Japan stands as the world’s second-biggest medical device market, after the US. The Japanese medical device market is expected to reach from $54.5 billion in 2018 to $74.7 billion in 2025, growing at a compound annual growth rate (CAGR) of 4.6% according to GlobalData,

The rapidly aging Japanese population, an increasing number of patients with chronic and lifestyle diseases, universal health insurance coverage, and regulatory measures are assumed to drive the Japanese medical device market.

The Japanese government has taken new initiatives to streamline the regulatory approval review process and accelerate the launch of innovative medical products.

The Ministry of Health, Labor, and Welfare (MHLW) has taken several steps and made to improve the transparency of the approval review system to accomplish a quick review process, which is equivalent to, or faster than that of North American and European markets.



Which is the regulatory body for medical devices?

Pharmaceutical Medical Devices Agency (PMDA) is an independent administrative agency that works with the MHLW to ensure the safety and quality of drugs and medical devices in Japan and is the technical arm of the MHLW

The Ministry of Health, Labor, and Welfare (MHLW) is Japan’s primary regulatory body for creating and implementing safety standards for medical devices and drugs and within the MHLW, the Pharmaceutical and Food Safety Bureau is in charge of pharmaceutical and medical device regulatory policy.

The PMDA’s handles 

  • Approval review of medical devices
  • QMS/GLP/GCP inspection
  • Collection and analysis of Adverse Event Reports

Medical Devices are required to undergo regulatory approval based on the Pharmaceuticals and Medical Devices Law (PMDL) in order to enter the Japan market


Click here to learn about the drug approval process in Japan


How can foreign manufacturer market their medical device in Japan?

Foreign companies who intend to manufacture drugs, quasi-drugs, active pharmaceutical ingredients (APIs) or medical devices overseas and import them into Japan must be registered with the Ministry of Health, Labor and Welfare (MHLW)

  • This process is known as Toroku, or Foreign Manufacturer Registration (FMR)
  • It is a separate process from the product registration process and is required for obtaining product registration approval.

Japan PMDA requirements & approval process for medical devices

Based on the category & class to which the medical device belongs, the requirements, regulatory, and process flow varies. so let’s discuss each class of medical device one by one in detail

Japan Medical Device Nomenclature (JMDN codes)

  • A database of generic medical device descriptions with associated Japan Medical Device Nomenclature (JMDN) codes is maintained by MHLW.
  • JMDN system is similar to the Global Medical Device Nomenclature (GMDN) system or the US FDA system.
  • If the medical device code does not exist in this database, then products must undergo a new registration pathway based on the class to which it belongs.

Medical devices classification

  • Class I Devices: General Medical Devices 
    • The risk to patients in the event of a malfunction is regarded as almost negligible (e.g. s-ray Film)
  • Class II Devices: Controlled Medical Devices
    • The risk to patients in the event of a malfunction is regarded as relatively low (e.g. MRI, digestive catheters)
  • Class III Devices: Specially Controlled Medical Devices
    • The risk to patients in the event of a malfunction is regarded as relatively high (e.g. artificial bones, dialyzer)
  • Class IV Devices: Specially Controlled Medical Devices 
    • The device is highly invasive with potential fatal risk to patients (e.g. pacemaker, artificial heart valves)

Regulatory for Class I Devices

The approval process of Class I Devices is called as Todokede

Requirements for Class I devices

Here are the list of requirements for approval of Class I devices

  1. Category
  2. Generic name
  3. Proprietary name
  4. Intended use
  5. Shape, structure, and principle, including the following items where applicable:
    • Color photo
    • Size and weight
    • Components and accessories
    • Electrical rating
    • Block diagram
    • When describing liquids, state clearly whether it is in the form of solution (clear), suspension, emulsion, etc.
  6. Raw materials
    • Quantity (weight, weight percent)
    • Specifications (Standard number; JIS, ISO, ASTM, if applicable)
    • Each raw material’s specification (Chemical and/or physical characteristics, etc.)
  7. Product specifications (defined according to each product)
    • Ex. Appearance, characteristics, etc.
  8. Directions for use
  9. Manufacturer(s) and manufacturing method:
    • Flow chart from raw material acceptance to packaging, labeling, and storage for shipment
    • Name and address of entity responsible design and development of the product
    • Name and address of the manufacturer(s) of each manufacturing process including a manufacturer who does only labeling, packaging and storage
    • License number or Foreign Manufacturer Registration (FMR) number with category of license or accreditation (non-sterile medical devices, sterile medical devices or packaging/labeling
  10. Storage conditions and shelf life
  11. Notes including those on the following items where applicable:
    • Single-use or not
    • Usage of components of other medical devices
  12. Package insert (directions for use) draft
  13. Color photo (digital image)

Approval process

  • The MAH only needs to file a notification Todokede to the PMDA with no assessment by the PMDA.
  • The sponsor must file a premarket submission to the PMDA and all documents must be in Japanese. 
  • Sponsor shall appoint a MAH in Japan
  • Japanese manufacturers must register domestic facilities with local prefectural authorities. Foreign manufacturers must submit a Foreign Manufacturer Registration (FMR) application to the Pharmaceuticals and Medical Devices Agency (PMDA).
  • Implement Quality Management System (QMS) that complies with the PMD Act and Ministry of Health, Labour and Welfare (MHLW)
  • A reimbursement application should be filed with the Economic Affairs Division of MHLW if applicable.
  • A sponsor can  now begin marketing your device in Japan

Process flow

Regulatory for Class II Devices

The approval process of Class II Devices is called as Ninsho

Requirements for Class II devices

  1. Category
  2. Generic name
  3. Proprietary name
  4. Intended use
  5. Shape, structure, and principle, including the following items where applicable:
    • Color photo
    • Size and weight
    • Components and accessories
    • Electrical rating
    • Block diagram
    • When describing liquids, state clearly whether it is in the form of solution (clear), suspension, emulsion, etc.
  6. Raw materials and their specifications, including the following items where applicable:
    • Quantity (weight, weight percent)
    • Molecular weights
    • Chemical name and /or structural formula
    • CAS No.
    • The purpose of its formulation
    • Name of an official standard (EC, JIS, ISO, ASTM, JP, USO, EP, etc,)
    • Vendors name
    • Specifications (chemical and/or physical characteristics, etc.)
  7. Product specifications and test methods (defined according to each product)
    • Ex. Appearance, characteristics, biocompatibility, etc.
  8. Directions for use
  9. Manufacturer and manufacturing method:
    • Flow chart from raw material acceptance to packaging, labeling, and storage for shipment
    • Name and address of entity responsible design and development of the product
    • Name and address of the manufacturer(s) of each manufacturing process including a manufacturer who does only labeling, packaging and storage
    • License number or Foreign Manufacturer Registration (FMR) number with category of license or accreditation (non-sterile medical devices, sterile medical devices or packaging/labeling
  10. Storage conditions and shelf life
  11. Notes including those on the following items where applicable:
    • Single-use or not
    • Use or non-use of new raw materials
    • Use or non-use of biological materials
    • Use or non-use of genetic recombination method
  12. Package insert (directions for use) draft
  13. Color photo (digital image)

Approval process

  • Class II devices specified as designated controlled devices with certification standards are subject to Ninsho. 
  • The MAH needs to file a Ninsho application with a notarized body to obtain their certification.
  • Certain Class II devices require both a review by the PMDA  and a Shonin approval from the MHLW. 
  • Class II devices that do not meet the MHLW’s approval certification standards must file a Shonin application that is reviewed by the PMDA and subsequently by the MHLW
  • The sponsor shall appoint Marketing Authorization Holder (MAH or D-MAH) to manage your device registration in Japan.
  • Japanese manufacturers must register domestic facilities with local prefectural authorities. Foreign manufacturers must submit a Foreign Manufacturer Registration (FMR) application to the Pharmaceuticals and Medical Devices Agency (PMDA).
  • Implement Quality Management System (QMS) that complies with the PMD Act and Ministry of Health, Labour and Welfare (MHLW) Ordinance #169. Ordinance #169 is based on ISO 13485. 
  • Submit a Pre-Market Certification application to a Registered Certified Body (RCB) authorized to issue certifications. All documents must be in Japanese.
  • QMS audit by Registered Certification Body (RCB) and QMS certificate will be issued by the PMDA or Registered Certification Body.
  • The pre-Market Certificate is issued by RCB.
  • A reimbursement application should be filed with the Economic Affairs Division of MHLW if applicable. 
  • Sponsor may now begin marketing medical device in Japan

Timeline

Time for review and approval takes about 4-9 months

Process flow

Regulatory for Class III & Class IV Devices

The approval process of Class III and Class IV Devices is called as Shonin

Requirements for Class III & IV devices

Application form

  1. Medical Device Category
    • JMDN Code and Class I, II, III, or IV
    • If a single product belongs to multiple categories, select the category of the medical device with the highest risk class
  2. Name (General Nomenclature/Trade Name)
  3. Intended Use and Efficacy or Effects
    • Target patient population and disease, usage conditions, anticipated effects, etc.
  4. Shape, Structure, and Principle
  5. Raw Materials or Components
  6. Product Specifications
    • Specifications ensuring the quality, safety, efficacy of the device
  7. Operation or Usage Method
  8. Manufacturing Method
  9. Storage Method and Shelf Life
  10. Manufacturing Site of the Product to be Marketed
  11. Manufacturing Site of Raw Materials
  12. Remarks
    • Medical device classification
    • Package insert
    • MAH license number of the applicant, etc.

Attachments

  1. Origin or history until the discovery and regulatory status in foreign countries
    • Materials regarding the background of origin or development
    • Status of use overseas
    • Comparison with similar medical devices
  2. Reason/background for specification
    1. Materials regarding specifications and set of specifications
  3. Stability & Endurance
    • Materials regarding stability and durability
  4. Document for compatibility with Essential Principle – Conformity to Essential Requirements (Article 41, Paragraph 3 of the PAL).
    • Materials regarding declarations of conformity to Essential Requirements
    • Materials regarding conformity to Essential Requirements
  5. Performance
    • Materials regarding tests supporting performance and safety
    • Materials regarding tests supporting efficacy
    • Materials regarding tests methods of use
  6. Risk Analysis
    • Materials regarding systems for implementing risk analysis
    • Materials regarding important hazards
  7. Manufacturing (Process, QC, Sterilization)
    • Materials regarding manufacturing processes and manufacturing facilities
    • Materials regarding sterilization methods
    • Materials regarding quality control
  8. Clinical Data
  9. Materials regarding test results of clinical trials
  10. Investigation plans (proposals) regarding records of use, etc. of new medical devices.

Click here to learn about the clinical trial approval process in Japan


Summary of Technical Documentation (STED)

  1. A general overview of the product
    • Overview of the product requiring color photos for confirming the outer appearance of the product
    • Background of origin or discovery and history of the development
    • Status of use in foreign countries
  2. Essential requirements and conformity to the essential requirements
    • List of reference standards
    • Essential requirements and evidence of conformity using the checklist for conformity to the essential requirements
  3. Device description
    • General information
    • Raw materials
    • Product specifications describing why the established product specifications are necessary and sufficient for securing the effectiveness, safety, and quality of the product.
    • Storage method and shelf life
    • Comparison with similar medical devices
  4. Overview of design verification and validation documents
    • General Information
    • Declaration of Conformity to Standards
    • Overview of validation of design
    • Test to support device safety
    • Physical and chemical properties
    • Electrical safety and electromagnetic compatibility
    • Biological safety
    • Radiation safety
    • Mechanical safety
    • Stability and durability
    • Tests to support performance
    • Tests to support the efficacy
    • Tests to support usage method
  5. Test results of clinical trials
    • Clinical trial results
    • Summary of clinical trial results
    • Other(s)
  6. Labeling
    • Instructions for Use (Draft)
    • Label (Draft)
  7. Risk Analysis
    • System for implementing risk analysis
    • Important hazards
  8. Manufacturing Information
    • Information on manufacturing process and manufacturing facilities
    • Sterilization method
    • Quality control
  9. List of supporting data and attachments
  10. Ex. Certificate of conformity, test reports, etc

Process

  • This process also applies to Class II Controlled medical devices
  • The sponsor shall appoint a Marketing Authorization Holder (MAH or D-MAH) to manage the medical device registration and MAH or D-MAH will control the medical device registration.
  • An application is submitted to the PMDA (from MAH)
  • PMDA reviews the application based on the category for the summary of Technical Documentation (STED) and attachments
  • Japanese manufacturers must register domestic facilities with local prefectural authorities. Foreign manufacturers must submit a Foreign Manufacturer Registration (FMR) application to the Pharmaceuticals and Medical Devices Agency (PMDA).
  • Then PMDA conducts a QMS conformity assessment inspection at the manufacturing site. 
  • The sponsor shall prepare the Pre-Market Approval application as well as registration dossier in Summary Technical Document (STED) format. Submit documents to PMDA and all documents must be in Japanese.
  • QMS audit is conducted by PMDA. On-site audits are typically required for “new” devices with no existing JMDN code, Class IV devices, and those requiring clinical investigations.
  • QMS certificate will be issued by the PMDA
  • The pre-Market Approval certificate is issued by MHLW
  • A reimbursement application should be filed with the Economic Affairs Division of MHLW if applicable.
  • The sponsor may now begin marketing medical device in Japan.
  • During the renewal of a business license a Periodic QMS conformity assessment inspection is conducted as part of the post-approval inspection process.

Time for review and approval

  • Class III – Application with approval standard, without clinical trial takes about 9-12 months
  • Class III – Application without approval standard, without clinical trial takes about 12-15 months
  • Class III – Application (improved) without approval standard, with clinical trial takes about 16 months
  • Class III – Application (new) without approval standard, with the clinical trial, takes about 18 months

Process flow

What are the various application categories?

  • New medical devices (require clinical trial data required)
    • New medical devices that are clearly different from those with already approved in Japan in terms of structure, principle, method of use, efficacy, and/or performance. GCP clinical trial data must be provided to prove clinical safety and efficacy.
  • Improved medical devices (require clinical trial data)
    • This category is for medical devices that 
      • Do not have an applicable approval standard or do not meet the requirements of the approval standard
      • Cannot be proven to be “me-too” devices
      • Are not regarded as new medical devices (refer to the section above) and 
      • Those which cannot be proven safe and effective with non-clinical data
  • Improved medical devices (doesnot require clinical trial data)
    • This category is for those 
      • That does not have an applicable approval standard or do not meet the requirements of the approval standard; 
      • Which cannot be proven to be “me-too” devices 
      • Those which are not regarded as new medical devices and 
      • Those that can be proven safe and effective with non-clinical data.
  • Me-too medical devices (doesn’t require clinical trial data)
    • This category is for those medical devices regarded as the “me-too” type that 
      • That does not have an applicable approval standard or does not meet the requirements of the approval standard; 
      • Which are not regarded as new medical devices or improved medical devices and
      • Those which can be proven safe and effective with non-clinical data.
  • Me-too medical devices (doesn’t require clinical trial data and compliant with approval standards)
    • This category is for medical devices that are regarded as the “me-too” type that 
      • Which have an applicable approval standard and meet the requirements of the approval standard; and, 
      • That can be proven compliant to the approved standard.

Medical device registration expiration and renewal

  • Medical device registration doesn’t expire, however, Quality Management System (QMS) certificates shall be renewed every 5 years, and should be processed 6 months prior expiration.
  • Pre-Market Certification applications may also be subject to annual surveillance audits.

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References

  1. https://drug-dev.com/japans-medical-device-market-set-to-reach-74-7-billion-in-2025/
  2. https://www.emergobyul.com/resources/japan-process-chart
  3. https://www.pacificbridgemedical.com/regulatory-services/medical-device/product-registration/japan/