On July 20, 2015, the National Health and Family Planning Commission and the State Food and Drug Administration issued the “Stem Cell Clinical Research Management Measures (Trial)” in the form of National Health Science and Education Development [2015] No. 48. The “Measures” are divided into general principles, conditions and responsibilities of institutions, research project establishment and filing, clinical research process, research reporting system, responsibilities of expert committees, supervision and management, and 8 chapters and 55 articles in the appendix.
The following is the official interpretation of the Measures:
1. Why should management measures for stem cell clinical research be formulated?
Stem cells are a type of pluripotent cells with the ability to self-replicate and can differentiate into a variety of functional cells under certain conditions. Due to their proliferation and differentiation properties, stem cells, as “seed” cells, can participate in cell replacement and tissue regeneration. Stem cell research, as a key development field at the forefront of medicine in recent years, has shown good development prospects, brought hope for effective treatment of some difficult diseases, and received widespread attention. my country has given key support to stem cell research in the “Twelfth Five-Year Plan” science and technology plan, and has made gratifying progress. While stem cell research and translational applications are developing rapidly, some problems have also emerged, such as institutionsâ obvious profit-seeking tendency and charging high fees; stem cell preparation standards are not uniform, and there are serious quality risks; and due to the lack of effective academic and ethical review and informed consent, it is difficult to protect the rights and interests of subjects. Some stem cell treatments that evade government regulation and lack preclinical research data are repeatedly banned. It is imperative to formulate relevant management measures, standardize stem cell clinical research, and fully protect the rights and interests of subjects.
2. What is the scope of application of the “Management Measures”?
“Management Measures” apply to stem cell clinical research conducted in medical institutions.
The “Management Measures” do not apply to hematopoietic stem cell transplantation with mature technical specifications, as well as stem cell clinical trials declared as drugs. The “Administration Measures” states that after medical institutions complete stem cell clinical research in accordance with the requirements of the “Administration Measures”, they are not allowed to directly enter clinical applications; if they apply for drug registration for clinical trials, they can submit the obtained clinical research results as technical application materials and use them for drug evaluation.
“Stem Cell Clinical Research Management Measures (Trial)” Interpretation source: The “Management Measures” of the Health and Family Planning Commission of the People’s Republic of China proposes that from the date of release of the document, stem cell therapy-related technologies will no longer be managed according to the third category of medical technology.
3. What are the principles that should be followed in stem cell clinical research?
Stem cell clinical research must follow the principles of science, standardization, and openness. Medical institutions must conscientiously perform the filing and information disclosure procedures for stem cell clinical research institutions and projects, and accept the supervision of relevant national departments.
Stem cell clinical research must follow the principles of ethics and fully protect the rights and interests of subjects, comply with the requirements of the “Ethical Review Measures for Biomedical Research Involving Humans (Trial)” and the “Ethical Guiding Principles for Human Embryonic Stem Cell Research” to ensure that the rights and interests of subjects are fully respected and protected.
4. Are charges allowed for stem cell clinical research?
Institutions that conduct stem cell clinical research shall not charge stem cell clinical research-related fees from subjects, and shall not publish or disguised stem cell clinical research advertisements.
5. What are the overall requirements for stem cell clinical research projects?
Clinical research on stem cells refers to clinical research in which stem cells derived from human autologous or allogeneic sources are injected (or implanted) into the human body after in vitro manipulation for disease prevention or treatment. The “Management Measures” stipulate that research must have sufficient scientific basis, and the effect of preventing or treating diseases is better than existing means; or be used for diseases for which there are no effective intervention measures, for diseases that threaten life and seriously affect the quality of life, and for major medical and health needs. Stem cell clinical research should comply with the requirements of the Good Clinical Practice for Drugs. Stem cell preparations should comply with the requirements of the “Guiding Principles for Quality Control and Preclinical Research of Stem Cell Preparations (Trial)”.
6. Who is responsible for stem cell clinical research?
The “Management Measures” clearly stipulate that stem cell clinical research institutions are the responsible entities for quality management of stem cell preparations and clinical research. Institutions should conduct project review, filing, information disclosure and process supervision for stem cell clinical research projects, and conduct quality management and risk control over the entire process of stem cell preparation preparation and clinical research.
7. What conditions must be met for medical institutions to conduct clinical research on stem cells?
The “Administrative Measures” stipulate that medical institutions that carry out stem cell clinical research should meet seven conditions: 1. A tertiary-level hospital; 2. Obtain relevant professional drug clinical trial institution qualifications in accordance with the law; 3. Have strong comprehensive medical, teaching and scientific research capabilities; 4. Have complete stem cell quality control conditions and a comprehensive stem cell clinical research quality management system and an independent stem cell clinical research quality assurance department; establish a stem cell preparation quality authorized person system; have a complete stem cell preparation preparation and the entire process of clinical research quality management and risk control procedures and related documents; have a stem cell clinical research audit system; 5. Stem cell clinical research project leaders and preparation quality authorized persons must have senior professional and technical titles, and the main researchers have been trained in Good Clinical Practice (GCP); 6. Have an academic committee and an ethics committee that are suitable for the stem cell clinical research being carried out; 7. Have a management mechanism to prevent stem cell clinical research risks and measures to deal with adverse reactions and adverse events.
8. How are stem cell clinical research institutions and research projects registered and disclosed?
The “Administrative Measures” stipulate that before clinical research institutions carry out stem cell clinical research projects, they should conduct academic and ethical reviews of stem cell clinical research projects in accordance with the requirements, and submit relevant project approval paper materials to the provincial health and family planning administrative departments and food and drug regulatory authorities. The provincial health and family planning administrative departments will jointly review with the food and drug regulatory authorities and then file with the National Health and Family Planning Commission and the Food and Drug Administration. At the same time, in accordance with the principle of information disclosure, clinical research institutions should disclose relevant information about stem cell clinical research institutions and projects in the medical research registration and filing information system (website: http://114.255.123.14), and be responsible for ensuring the authenticity of the registration content.
9. How to manage the stem cell clinical research process?
The “Management Measures” require clinical research institutions to supervise researchers to conduct research in strict accordance with the reviewed and filed research plans. During the clinical research process, all original records of all information about stem cell providers and subjects must be accurate, clear, electronically backed up, and kept for 30 years after the end of the clinical research. Tracking data for stem cell preparations must also be kept for at least 30 years from the date of final processing.
During the research process, institutions should promptly report stem cell clinical research progress reports, research results reports, serious adverse reactions, errors or accidents and handling measures, and rectification situations that occur during the research to the national and provincial health and family planning administrative departments and the food and drug regulatory authorities.
After the stem cell clinical research is completed, long-term follow-up monitoring of the subjects should be carried out to evaluate the long-term safety and effectiveness of the stem cell clinical research.
10. How to effectively protect the rights of subjects in stem cell clinical research?
The “Administrative Measures” stipulate that institutions conducting clinical research on stem cells should strengthen the protection of subjects. Stem cell clinical researchers must use plain, clear, and accurate language to inform donors and subjects of the purpose, significance, and content of the stem cell clinical research in which they participate, as well as expected benefits and potential risks, and sign an informed consent form on a voluntary basis. For projects with higher risks, research institutions should take effective measures to conduct key supervision and provide corresponding protection for subjects by purchasing third-party insurance.
If a subject experiences serious adverse events during stem cell clinical research, such as infectious diseases, permanent damage to human body functions or organs, life-threatening conditions, death, or situations that require medical rescue, researchers should immediately stop the clinical research.
11. What are the responsibilities of the Stem Cell Clinical Research Expert Committee and the Ethics Expert Committee?
The “Administrative Measures” stipulate that the national and provincial health and family planning administration and food and drug regulatory authorities should establish stem cell clinical research expert committees and ethics expert committees based on work needs, and clarify the responsibilities and requirements of the expert committees. It is pointed out that the expert committee should provide technical support and ethical guidance for stem cell clinical research management, conduct on-site verification and evaluation of registered medical institutions and research projects, supervise and inspect the institutional academic and ethics committee research project management work, and promote the standardized conduct of stem cell clinical research.
12. What are the main regulatory measures for stem cell clinical research?
National and provincial health and family planning administrative departments and food and drug regulatory authorities shall, in accordance with the “Administrative Measures”, strengthen the supervision of stem cell clinical research, conduct random inspections, special inspections or justified inspections of registered stem cell clinical research institutions and projects, and conduct sampling inspections of stem cell preparations of institutions when necessary. If there are violations stipulated in the “Administration Measures”, the provincial health and family planning administrative departments and the food and drug regulatory authorities will order them to suspend stem cell clinical research projects, make rectifications within a time limit, and handle them accordingly in accordance with the law; if the rectifications are still unqualified or the circumstances are serious, the National Health and Family Planning Commission and the Food and Drug Administration will order them to stop stem cell clinical research work and give a notice of criticism. If the circumstances are serious, they will be dealt with in accordance with the requirements of relevant laws and regulations. Institutions and personnel that conduct research without stem cell clinical research registration, as well as institutions and personnel that directly enter clinical applications in violation of regulations, will be dealt with in accordance with laws and regulations such as the Drug Administration Law of the People’s Republic of China and the Regulations on the Administration of Medical Institutions.