Registration and Approval Process of Medical Device in Japan

The healthcare sector in Japan boasts the most extensive and sophisticated system in the region, posing several challenges for international manufacturers of medical devices. Succeeding in the Japanese market opens doors for medical device makers to elevate their business to unprecedented heights, given the anticipated 7% growth and a market value of $29.3 billion. Japan is a crucial market for any medical device manufacturer striving for substantial expansion in Asia, owing to factors such as an aging population, high per capita income, and a substantial demand for cutting-edge products. Beyond traditional medical devices, areas of great potential include self-care, preventative care, at-home care, health IT devices, and advanced diagnostics that harness AI for assessment and treatment support.

However, some types of medical devices, like those used at home, imaging equipment, dialyzers, endoscopes, and surgical tools, might encounter challenges in the advanced Japanese market. The Ministry of Health, Labour and Welfare (MHLW) oversees the medical device market in Japan. Similar to other markets, they have set up systems to help control costs, especially due to their growing elderly population. One approach is having a robust reimbursement system that applies to both private and public insurance plans.

They've also established a Cost-Effectiveness Assessment (CEA) system and recently introduced the 2018 Basic Policy on Economic and Fiscal Management and Reform, commonly known as "honebuto," to keep an eye on healthcare spending and offer suggestions for improving the reimbursement system. Foreign manufacturers of medical devices are strongly recommended to investigate how their products will be assessed and priced in the early stages of planning for the Japanese market.

Japan MHLW and PMDA Medical Device and Pharmaceutical Regulation

• The organization in charge of enforcing laws governing food and medications in Japan, the Ministry of Health, Labor, and Welfare (MHLW), also develops and enforces safety standards for pharmaceuticals and medical equipment.
• The Pharmaceutical and Medical Device Agency (PMDA), a separate organization that works with the MHLW, is in charge of examining applications for drugs and medical devices. The PMDA works with the MHLW to assess the safety of new products, develop comprehensive regulations, and monitor post-market safety.

The Pharmaceutical Medical Device Act (PMD Act)

• The Pharmaceuticals and Medical Devices Act (PMD Act), also referred to as the Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics, outlines the current PMDA rules in Japan.
• All facets of the Japanese medical product registration process, including as in-country representation, certification procedures, licensing, and quality assurance systems, are impacted by the PMD Act. On November 25, 2014, the Pharmaceutical Affairs Law (PAL) was replaced with the PMD Act. 
• The regulations main components are as follows:

1. Certain Class III medical devices can go through independent certification.
2. Programs for creating medical software are independently governed.
3. Manufacturers must register rather than obtain a licence.
4. Systems for quality management (QMS) have been streamlined. The Japanese Marketing Authorization Holder is the subject of a QMS inspection, which is carried out per product family rather than per item.

Classification of Medical Device

CLASS	CATEGORY
Class I	General medical Device eg. X-ray film, steel surgical instruments
Class II	Controlled /Designated controlled medical device eg. MRI units, dental alloys
Class III	Specially controlled medical device eg. Artificial bones, Dialyzer
Class IV	Specially controlled medical device eg. Pacemaker, Artificial heart valves

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Information on Classes of Medical Devices

Class I

• Other than particularly controlled medical devices and controlled medical devices, general medical devices (Class I) are those that MHLW deems to represent a practically negligible risk to human life and health in the case of malfunction or adverse effects. Although they do not need approval, communication with PMDA is necessary, and the conditions listed below must be satisfied.
• After completing a registration procedure called notification, Class I medical devices can be marketed. Applications for notice should include information about the equipment, such as its appearance, characteristics, materials, and manufacturing method. Notification is a self-certification process that does not include evaluation.
• No QMS Audit is required.

1. A third-grade Marketing Authorization Holder (MAH) license is required of the application.
2. The manufacturing facility needs to be licensed to produce medical devices.

Class II

• Other than specially controlled medical devices, controlled medical devices/designated controlled medical devices (Class II) are those that MHLW deems to need management due to the relatively low risk they may in the case of a malfunction or side effects, represent a risk to human life and health.
• The majority of Class II medical devices need to be certified, which entails inspection by a Registered Certification Body (RCB). RCBs carry out reviews by the relevant certification standards and put QMS audits into practice.
• Class II medical devices that fall short of certification standards must go through the approval process. See the descriptions for Classes III and IV below for more information.
• Class II medical equipment is subject to the following additional regulations:

1. Medical devices that do not meet appropriate certification standards fall under the category of regulated medical devices and require PMDA approval review.
2. Medical devices classified as restricted medical devices must have their certification requirements assessed by a Registered Certification Body (RCB) to be certified.
3. Typical specifications for class II medical devices.

• The candidate must hold an MAH license for the second grade.
• The producer needs to be licensed to make medical devices.
• The MHLW regulation 169's requirements for quality management systems (QMS) must be followed by the manufacturer.

Class III & IV

• Class III and Class IV medical devices are those that MHLW has determined need special care due to the relatively significant or potentially deadly risk to human life and health they pose in the event of malfunction or adverse consequences. These gadgets fall under the Class III or Class IV categories.
• Applications for Class III and Class IV medical device approval must be submitted, and PMDA (the Pharmaceuticals and Medical Devices Agency) will review them. There are various application categories as stated in the table below since Class III and Class IV encompass a wide range of medical equipment. The application categories affect the requirements, review period, and price.

Medical Device Clinical Trials in Japan

• As medical gadgets get more complicated, clinical trials for new ones are popping up more frequently. Clinical data proving the usefulness and safety of devices are required due to the increased complexity. Now, American businesses are attempting to enter Japan's expanding medical equipment sector. The creation of clinical trial strategies would be impacted by the recently updated Japanese Pharmaceutical Affairs Law (PAL), according to clinical and regulatory affairs managers.
• The Japanese government is updating its regulatory framework for medical devices to keep up with developments in science and the global medical device industry. The Ministry of Health, Labor, and Welfare (MHLW) started the first stage of its extensive modernization effort in April 2004.
• The Organization for Pharmaceutical Safety and Research (OPSR), the Japan Association for the Advancement of Medical Equipment (JAAME), and the Pharmaceuticals and Medical Devices Evaluation Center (PMDEC) were all combined into the new Pharmaceuticals and Medical Devices Agency (PMDA). Previously, the three pillars of Japan's device and pharmaceutical regulation system were PMDEC, JAAME, and OPSR.
• The government of Japan has made significant modifications to clinical trial regulations to enhance patient safety and the standard of clinical research. Additionally, the government will streamline the ministry's clinical trial evaluation procedures. This article concentrates on the new PAL rules about the design and execution of clinical studies.

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Clinical Trial Notification

• As a result of the PAL modification, clinical investigation sponsors are now required to file a clinical trial notification (CTN) 30 days before to the start of a new device study.
• The amendment also mandates that adverse events during a clinical trial be reported to MHLW. Additionally, it has clauses protecting patient privacy. Similar to a U.S. IDE application, the CTN includes a device description, preclinical data, a clinical trial protocol, and an analytic plan.

Market Authorization Holder (MAH)

• Japanese DMAH Agent To commercialize devices in Japan, foreign manufacturers are required to appoint a commercialized Authorization Holder (MAH) or Japan DMAH agency. The Designated Market Authorization Holder (D-MAH) can be appointed, according to the PMDA. 
• In the first situation, MAH is in charge of and owns the product's registration, certification, and approval. In the second instance, a foreign manufacturer owns and is in charge of the product's registration, certificate, and certification, with D-MAH serving as their agent in Japan. Because it is simpler to replace a D-MAH than an MAH, it is preferable to appoint one.

Foreign Manufacturer Registration (FMR)

The Ministry of Health, Labor and Welfare (MHLW) requires all foreign manufacturers who want to sell their products to Japan to register. Foreign Manufacturer Registration (FMR) is the new name for the registration process that was formerly known as "Foreign Manufacturer Accreditation (FMA)" or "Accreditation of Foreign Manufacturers (AFM)".

Pre-market Submission

Manufacturers may submit a pre-market submission to the PMDA for general medical devices (Class I). There will be no review or evaluation by the PMDA of this notification.

Pre-market Certification

It applies to Class II (and a few Class III) devices that must undergo pre-market certification and have an associated certification standard (JIS). Like the European CE Marking procedure, reviews are contracted out to a Notified Body or other outside organization.

Registration Process for Medical Device

Pre-market Approval

All Class IV devices and some Class II and III devices without a specified certification standard are subject to the pre-market approval procedure, often known as Shonin. The MHLW must ultimately approve this proposal after it is presented to the PMDA.

Post Marketing Surveillance

• Manufacturing/Marketing Authorization Holders (MAH) selling medicines or medical devices in Japan are obligated to conduct post-market surveillance. 
• A product recall and/or loss of market access could result from failure to comply with reporting obligations. In Japan, post-market surveillance entails documenting and disclosing negative incidents, or fuguai, and taking appropriate corrective action when necessary.

The Ministry of Health, Labor, and Welfare (MHLW) and the Pharmaceuticals and Medical Devices Agency (PMDA) are both in charge of post-market surveillance. Together, the organizations list package inserts, product recalls, patient drug information, other urgent safety alerts, reports on adverse drug reactions, and adverse events of medical devices that have been submitted to the PMDA to gather information on adverse events and promote the safe use of medical and pharmaceutical devices.

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