Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices

At present, China's pharmaceutical and medical device industry is developing rapidly, innovation and entrepreneurship are in the ascendant, and the reform of the review and approval system continues to advance. But on the whole, the scientific and technological innovation support of China's pharmaceutical and medical devices is not enough, and there is a gap between the quality of listed products and the international advanced level. In order to promote the structural adjustment and technological innovation of the pharmaceutical and medical device industry, improve industrial competitiveness, and meet the clinical needs of the public, the following opinions are put forward on deepening the reform of the review and approval system to encourage the innovation of pharmaceutical and medical devices.

1. Reform Clinical Trial Management

The qualification of (I) clinical trial institutions shall be subject to record management. Institutions that have the conditions for clinical trials can accept the registration of drug and medical device applicants to carry out clinical trials after registering on the website designated by the food and drug regulatory department. The principal investigator of clinical trials should have a senior professional title and have participated in more than 3 clinical trials. Registration applicants can hire a third party to assess whether the clinical trial institution has the conditions for certification. Encourage social forces to invest in the establishment of clinical trial institutions. The regulations on the administration of clinical trial institutions shall be formulated by the Food and Drug Administration in conjunction with the National Health and Family Planning Commission.

(II) support clinical trial institutions and personnel to conduct clinical trials. Support medical institutions, medical research institutions and medical colleges and universities to carry out clinical trials, and incorporate the evaluation of clinical trial conditions and capabilities into the grade evaluation of medical institutions. A separate evaluation and assessment system shall be established for medical institutions that carry out clinical trials. Beds used only for clinical trials shall not be included in the total beds of medical institutions, and evaluation indicators such as bed benefit, turnover rate and utilization rate shall not be specified. Medical institutions are encouraged to set up full-time clinical trial departments with professional clinical trial researchers. Improve the unit performance salary distribution incentive mechanism to protect the income level of clinical trial researchers. Encourage clinicians to participate in drug and medical device technology innovation activities, and treat clinical trial researchers equally with clinicians in terms of job promotion and title promotion. Foreign enterprises and scientific research institutions are allowed to carry out clinical trials of new drugs simultaneously in China in accordance with the law.

(III) improve the ethics committee mechanism. Clinical trials should comply with ethical and moral standards, ensure that subjects are informed of sufficient trial information before voluntary participation, understand and sign informed consent, and protect the safety, health and rights of subjects. The clinical trial institution shall set up an ethics committee to review the clinical trial scheme of the institution, review and supervise the qualification of clinical trial researchers, supervise the development of clinical trials and accept the inspection of regulatory authorities. All localities may set up regional ethics committees as needed to guide the ethical review of clinical trial institutions, and may accept institutions or registration applicants that do not have the conditions for ethical review to conduct ethical review of clinical trial protocols and supervise the development of clinical trials. Health and family planning, traditional Chinese medicine management, food and drug supervision and other departments should strengthen the management guidance and business supervision of the work of the ethics committee.

(IV) improve the efficiency of ethical review. The registration applicant shall submit the clinical trial protocol to the ethics committee of the clinical trial institution for review and approval before submitting the clinical trial application. If a multi-center clinical trial is carried out in China, after the ethical review of the clinical trial leader unit, other member units shall recognize the review conclusion of the team leader unit and will not repeat the review. The National Clinical Medical Research Center and clinical trial institutions that undertake major national science and technology projects and national key research and development programs should integrate resources to establish a unified ethical review platform and gradually promote mutual recognition of ethical review.

(V) optimize the clinical trial approval process. Establish and improve the communication mechanism between registration applicants and review institutions. Before accepting applications for drug clinical trials and medical device clinical trials that need to be approved, the review agency shall communicate with the registration applicant at a meeting and put forward opinions and suggestions. Within a certain period of time after accepting the clinical trial application, the food and drug regulatory department shall be deemed to have agreed without giving a negative or questioning opinion, and the registered applicant may carry out the clinical trial in accordance with the submitted plan. During the clinical trial, if the clinical trial protocol changes, major pharmaceutical changes or non-clinical research safety issues occur, the registration applicant shall promptly submit the changes to the review agency; if safety and other risks are found, the clinical trial protocol shall be modified in a timely manner, and the clinical trial shall be suspended or terminated. The applicant for drug registration may issue an inspection report on the clinical trial samples by itself or by entrusting an inspection institution, submit it together with the samples to the drug review institution, and ensure that the samples actually used in the clinical trial are consistent with the submitted samples. Optimize the approval process for human genetic resources activities involving international cooperation in clinical trials and speed up the process of clinical trials.

(VI) accept overseas clinical trial data. If the clinical trial data obtained from overseas multi-centers meet the relevant requirements of China's drug and medical device registration, it can be used to apply for registration in China. For drugs and medical devices that are first applied for marketing in China, the registration applicant shall provide clinical trial data on whether there is any race difference.

(VII) support extended clinical trials. For drugs and medical devices that are undergoing clinical trials for the treatment of serious life-threatening diseases with no effective treatment, if they may benefit from preliminary observation and meet ethical requirements, they can be used for other patients in the institution that conducts clinical trials after informed consent, and their safety data can be used for registration applications.

(VIII) seriously investigate and deal with data fraud. The signatory of the clinical trial entrustment agreement and the clinical trial researcher are the first persons responsible for the clinical trial data and shall bear legal responsibility for the reliability of the clinical trial data. Establish an inspection model based on risk and review needs, strengthen on-site inspections and cause-based inspections of non-clinical studies and clinical trials, and make the inspection results public. If the inspection fails, the relevant data will not be accepted; if there is a problem of authenticity, the case shall be filed for investigation in a timely manner, and the responsible persons of relevant non-clinical research institutions and clinical trial institutions, those responsible for providing false reports, registration applicants and contract research organizations shall be investigated in accordance with the law Responsibilities; those who refuse, evade, or hinder the inspection shall be severely punished in accordance with the law. If the registration applicant finds the problem on his own initiative and reports it in time, the penalty may be reduced or exempted as appropriate.

2. speed up listing review and approval

(IX) speed up the review and approval of clinically urgently needed drugs and medical devices. For the treatment of serious life-threatening diseases with no effective treatment and public health and other urgently needed drugs and medical devices, the early and mid-term indicators of clinical trials show efficacy and can predict their clinical value, can be approved for listing with conditions, enterprises should develop risk control plans, as required to carry out research. Encourage the research and development of new drugs and innovative medical devices, and give priority review and approval to new drugs and innovative medical devices supported by major national science and technology projects and national key research and development plans, as well as clinical trials carried out by the National Clinical Medical Research Center and approved by the central management department.

(X) support the research and development of medical devices for the treatment of rare diseases. The National Health and Family Planning Commission may entrust the relevant industry associations (academies) to publish the catalogue of rare diseases and establish a registration system for patients with rare diseases. Applicants for registration of rare disease therapeutic drugs and medical devices may apply for exemption from clinical trials. For rare disease treatment drugs and medical devices that have been approved for listing overseas, they can be approved for listing with conditions. Enterprises should formulate risk control plans and carry out research as required.

(11) strict drug injection review and approval. Strict control of oral preparations to injection preparations, oral preparations can meet clinical needs, not approved injection preparations listed. Strictly control the intramuscular injection preparation to intravenous injection preparation, intramuscular injection preparation can meet the clinical needs, not approved intravenous injection preparation market. Applications for mutual modification of dosage forms between large-volume injections, small-volume injections, and sterile powder needles for injection will not be approved if there is no obvious clinical advantage.

(12) The implementation of drug and pharmaceutical raw materials and packaging materials related to the examination and approval. API, pharmaceutical excipients and packaging materials shall be reviewed and approved together with the approval of drug registration applications, and the approval number of API shall no longer be issued. API, pharmaceutical excipients and packaging materials and their quality standards approved by the relevant review shall be publicized on the designated platform for selection by relevant enterprises. The drug marketing authorization holder is responsible for the quality of the raw materials, pharmaceutical excipients and packaging materials selected for the production of the preparation.

(13) Support the inheritance and innovation of traditional Chinese medicine. Establish and improve the registration management system and technical evaluation system in line with the characteristics of traditional Chinese medicine, and handle the relationship between maintaining the traditional advantages of traditional Chinese medicine and the requirements of modern drug research and development. Innovative drugs of traditional Chinese medicine should highlight the new characteristics of curative effect; improved new drugs of traditional Chinese medicine should reflect the advantages of clinical application; classic famous Chinese medicines should be reviewed and approved according to simplified standards; natural medicines should be reviewed and approved according to modern medical standards. To improve the ability of clinical research of traditional Chinese medicine, the application for registration of traditional Chinese medicine shall submit the marketing value and resource evaluation materials, highlight the clinical value-oriented, and promote the sustainable use of resources. Encourage the use of modern science and technology to research and develop traditional Chinese patent medicines, encourage the use of traditional Chinese medicine dosage forms to develop new Chinese medicine drugs, and strengthen the quality control of Chinese medicine.

(14) Establishing a priority review and approval system for patent compulsory licensing drugs. In the case of a major threat to public health, priority shall be given to review and approval of drug registration applications that have obtained compulsory licenses. The situation of major threats to public health and the procedures for starting compulsory licensing shall be prescribed by the National Health and Family Planning Commission in conjunction with relevant departments.

3. promotes drug innovation and generic drug development

(xv) Establishment of a catalogue of listed drugs. Drugs newly approved for listing or passing the quality and efficacy consistency evaluation of generic drugs shall be included in the catalogue of drugs listed in China, indicating the attributes of innovative drugs, improved new drugs and generic drugs consistent with the quality and efficacy of the original drugs, as well as effective ingredients, dosage forms, specifications, marketing license holders, patent rights obtained, trial data protection period and other information.

(16) Exploring the establishment of a drug patent link system. In order to protect the legitimate rights and interests of patentees, reduce the risk of patent infringement of generic drugs, encourage the development of generic drugs, and explore the establishment of a drug review and approval and drug patent linkage system. When submitting an application for registration, the applicant for drug registration shall state the relevant patents involved and their ownership status, and inform the relevant drug patentee within the prescribed time limit. Where there is a dispute over the patent right, the parties may bring a lawsuit to the court, and the technical review of the drug shall not be stopped during the period. For drugs that have passed the technical review, the food and drug regulatory department shall make a decision on whether to approve the listing according to the effective judgment, ruling or mediation statement of the court; if the effective judgment, ruling or mediation statement is not obtained within a certain period of time, the food and drug regulatory department may approve the listing.

(17) to carry out the drug patent term compensation system pilot. Select some new drugs to carry out pilot projects, and give appropriate patent term compensation for delays in marketing due to clinical trials and review and approval.

(18) Improve and implement the drug test data protection system. An applicant for drug registration may submit an application for trial data protection at the same time when submitting an application for registration. A certain period of data protection is granted to self-obtained and undisclosed test data and other data submitted by applicants for the registration of innovative drugs, rare disease treatment drugs, children-specific drugs, innovative therapeutic biological products, and successful drug registration challenging patents. The data protection period shall be calculated from the date when the drug is approved for marketing. During the data protection period, the application for listing of the same variety by other applicants shall not be approved, except for the data obtained by the applicant himself or the applicant who has obtained the listing license.

(xix) Promoting the production of generic drugs. Insisting on encouraging innovation and promoting the production of generic drugs, reducing the burden of drug use, regularly publishing a list of drugs whose patent rights have expired, terminated, invalid and no generic applications, guiding the development and production of generic drugs, and improving the accessibility of drug use to the public. Improve relevant research and evaluation technical guidelines to support the imitation of biosimilar and clinically valuable drug combinations. Accelerate the evaluation of the quality and efficacy of generic drugs.

(20) Give full play to the role of enterprises as the main body of innovation. Encourage pharmaceutical and medical device companies to increase investment in research and development, strengthen new product research and development and continued research on listed products, and continue to improve production processes. Scientific research institutions and researchers are allowed to apply for clinical trials under the premise of assuming relevant legal responsibilities. Where the state financial allocation is used to carry out research and development of new drugs and innovative medical devices and related technical research and transformation of scientific and technological achievements as posts, the unit may stipulate or agree with scientific researchers on the method, amount and time limit of rewards and remuneration, mobilize the enthusiasm of scientific researchers to participate, and promote the transfer and transformation of scientific and technological achievements.

(21) Support the clinical application of new drugs. We will improve the dynamic adjustment mechanism of medical insurance drug catalogue, explore the establishment of a negotiation mechanism for medical insurance drug payment standards, timely bring new drugs into the scope of basic medical insurance payment according to regulations, and support the research and development of new drugs. All localities may, according to the needs of disease prevention and control, timely incorporate new drugs into the scope of centralized drug procurement in public hospitals. Medical institutions are encouraged to give priority to the procurement and use of new drugs with clear curative effects and reasonable prices.

4. strengthen the whole life cycle management of drugs and medical devices

(22) Promote the full implementation of the listing permit holder system. Summarize the pilot experience of the drug marketing license holder system in a timely manner, promote the revision of the Drug Administration Law, and strive to promote it throughout the country as soon as possible. Allow medical device research and development institutions and researchers to apply for medical device marketing license.

(23) To implement the legal liability of the holder of the listing license. The drug marketing authorization holder shall bear all legal responsibilities for drug preclinical research, clinical trials, manufacturing, sales and distribution, adverse reaction reports, etc., to ensure that the research data and clinical trial data submitted are true, complete and traceable, to ensure that the production process is consistent with the approved process and the production process is in continuous compliance, to ensure that the quality of each batch of drugs sold is consistent with the declared samples, and to ensure continuous research on listed drugs, timely report the adverse reactions, assess the risk situation, and propose improvement measures. Medical device marketing license holders shall bear all legal responsibilities for medical device design and development, clinical trials, manufacturing, sales and distribution, adverse event reports, etc., to ensure that the submitted research data and clinical trial data are true, complete and traceable, to ensure continuous research on listed medical devices, to report adverse events in a timely manner, to assess risks, and to propose improvement measures. Enterprises, institutions and individuals entrusted by the drug and medical device marketing license holder to carry out research and development, clinical trials, manufacturing, sales and distribution shall bear the responsibilities stipulated by laws and regulations and the responsibilities stipulated in the agreement.

(xxiv) Establish a system for direct reporting of adverse reactions and adverse events by listing permit holders. The holder of the listing license shall bear the main responsibility for the report of adverse reactions and adverse events, and those who conceal the report or report late shall be severely punished according to law. The food and drug regulatory authorities shall investigate and analyze the reported adverse reactions and adverse events, and order the marketing license holders to take measures such as suspension of sales, recall and improvement of quality control.

(xxv) Reevaluation of drug injections. According to the progress of pharmaceutical science, re-evaluate the listed drug injections, and strive to basically complete it in about 5 to 10 years. The marketing authorization holder shall conduct a comprehensive analysis of the research at the time of approval for marketing, the continuing research after marketing, etc., conduct research on product composition, mechanism of action and clinical efficacy, and evaluate its safety, effectiveness and quality control. Through re-evaluation, enjoy the relevant incentive policies for the evaluation of the quality and efficacy of generic drugs.

(26) Improve the re-evaluation system of medical devices. The marketing authorization holder shall take the initiative to re-evaluate the listed medical device according to the scientific progress and adverse event evaluation results. If the re-evaluation finds that the product cannot be guaranteed to be safe and effective, the listing permit holder shall apply for cancellation of the listing permit in a timely manner; if the re-evaluation results are concealed and the cancellation application should be filed but not filed, the listing permit shall be revoked and investigated and dealt with in accordance with the law.

(27) Standardize the academic promotion of drugs. The drug marketing license holder shall record the list of medical representatives on the website designated by the food and drug regulatory department and make it public to the public. The medical representative is responsible for the academic promotion of drugs, introducing drug knowledge to medical staff, and listening to opinions and suggestions on clinical use. The academic promotion activities of medical representatives shall be carried out in public and put on record in the designated departments of medical institutions. Medical representatives are prohibited from undertaking drug sales tasks, and it is prohibited to provide medical representatives or relevant enterprise personnel with the number of drug prescriptions issued by individual doctors. Medical representatives who mislead doctors into using drugs or conceal adverse drug reactions shall be seriously investigated and dealt with; those who carry out drug trading activities in the name of medical representatives shall be investigated and dealt with as illegal drug trading.

5. enhance technical support capacity

(28) Improve the technical review system. Establish a technical review system led by review and supported by inspection and inspection, improve the review project manager system, the communication system between the review agency and the registered applicant meeting, and the expert advisory committee system, strengthen internal management, and standardize the review process. Set up a drug review team composed mainly of clinical medical professionals, pharmacy, pharmacology and toxicology, statistics and other professionals, responsible for the review of new drugs. Establish a medical device review team composed of professionals in clinical medicine, clinical diagnosis, machinery, electronics, materials, biomedical engineering, etc., responsible for the review of innovative medical devices. Except for technical secrets such as production processes, the conclusions and basis of the review are all made public and subject to social supervision. Unify the second type of medical device review standards, and gradually realize the national unified review.

(29) Implement the confidentiality responsibilities of relevant staff. The personnel involved in the supervision of drug and medical device acceptance review, review and approval, inspection and inspection shall have the obligation to keep confidential the technical secrets and test data submitted by the registration applicant. Those who violate the obligation of confidentiality shall be held accountable in accordance with laws and disciplines, and the results of the handling shall be disclosed to the public; if a crime is suspected, it shall be transferred to the judicial organ for criminal responsibility. Improve the management of registration application materials to ensure that access, copy of the situation can be traced back.

(30) Strengthen review and inspection capacity building. The review of drugs and medical devices will be included in the scope of services purchased by the government, and standardized and efficient review services will be provided. Accelerate the information construction of drug and medical device review and approval, formulate technical requirements for electronic submission of registration applications, improve the electronic general technical document system, and gradually realize the electronic submission and review and approval of various registration applications. Establish the variety files of listed drugs and medical devices.

(31) Implementation of the whole process of inspection responsibility. Drug medical device research and development process and drug non-clinical research quality management practices, drug clinical trial quality management practices, medical device clinical trial quality management practices, by the national food and drug regulatory authorities to organize the inspection. The food and drug regulatory authorities at or above the provincial level shall be responsible for the inspection of the production process and the implementation of production quality management norms for pharmaceutical and medical devices. The food and drug regulatory departments at the city and county levels shall be responsible for the inspection of the business process of pharmaceutical and medical devices and the implementation of business quality management norms. If problems are found in the inspection, they shall be investigated and dealt with in accordance with laws and regulations and risk control measures shall be taken in a timely manner; if a crime is suspected, it shall be transferred to the judicial organ for criminal responsibility. Promote the punishment of illegal acts to people, inspection and punishment results to the public.

(32) Building a team of professional inspectors. Relying on existing resources to speed up the construction of the inspection team, the formation of full-time inspectors as the main body, part-time inspectors as a supplement to the professional inspection team. Implement a hierarchical management system for inspectors, strengthen inspector training, strengthen inspection equipment, and improve inspection capabilities and levels.

(XXXIII) Strengthening international cooperation. Deepen multilateral and bilateral drug and medical device regulatory policies and technical exchanges, actively participate in the formulation and revision of international rules and standards, and promote the gradual realization of international sharing of review, inspection, inspection standards and results.

6. strengthen organization and implementation

(34) Strengthen organizational leadership. All relevant departments in all regions should fully understand the importance of deepening the reform of the review and approval system and encouraging the innovation of pharmaceutical and medical devices, attach great importance to the reform and innovation of the review and approval of pharmaceutical and medical devices, support it as an important content for building an innovative country and promoting the development of high-tech industries, strengthen overall planning and coordination, refine the implementation plan, improve the working mechanism, and earnestly grasp the implementation of tasks. Adhere to the use of rule of law thinking and methods to promote reforms, and continuously improve relevant laws, regulations and institutional systems. If reform measures involve legal amendments or require corresponding authorization, they shall be submitted to amend the law in accordance with procedures or be implemented after authorization by the legislature.

(35) Strengthen collaboration and cooperation. Give full play to the role of the inter-ministerial joint conference system for the reform of the drug and medical device review and approval system, and study and resolve the contradictions and problems encountered in the reform in a timely manner. The national food and drug regulatory authorities must play a leading role, grasp the specific implementation of reforms, and coordinate the implementation of tasks. All relevant departments should perform their duties in accordance with the law, work together, and form a joint force for reform. Development and reform departments should support the development of high-tech pharmaceutical products and incorporate the construction of clinical trial institutions into the important content of the construction and development of medical institutions. Science and technology departments should strengthen the planning and guidance of medical science and technology development, and do a good job in the implementation of scientific and technological plans (special projects and funds) related to the research and development of new drugs and innovative medical devices. Industry and information departments should strengthen the development planning and guidance of the pharmaceutical industry, and strengthen the guarantee of clinical drug production. The financial department shall do a good job in the examination and approval of drugs and medical devices, and guarantee the funds required for inspection and inspection. Human resources and social security departments should do a good job in medical insurance policies to support the development of new drugs. Health and family planning departments should strengthen the guidance for the construction of clinical trial institutions, strengthen the management of ethics committees and the training of clinical trial researchers. The intellectual property department shall do a good job in protecting the intellectual property rights of pharmaceutical and medical devices related to patents. Traditional Chinese medicine management departments should do a good job in the innovation of traditional Chinese medicine.

(36) Do a good job of propaganda and explanation. Positively publicize the importance of encouraging the innovation of drugs and medical devices, strengthen the interpretation of important policies and major measures for the reform of the review and approval system, promptly answer hot issues of concern to all sectors of society, actively respond to social concerns, reasonably guide the expectations of all parties, and create a good public opinion for the implementation of reforms Atmosphere.