Bản dịch văn bản 01/2007/QĐ-BYT
Decision 01/2007/QĐ-BYT
Cơ quan ban hành: Bộ Y tế
Ngày ban hành: 2007-01-11

DECISION Promulgating the regulation on clinical trials of medicines THE MINISTER OF HEALTH Pursuant to June 14, 2005 Law No. 34/2005/QH11 on Pharmacy; Pursuant to the Government's Decree No. 49/2003/ND-CP of May 15, 2003, defining the functions, tasks, powers and organizational structure of the Ministry of Health; At the proposal of the director of the Department of Science and Training, the director of the Vietnam Drug Administration and the director of the Legal Department, DECIDES: Article 1.- To promulgate together with this Decision the Regulation on clinical trials of medicines. Article 2.- This Decision takes effect 15 days after its publication in "CONG BAO". To annul the Health Minister's Decision No. 186/BYT-QD of May 6, 1975, on the Regulation on trial researches into clinical treatment, and instructions on clinical studies of traditional medicines in the Regulation on evaluation of safety and efficacy of traditional medicines promulgated together with the Health Minister's Decision No. 371/BYT-QD of March 12, 1996, and the Guidelines on the technical process of clinical trials of medicines issued together with Official Letter No. 505/BYT-K2DT of January 24, 2006. Article 3.- The director of the Office, the Chief Inspector and directors of Departments under the Ministry of Health, directors of provincial/municipal Health Services, heads of health agencies in all branches and heads of units attached to the Ministry of Health shall implement this Decision. Minister of Health TRAN THI TRUNG CHIEN REGULATION ON CLINICAL TRIALS OF MEDICINES (Promulgated together with the Health Minister's Decision No. 01/2007/QD-BYT of January 11, 2007) Chapter I GENERAL PROVISIONS Article 1.- Scope of regulation 1. This Regulation provides for medicines subject to clinical trial, medicines exempt from clinical trial and medicines exempt from some phases of clinical trial in Vietnam, including finished medicines, pharmaceutical chemicals, pharmaceutical materials, vaccines and medical biological products (hereinafter collectively referred to as medicines). 2. Medicines subject to clinical trial, medicines exempt from clinical trial, and medicines exempt from some phases of clinical trial include: a/ Medicines subject to clinical trial: - Medicines containing a newly invented substance. - Medicines containing a new combination of pharmaceutical substances already marketed. - Vaccines and medical bio-products used for the first time in Vietnam. b/ Medicines exempt from clinical trial: - Generic medicines. - Foreign medicines which have not yet granted a registration number for circulation in Vietnam but have been lawfully marketed for at least five years in the country of origin; have been widely used for many patients and have been certified by a competent state agency in the country of origin to be safe and efficacious; and have the same route of usage, content and use indications in Vietnam as in the country of origin. - Oriental remedies already recognized by the Ministry of Health. c/ Medicines exempt from some phases of clinical trial: - Medicines with new indications or medicines with new routes of usage or medicines with new forms of preparation in the world compared to their indications, routes of usage and forms of preparation of medicines in circulation. - Foreign medicines specified in Item 2, Clause b which have been lawfully marketed in the country of origin for less than five years. Apart from the above cases, the Minister of Health shall consider and decide on specific cases in which medicines are exempt from clinical trial or from some phases of clinical trial at the request of a management agency and on the basis of the consultation of the Science and Technology Council of the Ministry of Health. Article 2.- Subjects of application This Regulation applies to all domestic and foreign agencies, organizations and individuals carrying out clinical trials of medicines in Vietnam. Article 3.- Interpretation of terms The terms below in this Regulation are construed as follows: 1. Medicine means a substance or a mixture of substances for human use to prevent, treat or diagnose a disease or adjust the body's physiological function. Medicines include finished medicines, pharmaceutical materials, vaccines and medical biological products, except for functional food. 2. New medicine means a medicine containing a new substance which is invented for the first time or a new combination of pharmaceutical materials already in circulation. 3. Generic medicine means a finished product aiming to replace a brand-name medicine, which is manufactured without a license of the inventing company and marketed after the patent or exclusive rights have expired. 4. Vaccine means a preparation containing antigens that help the body be immune and is used for preventive purposes. 5. Medical biological product means a product of biological origin used for preventing, treating or diagnosing a human disease. 6. Medicine from pharmaceutical materials means a medicine manufactured from natural materials of animal, plant or mineral origin. Medicines containing pure active agents extracted from pharmaceutical materials and medicines containing a combination between pharmaceutical materials and synthetic chemical active agents are not regarded as medicines from pharmaceutical materials. 7. Oriental medicine means a medicine from pharmaceutical materials, which is prepared according to theories and methods of traditional medicine in oriental countries. 8. Preclinical trial of a medicine is scientific research to study the efficacy of a medicine intended to assess and prove the efficacy and safety of the medicine in animals and serve as a formality required for clinical trial. 9. Clinical trial of a medicine is a systematic scientific research of a medicine in humans intended to verify the clinical effects of an investigational product and identify any adverse reactions to the investigational product, and to study absorption, distribution, metabolism, and excretion of the product with the object of ascertaining its safety and efficacy. 10. Country of origin means the country in which the final product is manufactured and/or the country in which the stage of manufacture of the product batch is carried out or the country directly from which the medicine is sent to the country of importation. When it is impossible to identify a single country of origin from several countries of origin, many certificates of pharmaceutical product (CPP) are required. 11. Organization or individual with a medicine subject to clinical trial means an organization or individual having the function of studying, manufacturing, importing, exporting or distributing a medicine and wishing to get clinical trials for the medicine. 12. Organization accepting to conduct clinical trials of medicines means a health establishment having the scientific research function and sufficient conditions of personnel and material foundations for conducting clinical trials of medicines, which is evaluated and licensed by the Ministry of Health. 13. Participants in clinical trials of medicines are patients or healthy volunteers to participate in the studies. Article 4.- Principles of clinical trials of medicines 1. Clinical trials of medicines must follow the processes of scientific and technological management, abide by the principles set in the Health Ministry's guidelines on good practice of clinical trials of medicines and observe bio-medical research ethics. 2. Participants in clinical trials of medicines shall be selected on the principles on bio-medical research ethics and assurance of safety and privacy. 3. Clinical trial data and findings may be disclosed only after they are evaluated as satisfactory by a ministerial-level Science and Technology Council. Article 5.- Prohibited acts 1. Conducting clinical trials of medicines without permission of the Ministry of Health. 2. Altering the research protocols already approved by the Ministry of Health. 3. Using medicines subject to clinical trial for other purposes. Chapter II CONDITIONS AND DOSSIERS OF CLINICAL TRIALS OF MEDICINES Article 6.- Conditions on medicines subject to clinical trial A medicine subject to clinical trial must meet the following requirements: 1. There are findings of studies conducted in the previous phases which have been evaluated by a Science and Technology Council set up by a competent agency and based on which the Council adopted the recommendation that trials can be conducted in humans. 2. It has stable forms, formula and process of preparation. 3. It satisfies quality standards as indicated in the dossier of registration for clinical trials. 4. There are findings of previous phases of clinical trial, for the request for subsequent phases of clinical trial. 5. It has a label displaying the phrases "Product used for clinical trials. Use for other purposes is banned." Article 7.- Conditions on dossiers of clinical trials of medicines A dossier of registration for clinical trials of a medicine consists of: 1. An application for permission to conduct clinical trials of a medicine, made by the organization accepting to conduct clinical trials (made according to a set form); 2. The contract on clinical trials of a medicine (made according to a set form); 3. The protocol on clinical trials of the medicine (made according to a set form); 4. CVs of the research manager and principal researcher; 5. Written commitment to observe research ethics; 6. An application for evaluation of research ethics; 7. Documents on the medicine subject to clinical trial, including: a/ Documents on studies of the medicine: formula, manufacturing process and quality standards, enclosed with the medicine test card issued by a central medicine test agency or the manufacturer that satisfies standards of good manufacture practice (GMP). b/ Documents on preclinical studies of the medicine: reports on studies of pharmacological effects, toxicity and safety and proposed doses, routes of usage and methods of administration. c/ Documents on previous phases of clinical trials of the medicine (for an application for subsequent phases of clinical trials). 8. Report of the grassroots council on its evaluation of scientism and research ethics. 9. Properly labeled sample of the medicine, including one smallest packed unit. 10. For medicines proposed for phase-4 clinical trials, a certificate of pharmaceutical product (CPP) or a free sale certificate (FSC) and the good manufacture practice (GMP) certificate issued by a competent state agency are required. Original CPP, FSC and GMP certificate or their copies notarized in Vietnam should be submitted. For each dossier of application for clinical trials of a medicine, either in Vietnamese or English, two original sets which are duly signed and stamped are required. Article 8.- Conditions on protocols on clinical trials of medicines 1. Organizations that accept to conduct clinical trials of medicines shall develop detailed research protocols according to regulations of the Ministry of Health (made according to a set form) and may add other information if necessary. 2. Organizations or individuals with medicines subject to clinical trial, organizations accepting to conduct clinical trials of medicines and research managers shall reach agreement on research protocols and monitoring and supervision work to ensure that studies are conducted according to schedule and that the parties fully perform their duties. Article 9.- Conditions on organizations accepting to conduct clinical trials, research managers and researchers participating in clinical trials of medicines 1. Organizations accepting to conduct clinical trials of medicines must be agencies that have scientific research functions and operate independently without economic or organizational relations with individuals or organizations having medicines subject to clinical trial. 2. Organizations accepting to conduct clinical trials of medicines (also called responsible agencies) must have sufficient conditions of material foundations, medical equipment and facilities and research personnel relevant to each trial, ensure the principles of good clinical trial practice and sufficient conditions for conducting safe and effective studies. 3. Managers of clinical trials of medicines must be physical doctors who have profound clinical knowledge and experience and practice capability to ensure the principles of good clinical trial practice, firmly grasp the Regulation on clinical trials of medicines, and have the ability to carry out the approved research protocols according to schedule. 4. Researchers must have relevant specialized knowledge and have been trained in knowledge and skills necessary for conducting researches. 5. They have been evaluated and permitted by the Ministry of Health. Article 10.- Conditions on participants in clinical trials of medicines 1. Participants in clinical trials of medicines are volunteers who meet professional requirements and sign written commitments with the organization accepting to conduct clinical trials of medicines, excluding those with restricted, lost or no civil act capacity. 2. For those who have not yet reach maturity age, have their civil act capacity restricted, or have lost it, their participation in clinical trials is subject to permission of their lawful representatives in accordance with law. 3. For pregnant women, their participation in clinical trials is subject to consideration and approval of the Minister of Health on the basis of each study dossier and the conclusion and approval of the Bio-Medical Research Ethics Council. Article 11.- Conditions on funds for clinical trials of medicines 1. Funds for clinical trials of medicines shall be allocated by organizations or individuals with medicines subject to clinical trial under research contracts between these organizations or individuals and organizations accepting to conduct clinical trials (made according to a set form). 2. For studies of medicines funded by state budget-funded programs or projects or projects conducted in cooperation with domestic or foreign organizations or individuals, research managers and responsible agencies should prepare cost estimates for clinical trials in the total research funds. 3. Research managers and responsible agencies shall manage and use the allocated funds for researches, covering also the assessment, approval, management, monitoring, supervision and evaluation of take-over tests, payment of labor costs, procurement of supplies, remuneration for research participants and related expenses. Expense limits are as prescribed by law. Chapter III EVALUATION AND APPROVAL OF CLINICAL TRIALS OF MEDICINES Article 12.- Receipt and evaluation of dossiers 1. The Science and Training Department, the Ministry of Health, shall receive, check and evaluate dossiers of registration for clinical trials of medicines according to regulations. 2. When receiving a valid dossier, the director of the Science and Training Department shall propose the Minister to establish a ministerial-level Science and Technology Council to evaluate the scientific contents of the research protocol and establish a ministerial-level Bio-medical Research Ethics Council to evaluate ethical aspects in clinical trials of medicines and submit their evaluations. 3. The organization, functions, tasks, activities and responsibilities of the ministerial-level Science and Technology Councils and Councils for Bio-medical Research Ethics are as prescribed in the regulations on scientific and technological management and the regulations on organization and operation of Bio-medical Research Ethics Councils (promulgated together with the Health Minister's Decision No. 5129/2002/QD-BYT of December 19, 2002). Article 13.- Approval of clinical trials of medicines Within 60 days after receiving a complete dossier as required, the Ministry of Health shall give a reply to the organization accepting to conduct clinical trials of medicines on the approval of the research protocol on clinical trials of medicines according to current regulations (in case of disapproval, it must clearly state the reason). Chapter IV PHASES OF CLINICAL TRIALS OF MEDICINES AND CONDUCT OF CLINICAL TRIALS Article 14.- Phases of clinical trials of medicines: 1. Phase 1 At this phase, trials of a new active agent or formula of a medicine are conducted in humans for the first time. Phase 1 studies aim to preliminarily assess the safety, pharmacokinetics and pharmacodynamics of the active agent in human subjects. 2. Phase 2 Phase-2 trials are conducted on a limited number of patients. Phase 2 studies are intended to evaluate the therapy and safety of the active agent in patients in order to establish appropriate doses and dose ranges for the formulation of the optimum treatments for clinical trials. 3. Phase 3 At this phase, trials are conducted in a larger number of patients. Phase 3 studies aim to determine the stability of the formula and the short-term and long-term safety/efficacy of the active agent and assess its overall treatment value. Trials are also conducted to study frequent adverse reactions and discover special characteristics of the investigational product. At this phase, clinical trials are conducted under conditions similar to real usage conditions. 4. Phase 4 At this phase, clinical studies are conducted after a medicine is marketed. Clinical trials are conducted on the basis of special characteristics of the product already permitted for marketing, normally in the form of post marketing surveillance or evaluation of the treatment value or treatment strategies. Research methods may vary but involve scientific and ethical standards like those used before the medicine is marketed. 5. The ministerial-level Science and Technology Council and Bio-medical Research Ethics Council that have considered and approved the research protocol shall provide consultations in different cases in each specific study phase. Following each phase of clinical trials, the responsible agency and the research manager of the clinical trials of the medicine should review and report the results to the ministerial-level Science and Technology Council for evaluation. Only after the results are satisfactory may the subsequent phases be carried out. Any substantial changes in and adjustments to the research protocol should be reported to management agencies for consideration and decision. Article 15.- Clinical trials of medicines at different establishments 1. When conducting studies at different establishments, it is necessary to establish a steering committee consisting of the research manager, managers of component researches and representatives of responsible research agencies to unify the research objectives, contents, evaluation criteria, plan and schedule. 2. For multi-national clinical studies joined by Vietnam, their dossiers must comply with the provisions of Article 7 of this Regulation. The objectives and contents of trials conducted in Vietnam and studies conducted jointly with other states must be detailed in the research protocol (according to a set form). Article 16.- Handling of adverse events caused by clinical trials of medicines Abnormal events arising in the course of study shall be handled as follows: 1. When an adverse event occurs, threatening or endangering the life of clinical trial participants, the research manager and the organization accepting to conduct clinical trials shall immediately stop trials, render emergency treatment and overcome any consequences, make a written report and promptly send it to competent state management agencies. 2. When a trial results in damage to the health of clinical trial participants, the research manager must stop trials, provide medical treatment for these participants and monitor their health conditions before considering and deciding to continue or discontinue clinical trials. 3. If the abnormal event has been anticipated and measures have been taken to handle it effectively, clinical trials may still continue. Article 17.- Collection of information and data 1. Information collected in the process of clinical trials shall be recorded in the medical files, which are regarded as source documents to be preserved according to regulations, serving as a ground for the monitoring, test and evaluation of trial results. 2. Related documents necessary for the process of clinical trials (test slips, X-ray negative films and prescriptions) shall be copied from the originals, show the full names of examiners and their origin, and must be preserved according to regulations. Article 18.- Processing of data 1. Data on clinical study trials of medicines shall be processed according to bio-medical statistical methods. 2. Statistical analysis results shall be clearly presented to help identify differences in clinical results. Evaluation of treatment effects shall be based on the reliability and results of statistical tests. Statistical analysis reports must be consistent with final clinical study results. Article 19.- Preservation of documents on clinical trials of medicines 1. Data, source documents, test slips and collected materials related to clinical trials of medicines, minutes of meetings of councils, surveillance reports, progress reports, dossiers of registration for clinical trials and other documents shall be fully preserved for at least 15 years at research establishments, counting from the time of conclusion of studies. 2. Research managers are fully responsible for the process of preservation of research documents of their researches and shall produce them upon request of inspection and supervision teams or competent state management agencies. Article 20.- Reports on findings of clinical trials of medicines 1. A report on findings of clinical trials of a medicine must fully contain information on the medicine, description of the research methods, process of trials, analysis of data, evaluation of findings, assessment against the research objectives and tasks; and accurate, truthful and objective conclusions. The report's contents must be consistent with the research objectives and contents set out in the approved protocol. 2. The research manager shall take responsibility for scientism, accuracy and truthfulness of data, conclusions, judgments and other contents of the report. Article 21.- Management of medicines subject to clinical trial 1. Medicines used in clinical studies must be labeled according to regulations and preserved according to the Regulation. 2. The import and export of medicines subject to clinical trial must comply with current regulations on import and export of medicines. 3. The management of medicines subject to clinical trials must comply with current regulations from sampling, quality test, packing, transport, delivery, preservation to distribution. 4. Records shall be kept to monitor the use of medicines for clinical trials together with information on the quantity and quality of medicines. 5. Unused and preserved medicines shall be closely managed, separately stored and preserved according to regulations. Unused medicines shall be handed over to organizations or individuals having such medicines. 6. Medicines of inferior quality shall be disposed of according to the Health Ministry's regulations on handling of medicines of inferior quality. 7. Preserved medicine samples (three units) shall be preserved for at least three years (36 months) at the organizations accepting to conduct clinical trials after completion of studies. Chapter V RIGHTS AND OBLIGATIONS OF PARTICIPANTS IN CLINICAL TRIALS OF MEDICINES, PERSONS HAVING MEDICINES AND ORGANIZATIONS ACCEPTING TO CONDUCT CLINICAL TRIALS OF MEDICINES Article 22.- Rights of participants in clinical trials of medicines 1. Before participating in clinical trials, to be provided with full and truthful information on trials and possible risks. 2. To be entitled to compensations paid by organizations or individuals having medicines subject to clinical trial for damage caused by clinical trials. 3. To be entitled to privacy of their relevant personal information. 4. To bear no responsibility when they unilaterally terminate their contracts on participation in clinical trials. 5. To complain about and denounce violations of law committed by establishments or individuals having medicines subject to clinical trial or organizations accepting to conduct clinical trials. 6. To be given free healthcare in the process of trial. Article 23.- Rights of organizations and individuals having medicines subject to clinical trial 1. To select organizations that satisfy requirements on material foundations and specialized personnel for clinical trials of medicines. 2. To own all research findings on medicines subject to clinical trial. Article 24.- Obligations of organizations and individuals having medicines subject to clinical trial 1. To make applications and obtain written permission from the Minister of Health before conduct of clinical trials. 2. To pay compensations according to current regulations for damage caused to participants in clinical trials of medicines when a risk occurs. 3. To sign contracts on clinical trials of medicines with organizations accepting to conduct clinical trials. 4. To take responsibility before law for the quality and safety of medicines they supply. Article 25.- Rights of organizations accepting to conduct clinical trials of medicines 1. To be provided with medicines and funds by organizations or individuals having medicines subject to clinical trials for conducting clinical trials according to the provisions of law. 2. To use findings from clinical study trials of medicines as agreed upon with organizations or individuals having those medicines. Article 26.- Obligations of organizations accepting to conduct clinical trials of medicines 1. To observe regulations on good practice of clinical trials of medicines and report to the Ministry of Health on the process and findings of clinical trials and make urgent reports when necessary. 2. To sign contracts on clinical trials of medicines with organizations or individuals having medicines subject to clinical trials and with clinical trial participants. 3. To be responsible for further overseeing the health of and diseases in clinical trial participants as agreed upon in the contracts or research protocol. Chapter VI MONITORING AND SUPERVISION TO ENSURE RESEARCH QUALITY Article 27.- Monitoring and supervision of the process of clinical trials of medicines 1. Monitoring and supervision aim to ensure the rights, benefits and health of clinical trial participants and that study data are recorded fully, accurately, in time and according to regulations and the approved research protocols. 2. The Ministry of Health shall set up teams to conduct regular and irregular monitoring and supervision of each specific case. 3. Competent state management agencies and organizations and individuals having medicines subject to clinical trial may propose and appoint persons to monitor the research process in a systematic manner. Persons assigned the monitoring task must not be members of the research group, observe regulations on confidentiality of research data and privacy of information relating to clinical trial participants and take responsibility to their management agencies for their tasks. 4. Research managers and researchers are responsible for creating conditions for monitoring team members to access research data upon request. 5. Monitoring and supervision teams have the responsibility and power to report and propose in the monitoring and supervision reports the monitored contents to competent state management agencies as a basis for the latter's consideration and handling according to the provisions of law. Article 28.- Assurance of reliability of findings of clinical study trials of medicines 1. To ensure reliable studies, all analyses, judgments and conclusions on their findings must stem from source data. In each phase of study, it is necessary to verify all clinical data and test criteria. 2. When necessary, the take-over councils at all levels may invite specialists to evaluate the findings, check data and inspect research products of the researches. Chapter VII TAKE-OVER AND EVALUATION OF FINDINGS OF CLINICAL TRIALS OF MEDICINES Article 29.- Procedures for take-over of findings of clinical trials of medicines 1. Take-over of findings of clinical trials of medicines shall be carried out according to current regulations on evaluation and take-over of ministerial-level scientific and technological researches. 2. Take-over shall be carried out at two levels: grassroots and ministerial levels. Upon completion of studies, the research manager shall send a report to the responsible agency for evaluation of the study findings at the grassroots level and complete the dossier and send a report to the Ministry of Health for ministerial-level take-over. Article 30.- A dossier of ministerial-level take-over consists of: 1. An official letter of the agency responsible for the research, requesting ministerial-level take-over. 2. A copy of the approved research protocol. 3. The decision on the approval of the research. 4. The decision on the establishment of the grassroots-level council for evaluation of the research. 5. Minutes of meetings of the grassroots-level council. 6. A report on all findings of the clinical study trials of a medicine, made according to regulations and possibly added with other relevant information, if necessary. The dossier of take-over is made in one original set, which is duly signed and stamped. Article 31.- Completion of clinical trials of medicines 1. Within 30 days after receiving the complete dossier of application for take-over, the Ministry of Health shall hold a meeting of the ministerial-level Science and Technology Council to take over the study findings according to current regulations. 2. Clinical trials of medicines shall be considered complete when the final findings report is evaluated and taken over by the ministerial-level Science and Technology Council and supplements made by the research manager based on the Council's opinions (if any) are accepted by the Council. Chapter VIII ORGANIZATION OF IMPLEMENTATION Article 32.- Assignment of implementation The Minister of Health assigns the Science and Training Department to assume the prime responsibility for and coordinate with related departments in: 1. Receiving and checking dossiers of registration, guiding organizations and individuals having medicines subject to clinical trial and organizations accepting to conduct clinical trials of medicines to observe the provisions of this Regulation and relevant provisions of law and professional rules. 2. Examining the conditions on dossiers of clinical trials of medicines, professional capacity, material foundations and legality of organizations accepting to conduct clinical trials, and report to the Ministry's leadership for permission for clinical trials. 3. Holding meetings of the Science and Technology Council and Bio-Medical Research Ethics Council to consider and approve research protocols, evaluate ethical aspects of researches, evaluate and take over the findings of clinical trials of medicines, review and report them to the Ministry's leadership for approval. 4. Conducting regular or irregular monitoring and supervision of the process of trials. 5. Disseminating and explaining this Regulation and guidelines on good practice of clinical trials of medicines to concerned units, organizations and individuals. Article 33.- Complaints, denunciations and handling of violations 1. Organizations or individuals that violate this Regulation and relevant provisions of law shall, depending on the nature and seriousness of their violations, be disciplined, administratively sanctioned or examined for penal liability; if causing any damage, they shall pay compensation in accordance with law. 2. Organizations and individuals have the right to complain about or denounce acts of violation of the law on clinical trials of medicines. 3. Complaints and denunciations shall be settled in accordance with the law on complaints and denunciations.-