NMPA Announcement on Further Strengthening the Supervision and Management of Medical Device Registrants' Contract Manufacturing
To fully implement the "Regulations on the Supervision and Management of Medical Devices" and ensure the comprehensive fulfillment of quality and safety responsibilities by medical device registrants, China's National Medical Products Administration (NMPA) has announced new measures to enhance the oversight of contract manufacturing for medical devices. These measures aim to effectively control quality and safety risks associated with medical devices on April 2, 2024.
Key points include:
1. Strengthening Registrants' Principal Responsibilities: Registrants must establish and effectively maintain a quality management system covering the entire lifecycle of medical devices. For contract manufacturing, registrants are required to set up appropriate management structures, fulfilling responsibilities such as product risk management, change control, product release, after-sales service, product complaint handling, adverse event monitoring, and product recall.
2. Choosing Contract Manufacturers Wisely: Registrants should prioritize contract manufacturers with high levels of quality management, larger production scales, good credit records, and advanced levels of automation and information management. Before engaging in contract manufacturing, registrants must assess the contract manufacturer's credit and compliance history.
3. Implantable Medical Devices: For implantable medical devices, registrants are encouraged to manufacture in-house. If contract manufacturing is necessary, registrants should ensure on-site supervision by experienced personnel to oversee production and quality management.
4. Quality Agreements: Registrants and contract manufacturers must sign quality agreements, detailing standards for document control, procurement, process control, inspection, product release, and change control, among others.
5. Collaboration and Supervision: Registrants and contract manufacturers should work together to implement the quality agreement's requirements into actionable management documents and supervise their execution.
6. Annual Review: The suitability, adequacy, and effectiveness of the quality agreement and related management documents should be reviewed annually.
7. Procurement and Supplier Management: Registrants, together with contract manufacturers, must manage procurement items and suppliers based on their impact on product quality, especially for critical materials and components.
8. Product Release: Registrants must establish product release procedures, ensuring that production records and quality inspection results meet standards before market release.
9. Corrective and Preventive Measures: The quality agreement should specify mechanisms for communication, responsibilities, and requirements for corrective and preventive actions.
10. Change Control: Registrants must strengthen change control capabilities, assessing and validating any changes that might affect the quality management system's effectiveness.
11. Adverse Event Monitoring: Registrants are responsible for monitoring adverse events and re-evaluation management, allocating sufficient resources and strengthening capabilities in line with product risk profiles.
12. Registrants involved in contract manufacturing must integrate contract manufacturing processes into their quality management system documentation. This includes detailing procedures for evaluating, analyzing, and enhancing the performance of contract manufacturers within the "Quality Management System Document - Measurement, Analysis, and Improvement Procedures" of their registration dossier.
During the quality management system verification for registration, emphasis should be placed on the setup of quality management structures, the assignment and performance of key quality personnel, the execution of quality agreements, and the oversight of contracted research and manufacturing processes. For domestic cross-regional contract manufacturing, verification ought to be performed by the drug regulatory department where the registrant is located, either independently or in cooperation with the contract manufacturer's local drug regulatory department. In cases where it's not feasible for the registrant's local drug regulatory department to send inspectors, the responsibility can be transferred to the drug regulatory department of the contract manufacturer's location. The inspection findings from the contract manufacturer should be reviewed and validated in conjunction with the registrant's system verification.
13. For domestic contract manufacturing registration or renewal, the production address on the medical device registration certificate should reflect the contract manufacturing site, marked as "(Contract Manufactured)". The contract manufacturer’s name and Unified Social Credit Code must be included in the remarks section. Changes in registration due to contract manufacturing must also incorporate relevant details in the change documentation, updating the production address and remarks in the registration certificate as needed. Registrants and contract manufacturers are required to inform their local provincial drug regulatory departments of any changes for inclusion in corporate credit records.
A change record application is not needed solely for textual modifications in the contract manufacturer's name; an updated registration certificate can be issued at the time of renewal registration.Provincial drug regulatory departments have the responsibility to review all previously issued contract manufacturing registration certificates within their jurisdiction. Certificates not adhering to these guidelines must be corrected by urging registrants to apply for the necessary updates with the original registration authority, to be completed within 3 months from this announcement's implementation date.
14. Changes in the production address of a domestic medical device that do not affect the production license's scope, provided the contract manufacturer's scope includes the contracted products, should be accompanied by a statement from the contract manufacturer's local drug regulatory department during the registration certificate change record procedure.
Registrants discontinuing contract manufacturing must immediately inform the original registration department to eliminate the contract manufacturing address; contract manufacturers must likewise promptly report such changes to their local provincial drug regulatory departments.
15. Provincial drug regulatory bodies are tasked with robust oversight of contract manufacturing, including tracking registration certificates, encouraging reporting on product varieties, and managing cross-regional product notifications. This approach aims to comprehensively manage and supervise contract manufacturing activities, focusing on risk management principles.
Local regulatory departments must monitor registrants' quality management throughout the product lifecycle, including their oversight of contract manufacturers and management of changes. Inspections of contract manufacturing facilities are crucial to verify compliance with regulatory standards and agreements.
16. Registrants must notify their local regulatory body when transitioning to or changing contract manufacturers. Thorough inspections of both parties' quality management systems are required, potentially in collaboration with the contract manufacturer's local regulatory department.
17. Recognizing the complexity of overseeing contract manufacturing, regulatory departments should efficiently allocate resources and employ diverse supervisory methods. Special meetings to discuss contract manufacturing oversight, analyze risks, and implement preventive measures are encouraged, particularly in areas with a high concentration of contract manufacturing activities. The use of technology for simultaneous inspections and information sharing can enhance the efficiency and consistency of oversight.
18. The National Medical Products Administration (NMPA) is improving the management of medical device information, including contract manufacturing details, to facilitate data exchange and regulatory oversight across regions. Provincial departments are responsible for maintaining comprehensive data on medical device regulation and updating credit archives for both registrants and contract manufacturers, contributing to a national data sharing platform.
Cross-regional contract manufacturing requires prompt communication between the relevant provincial regulatory departments regarding product varieties and inspection outcomes.
19. If inspections identify deficiencies in quality management systems, regulatory departments must demand corrective actions. Failure to address quality and safety risks may lead to warnings or further regulatory actions. Severe violations affecting product safety and efficacy can trigger emergency measures, including production suspension and strict penalties, in line with regulatory standards.
20. Implementation of these guidelines begins on June 1, 2024, marking a significant step towards strengthening the supervision and management of contract manufacturing in the medical device industry.