Preparation for QMS conformity assessment: From application to issuance of conformity certificate

Table of Contents

1. What is a QMS Conformity Assessment?
2. Types of Assessments: Pre-Approval and Post-Approval
3. Manufacturing Sites and Facilities Subject to Assessment
4. Determination of Document Review vs. On-site Inspection
5. Documents to be Submitted for Application
6. Relationship between ISO 13485 Certification and QMS Ordinance
7. Structure of Assessment Fees
8. Responding to Deficiencies
9. Assessment of Overseas Manufacturing Sites
10. Certificate of Conformity and Renewal
11. Summary

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To obtain PMDA approval or certification from a Registered Certification Body for medical devices, it is necessary not only to review the product itself but also to confirm that the manufacturing and quality management system conforms to Japan's QMS Ordinance. This is the QMS Conformity Assessment.

The QMS Conformity Assessment is a crucial process that affects the feasibility and timing of approval/certification. This article organizes the entire QMS Conformity Assessment system, the differences between pre-approval assessments and periodic assessments, the determination of document review vs. on-site inspection, application documents, the relationship with ISO 13485, handling of overseas manufacturing sites, and how to utilize the Certificate of Conformity, all based on official documents.

*This article provides a general explanation based on the system and notifications available at the time of publication. For actual applications, individual confirmation is necessary as decisions may vary depending on the product category, manufacturing site configuration, product group classification, past assessment results, and the latest notifications.

What is a QMS Conformity Assessment?

The QMS Conformity Assessment is a system to confirm whether the manufacturing and quality management methods for medical devices and in-vitro diagnostic medical devices conform to the QMS Ordinance (MHLW Ordinance No. 169). The assessment is conducted by the PMDA or a Registered Certification Body (RCB), depending on the product category and application route.

The QMS Ordinance has been developed in line with international harmonization with ISO 13485:2016, but it is not entirely identical to ISO 13485. Since it includes requirements based on Japan's Pharmaceuticals and Medical Devices Act (PMD Act) system, even manufacturing sites holding ISO 13485 certification need to separately confirm and be able to demonstrate conformity to Japan's QMS Ordinance.

The purpose of the assessment is not merely a document review, but to confirm that manufacturing and quality management are functioning in practice. It involves not only the preparation of documents but also the operational performance of records, implementation status, internal audits, management reviews, CAPA, and risk management.

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Types of Assessments: Pre-Approval and Post-Approval

QMS Conformity Assessments are categorized into several types based on their timing and legal basis.

Pre-Approval Conformity Assessment

This assessment is conducted when obtaining new approval/certification, partial change approval/certification, manufacturing medical devices for export, or confirming conformity related to a change plan.

It proceeds in parallel with the approval/certification review, and a determination of conformity in the QMS Conformity Assessment is a crucial prerequisite for obtaining approval/certification. Even if the product review is progressing, the timing of approval/certification may be affected if the QMS Conformity Assessment is not completed.

Post-Approval Conformity Assessment / Periodic Conformity Assessment

After obtaining approval/certification, a periodic conformity assessment is generally required every 5 years. For medical devices for export, an assessment is also required every 5 years after the start of manufacturing.

In the case of succession applications or minor change notifications, new QMS Conformity Assessments are generally not required. However, if there are additions or changes to manufacturing sites, significant changes to manufacturing processes, or changes that significantly affect the quality management system, it is necessary to individually confirm whether an additional assessment is required.

Partial Change Conformity Assessment / Additional Assessment

Additional QMS confirmation may be required due to partial changes in approved/certified matters, additions or changes to manufacturing sites, significant changes under the QMS Ordinance, or responses related to change plans. The scope of the assessment is determined based on the content of the changes, manufacturing site configuration, product risk, and past assessment results.

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Manufacturing Sites and Facilities Subject to Assessment

The implementing body and scope of the QMS Conformity Assessment vary depending on the medical device class, the presence of certification standards, the manufacturing site configuration, and product characteristics.

Main Cases Assessed by PMDA

PMDA primarily conducts QMS Conformity Assessments for approved items such as:

• Class IV medical devices
• New medical devices
• Cell and tissue-based medical devices
• Specified biological products
• Items subject to national testing
• Class III and Class II medical devices for which no certification standards exist
• Other medical devices and in-vitro diagnostic medical devices not subject to certification by a Registered Certification Body

Main Cases Assessed by Registered Certification Bodies

Registered Certification Bodies primarily conduct QMS Conformity Assessments for certified items such as:

• Class II medical devices for which certification standards exist
• Some Class III medical devices for which certification standards exist
• In-vitro diagnostic medical devices for which certification standards exist

Therefore, it is not possible to simply categorize "all Class III by PMDA" or "all Class II by Registered Certification Bodies." In practice, it is important to confirm the presence of certification standards and the application route.

Facilities and Scope of Operations Subject to Assessment

The assessment generally targets the primary office of the Marketing Authorization Holder (MAH) and the registered manufacturing sites listed in the approval/certification application. Specifically, facilities performing the following operations are subject to assessment:

• Facilities conducting design and development
• Facilities conducting primary assembly
• Facilities conducting sterilization
• Facilities storing final products
• Departments within the MAH responsible for domestic quality operations and market release decisions

Furthermore, external testing laboratories, external contractors, and facilities involved in packaging, labeling, and storage may also be subject to assessment or confirmation if they have a significant impact on product quality assurance.

In practice, it is necessary to be able to explain the division of responsibilities and management relationships for quality assurance, including design, raw materials, manufacturing, sterilization, testing, storage, and market release decisions, rather than just looking at "individual manufacturing sites."

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Determination of Document Review vs. On-site Inspection

QMS Conformity Assessments are divided into document reviews (assessments primarily based on document review) and on-site inspections (assessments including on-site verification at manufacturing sites, etc.). The determination of which type of assessment will be conducted is not solely based on the applicant's request, but is made by the assessment body based on the applicant's product and facility status.

Overview of Determination Criteria

The assessment body determines whether a document review or an on-site inspection is necessary based on elements such as the following, in accordance with the "QMS Assessment Guidelines" and related notifications:

• Past QMS assessment results
• Time elapsed since the previous assessment
• Scale of the manufacturing site, complexity of the manufacturing process
• Class, risk, and novelty of the applied product
• Scale of changes in the application content
• Presence of MDSAP reports, ISO 13485 certificates, overseas authority assessment results, etc.
• Status of recalls, serious malfunctions, and quality problems

Please note that the QMS Assessment Guidelines may be revised, so it is important to check the latest notifications and administrative communications at the time of application.

Utilization of Assessment Results from Other Countries

In recent years, a system has been established to utilize the results of other assessment bodies from a global harmonization perspective. For example, the following documents are used as reference materials:

• ISO 13485 certificate and audit report
• On-site inspection reports by other assessment bodies conducted at the assessed facility within the past 3 years from the application date
• MDSAP (Medical Device Single Audit Program) report
• Certificates or assessment reports from partner countries based on MOUs, etc.
• Certificates of conformity from foreign authorities

Submitting these documents appropriately may increase the likelihood of the assessment being processed as a document review. However, the presence of an MDSAP report or ISO 13485 certificate does not guarantee that an on-site inspection will be omitted. The final assessment method is determined by the assessment body based on a comprehensive evaluation of the product, facility, past performance, risk information, etc.

Applicant's Request

Applicants can indicate their desired assessment category in the application form, etc. However, the final decision is made by the assessment body. If an application expected to proceed as a document review becomes an on-site inspection, it may require additional document preparation, schedule adjustments, and in some cases, additional fee payments, so prior simulation is important.

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Documents to be Submitted for Application

For a QMS Conformity Assessment application, documents for the application, documents for determining on-site vs. document review, documents for document review, and additional documents for on-site inspection are prepared based on the latest version of the submission document list published and guided by the PMDA or Registered Certification Body.

For QMS Conformity Assessments conducted by the PMDA, please refer to the "QMS Conformity Assessment Services" page and related notifications and documents.

Main Documents Required for Determining On-site vs. Document Review

While it varies depending on the application content, typical documents to prepare include:

• Application form for Medical Device, etc. Conformity Assessment
• Copy of the approval application, certification application, partial change application, etc. for the applied product
• Copy of partial change approval/certification, minor change notification, etc. since the previous assessment
• List of sub-items
• Copy of the Certificate of Conformity for the applied product
• Calculation result from the QMS Conformity Assessment Fee Calculation Tool
• Overview of the manufacturing process for the assessed product
• Overview of activities performed at each assessed facility
• Documents confirming the interrelationship of quality management systems at each facility
• ISO 13485 certificate and audit report
• MDSAP report
• Assessment reports by other assessment bodies
• Certificates or assessment reports from partner countries based on MOUs, etc.
• Certificates of conformity from foreign authorities
• Overview of recalls since the previous assessment, if any
• Declaration of Conformity

When submitting ISO 13485 certificates or overseas authority assessment reports, it is important to organize them to clearly indicate the relevant facility, product category, and scope of application.

Main Documents to be Submitted Additionally after Determination of Document Review

If a document review is determined, the assessment body will request additional documents depending on the product, facility, and process. Typical documents include:

• Quality Manual
• Documents showing the correspondence with the QMS Ordinance
• Key SOPs (Standard Operating Procedures)
• Procedures and records related to design and development
• Procedures and records related to manufacturing process control
• Records of sterilization validation, process validation, etc.
• Procedures and records related to testing and inspection
• Documents related to supplier management and external contractor management
• Internal audit records
• Management review records
• CAPA (Corrective Action and Preventive Action) records
• Records related to complaints, malfunctions, and recall responses
• Risk management records (ISO 14971, etc.)

Additional Actions for On-site Inspection

If an on-site inspection is determined, the assessment officer will notify the specific inspection schedule, required documents, and on-site verification items. On-site inspections involve on-site verification at the manufacturing site, record review, interviews with personnel, and verification of process, equipment, and environmental control.

For overseas manufacturing sites, it is necessary to prepare early, including time differences, travel schedules, interpreters, translated documents, and the availability of local personnel.

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Relationship between ISO 13485 Certification and QMS Ordinance

ISO 13485:2016 is an international standard for QMS for medical devices and is referenced in medical device regulations worldwide. While Japan's QMS Ordinance is harmonized with ISO 13485, having ISO 13485 certification is not synonymous with conforming to Japan's QMS Ordinance.

Matters Requiring Special Confirmation Regarding QMS Ordinance

Even for manufacturing sites with a QMS based on ISO 13485:2016, the following matters need to be confirmed and organized for Japan:

• Duties of the Domestic Quality Assurance Manager: This role is crucial under the QMS Ordinance for appropriately managing quality control operations in Japan.
• Market Release Decision: The system for deciding market release for products destined for Japan and its records must be clearly defined.
• Division of Responsibilities between MAH and Manufacturing Site: When overseas manufacturing sites are involved, it is important to be able to explain the division of roles among the MAH, designated MAH, foreign manufacturer, manufacturing site, and external contractors.
• Linkage with GVP Ordinance: Information sharing with the post-market safety management system and sharing of malfunction, complaint, and recall information are practically important.
• Document and Record Retention Periods: It is necessary to confirm retention periods based on Japan's QMS Ordinance, etc.
• Japanese Explanations and Inquiry Responses: While it is not always mandatory to translate all procedures into Japanese, it is practically important to have a system in place to explain assessment documents, summaries, inquiry responses, and important records in Japanese.

Among the three key roles under the PMD Act (General Marketing Supervisor, Domestic Quality Assurance Manager, and Safety Management Supervisor), the General Marketing Supervisor and Safety Management Supervisor are requirements based on the PMD Act itself and the GVP Ordinance, etc. In relation to the QMS Ordinance, the duties of the Domestic Quality Assurance Manager and the operation of market release decisions are particularly important.

Overview of Document and Record Retention Periods

The retention periods for documents and records at MAHs, etc., vary depending on the product category and type of record. The general guidelines are as follows:

For specified biological products and products derived from blood products, longer retention periods than for general medical devices may be required from the perspective of traceability of infection risks. For applicable products, it is necessary to check not only the QMS Ordinance but also the PMD Act, related ordinances, enforcement notifications, and GVP/GPSP-related documents.

Importance of Gap Analysis

When a manufacturing site with ISO 13485 certification aims to enter the Japanese market, it should first conduct a gap analysis between ISO 13485 and Japan's QMS Ordinance to identify procedures, records, division of responsibilities, and inquiry response documents that need to be additionally prepared.

Failure to conduct a gap analysis can lead to an increase in deficiencies identified during the QMS Conformity Assessment and delays in approval/certification timing.

Utilization of MDSAP

MDSAP (Medical Device Single Audit Program) is a medical device QMS audit program that considers regulatory requirements from multiple countries. Japan also utilizes MDSAP, and MDSAP reports are useful documents in QMS Conformity Assessments.

Appropriate submission of MDSAP reports may increase the likelihood of the assessment being processed as a document review, potentially reducing the assessment burden. However, obtaining MDSAP does not guarantee that an on-site inspection will be omitted; the final decision is made by the assessment body.

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Structure of Assessment Fees

The fees for QMS Conformity Assessments are calculated based on the application content, assessed facilities, manufacturing processes, assessment methods, presence of overseas manufacturing sites, etc. For assessments conducted by the PMDA, the QMS Conformity Assessment Fee Calculation Tool is used for calculation.

Main Fee Items

While fees vary for each individual case, they are mainly composed of the following elements:

• Basic fee for the MAH, etc.
• Fees corresponding to the assessed processes, such as design, primary assembly, sterilization, and final product storage
• Fees per facility when multiple manufacturing sites are involved
• Additional fees for optional items
• Additional fees if a document review becomes an on-site inspection
• Additional costs and coordination burden for overseas on-site inspections

For products with multiple manufacturing sites, or products involving sterilization, design and development, or complex processes, the total fees may be substantial. It is important to simulate the fees with the calculation tool before application and incorporate them into the budget and schedule.

Confirmation of Optional Items

If there are processes, technologies, or product characteristics that fall under optional items, additional assessments may be required. For example, for sterilization validation, computerized systems, specified biological product-related processes, or products using special materials/technologies, more detailed verification may be required than usual.

Fees may be revised, so it is necessary to confirm with the latest version of the tool/notification at the time of application, rather than using amounts stated in articles or past cases.

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Responding to Deficiencies

If deficiencies are identified during the QMS Conformity Assessment, the assessment body will issue a "QMS Assessment Deficiency Report". Deficiencies are ranked according to their severity, and the response deadline and method vary depending on the rank.

Main Rank Classifications

While the actual evaluation categories and expressions are based on the QMS Assessment Guidelines, etc., in practice, the weight of the response changes based on the following perspectives:

• Major Deficiency: A deficiency that could directly affect the issuance of a Certificate of Conformity or a conformity determination. Confirmation after correction may be required.
• Medium Deficiency: A deficiency for which a corrective action plan or improvement results are required to be submitted within a deadline.
• Minor Deficiency: A deficiency that requires improvement in the quality system but is not directly linked to a major quality risk.

Submission of Improvement Documents

The assessed party must submit one of the following documents within the deadline stated in the deficiency report:

• QMS Deficiency Improvement Report: If improvements have already been completed.
• QMS Deficiency Improvement Plan: If improvements require a certain period.

For corrective actions, simply stating "procedures have been revised" is insufficient. It is important to be able to consistently explain the root cause of the deficiency, corrective actions, preventive actions, confirmation of impact, responsible person, completion deadline, training, and effectiveness verification.

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Assessment of Overseas Manufacturing Sites

Even when overseas manufacturing sites are involved, it is necessary to demonstrate conformity to the QMS Ordinance for products destined for Japan. Assessments of overseas manufacturing sites may be conducted as document reviews, but on-site inspections may also be conducted as needed.

Practical Points for Overseas Manufacturing Sites

Interpreter and Translation System

During on-site inspections, there may be situations where explanations and documentation in Japanese are required for communication with the PMDA or Registered Certification Body, inquiry responses, and responses to deficiencies. If local manufacturing site personnel cannot communicate in Japanese, prepare English documents, Japanese translations, interpreters, and pre-briefing materials.

Coordination of Travel Schedule

If an overseas on-site inspection is conducted, it is necessary to coordinate early the travel schedule of the inspectors, operating days of the local manufacturing site, availability of key personnel, time differences, holidays, and visa/entry procedures.

Establishment of Local System

Ensure that personnel who can answer questions, such as the manufacturing site manager, quality assurance manager, manufacturing manager, design and development manager, and testing and inspection manager, are available. It is also effective to rehearse in advance to ensure that explanations of manufacturing processes and records can be provided in accordance with the requirements of the QMS Ordinance.

Utilization of MDSAP and Overseas Authority Assessment Results

If MDSAP reports, ISO 13485 certificates, overseas authority assessment results, or certificates based on MOUs, etc., are available, they may be used as reference materials for determining the assessment category or for deciding to conduct a document review. Confirm in advance that the scope of application, facility, and product category match the applied product.

Explanation Materials for Japanese Requirements

For overseas manufacturing sites, it is necessary to explain in advance Japan's QMS Ordinance, domestic quality operations, market release decisions, division of responsibilities with the MAH, and the flow of inquiry responses. Even manufacturing sites with ISO 13485 certification may not understand Japan's unique operations, so prior gap analysis is important.

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Certificate of Conformity and Renewal

As a result of the QMS Conformity Assessment, if conformity to the QMS Ordinance is confirmed, the assessment body will issue a Certificate of Conformity.

Positioning of the Certificate of Conformity

The Certificate of Conformity is an important document that indicates that conformity to the QMS Ordinance has been confirmed in relation to specific products, product group classifications, manufacturing sites, manufacturing processes, etc.

QMS Conformity Assessments related to approval/certification applications are, in principle, considered for each applied product, unless an assessment exemption is granted. On the other hand, if a valid Certificate of Conformity is held, it may be utilized for survey exemption/rationalization in approval/certification applications for other products or periodic conformity assessments, within the scope where the combination of product group classification, registered manufacturing site, and manufacturing process matches.

Therefore, it is important not only to understand it as "per product" but also to manage the product group classification, registered manufacturing site, manufacturing process, and validity period of the Certificate of Conformity as a set.

Rationalization of Assessments within the Same Product Group Classification

When developing multiple products within the same product group classification, there is a possibility of strategically utilizing a valid Certificate of Conformity. Especially when multiple products are handled at the same manufacturing site, with the same processes, and the same quality system, there may be room to reduce the assessment burden for additional applications or renewals.

However, if there are additions of manufacturing sites, additions of sterilization processes, changes in design and development facilities, differences in product group classifications, or if MDSAP or ISO certification is outside the scope of application, the Certificate of Conformity may not be directly utilized.

Validity Period of the Certificate of Conformity

The validity period of the Certificate of Conformity is generally 5 years. It is necessary to undergo a periodic conformity assessment before the expiration of the period to continuously maintain conformity.

In the case of succession applications or minor change notifications, new QMS Conformity Assessments are generally not required. However, if there are changes affecting manufacturing and quality management, individual confirmation is necessary.

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Summary

Key points to consider for QMS Conformity Assessments are as follows:

1. Crucial process directly linked to approval/certification acquisition: A determination of conformity in the QMS Conformity Assessment significantly impacts the timing of approval/certification acquisition.
2. Accurately identify the scope of PMDA and Registered Certification Bodies: Confirm not only the class but also the presence of certification standards, application route, and product characteristics.
3. Gap analysis between ISO 13485 and QMS Ordinance is important: ISO certification alone does not automatically prove conformity to Japanese requirements.
4. Utilize MDSAP and overseas authority assessment results: These can be used as reference materials for determining document review or reducing the assessment burden, but they do not guarantee the omission of on-site inspections.
5. Organize the quality assurance system, including manufacturing sites and external contractors: Clearly define the division of responsibilities for design, assembly, sterilization, testing, storage, and market release decisions.
6. Manage the Certificate of Conformity as a set with product group classification, manufacturing site, and process: A valid Certificate of Conformity can be utilized for assessment rationalization for other products or at the time of renewal.
7. Plan for periodic assessments every 5 years: Manage the validity period of the Certificate of Conformity and prepare for continuous quality system maintenance and renewal assessments.
8. The quality of responses to deficiencies affects the schedule: In improvement reports and improvement plans, clearly state the root cause, corrective actions, preventive actions, and effectiveness verification.

The QMS Conformity Assessment confirms the quality system that supports product efficacy and safety, and it is directly linked to the success of the overall regulatory strategy. By integrally planning the QMS system design, gap analysis with ISO 13485, utilization of MDSAP, management of manufacturing sites and external contractors, and utilization of the Certificate of Conformity from the stage of aiming for approval/certification, the assessment burden and the risk of approval delays can be minimized.