Deepening the Reform of the Evaluation and Approval Systems and Encouraging Innovation on Drugs and Medical Devices
- Area of Law： Health and Sanitation
- Level of Authority： Group Provisions
- Date issued：10-2017
- Effective Date：10-2017
- Status： Effective
- Issuing Authority： General Office of the Central Committee of the Communist Party of China (General Office, CCCPC) General Office of the State Council
The General Office of the
CPC Central Committee and the General Office of the State Council on Issuing
the Opinions on Deepening the Reform of the Evaluation and Approval Systems and
Encouraging Innovation on Drugs and Medical Devices
Currently, China's drug and medical device industries see quick development, thriving innovation and entrepreneurship, and constant advancement of the reform of the evaluation and approval systems. Nevertheless, generally, China's drugs and medical devices are insufficiently supported by science and technology innovation, and there exists a gap between the quality of products sold on markets and international advanced standards. For purposes of promoting structural adjustment and technology innovation in drug and medical device industries, improving industrial competitiveness, and meeting the clinical need of the general public, the following opinions on deepening the reform of the evaluation and approval systems and encouraging innovation on drugs and medical devices are hereby offered.
I. Reforming the administration of clinical trials
(1) Implementing the recordation administration of clinical trial body qualification accreditation. A body qualified for clinical trials may, upon making registration and recordation on the website designated by the food and drug regulation department, conduct clinical trials as entrusted by registration applicants of drugs or medical devices. The main investigator in a clinical trial shall have a senior professional title and have participated in three or more clinical trials. A registration applicant may hire a third party to assess and certify whether the clinical trial body is qualified. Social resources shall be encouraged to invest in or fund clinical trial bodies. The China Food and Drug Administration shall develop provisions on the administration of clinical trial bodies in conjunction with the National Health and Family Planning Commission.
(2) Supporting clinical trial bodies and personnel in conducting clinical trials. Medical institutions, medical research institutions and medicine universities shall be supported in conducting clinical trials, and the conditions and capacity for clinical trials shall be included in the rating of medical institutions. For medical institutions conducting clinical trials, a separate assessment and appraisal system shall be established, beds used only for clinical trials shall not be included in the total beds of the medical institutions, and appraisal indicators such as profit, turnover and use of beds shall not be specified. Medical institutions shall be encouraged to establish separate clinical trial departments and assign professional clinical trial investigators. The entity performance-related pay distribution incentive mechanism shall be improved to ensure the income of clinical trial investigators. Clinical doctors shall be encouraged to participate in the innovation on drug and medical device technologies, and clinical trial investigators are treated the same as clinical doctors in the aspects such as job promotion and title ranking. Overseas enterprises and scientific research institutions shall be allowed to synchronically conduct clinical trials in new drug development in China.
(3) Improving the ethics committee mechanism. Clinical trials shall conform to ethical and moral standards, and shall be ensured that human subjects are informed of adequate research information before their voluntary participation and understand and shall sign an informed consent document so as to protect their safety, health, rights and interests. A clinical trial body shall establish an ethics committee responsible for examining the body's clinical trial plans, reviewing and supervising the qualifications of clinical trial investigators, supervising the conduct of clinical trials, and accepting the inspection of regulatory departments. Each region may establish a regional ethics committee to guide clinical trial bodies' ethnics review, conduct ethnics reviews of clinical trial plans as entrusted by bodies without ethnics review conditions or registration applicants, and supervise clinical trials. Health and family planning, traditional Chinese medicine administration, and food and drug regulation, etc. shall strengthen the administrative guidance to and business supervision of ethics committees.
(4) Raising the efficiency of ethnic reviews. A registration applicant shall, before applying for a clinical trial, submit a clinical trial plan to the clinical trial body's ethics committee for review and approval. In the case of a clinical trial conducted in several centers in China, where the leading entity of the clinical trial has conducted the ethnics review, the other member entities shall accept the review conclusions of the leader entity, instead of repeating the review. The National Clinical Medicine Research Center and clinical trial bodies tasked with major national science and technology projects and key national research and development plans support projects shall integrate their resources to establish a unified ethnic review platform and gradually advance mutual recognition of ethnic reviews.
(5) Optimizing the approval procedures for clinical trials. A mechanism of communication and exchange between registration applicants and evaluation bodies shall be established and improved. Before accepting applications for drug clinical trials and medical device clinical trials requiring approval, the evaluation body shall meet and communicate with registration applicants and offer opinions and suggestions. The food and drug registration department shall be deemed to have given its consent if it does not give a denial or doubting opinions within a given period after accepting an application for clinical trial, and the registration applicant may conduct the clinical trial according to the submitted plan. During a clinical trial, in the case of modification of the clinical trial plan, or material medical modification, or a nonclinical investigation safety problem, the registration applicant shall promptly file the modification with the evaluation body; and in the case of safety or other risks, the clinical trial plan shall be revised in a timely manner, or the clinical trial shall be suspended or terminated. A drug registration applicant may issue an inspection report on samples in the clinical trial alone or by entrusting an inspection institution, submit it to the drug evaluation body, attaching the samples, and ensure the consistency between the samples actually used in clinical trials and submitted samples. The procedures for approving human genetic resource activities involving international cooperation in clinical trials shall be optimized to accelerate the progress of clinical trials.
(6) Accepting overseas clinical trial data. Clinical trial data obtained in multiple overseas centers, conforming to China's requirements for registration of drugs and medical devices, may be used for the application for registration in China. In the case of drugs and medical devices the marketing of which is applied for in China for the first time, registration applicants shall provide clinical trial data on racial differences.
(7) Supporting expanded clinical trials. A drug or a medical device under a clinical trial, which is used to treat diseases seriously detrimental to life and for which there is no effective treatment means, which may bring benefits according to preliminary observations, and which conforms to ethical requirements, may be used to cure other patients within the clinical trial body with their informed consent, and the safety data may be used for registration application.
(8) Seriously investigating and dealing with data fraud. Signatories of entrusted clinical trial agreements and clinical trial investigators, as primary persons responsible for clinical trial data, shall assume legal liability for the reliability of clinical trial data. An inspection mode oriented on risks and evaluation need shall be developed, the on-site inspection and for-cause inspection of nonclinical investigations and clinical trials shall be strengthened, and inspection results shall be publicly disclosed. In the case of failure in inspection, relevant data shall not be accepted; in the case of authenticity problem, investigation shall be opened in a timely manner, and the persons in charge of the relevant nonclinical investigation body or the clinical trial body, persons liable for providing false reports, registration applicants, and persons in charge of investigation organization contractors shall be held accountable by law; and one that refuses, doges or obstructs inspection shall be heavily punished by law. A registration applicant who voluntarily discovers problems and makes a timely report may be subject to lighter punishment or exempt from punishment, as the case may be.
II. Accelerating marketing evaluation and approval
(9) Accelerating the evaluation and approval of drugs and medical devices much needed clinically. A drug or a medical device under a clinical trial, which is used to treat diseases seriously detrimental to life and for which there is no effective treatment means, and which is urgently needed in public health or other aspects, may be approved to be marketed conditionally, where the early-phase and intermediate indicators of the clinical trial indicate its therapeutic effect, and where its clinical value may be predicted, and the enterprise shall make a risk management and control plan and conduct research as required. The research and development of new drugs and innovative medical devices shall be encouraged, and new drugs and innovative medical devices supported by major national science or technology projects and key national research and development plans or for which the National Clinical Medicine Research Center conducts clinical trials and which the Center's administrative department accredits shall be evaluated and approved in priority.
(10) Supporting the research and development of drugs and medical devices for treatment of rare diseases. The National Health and Family Planning Commission or the relevant industry association (society) it entrusted shall publish a rare diseases catalog and establish a rare-disease patient registration system. An applicant for the registration of a drug or medical device for treatment of a rare disease may apply for a reduced clinical trial or exemption from clinical trial. A drug or medical device for treatment of rare disease whose marketing has been approved overseas may be approved to be marketed conditionally, and the enterprise shall make a risk management and control plan and conduct research as required.
(11) Making strict evaluation and approval of injectable drugs. The change of oral drugs to injectable ones shall be strictly controlled, and if an oral drug is sufficient to meet clinical demand, the marketing its injectable substitute may not be approved. The change of injectable drugs administered by intramuscular injection to injectable ones administered by intravenous injection shall be strictly controlled, and if an injectable drug administered by intramuscular injection is sufficient to meet clinical demand, the marketing its injectable substitute administered by intravenous injection may not be approved. An application for change of drug administration among large volume injection, small volume injection, and powder for solution for injection shall not be approved unless the clinical advantage is conspicuous.
(12) Implementing approval connecting drugs and raw and accessory materials for medical use with packaging materials. Raw-material drugs, accessory materials for medical use and packaging materials shall be evaluated and approved in a consolidated manner at the approval of applications for drug registration, no raw-material drug approval number shall be issued any more, and raw-material drugs, accessory materials for medical use and packaging materials so evaluated and approved and the quality standards therefor shall be published at a designated platform for the option of relevant enterprises. Drug marketing licensees shall be responsible for the quality of raw-material drugs, accessory materials for medical use and packaging materials used for production of drugs.
(13) Supporting the carrying forward of traditional Chinese drugs and the innovation thereof. A registration administration system and a technology assessment system conforming to the characteristics of traditional Chinese drugs shall be established and improved, and the relationship between maintaining the traditional advantages of traditional Chinese drugs and the research and development of modern drugs shall be properly handled. Innovative traditional Chinese drugs shall prominently feature new therapeutic effect; modified traditional Chinese drugs shall be advantageous in clinical application; traditional Chinese drugs in the category of classic and famous prescriptions shall be evaluated and approved according to simplified standards; and natural drugs shall be evaluated and approved according to modern medical standards. The capability of clinical investigation in traditional Chinese medicine shall be improved, applications for registration of traditional Chinese drugs shall be submitted, attaching marketing value and resource assessment documents, and the orientation of clinical values shall be highlighted so as to promote sustainable use of resources. The use of modern science and technology to develop traditional Chinese patent medicine and of advantages of the traditional forms of traditional Chinese drugs to research and develop traditional Chinese drugs shall be encouraged, and the quality control of traditional Chinese drugs shall be strengthened.
(14) Establishing a compulsory-patent-license drug prior evaluation and approval system. In the case of a major threat to public health, the application for registration of a drug under a compulsory patent license shall be evaluated and approved in priority. The National Health and Family Planning Commission shall specify the circumstances of major threats to public health and the procedures for invoking compulsory licensing, in conjunction with relevant departments.
III. Promoting drug innovation and development of generic drugs
(15) Establishing a marketed drug catalog. A drug whose marketing has been lately approved or which has passed the generic drug quality and therapeutic effect consistency assessment shall be included in the China market drug catalog, which shall specify the nature of innovative drugs, modified drugs, and generic drugs with the same quality and therapeutic effect as the brand-name drugs and such information as active ingredients, forms, specifications, holders of marketing licenses, obtained patents, and protection period of trial data.
(16) Exploring and establishing a drug patent link system. A system linking drug evaluation and approval with drug patents shall be explored and established to protect the lawful rights and interests of patentees, reduce the risks of patent infringements by generic drugs, and encourage the development of generic drugs. At his application for registration, an applicant for drug registration shall explain the relevant patents involved and the status of patent holders and inform relevant drug patentees within a specific period. In the case of a dispute over the patent right, a party may bring an action before the court, and the technical evaluation of the drug shall continue notwithstanding the legal action. With respect to a drug passing the technical evaluation, the food and drug regulation department shall decide whether to approve its marketing according to effective court judgment, ruling or mediation agreement; or may, if no effective court judgment, ruling or mediation agreement is obtained within a given period, approve its marketing.
(17) Conducting the pilot program of the patent term compensation system. Part new drugs shall be selected for the pilot program, and patent term compensation shall be made, taking into account the time when the marketing is delayed due to clinical trial, evaluation and approval.
(18) Improving and implementing the drug trial data protection system. An applicant for drug registration may apply for drug trial data protection at the application for registration. The trial data and other data obtained alone but not disclosed yet by an applicant for registration of an innovative drug, a drug for treatment of rare diseases, a child drug, an innovative biological product for treatment, or a drug arising from a successful patent challenge, shall be protected in a given period. The period of data protection begins from the day of approving drug marketing. Within the period of data protection, any other application for the marketing of drug of the same kind shall not be approved, unless the applicant obtains data alone or the person with marketing licensing gives his consent.
(19) Promoting production of generic drugs. Adherence shall be given to encouraging innovation and promoting production of generic drugs as well as reducing drug expenses, and a list of drugs in which the patent right has expired, terminated or avoided and of which the generic production has not been applied for shall be regularly published so as to guide the research, development and production of generic drugs and improve public availability of drugs. Relevant research and appraisal technical guiding principles shall be improved, and the production of biosimilar and products combining drug and medical device with clinical values shall be supported. The advancement of generic drug quality and therapeutic effect consistency assessment shall be accelerated.
(20) Using the role of enterprises as innovators. Drug and medical device enterprises shall be encouraged to increase investment in research and development, strengthen the research and development of new products and continuous research of marketed products, and constantly improve production techniques. Scientific research institutions and scientific researchers shall be allowed to apply for clinical trials on the premise of assuming relevant legal liability. Where a new drug or an innovative medical device is researched and developed, and the relevant technology is researched, as funded by national fiscal grants, and where they are transformed as job-related scientific and technological achievement, the entity may stipulate, by itself or together with scientific researchers, the modes, amounts and time limits of rewards and remunerations so as to motivate scientific researchers and promote the transformation of scientific and technological achievements.
(21) Supporting the clinical application of new drugs. The medical insurance drug catalog dynamic adjustment mechanism shall be improved, a medical insurance drug disbursement standard negotiation mechanism shall be explored and established, and new drugs shall be included in the scope of disbursement from the basic medical care insurance as provided in a timely manner to support the research and development of new drugs. All regions may, as needed by disease prevention and control, include new drugs in the scope of centralized procurement of drugs of public hospitals in a timely manner. Medical institutions shall be encouraged to procure and use new drugs with determinate therapeutic effects and at reasonable prices in priority.
IV. Strengthening the whole-life cycle administration of drugs and medical devices
(22) Promoting the comprehensive implementation of the marketing licensee system. The experience in the pilot program of the drug marketing licensee system shall be summarized in a timely manner, and efforts shall be made to amend the Pharmaceutical Administration Law so as to strive for promotion across the country as soon as possible. Medical device research and development institutions and scientific researchers shall be allowed to apply for market licensing for medical devices.
(23) Implementing the legal liability of marketing licensees. A drug marketing licensee shall assume all legal liabilities for the pre-clinical investigations, clinical trial, production or manufacturing, sale and delivery, and adverse drug reaction reporting of the drug, among others, ensure the authenticity, integrity and traceability of the submitted research documents and clinical trial data, consistency between production technique procedures and approved technique procedures and the constant compliance of production process, quality consistency between drugs of all batches for sale and samples submitted, and constant research of the marketed drug, report adverse drug reaction in a timely manner, assess risks, and make suggestions with regard to improvement measures.
A medical device marketing licensee shall assume all legal liabilities for the design and development, clinical trial, production or manufacturing, sale and delivery, and adverse event reporting of the medical device, ensure the authenticity, integrity and traceability of the submitted research documents and clinical trial data and the constant research of the marketed medical device, report adverse events in a timely manner, assess risks, and give suggestions with regard to improvement measures.
An enterprise, body or person that a drug or medical device marketing licensee entrusts with research and development, clinical trial, production or manufacturing, or sale and delivery shall assume the liability provided by laws and regulations and stipulated by agreement.
(24) Establishing a system for marketing licensees to directly report adverse drug reaction and adverse events. Marketing licensees shall assume primary liability for adverse drug reaction and adverse events and, if failing or delaying in reporting, be punished by law. Food and drug regulation departments shall investigate and analyze the reported adverse drug reaction and adverse events, and order marketing licensees to take measures such as sale suspension, recall, and improvement of quality control, as the case may be.
(25) Re-assessing injectable drugs. Based on the progress of drug science and technology, the re-assessment of marketed injectable drugs shall be made and basically completed in about five to ten years, wherever possible. A marketing licensee shall comprehensively analyze the research at the time of approving marketing and post-marketing research, among others, research product ingredients, mechanism of action, and clinical therapeutic effects, and assess the product's safety, effectiveness and quality controllability. Where any of them passes the re-assessment, it is entitled to encouragement policies relating to generic drug quality and therapeutic effect consistency assessment.
(26) Improving the medical device re-assessment system. A marketing licensee shall voluntarily re-assess the marketed medical device based on the progress of drug science and technology and assessment results of adverse events. Where a product is found incapable of ensuring safety or effectiveness in the re-assessment, the marketing licensee shall apply for deregistration of the marketing license in a timely manner; and if re-assessment results are concealed, or if the application for deregistration is not made as required, the marketing license shall be revoked, and investigation and dealing shall be undertaken by law.
(27) Regulating academic promotion of drugs. A marketing licensee shall upload a medical representative list on the website designated by the food and drug regulation department and publicly publish it. Medical representatives shall be responsible for academic promotion of drugs, introduce drug knowledge to medical personnel, and listen to the opinions and suggestions on clinical use. The academic promotion of drugs by medical representatives shall be public and filed with departments appointed by medical institutions for recordation. Medical representatives shall be prohibited from shouldering tasks for drug sale, and it shall be prohibited to provide medical representatives or relevant enterprise employees with the number of drugs prescribed by doctors. A medical representative who misleads any doctor over drug administration or conceals adverse drug reaction shall be seriously investigated and dealt with; and drug business in the name of medical representative shall be investigated and dealt with as illegal drug business.
V. Enhancing the capability of technology support
(28) Improving the technology evaluation system. A technology evaluation system dominated by evaluation and supported by examination and inspection shall be established, the evaluation project manager system, the evaluation body and registration applicant meeting-based communication system, and the expert consultant committee system shall be improved, internal management shall be strengthened, and the process of evaluation shall be regulated. A drug evaluation team mainly composed of personnel specializing in clinical medicine, consisting of personnel specializing in pharmacy, pharmaceutical toxicology, and statistics, among others, shall be established to take charge of new drug evaluation. A medical device evaluation team consisting of personnel specializing in clinical medicine, clinical diagnosis, machinery, electronics, materials, and biomedical engineering, among others, shall be established to be responsible for evaluation of innovative medical devices. Evaluation conclusions and bases shall be all disclosed for social supervision except manufacturing techniques and other know-hows. The Class II medical device evaluation standards shall be unified to gradually unify national evaluation.
(29) Implementing the confidentiality responsibility of relevant employees. A person who participates in regulatory work such as acceptance and examination, evaluation and approval, and examination and inspection of drugs and medical devices shall have the duty to keep confidential the know-hows and trial data submitted by registration applicants. Anyone who fails in the duty of confidentiality shall be held liable by law and discipline, and the handling results shall be publicly disclosed; and if he is suspected of any crime, he shall be handed over the judiciary and held criminally liable. The management of registration application documents shall be improved to ensure the trackability of consulting and reproduction.
(30) Strengthening the building of the capability of evaluation and examination. The evaluation of drugs and medical devices shall be included in the scope of government procurement of services, and regulated, efficient evaluation services shall be provided. The building of information-driven evaluation and approval of drugs and medical devices shall be accelerated, technical requirements for electronic submission of registration applications shall be developed, and the general electronic technical document system shall be improved so as to gradually realize electronic submission, evaluation and approval of various registration applications. The types of marketed drugs and medical devices shall be archived.
(31) Implementing whole-process inspection responsibility. The national food and drug regulation department shall organize the inspection of the implementation of the drug and medical device research and development process and nonclinical drug investigation quality management specifications, the drug clinical trial quality management specifications, and the medical device clinical trial quality management specifications. The food and drug regulation departments at or above the provincial level shall be responsible for the inspection of the implementation of the drug and medical device production process and production quality management specifications. The food and drug regulation departments at county and municipal levels shall be responsible for the inspection of the implementation of the drug and medical device business operation process and business operation quality management specifications. Problems found in the process of inspections shall be investigated and dealt with in accordance with the laws and regulations, and risk control measures shall be taken in a timely manner; and one suspected of any crime shall be handed over to the judiciary and held criminally liable. The punishment of persons making illegal acts shall be promoted, and the inspection and punishment results shall be publicly disclosed.
(32) Establishing a professional inspector team. The establishment of an inspector team shall be accelerated by depending on existing resources to form a professional inspector team mainly consisting of full-time inspectors, supplemented by part-time inspectors. A graded inspector administration system shall be implemented, inspector training shall be enhanced, the assignment of inspection equipment shall be strengthened, and the capability and level of inspection shall be improved or lifted.
(33) Strengthening international cooperation. Bilateral and multilateral drug and medical device regulation policy and technology exchange shall be deepened so as to participate in the development and revision of international rules and standards, and international sharing of evaluation, examination and inspection standards and results shall be gradually promoted.
VI. Strengthening organization and implementation
(34) Strengthening organization and leadership. All regions and all relevant departments shall fully recognize the great importance of deepening the reform of the evaluation and approval system and encouraging drug and medical device innovation, attach great importance to the reform of and innovation on evaluation and approval of drugs and medical devices, support the work as an important part of building an innovation-oriented country and promoting the development of the high-technology industry, strengthen overall coordination, substantiate the implementation plans, improve the working mechanisms, and practically, effectively ensure task implementation. The reform shall be advanced by adhering to the use of legal mindset and modes, the relevant laws, regulations and institutional system shall be constantly improved, and reform measures involving amendment of law or requiring corresponding authorization shall be taken upon request for amendment of law by procedure or authorization of the legislature.
(35) Enhancing cooperation. The role of the inter-ministerial joint meeting for the reform of the drug and medical device evaluation and approval system shall be fully utilized, and conflicts and problems encountered in the reform shall be solved in a timely manner. The national food and drug regulation department shall play a role in taking the lead, ensure the specific implementation of the reform, and coordinate the advancement of task implementation. All relevant departments shall perform their respective duties by law, cooperate with each other so as form joint reform forces. Development and reform departments shall support the development of high-scientific and technological medical and pharmaceutical products and set the building of clinical trial bodies as an important part of the building and development of medical institutions. Science and technology departments shall strengthen the planning of and guidance to the development of medical and pharmaceutical science and technology and ensure the implementation of science and technology plans (special projects and funds) relating to research and development of new drugs and innovative medical devices. Industry and information technology departments shall strengthen the planning of and guidance to the development of medical and pharmaceutical industries and enhance the guarantees for clinical drug production. Finance departments shall effectively guarantee the funds required by evaluation, approval, examination and inspection of drugs and medical devices. Human resources and social security departments shall effectively conduct the work regarding medical insurance policies supporting the development of new drugs. Health and family planning departments shall strengthen the guidance to the building of clinical trial bodies and strengthen the administration of ethics committees and the training of clinical trial investigators. Intellectual property departments shall effectively protect intellectual property in drugs and medical devices relating to patents. Traditional Chinese medicine administrative departments shall effectively innovate on traditional Chinese drugs.
(36) Effectively conducting publicity and interpretation. Positive publicity shall be given to the great significance of encouraging the innovation on drugs and medical devices, the interpretation of major policies and measures for the reform of the evaluation and approval system shall be strengthened, hot problems drawing the attention of all social parties shall be answered promptly, social concerns shall be voluntarily responded to, the expectation of all parties shall be reasonably guided, and a good public opinion atmosphere shall be created for the implementation of the reform.