Japan National Companion Guide

In Japan, PMDA distinguishes between five types of medical device applications in their review process:

• New medical devices.
• Improved medical devices (with clinical data).
• Improved medical devices (without approval criteria, without clinical data).
• Generic medical devices (without approval criteria, without clinical data).
• Generic medical devices (with approval criteria, without clinical data).

MHLW’s Next Generation Medical Device Evaluation Index specifically addresses evaluation indicators for medical device programs with behavior change. Publication highlights include:

• In establishing a control group, the need for standard treatment, existing behavior-altering medical device programs, sham applications, etc., should be appropriately considered, and evidence of clinical efficacy should be established.
• If it is necessary to evaluate the persistence of efficacy, an appropriate observation period should be established.
• Widely recognized standard objective indicators should be used to establish evaluation items whenever possible. Subjective indicators may be used depending on the target disease and clinical positioning of the device with behavior change.
• Matters to consider that could affect clinical outcomes:
  • Influence of race and cultural background: Even for products that have been used overseas and have clinical trial results, clinical trials should be conducted in Japan as necessary, taking into consideration that not only racial differences but also cultural backgrounds including religion, moral values, and living environment may affect efficacy in medical device programs involving behavioral changes. It is also desirable to evaluate the effects of generational differences and the effects of regional characteristics.
  • Influence of the timing of development and the age at which the clinical trials were conducted: The impact of the evaluated historical background on efficacy and safety should be evaluated. For example, when a product developed ten years ago is submitted for approval, or when disease guidelines, etc., are revised, it is necessary to reevaluate the impact on performance and the clinical positioning of the device in question.
  • Impact on patient adherence: Some behavior change medical device programs are considered to be effective with continued use, and therefore, factors that may affect the rate of continued use may also affect the clinical outcome of the device in question. For example, the following items may be mentioned:
    • Graphical user interface, including fonts and background colors.
    • Representation of messages to be output.
    • Matters that depend on preferences, such as dialects, characters, etc.
  • Safety considerations: For products that may present clinically unacceptable hazards, robust outcomes and risk assessments are required. It is important to consider the risk of inappropriate interventions (e.g., excessive exercise for the elderly, inappropriate dietary guidance for patients with dietary restrictions, etc.) for patients and others for whom the product is indicated, and to conduct a risk assessment that also takes into account product specifications and methods of alerting the public.

PMDA accepts and reviews foreign clinical data of medical devices that have applied for marketing approval in Japan. Japan has specific requirements for the acceptance of foreign data. Handling of clinical data for medical devices conducted in foreign countries (1997) and Handling of clinical study data on medical devices which was carried out in foreign countries (2006) provide further insights, in addition to PMDA’s FAQ page.

Broadly, Japan may accept foreign data when:

• Methods for the study and evaluation are congruent with Japanese standards.
• Studies were conducted by qualified researchers at reliable medical institutions.
• Studies were conducted in accordance with international standards on appropriate practices [i.e., Declaration of Helsinki, Japanese good clinical practice (GCP) regulations] and GCP standards in the source country should be equal to or exceeding Japanese guidelines. If there are differences, they must be enumerated and explained.
• The raw data is accessible if needed and endorsed (signed) by the responsible investigator.

Clinical data and related materials should be accompanied by an accurate Japanese translation, as well as the qualifications of the translator.

There are two regulatory authorities responsible for the regulation of medical devices in Japan: the Ministry of Health, Labour and Welfare (MHLW) and the Pharmaceutical and Medical Device Agency (PMDA). MHLW is responsible for administrative actions such as issuing guidance or decisions regarding product approval pursuant to the PMD Act, as well as judgment on whether a product is considered as a medical device. PMDA undertakes product reviews and post-market safety measures.

Any company intending to manufacture and distribute drugs or medical devices in Japan is required to submit an Application for Accreditation of Foreign Manufacturers. Information about the regulatory submission process is available on PMDA’s Regulations and Approval/Certification of Medical Devices page.

Certain Class II and Class III devices with established certification standards must be certified by a registered body; a list of registered certification bodies is available in Japanese. Additionally, consultation meetings are available for products which require MHLW approval (certain Class II and Class III; all Class IV).

PMDA provides information on standard review timelines (available only in Japanese):

• On the Standard Review Timeline for New Medical Devices.
• On the Standard Review Timeline for Improved Medical Devices (with clinical data).
• On the Standard Review Timeline for Improved Medical Devices (without clinical data).

PMDA’s Profile of Services provides a variety of insights on the agency’s work, including review times for medical devices (in English).

Medical devices that require “Approval of the MHLW” have to first be evaluated for safety and efficacy by the PMDA. Regulatory requirements for individual products to be approved are assessed on a case-by-case basis and answered in the PMDA’s face-to-face consultation meetings (fees applicable).

PMDA offers consultations to give guidance and advice on clinical trials of drugs, medical devices, and cellular and tissue-based products, as well as on data for regulatory submissions. PMDA also provides prior assessment consultations, in which its reviewers evaluate data on the quality, efficacy, and safety of a product in the pre-submission stage and the consultation process constitutes part of the review of the product once the application is submitted.

To achieve realization of innovative drugs, medical devices, and regenerative medical products, PMDA launched the Regulatory Science (RS) Consultations, mainly for universities, research institutions, and venture companies that possess promising “seed-stage” research or technologies. In the consultation, advice will be provided on the tests needed in the early product development stage and the necessary clinical trials, which are considered to play a part in important functions to promote creation of innovative products in Japan.

PMDA also offers a consulting service specific to software as a medical device (SaMD). More information about the service, and application procedures, are found on SaMD Unified Consultation Desk (Comprehensive Medical Device Program Consultation) [in Japanese].

An additional service to consider is MEDISO (Medical Innovation Support Offices), which is sponsored by MHLW. MEDISO provides support for business ventures, academia, and individuals intending to put into practical use medicines, medical devices, and regenerative medicinal products.

In order to market medical devices in Japan, a foreign manufacturer has to obtain approval/certification or submit notification, depending on the classification, pursuant to the PMD Act, through a Japanese Marketing Authorization Holder (J-MAH) or a Japanese manufacturer appointed by such a foreign manufacturer. While PMDA does not provide a specific list of J-MAHs, they do provide links to Japan’s pharmaceutical and medical device manufacture associations, to which a J-MAH must belong.

Japan’s Pharmaceutical Affairs Law requires all forms related to the marketing application to be submitted in Japanese.