Recently, in order to deepen the reform of the medical device review and approval system and strengthen the management of medical device clinical trials, the State Food and Drug Administration, together with the National Health Commission, organized the revision and release of the “Quality Management Standards for Clinical Trials of Medical Devices”, which will be effective from May 1, 2022. The State Food and Drug Administration has provided relevant interpretations on the revision background, main contents and key revised parts of the Specifications:
1. Revision background
In 2016, the former State Food and Drug Administration, together with the former National Health and Family Planning Commission, issued the “Good Quality Management Practices for Medical Device Clinical Trials” (State Food and Drug Administration Order No. 25) (hereinafter referred to as the “2016 “Code”). The implementation of this specification has established the guidelines for clinical trials of medical devices, and has played a positive role in strengthening the management of clinical trials of medical devices and safeguarding the rights and interests of subjects.
In recent years, as the reform of the medical device review and approval system has continued to deepen, many reform policies have been introduced, such as changing the qualification accreditation of medical device clinical trial institutions to filing management. Some of the contents in the 2016 “Specifications” can no longer meet the needs of today’s clinical trial development. In order to implement the reform requirements of the medical device review and approval system, cooperate with the implementation of the newly revised “Medical Device Supervision and Administration Regulations”, “Medical Device Registration and Filing Management Measures”, and “In Vitro Diagnostic Reagents Registration and Filing Management Measures”, and actively transform and apply international medical device regulatory coordination documents, it is necessary to modify and supplement the 2016 “Specifications” to adapt to the current needs of medical device clinical trial supervision.
2. Scope of application Within the territory of the People’s Republic of China, activities related to clinical trials of medical devices carried out for the purpose of applying for registration of medical devices (including in vitro diagnostic reagents) shall comply with the “Specifications”. The “Specifications” cover the entire process of medical device clinical trials, including plan design, implementation, monitoring, inspection, and inspection of medical device clinical trials, data collection, recording, preservation, analysis, summary, and reporting, etc.
3. Main content The “Specification” has nine chapters and 66 articles. The chapter names are general principles, ethics committees, medical device clinical trial institutions, researchers, sponsors, clinical trial protocols and trial reports, multi-center clinical trials, recording requirements and supplementary provisions. The general chapter clarifies the legal basis and scope of application; the ethics committee chapter stipulates the principles and review requirements for ethical review; the medical device clinical trial institution chapter clarifies that the medical device clinical trial institution should have a corresponding clinical trial management department to be responsible for the management of medical device clinical trials; the researcher chapter emphasizes the conditions and responsibilities that researchers should have; the sponsor chapter highlights the main responsibilities of the sponsor and requires the application The quality management system of the applicant should cover the entire process of clinical trials of medical devices; the clinical trial protocol and trial report chapters outline the general requirements, main contents, signature requirements, etc. of the plan and report; the multi-center clinical trial chapter clarifies the definition and requirements of multi-center; the recording requirements chapter stipulates the basic principles of clinical trial records, and requires the completion of case report forms and electronic data collection; the supplementary chapter proposes terminology and implementation dates.
4. Key revisions: (1) Adjust the overall framework: Chapters such as pre-clinical trial preparation, protection of subjects’ rights and interests, and management of experimental medical devices in the 2016 “Specifications” are classified into the responsibilities of each participant in the clinical trial. This structural adjustment makes it clearer and emphasizes the responsibilities of all parties. First, it highlights the main responsibility of the sponsor, introduces the concept of risk management, and clearly stipulates that the sponsor’s quality management system should cover the entire process of medical device clinical trials; second, it strengthens the requirements for medical device clinical trial institutions, and clinical trial institutions should establish a clinical trial management organizational structure and management system; third, it emphasizes the responsibilities of researchers, and researchers should implement medical device clinical trials in accordance with the “Specifications” and relevant laws and regulations. (2) Incorporating in vitro diagnostic reagents into the management of the “Specifications” In order to adapt to the needs of the in vitro diagnostic reagent industry and supervision, this revision has incorporated the clinical trial quality management requirements for in vitro diagnostic reagents into the “Specifications” to reflect the unity of clinical trial quality management concepts and requirements. (3) Adjustment of the safety information reporting process The “Standards” have optimized and adjusted the safety information reporting process. The first is to change “double reporting” to “single reporting”. The sponsor shall report to the local provincial drug regulatory department, the provincial drug regulatory department and the health management department where the medical device clinical trial institution is located. The second is to determine the reporting scope as serious adverse events related to experimental medical devices. Third, the reporting time limit for death or life-threatening risks is required to be within 7 days after the sponsor is informed, and the reporting time limit for non-death or non-life-threatening and other serious safety risks is within 15 days after the sponsor is informed. (4) Simplifying and optimizing relevant requirements: The “Specifications” combine industry needs and regulatory realities to effectively solve the current problems that are relatively concentrated. The requirement that “medical device clinical trials should be conducted in two or more medical device clinical trial institutions” is deleted, which solves the problem that it is difficult and unnecessary for some medical devices to conduct clinical trials in two clinical trial institutions. The one-year validity requirement for inspection reports has been removed, which is conducive to the smooth development of clinical trials. (5) Reflecting the latest international regulatory system requirements. The “Specification” draws on the relevant content of the regulatory coordination documents of the International Medical Device Regulators Forum (IMDRF), such as absorbing the content of IMDRF MDCE WG/N57 FINAL:2019 “Clinical Trials” and introducing the concept of multi-regional clinical trials conducted in different countries or regions, which is conducive to the simultaneous conduct of medical device clinical trials in China for global innovative products. During the revision process, full reference was made to the relevant contents of ISO 14155:2020 “Good Clinical Practice for Medical Devices” and ISO 20916:2019 “In vitro diagnostic medical devices – Clinical performance studies using human samples – Good Research Quality Management Practice”, and the latest versions of international standards are reflected in the text and terminology.
5. Regarding the connection between the old and new system documents. The “Standards” will come into effect on May 1, 2022. The 2016 “Standards” will be abolished on May 1, 2022 in accordance with the “Decision of the State Administration for Market Regulation on Amending and Abolition of Some Regulations” (State Administration for Market Regulation Order No. 55). Starting from May 1, 2022, medical device clinical trial projects that have not passed the ethical review should be adjusted in accordance with the “Specifications” before conducting clinical trials; projects that have passed the first ethical review can be carried out in accordance with the requirements of the original relevant documents.
6. Supporting documents for the “Specifications” In order to cooperate with the implementation of the “Specifications” and further guide the conduct of clinical trials, our bureau has formulated six documents: “Medical Device Clinical Trial Plan Template”, “Medical Device Clinical Trial Report Template”, “In Vitro Diagnostic Reagent Clinical Trial Plan Template”, “In Vitro Diagnostic Reagents Clinical Trial Report Template”, “Medical Device/In Vitro Diagnostic Reagents Clinical Trial Serious Adverse Event Report Form Template” and “Medical Device/In Vitro Diagnostic Reagents Clinical Trial Basic Document Catalog”, which are implemented simultaneously with the “Specifications”.