NMPA Release | Quality Management System for Medical Devices

Recently, the Beijing Municipal Drug Administration released the Q&A related to “New 300 Questions on Beijing Medical Device Review and Inspection (Volume II)”, which mainly focuses on six sections: active products, passive products, clinical inspection products, medical device quality management system, classification and definition, and innovative medical devices.

Medical Device Quality Management System

1. A certain active medical device A consists of a main unit B and an accessory C. The active medical device A has been approved for marketing. The accessory C intends to apply for registration separately. No changes have occurred to the accessory C (such as production process, personnel, and factory facilities, etc.). Can the design and development verification documents of the accessory C in the active medical device A be used as the design and development verification documents for the separate registration of the accessory C? Is it necessary to supplement new verification?

Answer: During the registration verification stage, when there are no changes in the product production conditions, production processes, and production address, the design and development verification materials in the attachment of the original registration certificate can be used as the design and development verification materials for the separate registration of the attachment, and there is no need to supplement new verification.

2. A certain product failed the inspection during the medical device registration quality management system verification, and the performance indicators of the product technical requirements are incomplete, so supplementary inspection is required. When reapplying for registration, is it acceptable to first apply with the draft product technical requirements and carry out testing, and then submit the supplementary inspection report during the later supplementary submission?

Answer: The verification of the quality management system for medical device registration is an intermediate link in the review process of medical device product registration. Through the means of registration verification, the authenticity of the products for inspection and clinical trial submitted by the applicant for registration is verified, the consistency between the application materials and the actual situation of the applicant is checked, and whether the products for inspection and clinical trial for registration meet the requirements of the production quality management specifications is examined to support the technical review decision. Therefore, the applicant should complete the safety and effectiveness research to support medical device registration, get ready to accept the verification of the quality management system, then submit a medical device registration application, and submit the registration application materials to the drug regulatory department through online registration applications and other channels in accordance with relevant requirements.

3. Previously, the registration application materials for Product A and Product B were prepared according to two registration units. Now, Product A and Product B can be declared under one registration unit. If Product A and Product B are declared under one registration unit, the raw materials, structure, packaging method, sterilization method, process flow, work instruction documents, performance indicators, etc. of the two products will all change. There are two sets of all design and development verification materials. In view of the above situation, is a design and development change required? Does a new trial production need to be carried out?

Answer: According to the “Good Manufacturing Practice for Medical Devices”, when the registration applicant identifies new customer needs or new regulatory requirements as inputs, changes should be made to the original output of the design and development results. Reviews, verifications, and confirmations should be carried out for design and development changes, and approval should be obtained before implementation. Additionally, trial production of the product to be declared should be organized.

4. Due to changes in production capacity requirements, the key equipment used for the production of products for registration inspection has been replaced. Can the old equipment be removed from the production site to other places?

Answer: (1) According to the “Guidelines for Inspection of Quality Management System for Medical Device Registration” (No. 50, 2022), the applicant shall retain the factory facilities, equipment, and relevant usage records for the research and development and production of products for registration inspection and clinical trials. In case of force majeure that makes it impossible to retain them, the applicant shall keep evidence materials that can prove the authenticity, integrity, and traceability of activities in the product realization process such as product research and development, production, and verification. The evidence materials include but are not limited to videos, photos, and relevant original records.

(2) According to the “On – site Inspection Guidelines for the Good Manufacturing Practice of Medical Devices” (Food and Drug Administration Medical Device Supervision (2015) No. 218) and the “Guidelines for Inspection of Quality Management System for Medical Device Registration” (No. 50, 2022), the applicant shall be equipped with production equipment and process equipment that match the products produced and the production scale, and ensure their effective operation. The production equipment and process equipment for products for registration inspection and clinical trials shall meet the requirements of product quality and production scale. The equipment at the inspection site shall be consistent with the relevant content in the equipment list. The applicant shall, in accordance with relevant regulations, conduct equipment verification, process verification on new equipment, and complete trial – production activities. The number of trial – production batches and the production quantity of each batch shall be determined by the applicant itself to meet the equipment verification requirements and sample – retention requirements.

5. Due to the lack of relevant equipment, the R & D personnel of Company A use the equipment of Company B to complete the design, development, verification and validation activities at Company B. Is this acceptable? Company A plans to sign a usage agreement with Company B and retain the usage records of the relevant equipment.

Answer: No. According to the “Good Manufacturing Practice for Medical Devices”, enterprises should be equipped with production equipment, process equipment, etc. that are commensurate with the products they produce and the scale of production, and ensure their effective operation. Enterprises should be equipped with inspection instruments and equipment that meet the product inspection requirements. If the enterprise’s R & D personnel carry out R & D activities on their own, they should use the self – equipped R & D equipment; if the commissioned R & D method is adopted, a commissioned R & D agreement can be signed with the entrusted R & D institution, and the R & D work can be carried out by the R & D personnel of the entrusted party.

6. Company A is a subsidiary of Company B. The lease contract for Company A’s ten – thousand – class clean workshop and some equipment was signed by Company B. Can it be sub – leased internally for Company A’s use?

Answer: According to the requirements of the Guidelines for the Quality Management System Inspection of Medical Device Registration (No. 50, 2022), the applicant shall be equipped with workshops and facilities suitable for the production of the products declared for registration. The applicant can lease workshops suitable for the production of the products declared for registration through a lease method to organize production and sign a lease agreement. However, there cannot be production licenses of two or more companies at the same production address.

7. There are 4 specifications for the optional components of a certain active medical device. Is it possible to produce the optional components separately, use fixtures for factory inspection, release, and storage in the finished product warehouse, and sell them in combination with the main unit or separately when users have demand?

Answer: According to the Measures for the Administration of Medical Device Registration and Filing (Order No. 47 of the State Administration for Market Regulation), the combination components specified in the “Structure and Composition” column of the medical device registration certificate, which are used for the original registered product for the purposes of replacing consumables, after-sales service, maintenance, etc., can be sold separately. The actual production process of the product should be consistent with the production process declared during registration. When a change occurs in the production process, a major matter report should be submitted to the directly affiliated branch of the local municipal food and drug administration.

8. If a Class II medical device registrant has multiple R & D sites, when applying for product registration, is extended inspection required for R & D sites located in other provinces?

Answer: As required by the Regulations on the Supervision and Administration of Medical Devices, when necessary, the department responsible for drug supervision and administration may conduct extended inspections on other relevant entities and individuals that provide products or services for activities such as the research, development, production, operation, and use of medical devices.

9. For Class II medical devices, if both R & D and production are outsourced, can they be entrusted to the same enterprise? Are there any additional requirements?

Answer: It can be entrusted to the same enterprise. When the registrant entrusts research and development and production, it should comply with the relevant requirements of the Guidelines for the Verification of the Quality Management System for Medical Device Registration (No. 50, 2022). Sign a research and development entrustment agreement with the entrusted research and development institution and a production entrustment agreement with the entrusted production enterprise to clarify the division of responsibilities and authorities between the two parties. The registrant shall form relevant document records and registration application materials under the operation of the quality management system. The drug supervision and administration department at the location of the registrant will conduct inspections on its own, jointly with or entrust the drug supervision and administration department at the location of the entrusted production enterprise. If necessary, the drug supervision and administration department will conduct extended inspections on the entrusted research and development institution.

10. The registrant intends to develop a drug coated balloon dilation catheter (drug device combination), and the product design is led by the registrant. The registrant now entrusts another company (trustee) to do the output of design and development, partial process validation, production of registration inspection samples/clinical trial samples, and post market production work. The registrant completes the registration inspection and submission, animal experiments, clinical confirmation, and registration application work. During the design and development output phase, should the entrusted party output technical documents such as work instructions according to the entrusted party’s quality management system, or should they output them according to the requirements of the entrusted party’s quality management system?

Answer: According to the “Announcement of the National Medical Products Administration on Further Strengthening the Supervision and Administration of the Entrusted Production by Medical Device Registrants” (No. 38, 2024), the registrant shall, together with the entrusted manufacturing enterprise, convert the relevant requirements of the quality agreement into executable management documents related to the entrusted production, and supervise the entrusted manufacturing enterprise to implement them effectively. According to the “Guidelines for Compiling Quality Agreements for the Entrusted Production of Medical Devices” (No. 20, 2022), both parties shall negotiate and confirm their respective division of responsibilities and obligations for each process of the entrusted production products. The entrusting party and the entrusted party shall stipulate the management requirements for quality documents and quality records in the production process. The “Quality Agreement” shall clarify that the entrusting party shall establish and maintain production technical documents for each type of product under entrusted production, and be responsible for implementing product design transfer to the entrusted party; at the same time, the requirement for the entrusted party to compile and maintain production technical documents for each type of product under entrusted production (usually one registration unit is appropriate) shall be considered. The entrusting party shall formulate a transfer document list with specific documents attached. The transfer method, confirmation of transfer documents, and usage rights, etc., shall be agreed upon by both parties in the agreement. Both the registrant and the entrusted manufacturing enterprise shall implement their respective quality management systems. For the documents and records involved in the links that require communication, coordination, transfer, and transformation, both parties shall conduct a full review to evaluate the suitability of their respective documents and records.

11. Company A has a product under research which is currently in the design and development output stage. It plans to entrust the production. The product produced by the entrusted manufacturer, Company B, is basically equivalent to the product under research of Company A. For raw materials, packaging materials, etc., the existing suppliers of Company B are adopted, and Company B makes direct purchases. If, after evaluation, the typical products verified by Company B can cover the products of Company A, and during the trial production of Company A’s products, the existing process verification parameters (such as cleaning, packaging, sterilization, etc.) of Company B are directly used. After production, if the product passes the inspection according to the product technical requirements, it is considered that the process verification is qualified. Is this acceptable?

Answer: According to the “Guidelines for Quality System Inspection of Medical Device Registration Management” (No. 50, 2022) “4.5.4 (Verification and Validation) The applicant shall determine the scope and degree of work that needs to be verified or validated based on the risk assessment results, and ensure that the key elements of the relevant operations can be effectively controlled.” The registrant should assess the impact of the risks and differences in production and inspection personnel, processing and testing equipment, raw materials, relevant processes and processing parameters, environment, etc. between the products produced under commission and the products produced by the commissioned production enterprise on the process verification and validation of the products. In the daily production activities of the registrant, the first-time and periodic verification work should be carried out for the above-mentioned key and special processes such as cleaning, packaging, and sterilization to ensure the stability of the relevant processes and the controllability of product quality and safety.

12. Can the product final inspection data be used for registration self-inspection?

Answer: The evaluation contents of registration self-inspection and product final inspection are different. Under the premise that registration self-inspection and product quality inspection respectively meet the “Regulations on the Management of Self-Inspection for Medical Device Registration” (No. 126, 2021) and the “Good Manufacturing Practice for Medical Devices” and its relevant appendices, product final inspection also needs to meet the relevant requirements such as the “Guidelines for Quality Control and Release of Finished Products of Medical Device Manufacturers” (No. 173, 2016).

13. The production addresses of a company’s medical device production license are in Changping District and Daxing District. Each production address can independently carry out activities such as design and development, product production, quality control, and warehousing. The registered address of the business license is in Changping District. If the production address in Changping District is cancelled, will the fact that the production address and the registered address in the business license are not in the same district have an impact on the company’s production of medical device products?

Answer: There is no regulation that the production address of the Medical Device Manufacturing License must be in the same administrative division as the domicile of the business license. Enterprises should ensure that they have factory facilities and equipment suitable for the types and scale of products they produce, and shall not reduce production conditions without authorization.

14. Is it necessary to complete the signing of the quality agreement with the main raw material suppliers before the registration verification? Since the main raw material suppliers of the products to be registered are Japanese manufacturers, in Japan, the quality agreement with the main raw material suppliers can only be signed during mass production. Currently, the other party is reluctant to formally sign this agreement with us. Can only the draft agreement (finalized but not signed) be provided during the registration verification?

Answer: It is not allowed to only provide the draft agreement. Medical device manufacturers should, in accordance with the requirements of the “Good Manufacturing Practice for Medical Devices” and the “Guidelines for Supplier Audits of Medical Device Manufacturers” (No. 1, 2015), sign a quality agreement with major suppliers, stipulating technical requirements, quality requirements, etc. of the purchased items, and clarifying the quality responsibilities borne by both parties to ensure the quality and stability of the materials. Enterprises can adopt the method of signing an intention agreement with suppliers to clarify the relevant regulatory requirements and actual needs of the quality agreement, and sign a formal agreement when mass production begins.

15. Due to the minimum order quantity requirements for procurement by some manufacturers, can the R & D materials involved in the product R & D stage and the materials for registration inspection samples be purchased from the group’s parent company? Can the group’s parent company be listed as a qualified supplier, and can the access information of the original suppliers of relevant materials and the material inspection records be obtained?

Answer: Medical device manufacturers should, in accordance with the requirements of the “Good Manufacturing Practice for Medical Devices” and the “Guidelines for Supplier Audits of Medical Device Manufacturers” (No. 1, 2015), establish a supplier audit system to audit and evaluate suppliers, ensuring that the purchased items meet the quality requirements of their product production. Internally, medical device manufacturers should control the quality of raw materials in accordance with the requirements of the company’s quality management system to ensure that the raw materials meet the requirements; externally, they should audit and evaluate manufacturers in accordance with regulatory requirements. The audit report of the raw material manufacturer by the parent company can be used as the basis for the subsidiary to audit and evaluate the supplier. However, as the registrant, the subsidiary should still carry out relevant audit and evaluation work. The subsidiary can send qualified personnel to participate in the parent company’s audit process of the supplier to ensure that the source of raw materials is legal and the quality is controllable. If the supplier is a raw material distributor, a comprehensive and complete evaluation of the distributor should be carried out during the supplier audit. The distributor needs to provide the sales agency agreement between the distributor and the raw material manufacturer or the general agent, as well as the relevant records of the distributor’s audit and control of the raw material manufacturer, so as to ensure that the raw materials purchased from the distributor comply with laws, regulations, and the requirements of the enterprise.

16. A medical device enterprise intends to lease a Class III active medical device product (a product with a medical device registration certificate held by another company) for the testing of control products in animal experiments. The business scope of the leasing company’s business license includes “medical equipment leasing”. The two parties sign a medical device lease contract. Can the leasing company providing the business license and the medical device instruction manual meet the relevant requirements?

Answer: There is no clause in the “Good Manufacturing Practice for Medical Devices” and the “Guidelines for the Quality Management System Inspection of Medical Device Registration” (No. 50, 2022) that “prohibits the use of leased equipment for R & D activities”. Enterprises should sign a lease agreement in accordance with the requirements of the above – mentioned regulations, clearly stating that the user shall effectively manage the leased equipment to ensure the authenticity, accuracy, and traceability of the R & D process and documentation records.

17.  For a fully automatic coagulation analyzer, is it necessary to have records of the complete software version and release version in the factory inspection records? Is it necessary to have software version records in the production release records and market release records?

Answer: According to the “Good Manufacturing Practice for Medical Devices”, enterprises shall formulate product inspection procedures based on mandatory standards and the product technical requirements that have been registered or filed, and issue corresponding inspection reports or certificates. The inspection records shall document the complete version and release version information to meet the traceability requirements. According to the “Appendix to the Good Manufacturing Practice for Medical Devices – Standalone Software” (No. 43, 2019) (also applicable to software components), the release of software products shall be documented, and the requirements for activities such as software version identification, installation and uninstallation testing, product integrity inspection, and release approval shall be determined, and relevant records shall be maintained.

18. A company plans to register and declare a Class II puncture needle product. The physical properties of its product technology include 8 performance indicators. Among them, for the 3 indicators of the rigidity, toughness, and hardness of the puncture needle, during the incoming inspection process, the supplier is required to provide a qualified inspection report and verify each batch. During the production process, only cleaning and assembly are carried out, and these 3 indicators are not affected. In the finished product inspection procedure, only the remaining 5 indicators are inspected. Is this acceptable?

Answer: According to the “Good Manufacturing Practice for Medical Devices” and the “Guidelines for Quality Control and Release of Finished Products of Medical Device Manufacturers” (No. 173, 2016), the content of the finished product inspection procedures should, in principle, cover the inspection items and methods that need to be routinely controlled in the registered or filed product technical requirements. If it cannot be covered, it should be explained in the finished product inspection procedures, and the control methods and inspection cycles for relevant indicators should be clarified and verified. When necessary, a confirmed alternative solution should be provided based on risk assessment.

19. Can the registration self-inspection site be shared with the product quality inspection site? Can the registration self-inspection personnel be the same group as the product quality inspection personnel?

Answer: Registration self-inspection belongs to the quality control of design and development verification and should meet the relevant requirements of the “Regulations on the Management of Self-Inspection for Medical Device Registration” (No. 126, 2021). Finished product inspection belongs to quality inspection control and should meet the relevant requirements of the “Good Manufacturing Practice for Medical Devices”. (1) The registration self-inspection site and the product quality inspection site can be shared on the premise of meeting the above regulations respectively. According to the requirements for the registration self-inspection site in the “Regulations on the Management of Self-Inspection for Medical Device Registration” (No. 126, 2021): “The registration applicant shall be equipped with instruments, equipment and environmental facilities that meet the requirements of the inspection methods, establish and maintain files, operating procedures, measurement/calibration certificates, use and maintenance records of the equipment and environmental facilities, and conduct traceability of quantity values in accordance with relevant regulations.” (2) The registration self-inspection personnel can be the same group as the product quality inspection personnel, but they must meet the requirements of relevant regulations and ensure that the inspection personnel have received relevant training and assessment and have relevant professional capabilities. The inspection personnel, reviewers, approvers, etc. shall be authorized by the registration applicant in accordance with regulations. According to the requirements of the “Regulations on the Management of Self-Inspection for Medical Device Registration” (No. 126, 2021), “The registration applicant shall be equipped with full-time inspection personnel. The inspection personnel shall be formally employed and can only work in this enterprise. The educational background, technical capabilities and quantity of the inspection personnel shall be compatible with the product inspection work. The inspection personnel shall be familiar with relevant laws, regulations, standards and product technical requirements of medical devices, master the principles of inspection methods, detection operation skills, work instructions, quality control requirements, laboratory safety and protection knowledge, measurement and data processing knowledge, etc., and shall have received training and assessment on relevant laws, regulations, quality management and relevant professional technologies of medical devices.”

20.Can the ethylene oxide sterilization be entrusted to an enterprise in another province?

Answer: An enterprise from another province can be entrusted to carry out ethylene oxide sterilization. According to the “Guidelines for Inspection Points of Entrusted Sterilization Methods for Medical Device Products in Beijing (2023 Edition)”, the manufacturing enterprise that entrusts sterilization should manage the entrusted sterilization enterprise in accordance with relevant regulations on supplier management.

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Source：CMDRA
Translated & edited：Bradyknown