40 years of reform and opening up: changes in China's pharmaceutical research and development environment

During the 40 years of reform and opening up, what changes have taken place in China's pharmaceutical research and development environment? What reforms has the policy of drug technology transfer gone through? See below In the past 40 years of reform and opening up, the environment of drug research and development has changed In particular, in 2017, there was a significant increase in the application of innovative drugs for domestic chemical and biological drugs Compared with 2016, the application of biological innovative drugs in 2017 increased by 126.7% Figure 1-2-1 application of innovative drugs (variety plan) in 2013-2017, but it is not difficult to find that the analysis of innovative drugs listed and declared in China in the past five years from the target point is basically the tracking innovation on the known target point, the basic research and transformation research in China are relatively weak, and the deep level innovation ability needs to be strengthened In contrast, the pharmaceutical powers in Europe and the United States are mainly engaged in the research and development of new drugs, including three [1]: 1 Universities and non-profit scientific research institutions are engaged in the research of disease mechanism - finding new drug targets and creating new clinical treatment means; the establishment of new drug molecules (platform technology) (such as humanized and all humanized therapeutic antibodies) The research funds mainly come from the national and professional funds The successful way out for research results is to authorize or transfer technology to large pharmaceutical companies; researchers get venture capital or government funding to establish small companies in University Science Park to start their own businesses 2 Small and medium-sized technological innovation companies are committed to the early research and development of new drugs based on the independent innovation technology of entrepreneurs The funds are mainly from early venture capital The way out for success is to be wholly or partially merged by giant pharmaceutical companies Occasionally, small companies develop into large companies by virtue of excellent platform technology, such as Genetech in the United States, but he is still merged by Roche in Switzerland for nearly $50 billion 3 Super large pharmaceutical companies concentrate a large number of first-class scientists and engineering technicians, with extremely fine technical and professional division of labor, adopt a collaborative form similar to the factory assembly line, research and develop innovative drug molecules for new targets based on mature platform technology, or research and develop innovative drugs for new and old targets based on new technology platform The huge R & D funds come from the profits of enterprises and capital market funds, and the way out of the achievements is product listing According to the research and development of new drugs in foreign pharmaceutical developed countries, the main body of new drug research and development is enterprises, while universities and scientific research institutions mainly focus on basic research Similarly, China's basic research forces are mainly concentrated in scientific research institutes, such as Peking University Pharmaceutical College, China Pharmaceutical University, Shenyang Pharmaceutical University, and State Key Laboratory of new drug research, Shanghai Institute of pharmaceutical research, Chinese Academy of Sciences At present, there are also quite a number of innovative enterprises to develop new drugs through cooperation with National Institutes of internal medicine or foreign research institutions, or independent research and development of enterprises The path and method of new drug research and development in China are gradually diversified, but they cannot leave basic research Which disease area is more difficult to develop new drugs? Many people think of Alzheimer's disease first Although we have a certain understanding of the disease characteristics of Alzheimer's disease, its pathogenesis has been in the stage of "hypothesis" So it's not surprising that new drugs for Alzheimer's have failed repeatedly 2、 Drug regulation and regulation the United States can become the world's top pharmaceutical Empire, which is closely related to the powerful drug regulatory agency behind it, the U.S Food and Drug Administration (FDA) FDA is reasonable and advanced in the fields of drug research and development, registration, supervision, circulation and so on It has great reference significance for drug regulation in China There are a lot of historical problems left over in China's drug regulation, and many reforms have been carried out Looking back on every reform, most of them are overstocked with old problems, and new problems come to an end The reform is not thorough and thorough Therefore, since the State Council issued the opinions on the reform of the review and approval system of medical devices on August 18, 2015, the review and approval system of medical devices in China has been greatly reformed again （1） The redefinition of new drugs the definition of "new drugs" in China has experienced many changes The definition of "new drugs" has changed from "drugs not produced in China" in 1985 to 2002 "Drugs that have not been listed and sold in China" were finally identified as "drugs that have not been listed and sold in China and abroad" in 2015 The transformation of new drugs from "China new" to "global new" has been explored for 30 years Through continuous reform, China has a clear understanding of innovative drugs, improved drugs and generic drugs 2 The establishment of the pilot drug marketing license holder system (MAH) is a major reform for the internationalization of China's drug regulation Before MAH was introduced, the management mode of unified binding of marketing license and production license was implemented in China Only the manufacturer can apply for drug registration and obtain the final drug approval number After the implementation of MAH, drug R & D and drug production are separated, and drug R & D institutions and researchers also have approval numbers of drugs, which changes the pattern of drug R & D in China, favors new drug R & D, and puts forward stricter requirements for the safety and effectiveness of the whole life cycle of drugs The implementation of the system is conducive to promoting the rapid development of new drug research and development in China 3 Reform of clinical trial management of new drugs; the qualification of clinical trial institutions shall be subject to record management After the institutions with clinical trial conditions register on the website designated by the food and drug administration, they can accept the entrustment of the applicant for registration of medical devices to carry out clinical trials Although the determination system of GCP (drug clinical trial management standard) is cancelled, it does not mean that the access threshold is lowered On the contrary, we should increase the resources of clinical research, enhance the efficiency of supervision of clinical trial institutions, and further ensure the quality of clinical trials Optimize the approval procedure of clinical trials, and apply for implied permission system of clinical trials Establish and improve the communication and exchange mechanism between the registration applicant and the review institution Before accepting the clinical trial of drugs and the clinical trial application of medical devices to be approved, the review institution shall communicate with the registration applicant at a meeting and put forward opinions and suggestions Within a certain period of time after the acceptance of the clinical trial application, the food and drug regulatory department shall be deemed to agree without giving a negative or questioning opinion, and the registration applicant may carry out the clinical trial according to the submitted scheme The setting of time limit exerts pressure on the drug review part, and the technical review must be completed within the specified time; for enterprises, the risk of too long review cycle caused by the review backlog is reduced, and the resources can be reasonably applied through effective adjustment Accept the data of overseas clinical trials The clinical trial data obtained in overseas multi centers that meet the relevant requirements of China's drug and medical device registration can be used to apply for registration in China A positive step has been taken to realize the simultaneous listing of drugs at home and abroad （2） "Generic" is an alternative drug with the same active ingredients, dosage forms, delivery routes and therapeutic effects as the generic drugs It has important economic and social benefits such as reducing medical expenditure, improving the accessibility of drugs and improving the level of medical services In the world, we generally adopt the policy orientation of encouraging both innovation and imitation, and actively explore the promotion of R & D innovation, supply guarantee and clinical use of generic drugs India mainly promotes the development of generic drugs by formulating strict drug patent granting standards, strictly restricting "evergreen patents", focusing on the deterrent role of compulsory licensing, and encouraging competent enterprises to actively apply for compulsory licensing The United States has simplified the review and approval process of generic drugs, promoted the alternative use of generic drugs, and established the "orange book" system (the United States has compiled and printed the list of all FDA approved prescription drugs and over-the-counter drugs that have been evaluated for safety and effectiveness into a book, and published the patent information related to the approved drugs in the appendix, and published it regularly Because the book cover color is orange, commonly known as "orange book"), and the implementation of drug compulsory licensing and other policies to promote the development of the generic pharmaceutical industry Since the reform and opening up, China's generic pharmaceutical industry has made rapid development, the scale of the industry continues to expand, and the number and variety continue to be rich More than 95% of the nearly 170000 drug approvals are generic drugs, which has made a significant contribution to the protection of the health of the people However, due to various reasons, China's generic industry is still large but not strong, and the situation of "how small and scattered is poor" still exists There is a large difference in drug quality The high-quality drug market is mainly occupied by foreign original research drugs, and the prices of some original research drugs are falsely high Compared with the current drug accessibility and affordability, the demand for high-quality generic drugs by the general public still lags behind, There is an urgent need for reform and improvement 1 The implementation of consistency evaluation was as early as 2013, and the State Food and drug administration proposed to carry out the consistency evaluation of quality and efficacy of generic drugs In 2015, the former State Food and Drug Administration issued the announcement on the filing management of bioequivalence test of chemical drugs The be test was approved by the State Food and drug administration to be carried out independently by the enterprise after the filing It was not until March 2016 that the State Council issued the opinions of the general office of the State Council on carrying out the conformity assessment of quality and efficacy of generic drugs that the conformity assessment was implemented Provinces and municipalities have also issued very awesome policies to support enterprises in carrying out consistency work, including financial support, and giving preferential treatment through bidding for procurement through consistent evaluation The successful development of drug consistency evaluation is of great significance to the regulation of generic drug market in China 2 Set up China listing catalog and China listing catalog, which has a more well-known name in the industry: China orange peel book As the same as the American FDA's orange book, China orange book has the same significance for drug research and development in China It includes the drugs with safety, effectiveness and quality control in China, and determines the reference and standard preparations for real-time update 3 In 2012-2016, 631 patents of original research drugs expired in the world Due to information asymmetry, technical difficulty and the small scale of some rare disease drugs market, the speed of domestic follow-up is still very slow Many patents expired, and no enterprises put forward copy registration applications On the basis of the establishment of China's listing catalogue, a catalogue of drugs to be imitated is formulated By giving priority to the review and approval of drug registration applications listed in the catalogue, pharmaceutical enterprises and R & D institutions are encouraged to conduct orderly R & D, registration and production, so that more pharmaceutical enterprises can obtain the rights and interests of imitated R & D through open competition and promote more clinically necessary, effective and supply The shortage of generic drugs can be listed as soon as possible On the one hand, it can solve the problem of high price of some original research drugs On the other hand, it can solve the problem of short shortage of some drugs in China, and greatly improve the accessibility and supply guarantee ability of drugs In 2017, the former State Food and Drug Administration officially became the international human drug injection