device immediately after enlistment in the system. Also, the law mandates that a sufficient supply of devices be available until replacement by a successive device.

Quality

When medical devices are manufactured, Japan requires that all product batches should be of the same quality as that of the product which is approved. To ensure this, the manufacturing site should have appropriate manufacturing facilities, and the manufacturing process and quality-management system should be maintained and controlled properly.

For medical devices and in vitro diagnostics, PMDA conducts on-site and document-based inspections of the registered manufacturing sites (of products under review or approved products) located in Japan or overseas, in order to ascertain whether their manufacturing facilities and manufacturing and quality controls comply with standards such as the Quality Management System (QMS), and whether the manufacturing sites have a system for manufacturing products of adequate quality.

Conclusion

As noted at the outset of this paper, Japan represents an important market for medical device manufacturers. Even if authorities have started to simplify the regulatory process in the past years, it is still complex for foreign manufacturers to penetrate this market, especially since Japan still does not accept CE and FDA approvals. Having a clear understanding of the regulatory and market hurdles is key to decrease time and cost to market and avoid hazardous strategies. No doubt regenerative medicines and digitalized health will impact the regulatory landscape for medical devices in the future, with the complexity they can introduce; manufacturers will have to adapt their strategy.

For an extended version of this paper, including additional charts as well as sources, click here.