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Key Strategies for Successfully Passing NMPA Inspections for Medical Device Manufacturers | Part 4. Verification of the QMS for Medical Device Registration

Part 4. Verification of the QMS for Medical Device Registration (Manufacturer/R&D Center/Outsourced Manufacturer) based on Announcement No. 50 of 2022, "Guidelines for Inspection of the Quality Management System for Medical Device Registration"

Our previous blog post was dedicated to summarizing the necessary preparation steps for NMPA inspections. We highlighted that medical device manufacturers could improve their chances of passing the inspection by undertaking a comprehensive preparation, which entails understanding the regulations, performing an internal audit, reviewing documentation, conducting a mock inspection, training personnel, and so on. 

One key step for entering the Chinese market is understanding the regulatory requirements applicable to the medical device in scope. 

This blog post aims to provide a comprehensive review and aims to emphasize the crucial aspects of the NMPA Announcement on Issuing the Guidelines for Inspection of the Quality Management System (QMS) for Medical Device Registration (2022 No. 50). The Announcement No. 50 was issued and implemented on October 10, 2022, which replaced the NMPA Announcement on "Issuing the Guidelines for the Inspection of the Quality Management System for Medical Device Registration" (2020 No. 19). 
This guideline applies to the on-site verification of the registration QMS carried out by the medical device regulatory authorities for Class II and Class III medical devices and outlines the basic requirements for the registration of medical devices. 

  • The applicant is required to establish a QMS that complies with Good Manufacturing Practice (GMP) for Medical Devices based on scientific knowledge, experience, and risk management principles and should ensure the authenticity, accuracy, and traceability of process data throughout the device's life cycle. 
  • The verification of the QMS should focus on design, development, procurement, production management, and quality control, and it should be comprehensive and objective. 
  • The applicant's QMS and capabilities should also be verified through self-inspection reports. 
  • Suppose the applicant entrusts (outsources) other enterprises with design, development, or production activities. In that case, the verification scope should cover these activities, and extended inspections may be conducted on other units involved in the research, development, and production of medical devices if necessary.

Each section of the guideline covers a specific aspect of QMS and provides detailed requirements and procedures to ensure compliance with quality standards in developing, producing, and controlling medical devices.

The structure of the guideline can be summarized as follows:

Quality Management System Principles 
Applicants are required to establish a comprehensive QMS that encompasses design, production, quality control, release review, commissioned production, clinical evaluation, and self-inspection while also implementing a risk management system to evaluate quality risks and ensure product quality.

Institutions and Personnel
The applicant must establish a well-defined organizational structure with clear departmental responsibilities, ensuring a reasonable and traceable design, development, and technology transfer process. Adequate personnel, including R&D, production, quality control, and key personnel, with appropriate knowledge and skills for the registered products, should be assigned, and the quality inspection department should have a sufficient number of qualified inspection personnel for self-inspection reports.

Plant, facilities, and equipment
The applicant must have appropriate plants, facilities, and equipment for the production of registered products, including designated facilities for design and development, and the production equipment and inspection instruments should meet the quality control requirements of the products, with proper documentation of use and evidence of product realization activities.

File/Document Management
The applicant must establish and maintain comprehensive document management for their registered products, including QMS documents, technical files, and data records, to ensure traceability and accuracy of activities throughout the product lifecycle. 
An important aspect emphasized in this section is the need to maintain auxiliary records during the design and development phase, including material collection and instrument use records. Additionally, it highlights the significance of effectively managing clinical trial documents in accordance with specific guidelines.

Design and Development
This section emphasizes the importance of comprehensive design and development documentation, including traceability of previous activities, adherence to input requirements, design verification and validation, clinical trial management, design changes, and commissioned research and development activities. It covers various types of medical devices:
- non-active devices, 
- active devices, 
- medical devices of animal origin, and 
- in-vitro diagnostic reagents. 
Each type has specific requirements related to raw materials, biocompatibility, sterilization, hazard protection, animal species, geographical origin, and research process compliance.

Purchasing
This section highlights the importance of establishing procurement control procedures to ensure that purchased items meet specified requirements, verifying the legal origin of raw materials, aligning purchase timing and quantity with production needs, maintaining accurate purchase records, and ensuring stability and consistency of key materials for in-vitro diagnostic reagents after design and shaping.

Production
The production process shall comply with GMP for Medical Devices during all production activities for registered inspection products and clinical trial products, including the preparation of production process documents, adherence to production and record requirements, and specific considerations for the production of in-vitro diagnostic reagents, such as ensuring stable concentrations of bioactive materials and meeting material balance requirements.

Quality Control
This section focuses on establishing quality control procedures, incorporating self-inspection into the QMS, maintaining inspection equipment and records, formulating inspection procedures based on scientific principles, keeping inspection records, establishing product release procedures, ensuring traceability for in-vitro diagnostic reagents, and retaining samples of registered inspection products and clinical trial products for inspection and evaluation purposes.

Outsourced production
When outsourcing production, it's important to highlight that the applicant needs to establish clear responsibilities and appoint a management representative to oversee quality management. 
An agreement should be signed to outline production conditions, technical document transfer, material procurement control, and more. 
Regular audits and effective communication mechanisms are necessary to ensure compliance, traceability, and continuous improvement throughout the entire production process.

Product Authenticity
This section emphasizes the importance of product authenticity by ensuring that registered inspection and clinical trial products have consistent batch numbers, specifications, and traceability information, maintaining traceability of production batches, procurement records, and retained samples, and keeping accurate production and inspection records.

The guideline defines 73 items or QMS elements that need to be verified during on-site inspections. Of these, 32 are considered key items, while 41 are general items. The on-site inspection team carefully assesses each item, determining whether it is "compliant," "non-compliant," or "not applicable." If any non-compliant items are found, inspectors make detailed records of the specific problems identified.
The results of the on-site verification can fall into four categories: 

  • "Passed verification": This conclusion is reached when the on-site inspection does not identify any non-conformities with the project requirements.
  • "Failed verification": If the on-site inspection discovers authenticity issues with the applicant or if more than three key items or more than ten general items do not meet the requirements. This suggests that the applicant has not met the necessary standards.
  • "Review after rectification": When no authenticity problems are found, but the applicant has fewer than three non-compliant key items and fewer than ten non-compliant general items. The applicant is given six months after the registration verification ends to rectify the identified problems. 

They must submit a one-time rectification report to the verification department, which may conduct additional on-site reviews if necessary. If all the projects are successfully rectified and meet the requirements, the conclusion will be "pass the verification after rectification." 

  • "Failure to pass the verification after rectification": If the applicant fails to submit the rectification report within the specified time limit or if there are still non-compliant items after the review, the conclusion will be "failure to pass the verification after rectification."

These principles ensure that the on-site verification process is thorough and fair, clearly determining whether the applicant meets the required standards.

In summary, this article highlights the importance of understanding and complying with the regulatory requirements outlined in the NMPA Guidelines for Inspection of the Quality Management System (QMS) for Medical Device Registration (2022 No. 50) for the inspection of the QMS for medical device registration, covering various aspects such as QMS principles, personnel, facilities, documentation, design and development, purchasing, production, quality control, outsourced production, and product authenticity. 
The on-site verification process evaluates compliance with these requirements and results in one of four possible conclusions: passed verification, failed verification, review after rectification, or failure to pass verification after rectification.

Becoming curious about what the NMPA inspection process entails?
Read our blog series - 7 parts:

Part 1. China NMPA inspection types
Part 2. China NMPA inspection process
Part 3. Preparation for China NMPA inspection
Part 4. Verification of the QMS for Medical Device Registration
Part 5. Verification of the QMS for Medical Device Production
Part 6. Verification of the QMS for Medical Device Distribution
Part 7. China NMPA Inspection Results and Common Findings

If you need assistance with the preparation to upcoming NMPA inspection, mock-inspection, gap assessment of QMS compliance with China regulations, or need subject-matter expertise contact us

 

Olena Hoi, MSc
Stephanie (Xing) Huang
Post date: June 19, 2023
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