The National Market Supervision Administration adopted the Measures on the Supervision and Administration of Medical Devices Manufacturing (“Measures”) on 10 March 2022, which will take effect as of 1 May 2022.
The Measures are promulgated to adapt to the newly revised Regulations on Supervision and Administration of Medical Devices (“Regulations”) issued by the State Council and which took effect as of 1 June 2021. The 2014 version of the Measures on the Supervision and Administration of Medical Devices Manufacturing (“Previous Version of Measures”) will be repealed as of 1 May 2022.
The Measures provide relevant requirements from the Regulations and the Medical Devices Good Manufacturing Practice Standard (“Medical Devices GMP”, with effect from 1 March 2015), and implement stricter regulatory requirements and strengthen the supervision and management of medical devices manufacturing enterprises, under both self-manufacturing and entrusted manufacturing modes. Below we introduce main changes compared with the Previous Version of the Measures.
1. Manufacturing Quality Requirements
The structure of the Previous Version of Measures has been adjusted, by deleting the whole of original Chapter III Entrusted Manufacturing Management, in order to adapt to the market authorized holder regime established in the Regulations. Medical devices registrant and filing entities shall be responsible for the quality of medical devices they manufactured, regardless of whether they are self-manufactured or manufactured by a third party under entrusted manufacturing mode.
a) Responsible Person
Article 26 of the Measures provides that the legal representative and principal person in charge of a medical device registrant and filing entity shall be fully responsible for the quality and safety of the medical devices they manufacture.
b) Management Representative
Article 27 of the Measures provides that medical devices registrants, filing entities, and entrusted manufacturing enterprises shall be equipped with management representatives. The management representative is appointed by the legal representative or the main person in charge to perform the responsibilities of establishing, implementing and maintaining the effective operation of quality management system. This provision actually comes from the requirements under Article 7 of the Medical Devices GMP.
c) Training, Equipment and Design Development
Article 28 to Article 30 impose requirements for medical devices registrants, filing entities, and entrusted manufacturing enterprises in terms of training, equipment and design development. Specifically, such entities shall:
(1) establish a training system, formulate training plans, strengthen assessment and make training records;
(2) ensure that facilities and equipment are reasonably equipped and used, the management of facilities and equipment is strengthened, and the effective operation of facilities and equipment is maintained;
(3) carry out conversion activities from design and development to manufacturing, and conduct sufficient verification and confirmation to ensure that design and development output is suitable for manufacturing.
The above requirements correspond with those stipulated in the Medical Devices GMP.
d) Assessment and Entrustment Agreement
Article 32 provides that in case of entrusted manufacturing, medical device registrants or filing entities shall evaluate quality assurance ability and risk management ability of the entrusted party, and sign a quality agreement and an entrustment agreement with the entrusted party in accordance with the Guidelines for the Quality Agreement of Entrusted Manufacturing formulated and issued by the National Medical Products Administration (“NMPA”) on 22 March 2022.
e) Product Release
Article 34 of the Measures provides that medical device registrants and filing entities shall be responsible for product release, establish product release procedures, clarify release standards and conditions, and review medical device manufacturing process records and quality inspection results. If the standards and conditions are met, the products can be released after the authorized release personnel has signed his name on the release documents. In the case of entrusted manufacturing, medical device registrants and filing entities shall also review manufacturing release documents of the entrusted manufacturer. The entrusted manufacturing enterprise shall establish manufacturing release procedures, clarify the standards and conditions for manufacturing release, and confirm that the standards and conditions are met before the products leave factory.
Products release was not included in the Previous Version of Measures, but already regulated under the Medical Devices GMP, while the Measures provide more specific product release requirements compared to the Medical Devices GMP.
f) Unique Device Identification (“UDI”) System
The Measures stipulate that medical devices registrants, filing entities, and entrusted manufacturing enterprises shall implement a UDI system for medical devices. We believe that this is referring to the Announcement of the National Medical Products Administration on Issuing the Rules for the Unique Device Identification System for Medical Devices, with effect from 1 October 2019). The process of UDI system for medical devices are being implemented step by step and as of today, the NMPA together with the National Heath Commission and the National Healthcare Security Administration has published the lists of two batches of medical products that are subject to UDI system, including all Class-III medical devices.
g) Traceability, Correction Measures, Precaution Measures, Change of Raw Material or Processing, Adverse Effect and Recall
To implement market authorization holder regime and to adapt to regulatory requirements included in the Medical Devices GMP, the Measures stipulate provisions relating to traceability, correction measures, precaution measures, change of raw material or processing, adverse effect and recall that are either included in the Regulations or in the Medical Devices GMP.
The Measures, however, further clarify that, for instance, although both medical devices registrants/filing entities and entrusted manufacturing entities are under the obligation to establish product traceability, entrusted manufacturing entities shall assist medical devices registrants and filing entities in implementing product traceability (Article 35). Also, entrusted manufacturers shall perform their responsibilities in accordance with the relevant provisions on medical devices recall, and assist medical devices registrants and filing entities in recalling the medical devices produced under entrusted manufacturing mode (Article 41).
h) Product Types
According to the Previous Version of Measures, a product registration form shall be affixed to medical devices manufacturing license specifying the name of products to be manufactured. According to Article 14 of the Measures, the name of products to be manufactured is no longer a registered item on medical devices manufacturing license or its duplicate, while the list of products to be manufactured should be submitted when applying for the medical devices manufacturing license.
Accordingly, Article 42 of the Measures modifies the procedures for adding product types compared with Article 14 of the Previous Version of Measures. According to the Measures, adding product types only needs to be reported to the original license-issuing or filing authorities instead of being recorded in the product registration form.
Moreover, if the increase in product types involves changes in manufacturing conditions that may affect the safety and effectiveness of products, it shall be reported to the original license-issuing authorities 30 working days before the manufacturing of new products types, and the original license-issuing authorities shall conduct on-site inspections in a timely manner. In the case of changes in licensing items, it shall be handled in accordance with the procedures for change of licensing items specified by the Measures.
i) Self-inspection Report
Article 45 of the Measures provides that medical device registrants, filing entities and entrusted manufacturing enterprises shall conduct self-inspection on the operation of the quality management system every year, and submit a self-inspection report to the local drug administrative authorities before March 31 of the following year. Registrants and filing entities for imported medical device shall submit self-inspection reports by their agents to drug administrative authorities of the province, autonomous region, or municipality directly under the central government where the agent is located.
2. Adjustment in Formalities for License or Record-Filing
The Measures adjust the formalities for obtaining license or record-filing for medical devices manufacturing. The main adjustments are described as below:
a) Documents submitted for Class-II and Class-III Medical Devices Manufacturing License
Compared with Article 8 of the Previous Version of Measures, Article 10 of the Measures newly requires the submission of relevant materials proving after-sales service abilities, which means that in order to obtain medical devices manufacturing license, the applicant needs to have after-sales service capacity.
Article 10 of the Measures also changes the original requirements of submission of quality manual and procedures documents into submission of the catalogue of quality manual and procedures documents. However, it should be noted that Article 13 of the Measures provides that on-site inspection for medical devices manufacturing license shall be conducted according to the Medical Devices GMP so that all the quality aspects shall be in line with the Medical Devices GMP.
b) Reporting of Change in Manufacturing Conditions
Article 15 of the Measures newly provides that if workshop or production line is modified, resulting in changes in manufacturing conditions which may affect safety and effectiveness of medical devices, such modification shall be reported by medical devices registrants to the original authority issuing the license. In the event of a change in licensing matters, for instance change of manufacturing address or expansion of manufacturing scope, then the relevant licensing change procedures shall be handled in accordance with the regulations. This provision implies that some changes in manufacturing conditions would only require reporting while others will require going through the change in licensing matters. We advise medical devices registrants should timely communicate with the original authority issuing the license to see whether any change in manufacturing conditions requires change in licensing matters.
c) Deletion of Requirement for Public Notification on Newspaper
Article 19 of the Measures provides that if a medical devices manufacturing license is lost, the relevant entity shall apply to the original license-issuing authority for reissuance. This provision deletes the original rule in Article 19 of the Previous Version of Measures requiring that a public notification on newspaper concerning the loss of license should be carried out.
d) Formalities for Class-I Medical Devices Manufacturing Filing
Article 22 of the Measures modifies Article 11 of the Previous Version of Measures in terms of formalities for Class-I medical devices manufacturing filing in the following three aspects:
(1) for Class-I medical devices manufacturing filing, only the serial number of filing will be issued to the applicant. Thus, there will no longer be any filing proof;
(2) the Class-I medical devices manufacturing filing can be carried out together with the filing of the Class-I medical devices product;
(3) drug administrative authorities shall conduct an on-site inspection in accordance with Medical Devices GMP within three months of completion of filing for Class-I medical devices manufacturing.
3. Stricter Supervision Measures
The Measures introduce a set of supervision measures which are stricter than those contained in the Previous Version of the Measures.
a) Extension of Inspection
Article 46 of the Measures provides that when necessary, drug administrative authorities may extend inspections to other units and individuals that provide products or services for medical device manufacturing activities.
b) Grading Management
Article 48 of the Measures provides that drug administrative authorities implement grading management and dynamic adjustment of medical device registrants, filing entities and entrusted manufacturing enterprises according to the risk level of products and enterprises. On one hand, drug administrative authorities will formulate the list of key supervision products on provincial level; on the other hand, they will grade the relevant entities taking into consideration their manufacturing quality management status, adverse events, product complaints and reports, and corporate credit status, etc.
For those manufacturers of the products included in the provincial-level list of key supervision products, such manufacturers will be inspected at least once a year (Article 49 of the Measures).
c) Key Inspection Aspects
Compared to the Previous Version of Measures, the Measures specifically list, the key inspection aspects respectively for those medical devices registrants and filing entities which self-manufacture medical devices and which adopt entrusted manufacturing mode.
Article 51 of the Measures provides that for those medical devices registrants and filing entities that self-manufacture, the key inspection aspects are:
(1) the implementation status of laws and regulations and Medical Devices GMP by medical device registrants and filing entities;
(2) whether they organize manufacturing in accordance with mandatory standards and registered and filed product technical requirements, and whether the actual manufacturing is consistent with medical device registration or filing, medical device manufacturing license or filing, etc.;
(3) the continuous compliance and effectiveness of the operation of quality management system;
(4) whether legal representative, person in charge of the enterprise, management representative and other personnel are familiar with the relevant laws and regulations of medical devices;
(5) the performance of management representative;
(6) changes in legal representative, person in charge of the enterprise, management representative, quality inspection agency or full-time personnel, manufacturing site, environmental conditions, key manufacturing inspection equipment, etc.;
(7) corrective and preventive measures for problems found in user feedback and internal audit of the enterprise;
(8) the rectification and implementation of the problems found in product sampling inspection, supervision and inspection, complaints and reports;
(9) internal audit, management review, change control, annual self-inspection report, etc.;
(10) other aspects that should be checked.
Article 52 of the Measures provides that for those medical devices registrants and filing entities that adopt entrusted manufacturing mode, the key inspection aspects are:
(1) the implementation status of laws and regulations and Medical Devices GMP by medical device registrants and filing entities;
(2) whether the operation of the quality management system is continuously compliant and effective;
(3) the performance of management representative;
(4) whether they organize manufacturing in accordance with mandatory standards and registered or filed product technical requirements;
(5) corrective and preventive measures for problems found in user feedback, internal audits, etc.;
(6) internal audit, management review, change control, annual self-inspection report, etc.;
(7) status of carrying out adverse event monitoring, re-evaluation, and product safety risk information collection and evaluation;
(8) the release status of product;
(9) the supervision of the entrusted manufacturing enterprises, the performance of quality agreement of entrusted manufacturing, design conversion and change control of entrusted manufacturing products, release of entrusted manufacturing products, etc.;
(10) other contents that should be checked.
When necessary, inspections of entrusted manufacturing enterprises may be carried out by drug administrative authorities.
d) Inspections with Cause, Follow-up Inspections and Cross-Region Inspections
Article 54 to Article 59 of the Measures provide inspection methods, including inspections with cause which are in principle conducted without prior notice, follow-up inspections regarding the rectification status of the relevant entities and cross-region inspections where medical devices registrants or filing entities and entrusted manufacturing enterprises are located in different provincial areas.
e) Imported Medical Devices
Article 61 and Article 62 of the Measures stipulate that manufacturing of imported medical devices shall be subject to overseas inspections organized by the NMPA. The domestic agent designated by imported medical devices registrants or filing entities is responsible for coordinating and cooperating with overseas inspections.
If imported medical device registrants, filing entities and agents refuse, obstruct, delay or evade the overseas inspection organized by the NMPA, resulting in the inability of NMPA to carry out inspection work and its inability to confirm the effective operation of quality management system, this would be regarded as if that it might do harm to human health. The NMPA can order emergency control measures to suspend production, import, trading, and use, and issue safety warnings.
f) Credit File
Compared with Article 57 of the Previous Version of Measures, Article 67 of the Measures changes supervision file to credit file for Class-II and Class-III medical devices registrants and entrusted manufacturing enterprises. It also provides that for medical device registrants, filing entities, and entrusted manufacturing enterprises with bad credit records, drug administrative authorities shall increase frequency of supervision and inspection, and strengthen punishments for dishonesty in accordance with the law.
4. Heavier Legal Liabilities
Except for those acts of violation that are subject to the relevant clauses concerning legal liabilities laid down in the Regulations, the Measures intensify the punishment for those acts specifically regulated under the Measures.
a) Article 78 of the Measures provides that under any of the following circumstances, drug administrative authorities shall give a warning and impose a fine of not less than 10,000 RMB but not more than 50,000 RMB:
(1) A medical device manufacturing entity fails to report product types and relevant information to drug administrative authorities;
(2) Manufacturing has been discontinued for more than one year and there is no similar product in manufacturing and no necessary verification and confirmation are carried out during the restart of manufacturing and they are not reported to the local drug administrative authorities.
b) Article 79 of the Measures provides that under any of the following circumstances, drug administrative authorities shall order corrections within a time limit. If the relevant medical devices registrants, filing entities or entrusted manufacturing entities refuse to make corrections, a fine of not less than 10,000 RMB but not more than 50,000 RMB shall be imposed. In serious circumstances, a fine of not less than 50,000 RMB but not more than 100,000 RMB shall be imposed:
(1) Failure to change the registration items of medical devices manufacturing license in accordance with the Measures;
(2) Failure to organize and carry out design and affixing of UDI code, data upload, maintenance and update work in accordance with the relevant requirements of the state for the implementation of UDI of medical devices.
Medical devices registrants, filing entities and entrusted manufacturing entities should follow the new requirements contained in the Measures in order to achieve full compliance.
1In the Announcement on Matters relating to the Implementation of the Medical Devices GMP Standard (issued on 5 September 2014), Article 4 provides that as of 1 January 2018, all medical device manufacturing entities shall be compliant with the Medical Devices GMP Standard.
2According to the Announcement of the NMPA on the Implementation of the Measures on the Supervision and Administration of Medical Devices Manufacturing (issued on 11 March 2022), however, the Class-I medical devices filing proof can be provided at the request of the enterprises.
3To be carried out when it is found that there may be serious quality and safety risks due to adverse event monitoring, random inspection, complaint reporting, etc. (Article 54 of the Measures)