On February 9, 2021, the State Council issued order 739, and promulgated the newly revised regulations on the supervision and administration of medical devices (hereinafter referred to as the new regulations), which will come into effect on June 1st, 2021. The new regulations have comprehensively revised the relevant requirements for clinical evaluation of medical devices, including the situation of exemption from clinical evaluation (Article 24), the path of clinical evaluation and the medical devices (Article 25) for which clinical trials should be conducted, encouraging and supporting medical institutions to develop clinical trials (Article 26), and implied permission for examination and approval of clinical trials (Article 27), The ethical review and informed consent of clinical trials (Article 28), the expansion of the use of medical devices in urgent need of clinical use (Article 29) and so on.

This paper, based on the background, content, practical significance and implementation measures of the new regulations on clinical evaluation of medical devices, expounds how the new regulations consolidate the reform results of the review and approval system in the form of regulations, and promote the reform of medical equipment temporary evaluation to the vertical and deepening development from the system level, and further promote the industrial innovation and development, In order to better meet the people's needs for high-quality and high-performance medical devices.

Background of revision: review of the reform results of the examination and approval system and the International Coordination Document led by China

（1） Consolidate the reform results of the examination and approval system of medical devices

In October 2017, the general office of the Central Committee of the CPC and the general office of the State Council issued the opinions on deepening the reform of the review and approval system and encouraging innovation of medical devices for drugs and medical devices, and put forward the requirements for the reform of clinical trial management.

After three years of reform and practice, the stage achievements have been achieved in the formulation of clinical evaluation normative documents and the review of specific products, which effectively promotes the acceleration of the listing of innovative medical devices, and the access of patients who need medical devices in clinical《 The issuance and implementation of documents such as the management regulations on the extended clinical trials of medical devices (Trial), the technical guidelines for the application of real world data for clinical evaluation of medical devices (Trial), the technical guidelines for receiving overseas clinical test data of medical devices and the guiding principles for clinical trial design of medical devices enrich and broaden the source of clinical data, The problem of how to carry out clinical trials has been solved, and new methods and tools of clinical evaluation have been produced, and scientific clinical evaluation ideas have been formed. In the review and approval of specific products, the clinical evaluation path of various products has basically reached consensus between regulatory agencies and the industry. The proportion of clinical trials in product registration and licensing items change projects has been effectively reduced and is at a reasonable level.

（2） Implement the international coordination document of clinical evaluation led by China

In March, 2018, the new project proposal of "clinical evaluation of medical devices (mdce)" proposed by the State Drug Administration was successfully established at the 13th imdrf Management Committee meeting of the international regulatory forum of medical devices (imdrf). In September 2019, the project outcome documents "clinical evidence - main definitions and concepts" and "clinical evaluation" and "clinical trials" which were led by China regulatory agencies and participated by major international regulators were successfully passed at the 16th imdrf Management Committee meeting. As an international coordination document in the field of clinical evaluation of medical devices, it was officially released on imdrf official website.

The three international coordination documents comprehensively and systematically clarified the related problems in the field of clinical evaluation of medical devices, including the main definitions and concepts, the role, scope, process, path and data source of clinical evaluation, when to need and how to carry out clinical trials. The above documents are not only an effective reflection of new ideas, ideas and methods of clinical evaluation of medical devices in the world, but also a concentrated reflection of the reform results of China's review and approval system. As a member of imdrf, China, as the lead drafter of the above coordination documents, shall implement the issued coordination documents in accordance with the imdrf standard operating procedures.

Revised content: establish clear clinical evaluation requirements that are suitable for product characteristics and clinical risks

Through comprehensive analysis, in-depth analysis and precise refining of the reform results of the review and approval system and the relevant requirements of international coordination documents, the new regulations have revised the relevant provisions of clinical evaluation in a highly generalized language.

（1） The first time the "situation that can be exempted from clinical evaluation" is proposed

Article 24 it is suggested that "clinical evaluation shall be conducted for registration and filing of medical devices products, but it may be exempted from clinical evaluation if it meets any of the following circumstances:

The working mechanism is clear, the design is fixed, the production process is mature, the same medical devices of the same type have been listed for many years without serious adverse events records, and the conventional use is not changed;

Other medical devices can be proved safe and effective through non clinical evaluation.

（2） Clearly state the "path of clinical evaluation of medical devices", and accurately define "medical devices that should carry out clinical trials"

Article 25 it is clear that "in the clinical evaluation of medical devices, it is possible to prove the safety and effectiveness of medical devices by carrying out clinical trials according to the product design characteristics, clinical risks, existing clinical data and other situations, or through analysis and evaluation of clinical literature and clinical data of the same type of medical devices".

"When conducting clinical evaluation of medical devices in accordance with the provisions of the drug regulatory department under the State Council, the existing clinical literature and clinical data are not enough to confirm the safety and effectiveness of the products, clinical trials shall be carried out.".

（3） On the basis of strengthening the quality management of clinical trials, support and encourage medical institutions to carry out clinical trials of medical devices

On the basis of standardizing the quality management of clinical trials, clinical trials and clinical trial institutions, Article 26 further proposes that "the State supports medical institutions to carry out clinical trials, and integrates the evaluation of clinical test conditions and capabilities into the medical institutions' level evaluation, and encourages medical institutions to carry out innovative clinical trials of medical devices". Article 28 in order to carry out clinical trials of medical devices, ethical examination shall be conducted, informed consent of the subjects shall be obtained, and no fees related to clinical trials shall be charged.

（4） "Implied permission" is adopted for approval of high risk clinical trials

If the clinical test of the third type of medical device has a high risk to human body, it shall be approved by the drug regulatory department under the State Council. Article 27 it is clearly pointed out that the drug regulatory department under the State Council shall examine and approve clinical trials, "and shall make decisions within 60 working days from the date of acceptance of the application and notify the applicant of clinical trials.". If the notice is not given within the time limit, it shall be deemed to be consent. ".

（5） Expand the use of "medical devices for diseases that are seriously life-threatening and have no effective treatment"

Article 29 states that "medical devices used in clinical trials for diseases that are seriously life-threatening and have no effective means of treatment may benefit patients through medical observation. After ethical review and informed consent, they can be used for other patients with the same conditions free of charge in the institutions that carry out clinical trials of medical devices, The safety data can be used for medical device registration application.

Significance of revision: further guarantee the safety and effectiveness of products and promote the innovation and development of industry

（1） Strictly abide by the effective bottom line of product safety and protect people's life safety and health

With the safety and effectiveness of medical devices as the goal, the clinical evaluation requirements are set according to the product design characteristics, clinical risk, application history and other factors. If the non clinical evaluation can prove that the product is safe and effective, the clinical evaluation shall be avoided; For clinical evaluation, it can be proved that the product is safe and effective by analyzing and evaluating the clinical literature and clinical data of the same kind of medical devices; When the existing clinical literature and data are not enough to confirm the safety and effectiveness of the product, clinical trials should be carried out. The hierarchical clinical evaluation requirements are compatible with the safety and effectiveness evaluation of specific products, and the clinical evaluation objectives are clear and the key points are prominent, which is conducive to strictly observe the safety and effective bottom line and protect people's life safety and health.

（2） Further clarify the requirements of clinical evaluation, reasonably reduce the burden of the industry, and promote the innovation and development of the industry

The new "Regulations" clearly points out the path and related requirements of clinical evaluation, that is, the same kind of clinical evaluation path and clinical trial path. For whether to carry out clinical trials, from the current "Regulations" that "clinical trials should be carried out when applying for the registration of class II and class III medical devices" to the new "Regulations" that "clinical trials should be carried out when the clinical evaluation of medical devices is not enough to confirm that the products are safe and effective", the need to evaluate the safety and effectiveness of products is determined, The principle of deciding whether to carry out clinical trials greatly reduces the scope of carrying out clinical trials, which is consistent with the clinical trial decision-making ideas of international coordination documents, reasonably reduces the burden of the industry, and promotes the innovation and development of the industry.

（3） Encourage and support medical institutions to carry out clinical trials and provide high-quality data for clinical evaluation

The new regulation clearly points out that the State supports and encourages medical institutions to carry out clinical trials, and brings the evaluation of clinical trial conditions and capabilities into the level evaluation of medical institutions, which injects driving force for medical institutions to actively carry out clinical trials of medical devices and improve the ability and level of clinical trials, and is conducive to improving the quality of clinical trials, To provide high quality data for clinical evaluation of medical devices.

（4） Follow scientific principles, emphasize standardized management, expand international vision, and promote the reform of clinical evaluation of medical devices to deepen

Based on the needs of product safety and effectiveness evaluation, different clinical evaluation requirements are set to decide whether to carry out clinical trials, which follows the scientific principles of clinical evaluation; The drug regulatory department formulated relevant guidelines and catalogues, emphasizing the standardized management of clinical evaluation and the openness and transparency of relevant requirements; The overall requirements of clinical evaluation are highly consistent with imdrf international coordination documents, reflecting the international perspective, which is conducive to the interoperability of clinical evaluation documents of applicants in different countries and regions.

Implementation measures: to build a general guiding principle system for clinical evaluation of medical devices, and effectively guide the development of clinical evaluation

In order to implement the relevant requirements of clinical evaluation in the new regulations, a series of supporting general technical guidelines for clinical evaluation will be issued, It includes "technical guidelines for clinical evaluation of medical devices (Revised)", "technical guidelines for writing clinical evaluation reports of medical devices", "technical guidelines for deciding whether to carry out clinical trials of medical devices", "technical guidelines for equivalence demonstration of medical devices", "technical guidelines for clinical trials of in vitro diagnostic reagents (Revised)". The above guiding principles, together with the technical guiding principles related to clinical evaluation issued in the reform of the review and approval system, initially constructed the general guiding principles system for clinical evaluation of medical devices (see table), effectively guiding the regulatory agencies and the industry to carry out relevant work.

Author: Sun Lei, director of medical device technical evaluation center of State Food and Drug Administration

Source: Center for technical evaluation of medical devices, State Drug Administration