Regulatory Authority in Japan
The authorization of medical devices in Japan represents a challenge for European manufacturers. But it’s not one they should shy away from, because Japan is one of the 10 biggest markets in the world.
This article gives you an overview of the requirements you have to meet and the best way to overcome the hurdles in your submission process.
The Pharmaceuticals and Medical Devices Agency (PMDA) is Japan’s regulatory authority. It is subordinate to the Ministry of Health, Labour and Welfare (MHLW). The PMDA, which was created in 2004, is responsible for the actual tasks within the authorization procedures for medicinal products, medical devices and regenerative medicine products for the Japanese market. The PMDA performs review, inspection, and consultation about medical devices, whereas the MHLW regulates the law and performs ultimate governmental actions based on evidence provided by PMDA. The PMDA and MHLW work together to govern the pharmaceutical and medical device market.
The mission of the MHLW is to protect the population of Japan against health hazards caused by medical devices and pharmaceutical products that are not sufficiently safe or effective or not of sufficiently high quality. Regarding the regulation of medical devices, the MHLW’s tasks include:
- To register manufacturers
- To monitor the PMDA
- To license certain actors
- To enact guidelines and industry standards
- The final release of medical device authorizations
The Pharmaceutical and Medical Device Act (PMD Act) has been the most important law. It replaced the Pharmaceutical Affairs Law (PAL).
In contrast to the EU but like in the USA, devices are classified using predefined product codes: the Japanese Medical Device Nomenclature (JMDN). The JMDN was published in 2005 and is based on the fourth version of the Global Medical Device Nomenclature (GMDN).
The JMDN does not just include the eight-digit JMDN code itself, it also contains:
- The general name of the medical device
- Definitions
- The classification rules
- The risk-based classification according to the GHTF
- Information on whether the QMS requirements have to be complied with
- Applicable standards
If no JMDN code is available, a risk-based classification based on Global Harmonization Task Force (GHTF) rules should be used.
Classification for Medical Devices
There are four classes of medical devices in Japan. The required procedure for pre-market approval depends on the device classification.
The PMD Act differentiates between three types of medical device: general, controlled and specially-controlled medical devices. These are divided into four classes: I (low risk), II, III, IV (high risk) (see Table 1).
The following table shows some examples of medical device classifications in Japan.
Table 1: Classification of medical devices
Class | Risks | Regulation |
Class I: General medical device | Very low risks in the human body even if device malfunction occurs. Ex. In vitro diagnostic medical devices, scalpels, X-ray films, etc. | Notification (No approval needed) |
Class II: Controlled medical device | Relatively low risks in the human body even if device malfunction occurs. Ex. MRI, electronic endoscopes, ultrasound diagnostic equipment, etc. | Certification by third-party certification body / Approval from the minister* |
Class III: Specially controlled medical device | Relatively high risks in the human body if device malfunction occurs. Ex. Dialyzers, ventilators, artificial bones, etc. | |
Class IV: Specially controlled medical device | Highly invasive, risks in the human life if device malfunction occurs. e.g., pacemakers, heart valves, stent graft, etc. | Approval from the minister |
*Medical devices that are applied to certification standards will be certified by third-party certification bodies. Medical devices that don’t have or are not applicable to certification standards will be reviewed and approved by PMDA.
The following table shows some examples of medical device classifications in Japan, EU and in the US.
Table 2: Classification of medical devices in Japan, EU and US (FDA)
Country (Regulator) | Medical Devices Classification | ||||
US (FDA) | Class I | Class II | Class III | ||
Japan (PMDA, HMLV) | Class I | Class II | Class III | Class IV | |
EU (Notified Body) | Class I | Class IIa | Class IIb | Class III | |
Process of Pre-market Approval (Class III and IV)
In order to obtain pre-market approval for a medical device, it’s necessary to prove that the medical device has sufficient efficacy and safety. PMDA reviews the balance of benefit and risks, and the benefits should be superior to the risks. Whether or not pre-marketing clinical trial (Chiken) is required will be judged considering novelty, background, pre-clinical data, intended purpose, differences from similar devices, etc. It’s important to have a consultation meeting with PMDA before submitting an application to discuss whether a pre-marketing clinical trial is needed or not. If a medical device in question has been approved in other countries, it’s also possible to use foreign data for approval.
Approximately 70% of medical devices approved in 2011 utilized data from foreign clinical trials, with no pre-marketing clinical trials conducted in Japan.. However, it is necessary for clinical trials to be conducted in compliance with Japanese standards and to prove that differences between Japanese and foreign populations do not affect clinical outcomes. In such cases, post-marketing trials or surveillance would be required to obtain data from Japanese and various populations. Post-marketing trials/surveillance would be required to obtain data from Japanese/various populations in such cases.
Manufacturers submit an application to PMDA attaching pre-clinical and clinical data, etc. PMDA reviews the quality, safety, and efficacy of the medical device in question. PMDA also performs a Quality Management System inspection. PMDA then sends the review result to MHLW who reviews the medical device in collaboration with the review committee. After that, MHLW issues approval of the device and approval to be covered by health insurance.
As in Europe, before the medical device is authorized in Japan, manufacturer needs to provide evidence of the clinical performance and safety, and clinical benefits of medical device in a clinical evaluation.
Japan, like Europe, allows this proof to be provided, under certain circumstances, based on literature data. No clinical evidence needs to be submitted for generic/me-too devices. In contrast, clinical studies are required for novel medical devices. For improved devices whose safety and performance have not been sufficiently demonstrated by pre-clinical data and literature data, data from clinical studies also has to be submitted.
Clinical Trial Regulations in Japan
When conducting clinical trials, regulations that should be followed in Japan depend on the types of clinical trials. It is important to clarify your clinical trial in order to categorize which regulations are followed.
Since April 1st, 2018, the following regulations are applied to clinical trials as presented in Table below.
Tableau 3: Overview of study types and regulations
Study type | Clinical Studies for Medical Devices | Post-marketing Surveillance | |||
Pre-marketing Clinical Trials (Chiken) | Specified Clinical Studies | Others | |||
Clinical Studies for unapproved products or off-label use | Clinical Studies funded by a MAH company, etc. | ||||
Regulation | Pharmaceuticals and Medical Devices, etc. Act | Clinical Study Act (Obligation to comply) | Clinical Study Act (Make effort to comply) | Pharmaceuticals and Medical Devices, etc. Act | |
Japanese-GCP (J-GCP) for medical devices | Good Post-marketing Study Practice (GPSP) | ||||
Ethical Guidelines for Medical and Health Research Involving Human Subjects (https://www.mhlw.go.jp/file/06-Seisakujouhou-10600000-Daijinkanboukouseikagakuka/0000080278.pdf) need to be respected in any clinical research involving human subjects to protect human dignity and rights as well as to carry out research appropriately and smoothly.
Sponsors of clinical trials submit a Clinical Trial Notification (CTN) to PMDA and PMDA reviews the CTN and reports the result to MHLW in 30 days. Online submission has just started from January 11, 2023.
