Japan’s medical device regulatory landscape underwent a significant transformation with the revision of its Quality Management System (QMS) requirements under the Pharmaceutical and Medical Device Act (PMD Act) in 2015. The updated QMS ordinance introduced new inspection types, registration requirements, and harmonization with international standards, notably ISO 13485. This article provides an overview of the updated QMS regulations for medical devices and in-vitro diagnostics (IVDs) in Japan, based on the latest guidance from the Pharmaceuticals and Medical Devices Agency (PMDA).
Licensing and Registration: Foundations of Compliance
To market medical devices in Japan, companies must comply with three primary regulatory requirements:
- Marketing License – Issued to Marketing Authorization Holders (MAHs), this license is mandatory for companies marketing medical devices or IVDs in Japan. MAHs must be based in Japan and are responsible for ensuring compliance with QMS across all manufacturing sites.
- Manufacturing Site Registration (Toroku) – Registration is required for sites performing key manufacturing processes such as design, assembly, sterilization, and domestic distribution.
- Marketing Approval (Shonin) – Necessary for launching new devices or modifying existing approvals, marketing approval must be accompanied by a QMS inspection application. QMS inspections are required every five years to maintain marketing approval.
Types of QMS Inspections
Japan’s QMS inspections ensure that medical devices and IVDs are manufactured in compliance with regulatory and quality standards. The PMDA and registered certification bodies (RCBs) conduct four types of inspections:
- Pre-Approval Inspection
Required before initial marketing approval, this inspection verifies that the MAH and relevant manufacturing sites meet QMS requirements for the product family. It ensures readiness to produce the device in line with approved specifications.
- Pre-Partial Change Approval Inspection
Conducted when an approved device undergoes significant changes (e.g., in design or manufacturing process). The inspection focuses on QMS aspects affected by the proposed modification.
- Periodic Post-Approval Inspection
Performed every five years after marketing approval to confirm continued QMS compliance. It applies to both the MAH and manufacturing sites.
- Additional Inspections
Triggered by specific product risks or technologies (e.g., biologics, nanomaterials). These inspections provide additional scrutiny where needed for public health.
Inspection Authority
- PMDA inspects higher-risk products such as class IV medical devices and Class II and III devices that are not covered by Certification Standards (CS)
- Registered Certification Bodies (RCBs) inspect lower-risk Class II/III devices covered by CS.
Scope of Manufacturing Site Registration and Inspection
The following manufacturing site types must be registered if they perform core manufacturing processes:
- Design Facilities – Sites responsible for design and development.
- Main Assembling Plants – Sites handling final product realization.
- Sterilizers – Required only for sterile devices.
- Domestic Distribution Centers – Sites involved in storage and final product release in Japan.
Manufacturers must register these sites prior to any QMS inspection. Unlike the previous licensing system, the revised process eliminates the need for Building and Facility Regulation (BFR) conformity, streamlining the application process.
Product Families and Inspection Scope
QMS inspections are conducted based on “product families,” which group together devices with similar characteristics and manufacturing processes. For example:
- Class IV Families – Defined by the Japanese original definition (e.g., stents, pacemakers).
- Class II/III Families – Aligned with NBOG BPG 2009-3 definitions (e.g., non-active instruments, dental devices). NBOG BPG 2009-3, titled “Guideline for Designating Authorities to Define the Notification Scope of a Notified Body Conducting Medical Devices Assessment”, was issued by the Notified Body Operations Group (NBOG).
Exceptions apply for high-risk or unique products not categorized under any family. These require inspection per individual product or generic name.
QMS Inspection Process
The QMS inspection process consists of several steps:
- Application Submission: Companies must provide ISO 13485 certificates, manufacturing process flows, organizational charts, product lists, and quality control documentation.
- Inspection Type Determination: Based on a risk assessment, the PMDA decides whether to conduct an on-site or desktop inspection.
- Inspection Execution: Inspections follow a standardized timeline and procedures.
- Conformity Assessment: The PMDA evaluates findings and grades nonconformities.
On-Site Inspections
On-site inspections typically last 2–4 days and include:
- Opening meetings and company presentations
- Facility tours
- Review of documentation
- Interviews with staff
- Evaluation of CAPA (Corrective and Preventive Actions), design controls, risk management, and quality assurance processes
Inspectors issue a findings report, to which companies must respond with an improvement plan. If deemed acceptable, compliance is certified.
Desktop Inspections
Desktop inspections involve reviewing documentation remotely and are more likely when:
- ISO 13485 certificates are current (within 3 years)
- The company has recent inspection reports from trusted regulatory authorities (e.g., US FDA, EU, Australia, Canada)
- No serious prior nonconformities exist
However, the PMDA may escalate a desktop inspection to an on-site one if documentation is missing or inadequate.
Conformity Assessment and Grading
The PMDA uses a graded system to assess inspection findings:
- Grade 1 – Minor issues; generally conforming
- Grades 2–3 – Moderate issues; require further confirmation of effectiveness of corrective actions
- Grade 4 or Higher – Major deficiencies; likely nonconforming
Assessment outcomes depend on the seriousness and recurrence of the nonconformity, the impact on QMS processes, and whether the issue was direct or indirect.
Final Assessment and Impact on MAHs
If any registered manufacturing site is deemed nonconforming, the MAH’s application is also considered nonconforming. Thus, the MAH must ensure all sites under its purview maintain QMS compliance at all times.
Documentation Requirements
For desktop inspections, the following documents must be submitted:
- Facility layout of the registered manufacturer building (location map). Not necessary for a design facility and MAH(DMAH).
- Floor plan and list of equipment for manufacturing and inspection. Not necessary for a design facility and MAH(DMAH).
- Organization chart.
- Quality manual
- List of controlled SOP documents identified with QMS.
- Seihin Hyojun Sho (Standard Product Profile) of the product. Ex.: Outline of DMR.
- Outline of the product. Ex.: Package insert/IFU
- Implementation status of the validation of manufacturing and sterilization process.
- Documents of self-inspection performed about quality and safety of MD/IVDs in case biologically derived raw materials are used.
- The procedure of reporting adverse events from Registered manufacturer to MAH(DMAH)
- Self-Declaration of ability of the domestic quality assurance manager
- The operating procedures of the domestic quality assurance manager
- Quality agreement between MAH(DMAH) and Registered manufacturer
- Procedures for handling notifications from repairers and second-hand product dealers or leasers, and for ensuring quality at medical equipment dealers or leasers
Compliance Certification and Reporting
Upon successful inspection and conformity assessment, the PMDA issues a QMS Compliance Certification, which details the inspection type, results, and certification status for each manufacturing site.
A summary report is also compiled and includes:
- MAH and manufacturing site information
- Inspection scope and findings
- Final conformity status
This report is sent to the MAH and becomes part of the regulatory dossier for continued market access.
Conclusion
For companies seeking to enter or maintain their presence in the Japanese market, a clear understanding of QMS inspection types, documentation requirements, and the role of MAHs is essential. Proactive compliance with the QMS ordinance not only ensures regulatory approval but also reinforces a company’s commitment to quality and safety in one of the world’s most sophisticated healthcare markets.
Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)
Mr. Gross founded PBM in 1988 and has helped hundreds of medical companies with regulatory and business development issues in Asia. He is recognized nationally and internationally as a leader in the Asian medical markets. Mr. Gross has a BA degree, Phi Beta Kappa, from the University of Pennsylvania and an MBA from Columbia University.