[discussion on pharmaceutical matters] thoughts on the 2017 version of measures for the administration of drug registration (Revised Version)

Drug registration is also a system of special knowledge, involving many disciplines The problems studied are academic problems But it faces the objective and practical problems of public health medication and universal health insurance These problems should be treated with scientific attitude and innovative spirit Should academic laws and regulations also have relative continuity and stability? The 19th National Congress of the Communist Party of China put forward that China has entered a new era of socialism with Chinese characteristics, not forgetting its original intention and keeping its mission in mind; to have confidence in theory, road, system and culture, I understand that all walks of life should be so Of course, self-confidence is not self-confident, closed, self-esteem, self appreciation, not to be proud, self deception We are still developing countries, and there is still a gap compared with the developed countries in the world We should be open, learn, inclusive and win-win in the new era of building a community of shared future for mankind Read hastily and without thinking about the past Our predecessors have taught us the way to learn from each other's strengths and learn from our needs, to make the past serve the present and to serve the West We must take the essence and remove the dross, and we must inherit the old and develop it It is realized that the pharmaceutical industry today can only develop healthily and comprehensively if we do not forget our original intention and look forward, respect the objective laws of their own development and respect them After carefully studying the revised version of the registration management method, compared with the previous version, the following questions are not clear, so I would like to discuss with it 1 The purpose and quality of legislation The revised version is formulated according to the drug administration law Its legislative purpose is to ensure the safety, effectiveness and quality control of drugs, and regulate drug registration The legislative purpose of the 2015 reference drug administration law is: to strengthen drug supervision and management, ensure drug quality, ensure the safety of human drug use, and safeguard the people's health and legitimate rights and interests in drug use, this law is hereby formulated The drug administration law states that the purpose of strengthening the supervision and management of drugs from development to use is to ensure the quality of drugs Medicine is a very special commodity, and its special quality attributes have been summarized by predecessors: first, the specificity of treating diseases and saving people; second, the duality of treating diseases and causing diseases (life); third, it is not drugs such as diseases, but the timeliness of drugs and other diseases; fourth, it is not the priceless nature of drug prices So what is quality? There are a lot of interpreters I think the following explanations should be true and realistic The definition of quality in iso9000:2005 quality management system basis and terminology issued by international organization for Standardization (ISO) in 2005 is: the degree to which a set of inherent characteristics meet the requirements As far as drugs are concerned, the above drug quality attributes are: first, the inherent efficacy that drugs should have, that is, curative effect; no curative effect is not drugs, which not only requires effectiveness, but also hopes to be efficient, quick and long-term; second, the inherent material characteristics of drugs, the mechanism of drug treatment is mostly "attack poison with poison", and the hidden danger of safety is where the characteristics of drugs lie Under the premise of effective drugs, side effects of drugs can be caused Small toxicity and small dosage can also ensure the safety of drug use; third and fourth are the characteristics given to the drug The drug is for treating diseases, and the patients vary greatly, The priorities are different, which requires drugs and other diseases and long enough stability of drugs Similarly, as far as the practical value of drugs is concerned, low-cost drugs can become priceless if they can save people's lives The priceless nature of drugs is the requirement of China's public health and universal medical insurance To achieve priceless nature and meet the needs of drugs, drugs should also have the quality requirement of "five simplifications", That is to say, the production and evaluation are simple, and the storage, carrying and use are convenient If the five simple requirements can be met, the drug price will naturally be cheap To ensure the quality of drugs is to ensure the effectiveness, safety, stability and simplicity of drugs Only in this way can such drugs be evaluated as good quality or excellent quality In order to fully understand and understand the quality attributes of special commodities of drugs and the current situation of the national health cause, the legislative purpose of the drug management law is scientific and practical On the premise of ensuring the quality of drugs, it emphasizes the protection of human drug safety and the legitimate rights and interests of people's health and drug use This aim is in line with the national conditions It should be the aim of the pharmaceutical industry teaching, research and development, registration, production and use Since the revised draft is formulated in accordance with the drug administration law, it is obvious that the legislative purpose will put safety first, followed by effectiveness It is questionable to replace quality assurance with quality control In a broad sense, "the definition of quality has two meanings, i.e use requirements and satisfaction When people use products, they always put forward certain requirements for product quality, which are often affected by factors such as use time, use place, use object, social environment and market competition Changes in these factors will make people put forward different quality requirements for the same product Therefore, quality is not a fixed concept, it is dynamic, changing and developing; it varies with the time, place and object of use, and it is constantly updated and enriched with the development of society and technology The satisfaction degree of users to the use requirements of products is reflected in the performance, economic characteristics, service characteristics, environmental characteristics and psychological characteristics of products Therefore, quality is a comprehensive concept It does not require the higher the technical characteristics, the better, but pursues the best combination of factors such as performance, cost, quantity, delivery time, service, etc., that is, the so-called most appropriate ";" the quality requirements of customers and other interested parties for products, systems or processes are dynamic, developing and relative; it will change with the change of time, place and environment Therefore, the quality shall be reviewed on a regular basis, and the quality of products, systems or processes shall be improved accordingly according to the changing needs and expectations, so as to ensure that the requirements of customers and other interested parties are continuously met " Since product quality is not a fixed and unchanging concept, it is dynamic, developing and relative, involving the recognition of suitability and conformity of product users, product manufacturers and regulatory stakeholders, using "quality assurance" may be more accurate than "quality control" to reflect the quality attributes of drugs as special commodities What is the connotation of quality control in the revised draft? Does the quality standard of drugs control the quality of drugs or something else? Is the legislative purpose of the drug management measures more suitable for the quality attributes of drugs as special commodities and the objective reality of the pharmaceutical industry in China? 2 Article 6 the State implements the system of drug listing license holders As early as 2015, the general office of the State Council issued a notice on the pilot scheme of the drug listing license holder system, and recently learned articles on interpretation of relevant laws and regulations and policies, but there are still some unclear points for consultation With regard to the system of drug listing license holders and the current drug registration system in China, the article reads: "the system of drug listing license holders is a common practice in the field of drug supervision in developed countries and regions such as Europe, the United States and Japan, which adopts the management mode of separating drug listing license from production license, The holder of the drug listing license (the holder of the drug listing license document, i.e the drug manufacturing enterprise, research and development institution or scientific research personnel) is allowed to produce drugs by himself or entrust other manufacturing enterprises to produce drugs " "China implements the management mode of integration of marketing license and production license for domestic drugs Only drug manufacturers are allowed to produce the drugs after obtaining the drug approval number and being certified by the drug production quality management standard In practice, drug R & D institutions and researchers can not obtain drug approval number, and after new drug R & D institutions obtain new drug certificates, they can only transfer relevant drug technology to drug manufacturers This "bundling" mode of drug registration and production license is not conducive to encouraging innovation, safeguarding drug supply and inhibiting low-level repeated construction According to this and the terms of the holder system to be implemented in the revised draft, I understand that the actual contribution of the drug listing permit holder system in drug research and development, registration and approval for listing, that is, there is no difference between the responsibilities and obligations and the current management system in China, except that the applicant's rights to the listed drugs are different after the registration is successful Why? Drug R & D, registration and production involve many subjects, which is a system engineering with the characteristics of high investment, high risk and high return The multinational pharmaceutical giants in developed countries have the strength and financial resources, often integrating pharmaceutical research, basic medical research and production of drugs As long as the clinical trial is approved by the drug regulatory department of the authority, they are the owners of intellectual property rights and the decision-makers of the right to market production and operation This system focuses on the pure commodity attribute of drugs rather than the special commodity attribute of drugs, which is in line with developed countries Objective reality of drug research and development The current procedures of drug registration management in China are as follows: the applicant, after project approval, pharmaceutical research and basic medical research, applies for preclinical research of drugs, after obtaining the approval documents of clinical research, applies for clinical application of drugs, after completion, applies for production, issues new drug certificate, production approval documents, and drug registration approval documents (generic drugs, supplementary applications, etc.) Obviously, the applicant who has obtained the drug production approval is the holder of the drug listing license However, at that time, the system stipulated that the applicant who is not a manufacturer can have the new drug certificate, but does not issue the production approval, and can transfer the approval number to the manufacturer, that is, there is only intellectual property rights and no production and operation rights, which is the only difference between the system and the holder system Why? We are a developing country with a low concentration of pharmaceutical enterprises Drug applicants mainly come from manufacturers, medical colleges and universities, and drug research institutions These institutions are limited to their own strength and financial resources, so it is difficult to independently complete the system engineering of drug R & D, registration and production Therefore, they advocate the drug R & D mechanism combining production, learning and research, give full play to the advantages of all parties, closely cooperate and coordinate development Is not artemisinin's Nobel prize the result of the joint efforts of scientists represented by Tu youyou? This is the objective status quo of research and development of drugs in line with China's actual situation Of course, the system of "bundling" the drug applicant and the drug production license will deprive the non production enterprise applicants who have obtained the production approval documents of the right to go on the market, which is certainly not conducive to encouraging innovation Is it not innovation to abandon unreasonable regulations while advocating system self-confidence and encouraging system innovation? Can we learn the essence of the "drug registration permit holder system", untie the non production enterprises' drug applicants, cancel unreasonable provisions, and give all applicants the same obligations, responsibilities and rights? Is it because the holder system is the common practice of drug supervision in developed countries that we should give up the drug management system of our country, which has not been substantively implemented for many years? Do you have to copy the term "drug marketing license holder"? In the revised version, the relationship between applicants, overseas applicants, legal persons and holders in drug research, registration, production and use, as well as their responsibilities, obligations and rights are not clearly stated, some of which are repeated, some of which are inconsistent with each other As for some references, some professional terms will be mentioned later Compared with the previous edition, I learned a lot of new words and added a little strangeness Don't forget to make the people's Republic of China