After more than 20 years of development, medical device clinical trials have gradually become independent of drug clinical trials and formed a unique clinical trial regulatory system for medical devices. The supervision of medical device clinical trials has mainly gone through three stages: the initial stage of supervision, the regulatory transition period and the whole life cycle supervision, and this paper analyzes the development process of medical device clinical trials in China from the perspective of regulations, regulatory characteristics and requirements.
Phase 1: The initial stage of clinical trial supervision of medical devices (2000-2014).
The Regulations on the Administration of Medical Devices (Order No. 276) was promulgated and implemented on January 4, 2000, and for the first time put forward the provisions on clinical trials of medical devices, which stipulate that new products for Class II and Class III medical devices shall complete clinical trials, and the production of Class II and Class III conventional medical devices shall pass clinical verification, and clinical trials or clinical verification shall be carried out in designated medical institutions. On April 1, 2004, the "Regulations on Clinical Trials of Medical Devices" was promulgated and implemented, which formally put forward normative requirements for the development of clinical trials of medical devices, stipulating that clinical trials of medical devices are divided into two types: clinical trial and clinical verification.
With the development of the medical device industry, the original medical device clinical trial regulatory system can not meet the needs of clinical trials, and the medical device industry urgently needs to adjust and revise the regulations on medical device clinical trials, so in August 2012, when the State Food and Drug Administration issued the first edition of the "Medical Device Clinical Trial Quality Management Standards" (also known as medical device GCP) and solicited opinions from the industry, medical device GCP put forward more standardized requirements for the medical device clinical trial process.
Phase II: Transition period for the supervision of medical device clinical trials (2014-2021).On June 1, 2014, the new version of the Regulations on the Supervision and Administration of Medical Devices (Order No. 650) was officially promulgated and implemented, and the supervision of medical devices was comprehensively adjusted.
On May 4, 2017, the revised version of the Regulations on the Supervision and Administration of Medical Devices (Order No. 680) was promulgated and implemented, and the new regulations clarified the implementation of record management for medical device clinical trial institutions, providing a regulatory basis for the subsequent release and implementation of the "Medical Device Clinical Trial Institution Conditions and Filing Management Measures". Previously, medical device clinical trial institutions have been carried out in drug clinical trial bases, considering that the characteristics and methods of medical device clinical trials are quite different from drug clinical trials, it is necessary to standardize medical device clinical trial institutions, based on this, in 2015, the "Medical Device Clinical Trial Institutions Conditions and Filing Management Measures" was issued for comments and officially released and implemented in November 2017, and the measures stipulate that medical institutions will start filing from January 1, 2018. From January 1, 2019, all medical device clinical trials must be carried out in a medical device clinical trial institution that has been filed.
With the popularization of clinical trials of medical devices and the development of clinical trial verification, the provincial bureau for the filing of medical device clinical trials and the filing of human genetic resources have been implemented since 2015. On June 1, 2016, the "Medical Device Clinical Trial Quality Management Standards" (Medical Device GCP) was issued and implemented for the first time, which put forward comprehensive and standardized requirements for the development of medical device clinical trials, and the concept of multi-center clinical trials and team leader units, device defects, statistical requirements, and SAE declaration were put forward in the medical device GCP, of which multi-center clinical trials are required to be carried out in at least 3 centers.
In 2016, the national bureau and the provincial bureau issued a verification plan for clinical trials of medical devices, and the development of clinical trials of medical devices has become more and more stable after experiencing the verification storm. On October 8, 2017, the state put forward the "Opinions on Deepening the Reform of Review and Approval to Encourage the Innovation of Drugs and Medical Devices", Shaogang proposed to reform the clinical trial management system, implement the filing system for clinical trial institutions, and participate in clinical research institutions, improve the ethical mechanism, improve the efficiency of ethical review, optimize the approval process of clinical trials, accept overseas clinical trial data, and expand the clinical trial mechanism, etc., which provides regulatory support for the future reform of the clinical trial management system of medical devices.
Since the outbreak of the new crown epidemic in 2020, the supervision of medical devices has faced new problems, and the current regulations are not clear about emergency approval, urgent clinical needs, conditional approval, overseas clinical trials and other special clinical trials, which also paves the way for the subsequent revision of relevant regulations. The third stage: the whole life cycle supervision stage of medical devices (2021 to present).
On June 1, 2021, the new version of the "Regulations on the Supervision and Administration of Medical Devices" (*Order No. 739) was issued and implemented, the new regulations focus on reforming the clinical trial management system, putting forward the concept of clinical evaluation for the first time, and adding a conditional approval system for medical devices, an emergency use system for medical devices, an ethical review system for clinical trials for medical devices, and an expanded clinical trial management system for medical devices. Improve the clinical evaluation system of medical devices and the clinical trial management system of medical devices. The supervision of medical devices has entered the stage of supervision of the whole life cycle of products, and the clinical trials of medical devices have also entered a new stage. Based on the implementation of the new regulations, on June 1, 2022, the new version of the GCP for medical devices "Quality Management Standards for Clinical Trials of Medical Devices" (No. 28 of 2022) was officially released and implemented, and the new version of the GCP for medical devices included clinical trials of in vitro diagnostic reagents in the GCP of medical devices for the first time; Adjust the safety information reporting process; The relevant requirements have been simplified, such as the abolition of the requirement for the number of clinical trial institutions and the requirement of a one-year validity period of the test report.
With the development of the medical device industry and clinical research technology, more and more attention has been paid to real-world clinical trials in recent years, so since 2020, regulations and pilots related to real-world clinical trials have been successively issued and implemented, enriching the types of clinical trials of medical devices. Wrapping up
Medical device clinical trials are a way in clinical evaluation activities, so medical device clinical trials should first understand the requirements and specifications of medical device clinical evaluation, and be familiar with the clinical evaluation decision-making path and clinical trial decision-making path, in order to better carry out medical device clinical research. **CIRS Group website.