Main Changes in the New version of the Guidelines for the Verification of the Quality Management System for Medical Device Registration

On October 10, 2022, the NMPA issued a new version of the Guidelines for the Verification of the Quality Management System for the Registration of Medical Devices (Circular No. 50 in 2022) and implemented it from the date of promulgation. The original system verification guidelines (Circular No. 19 in 2020) were repealed at the same time. From now on, the medical regulatory departments of provinces, autonomous regions and municipalities directly under the Central Government shall carry out the quality management system verification related to product development and production in accordance with the requirements of the new version of the Guidelines for the Verification of the Quality Management System for Medical Device Registration.

The new version of the Guidelines for the Verification of the Quality Management System for Medical Device Registration mainly adds registration self -inspection verification requirements, commissioned R&D verification requirements, commissioned production verification requirements, the list of verification items, and the judgment principle of on-site verification results. The specific changes and requirements are summarized as follows:

1. New requirements for self- inspection

Quality management system principle – 4.1.3 (self inspection) If the applicant conducts self -inspection, the self- inspection work shall be incorporated into the product quality management system and meet the requirements.

Organization and personnel – 4.2.4 (Self inspection personnel) If the applicant submits the self- inspection report, the quality inspection department shall provide a sufficient number of full-time inspection personnel. The educational background and technical ability of the inspectors shall match the product inspection work. The inspectors, reviewers, approvers, etc. shall be authorized by the applicant in accordance with the provisions.

Quality control – 4.8.2 (Self- inspection) If the applicant conducts self- inspection, he/she shall incorporate the quality management requirements related to self- inspection into the enterprise’s quality management system documents (including quality manual, procedures, operation instructions, etc.) in accordance with the requirements of relevant inspection work and self- inspection of declared products, and ensure their effective implementation and control.

2. Requirements for new commissioned R&D

4.5.12(Entrusted R&D management) For entrusted R&D, the applicant shall have quality management measures for related activities.

4.5.12.1(Evaluation of the trustee’s ability) The applicant shall specify the scope and extent of the product R&D activities entrusted. The R&D capability and continuous technical support capability of the entrusted R&D institution shall be required and evaluated accordingly.

4.5.12.2(Entrusted R&D Agreement) The applicant shall sign an entrusted R&D agreement with the entrusted R&D institution, specifying the responsibilities of each party, R&D content and related technical matters. The applicant shall be responsible for the process and results of the commissioned R&D, and shall have measures to ensure the reliability of the commissioned R&D process data. The entrusted R&D institution shall comply with the requirements of the agreement and ensure that the R&D process is standardized and the data is true, accurate, complete and traceable.

4.5.12.3 (Entrusted R&D technical documents) The applicant shall ensure that the entrusted R&D institution hand over the design and development output documents according to the requirements of the agreement and meet the design and development input requirements.

3. New requirements for entrusted production

4.9.1(General requirements) In case of entrustment in the production process, the applicant shall specify the departments and personnel responsible for guiding and supervising the quality management system of the entrusted production enterprise. In principle, the management representative shall be designated to be responsible for the quality management of entrusted production.

4.9.2(Personnel) The applicant shall be equipped with full-time quality management personnel, who shall be familiar with the key quality control and key production operation requirements of the product, and be able to evaluate, review and supervise the quality management system of the applicant and the entrusted production enterprise. The production principal, quality principal, production release reviewer and other key personnel of the entrusted production enterprise shall be familiar with the key quality control and key production operation requirements of the entrusted production products.

4.9.3(Entrustment agreement) The applicant shall sign an entrustment agreement with the entrusted party to clarify the rights, obligations and responsibilities of both parties. The agreement shall at least include the production conditions of the entrusted production enterprise, the transfer of technical documents, the control of material procurement, the control of production process and process, the inspection of finished products, the control of product release, the control of documents and records, the control of changes, the audit of the quality management system, etc., to ensure that the entrusted production enterprise complies with laws and regulations, medical device production quality management specifications, mandatory standards, and product technical requirements organize production.

4.9.4. (On site audit) Before the entrusted production, the applicant shall conduct an on-site evaluation and audit of the quality management system of the entrusted production enterprise. The audit shall at least include the organization and personnel, plant and facilities, equipment, production management, quality control capabilities, etc., to ensure that the entrusted production enterprise has a quality management system that is compatible with the entrusted production products.

4.9.5(Design conversion) The applicant shall jointly plan and complete the design conversion activities with the entrusted production enterprise to ensure that the product technical requirements, production process, raw material requirements, instructions, labels and other product technical documents can be effectively transferred to the entrusted production enterprise.

4.9.6(Transformation of technical documents and process validation) The entrusted production enterprise shall, in combination with its own production conditions and quality management system, convert the applicant’s product technical documents into its own technical documents to ensure that the key technical parameters and operation methods required by the product technology are consistent with those handed over by the applicant. Trial production and process validation shall be carried out. Trial production shall include all transferred production processes and quality control processes.

4.9.7(Risk control of technology transformation) The applicant shall, in combination with the original production process documents, conduct a comparative evaluation of the production process documents implemented by the entrusted production enterprise to ensure that the risks arising from changes in the quality management system such as production conditions have been fully identified and controlled. The applicant shall participate in the verification and confirmation work related to the entrusted production products carried out by the entrusted production enterprise, and review the relevant process documents and reports.

4.9.8(Production of registered inspection products and clinical trial products) Where the applicant carries out the production of registered inspection products and clinical trial products in the entrusted production enterprise, it shall ensure that the entrusted production enterprise has plants, facilities and equipment suitable for the production of products. The applicant shall ensure the completion of process validation or confirmation and other related work.

4.9.9(Material procurement) The applicant shall specify the procurement method, procurement approach, quality standards and inspection requirements of the entrusted production products and materials, and implement the procurement in accordance with the requirements of the medical device entrusted production quality agreement. When necessary, the applicant and the entrusted production enterprise jointly screen, review, sign quality agreements, and periodically re- evaluate the material suppliers.

4.9.10(Production process management) The applicant shall, together with the entrusted production enterprise, specify the monitoring methods and standards for the product process flow, process parameters, outsourcing processing (such as irradiation sterilization, ethylene oxide sterilization, anodizing, spraying process, etc.), material flow, batch number and identification management, traceability of production records and other production processes, designate authorized monitoring personnel, and keep monitoring records.

4.9.11(Document management) The documents jointly held by the applicant and the entrusted production enterprise shall at least include: the entrustment agreement, product technical requirements, raw material requirements, production process and inspection procedures, product instructions and labels, and product release procedures implemented by the entrusted production enterprise.

4.9.12(Product release) The applicant shall establish product release review and approval procedures, and ensure that both parties release the registered inspection products, clinical trial products and marketed products according to their respective responsibilities. The entrusted production enterprise shall formulate production release review procedures, ensure that the entrusted products meet the acceptance standards of the applicant, and keep release records. All records related to product production shall be true, accurate, complete and traceable.

4.9.13(Regular review) The applicant shall regularly review the entrusted production management and relevant records of the entrusted production enterprise, and keep the review records. The entrusted production enterprise shall keep all the production records related to the entrusted production, and may provide them to the applicant at any time for future reference. If the entrusted production enterprise has the same product in production, it shall adopt the management method of serial number, batch number and process identification that are significantly different from the entrusted production product to avoid confusion.

4.9.14(Communication mechanism) The applicant shall establish an effective communication mechanism with the entrusted production enterprise. Any design change, procurement change, etc. shall be notified to the entrusted production enterprise in time and supervised for implementation. The applicant shall have measures to ensure that the entrusted production enterprise can timely inform the applicant and conduct joint evaluation of any change in the quality management system of the entrusted production enterprise that may affect the product quality.

4.9.15(Responsibility of the applicant) The applicant shall trace and monitor the whole process of design and development, production, storage and transportation, and adverse event monitoring, maintain the continuous improvement of the quality management system, and implement the supervision of the entrusted production enterprise.

4. Adding the verification item list

There are 73 verification items in this Guide, including 32 key items marked with “*” and 41 general items.

5  New judgment principles for on-site inspection results

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