In order to fully implement the main responsibility for the quality and safety of medical device registrants, prevent and control the hidden risks of medical device entrusted production, and strengthen the supervision of medical device entrusted production, the State Food and Drug Administration organized the drafting of “Opinions on Further Strengthening the Supervision of Medical Device Registrants’ Entrusted Production” (Draft for Soliciting Comments)” (see attachment) is now open to the public for comments.
Regarding further strengthening of medical device registrants
Opinions on Entrusted Production Supervision Work (Draft for Comment)
In order to fully implement the main responsibility for the quality and safety of medical device registrants (hereinafter referred to as “registrants”), prevent and control the hidden risks of medical device entrusted production, and strengthen the supervision of medical device entrusted production, in accordance with relevant laws and regulations, combined with the “Enterprise Implementation of Medical Device Quality Regulations on the Supervision and Management of Safety Subject Responsibilities (No. 124 of 2022, hereinafter referred to as the “Regulations on Implementing Subject Responsibilities”), “Opinions of the General Department of the State Food and Drug Administration on Strengthening the Collaborative Supervision of Cross-regional Entrusted Production of Medical Devices” (Drug Administration Comprehensive Equipment Guan [2022] No. 21, hereinafter referred to as the “Opinions on Cross-Regional Commissioned Production”), the following opinions are hereby put forward.
1.Strictly implement the main responsibility of medical device registrants
(1) Fully implement the main responsibility for the quality and safety of medical devices. The registrant shall establish a quality management system covering the entire life cycle of medical devices, and establish and improve a management organization that is compatible with the characteristics of the products produced and the scale of the enterprise in accordance with the requirements of the “Measures for the Supervision and Administration of Medical Device Production” and “Regulations on the Implementation of Subject Responsibilities”. Sufficient management personnel, fully perform the duties of product risk management, change control, product release, after-sales service, product complaint handling, adverse event monitoring and product recall, and fully implement the main responsibility of medical device quality and safety.
If the registrant conducts entrusted production, the legal representative or the person in charge of the enterprise shall focus on analyzing the management and regular review of the entrusted production enterprise when conducting quarterly scheduling in accordance with the requirements of the “Regulations on the Implementation of Subject Responsibilities”. For implantable medical devices, registrants are encouraged to produce by themselves. If entrusted production is really necessary, registrants should select personnel familiar with product production process and quality control to settle in entrusted production enterprises during the period of entrusted production activities. Management conducts on-site guidance and supervision. The products in the “Catalogue of Medical Devices Prohibited from Consignment Production” shall not be consigned for production.
If the registrant does not produce by itself, but only conducts commissioned production, it shall also maintain the quality management capability of the product life cycle and maintain the integrity of the quality management system; it shall set up a suitable management organization and be equipped with a sufficient number and capacity of full-time quality management personnel, and Technical personnel who are familiar with the products and have corresponding professional knowledge can effectively monitor and control the entrusted production activities.
(2) Efforts should be made to implement the management requirements of the quality agreement. If the registrant conducts entrusted production, it shall sign a quality agreement with the entrusted production enterprise in accordance with the requirements of the “Guidelines for the Preparation of Quality Agreements for Consigned Production of Medical Devices” and in combination with the actual situation of the enterprise. The validity period of the quality agreement shall not exceed the effective period of the product registration certificate and production license in principle the term. The registrant shall, together with the entrusted production enterprise, transform the relevant requirements of the quality agreement into executable entrusted production-related management documents, and supervise the entrusted production enterprise to implement them in place.
The registrant and the entrusted production enterprise shall review the suitability, adequacy, and effectiveness of the quality agreement every year, and confirm that the relevant requirements of the quality agreement are consistent with the entrusted production management documents and the actual production situation. If any inconsistencies are found, corrective measures shall be taken in a timely manner. Under the premise of meeting the requirements of relevant laws and regulations, the two parties can agree on the specific implementation methods of document control, procurement control, process control, inspection control, product release, and change control in the quality agreement, but the requirements for the control interface must be clarified. Encourage enterprises to adopt controlled information systems to optimize control processes and improve quality management efficiency.
(3) Continuously strengthen the change control capability. The registrant shall strengthen the change control capability, establish a complete change control procedure together with the entrusted production enterprise, and do a good job in change assessment, verification or confirmation. For registered Class II and Class III medical device product design, raw materials, production processes, scope of application, and use methods that have undergone substantial changes that may affect the safety and effectiveness of the medical device, the registrant shall comply with the “Medical Device Registration Article 78 of the “Administrative Measures for Registration and Recordation” stipulates that changes in registration, filing or reporting to the drug supervision and management department shall be carried out; for the introduction or change of outsourced suppliers such as entrusted research and development, production process outsourcing and service outsourcing, change control shall be done. , and determine whether relevant changes affect the effective operation of the quality management system through risk assessment.
(4) Strictly fulfill the responsibility and obligation of adverse event monitoring. The registrant shall, in accordance with the “Administrative Measures for Monitoring and Re-evaluation of Medical Device Adverse Events” and in combination with product risk characteristics, allocate sufficient resources, Improve mechanisms, strengthen capabilities, and earnestly undertake the responsibility for monitoring medical device adverse events. Encourage registrants with higher product risks to implement liability compensation capabilities by purchasing commercial insurance and other means.
If the registrant conducts commissioned production, the responsibilities and obligations of both parties in the investigation and disposal of adverse events and product re-evaluation shall be stipulated in the quality agreement, and the periodic risk assessment report shall include the risk analysis and evaluation of the commissioned production behavior. The adverse event monitoring responsibility that the registrant shall perform as stipulated in the “Regulations on the Supervision and Administration of Medical Devices” and other laws and regulations shall not be transferred to the entrusted production enterprise through a quality agreement.
2.Effectively strengthen the registration management of medical device entrusted production
(5) Continue to standardize the management of entrusted production registration certificates. For the registration declaration in the form of entrusted production, or the renewal of the registration certificate involves the entrusted production of medical devices by the registrant, the registration approval department shall list the entrusted production address and indicate “(entrusted production)” in the production address column of the medical device registration certificate , and at the same time, note the name of the entrusted production enterprise and the unified social credit code in the remarks column, and the form of the remark is “entrusted production enterprise: XXX company; unified social credit code: XXXX”. If the change registration involves entrusted production by the registrant, the relevant information of the entrusted production shall also be indicated in the change registration document according to the above method, and the change information shall be recorded in the corresponding fields of the production address and remarks of the registration certificate in accordance with the data collection requirements of the National Drug Regulatory Data Sharing Platform. Submitted after the update. If there is only a literal change in the name of the entrusted production enterprise, there is no need to apply for a change record, and the registrant can modify it by himself. When the registration is renewed, the revised registration certificate will be issued.
The drug regulatory department where the registrant and the entrusted production enterprise is located shall promptly record the information related to the entrusted production in the enterprise credit file. All provincial drug regulatory departments shall organize to sort out the registration certificates issued for entrusted production within their jurisdictions, and if they find that relevant information has not been marked in accordance with the requirements of the preceding paragraph, they shall urge the registrants to apply for marking to the original certificate issuing department in a timely manner, and in December 2023 Complete the re-marking by March 31.
(6) Continuously strengthen the management of commissioned production changes. When the registrant who entrusts production applies to the original certificate-issuing department for the recordation of the change of the production address of the registration certificate, if the change of the production license is involved, the changed production license shall be submitted. If it does not involve the change of the production license, the inspection report issued by the drug regulatory department where the registrant is located shall be submitted. The inspection report shall be issued by the drug regulatory department at the place where the registrant is located after a comprehensive inspection of the registrant’s quality management system, and may, if necessary, inspect the entrusted production enterprise together with the drug regulatory department at the location of the entrusted production enterprise.
If the registrant no longer conducts entrusted production, it shall promptly reduce the production address of the entrusted production enterprise to the original certificate issuing department. If it is no longer in production, the registrant shall take the initiative to apply for cancellation of the registration certificate.
(7) Strictly implement the verification requirements of the quality management system. For the entrusted production by the registrant (applicant), the quality management system inspection should focus on the establishment of the enterprise’s quality management organization, the transformation of the quality agreement regulations into the entrusted production management documents, the outsourcing process in the entrusted production process (such as R&D outsourcing, production process outsourcing, service outsourcing, etc.) control conditions, etc.
If cross-regional entrusted production is involved, the inspection of the quality management system of the registrant (applicant) should in principle be carried out by the local drug regulatory department itself or jointly with the local drug regulatory department of the entrusted production enterprise, and the quality management of the registrant (applicant) and the entrusted production enterprise A comprehensive inspection of system operation. Under special circumstances, if the drug regulatory department at the place where the registrant (applicant) is located is really unable to send inspectors, it may entrust the drug regulatory department at the location of the entrusted production enterprise to inspect the entrusted production enterprise. The (applicant) system verification shall review and confirm the verification report of the entrusted production enterprise.
(8) Gradually improve the registrant withdrawal management mechanism. If the registrant no longer conducts medical device production and business activities, it shall apply for the cancellation of the medical device registration certificate and production license in a timely manner, and continue to perform responsibilities such as adverse event monitoring, product recall, and liability compensation to ensure that the marketed products are safe and effective. When the drug regulatory department finds that the registrant’s whereabouts are unknown and cannot be contacted, it shall do a good job in collecting evidence materials, coordinate with relevant departments to include the registrant in the list of enterprises with abnormal operations, and make a public announcement on the Internet in a timely manner. Notify the drug supervision and management department where the entrusted production enterprise is located.
3.Continuously strengthen the supervision and management of entrusted production
(9) Continue to strengthen the daily supervision of commissioned production. The drug supervision and management department should effectively implement the territorial supervision responsibility, and comprehensively sort out and grasp the various types of registrants and entrustees within the jurisdiction by collecting information on entrusted production registration certificates, urging enterprises to report production varieties, and receiving notifications of cross-regional production varieties. Based on the base of production enterprises, according to the principle of risk management, the supervision should be strengthened in a targeted manner. The drug regulatory department where the registrant is located should continue to pay attention to the registrant’s full life cycle quality management capabilities, the ability to evaluate and control the entrusted production enterprise, and the change management ability, and verify the information provided by the registrant in combination with the inspection of the entrusted production enterprise. Pay attention to the registrant who changes from self-production to commissioned production, or changes the main body of the entrusted production enterprise, and take effective measures to prevent product risks. For enterprises that do not maintain effective operation of the quality management system, if it is determined by research and judgment that it affects product safety and effectiveness, it shall be punished in strict accordance with Article 86 of the “Regulations on the Supervision and Administration of Medical Devices”.
In areas where the entrusted production registrants are relatively concentrated, the local drug supervision and management department should take into account the progress of the supervision work, regularly conduct special consultations on the entrusted production supervision of the registrants, analyze the results of supervision and inspection and product sampling inspection, and comprehensively check the quality management system of the enterprise and the products. There are potential safety hazards in terms of quality, and targeted prevention and control measures are taken to eliminate systemic and regional risks.
(10) Do a good job in the exchange of commissioned production information. The State Drug Administration continues to promote the construction of medical device variety archives, and promotes the interconnection of registrants’ entrusted production-related information by standardizing the labeling of entrusted production information on registration certificates; Collect information on review and approval, registration quality management system verification, supervision and inspection, enterprise reports, supervision and random inspection, etc., and continuously improve and update the credit files of registrants and entrusted production enterprises.
If cross-regional entrusted production is involved, the drug regulatory department where the registrant and the entrusted production enterprise is located shall follow the requirements of the “Measures for the Supervision and Administration of Medical Device Production” and “Opinions on the Supervision of Cross-regional Consigned Production” to conduct interviews on the types of production, inspection results and responsibilities of the enterprise. Cross-regional notification of regulatory information. For the entrusted production enterprises that fail to report the information of production varieties according to law, the local drug supervision and management department shall punish them strictly in accordance with the provisions of Article 78 of the “Measures for the Supervision and Administration of Medical Device Production”.
(11) Continuously innovate supervision methods. Drug regulatory authorities at all levels should deeply understand the complexity and importance of entrusted production supervision by registrants, scientifically allocate supervision resources, continuously improve work processes, and continuously improve supervision methods. Encourage the drug regulatory department to explore simultaneous supervision and inspection at the two sites of the registrant and the entrusted production enterprise, connect the inspection site remotely through the network, communicate inspection information in a timely manner, and unify inspection standards.
Drug supervision and management departments at all levels should continuously improve the cross-regional collaborative supervision mechanism to improve inspection efficiency and supervision effectiveness. The drug regulatory department at the place where the registrant is located shall draw up a cross-regional entrusted production inspection plan before March 31 of each year, and notify the drug regulatory department where the entrusted production enterprise is located. For enterprises that have quality and safety risks found during the inspection and have not taken effective measures to eliminate them, the drug regulatory department where the registrant and the entrusted production enterprise is located may conduct a joint responsibility interview with the registrant and the entrusted production enterprise.