How to make innovative medicine

Research and development, clinical trials, payment system support and other links constitute the ecosystem of innovative drugs In the first half of this year, the approval of some imported innovative drugs by the State Food and Drug Administration ran out of the "rocket speed": the nine price HPV vaccine used to prevent cervical cancer took only 8 days from the drug manufacturer submitting the application for listing to being approved; the PD-1 monoclonal antibody drug opdivo used for the second-line treatment of non-small cell lung cancer took less than 7 months from the application for listing to being approved At the same time, measures such as zero tariff, value-added tax reduction and medical insurance negotiation are being implemented intensively, and the obstacles of the listing, supply and purchase of imported anticancer drugs in China are being solved one by one "To expand the opening up, we need to improve the innovation capacity of domestic medicine through opening up." Song Ruilin, executive director of China pharmaceutical innovation promotion association, said that when the country opens the door to the import of anti-cancer drugs, it needs to make supporting arrangements to build its own attraction Yang Dajun, chairman of Yasheng pharmaceutical, believes that the links of R & D, clinical trials and payment system support constitute the ecosystem of innovative drugs No matter which link is missing, it will make it difficult for domestic innovative drugs to break through in 3-5 years The process of importing innovative drugs into the domestic market is being simplified Before that, the data of foreign clinical trials were not recognized at all Even if foreign drugs had been put on the market, they would have to conduct clinical trials again in China In the past 10 years, the time of marketing of imported drugs in China is 5-7 years later than that in Europe and America In order to enable domestic patients to use foreign innovative drugs as soon as possible, many policies have been issued at the national level, which have accelerated the listing process of imported anticancer drugs by adjusting the approval procedures of imported drugs, establishing a priority review mechanism, and canceling the batch by batch compulsory inspection of imported drugs According to the data released by Li Jinju, deputy director of the pharmaceutical and chemical registration department of the State Food and drug administration, the average time for approving the clinical trials of imported anticancer drugs in 2017 was 114 days, 129 days shorter than that in 2014; the average time for approving the listing of imported anticancer drugs was 111 days, 309 days shorter than that in 2014 In May this year, the State Food and drug administration, together with the national health and Health Commission, issued a notice proposing that if there is no ethnic difference in the treatment of serious or life-threatening diseases, including anti-cancer drugs, which are on the market overseas and lack of effective treatment means, the applicant does not need to apply for clinical trials, but can directly try overseas Inspection data is applied for listing On July 10, the State Food and Drug Administration issued the technical guidelines for accepting overseas clinical trial data of drugs, which made clear the scope of application, basic principles, integrity requirements, technical requirements for data submission and acceptance degree of accepting overseas clinical trial data The move is expected to shorten the time for imported drugs to be listed in China by 1-2 years "It's a great advantage for patients that new overseas drugs can be launched in China faster." Song Ruilin said There are concerns in the industry about the process optimization There are a series of preferential policies for imported drugs, while the domestic review and approval and payment system reform measures have not been implemented in time, which may not only cause foreign drugs not to come to China for clinical trials, but more seriously, domestic innovative drug companies may choose to go abroad for clinical trials, and then enter the Chinese market as imported drugs Song Ruilin said that this may lead to the hollowing out of research and development of innovative drugs in China In the past, the problem of low level of clinical trials caused by generic drugs was also difficult to solve "For domestic innovative pharmaceutical enterprises, it is more important to speed up the review and approval." Said Yang Dajun, chairman of AXA pharmaceutical In recent years, with the deepening of pharmaceutical innovation policy reform, China's pharmaceutical supervision and approval environment has been gradually optimized For example, under the principle of encouraging innovation, the new drug review regulations redefine the concept of new drugs, establish a system of communication and expert advisory committee, speed up clinical trials and market approval of new drugs, and establish a priority review mechanism for innovative drugs urgently needed in clinical practice Moreover, the State Food and Drug Administration joined the ICH (International Coordinating Committee for registration technology of human drugs) to let China's evaluation standards connect with the international standards However, many insiders said that there are many reform measures, but affected by various factors, the actual effect needs to be further optimized First of all, "the professional level and scientific research level of the domestic ethics committee are not enough, and they do not have the ability to review the clinical trials of new drugs." Yang Dajun said that at present, the work of ethical review is undertaken by hospitals, but many hospitals are not enthusiastic about it, the results of the review are vague, and the frequency of the hospital's ethics committee meetings is low It is understood that it will take at least two or three months in the ethical review process Yang Dajun suggested that the approval of clinical trials should be carried out in parallel with the ethical review, and that the ethical approval should not be regarded as the premise of the approval of the drug administration Secondly, in the view of many people in the industry, according to relevant regulations, there are disputes on the requirements of applying for approval documents from the genetic office for clinical trials involving foreign pharmaceutical enterprises In the past, only the clinical trials of specimen export were affected, but now all the clinical trials involving foreign investment are affected, covering the clinical trial sponsor, contract research organization (CRO) and central laboratory "For example, pharmaceutical enterprises are domestic funded enterprises, but cros undertaking clinical trials may have foreign background, which should also be audited by the genetic office." Yang Dajun doesn't think it makes sense Many enterprises report that the audit of genetic office lacks clear basis and standard, which leads to many difficulties in the process "Generally speaking, due to this approval, the whole clinical trial project will be delayed for at least 3-6 months." Yang Dajun suggested optimizing the system from two aspects One is to decide whether to go through the approval of the genetic office according to the content of clinical trials, for example, if it involves large-scale genetic testing, it is necessary to go through the approval of the genetic office for the testing of a certain gene and susceptibility of tens of thousands of people; the other is to draw lessons from the practice of the United States, carry out patient privacy legislation, and protect the blood, tissue and other samples of patients used in clinical trials in three levels: simple clinical trials, Exemption can be applied for; patients' informed consent is required for biological exploratory research; for commercial development, not only informed consent but also payment is required Song Ruilin suggested that the examination and approval of human genetic genes should be filed before supervision On the way to a big country of innovative drugs, the shortcomings of clinical trials in China need to be supplemented "At present, the problem of China's innovative drug industry is the surge of clinical research demand, but the supply side capacity is still weak." Said Wu Chun, partner and managing director of Boston Consulting According to her introduction, from the demand side, the conformity assessment of generic drugs has greatly increased the need for bioequivalence (be) tests It is expected that the number of be tests will remain 1500 cases per year from 2018 to 2023 Meanwhile, with the acceleration of new drug research and development, the number of phase I clinical trials will maintain a compound growth rate of 15%, and will exceed 600 cases in 2023 The demand for international multi center clinical trials at the same time will also This leads to an increase in the number of phase I-II clinical trials to be undertaken in China The supply side is weak In terms of quantity, at present, there are more than 800 clinical trial institutions in China, only 1 / 4 of which can carry out be / I phase clinical trials, and most hospitals have less than 20 beds; in terms of quality, there may be less than 10 clinical trial institutions that can truly meet the requirements of both China and the United States, so it is urgent to improve the water level of major researchers (PI) and the standardization of process and data operation "In the past, there was very little PI for stage I clinical practice in China, mostly for stage III clinical practice in foreign countries, only the increase of samples It needs a lot of experience and the ability level of PI needs to be improved " Yang Dajun said that, especially in the first human clinical trial (FIH) of innovative drugs, not only the PI requirements are very high, but also the cooperation of research institutions, clinical pharmacology, safety assessment, regulatory system, quality control system and many other links is needed, while there is no perfect system engineering in China He suggested that, on the one hand, more investment should be made, on the other hand, domestic medical schools and hospitals should attach importance to clinical trials, especially the leading medical institutions and large general specialized hospitals in China, and put clinical research in an important position At the same time, innovative drugs should have more room to benefit, so as to stimulate the enthusiasm of researchers Song Ruilin suggested that provisions should be made in the drug administration law, the PI responsibility system should be implemented in clinical trials, and the responsibility of clinical design, organization and evaluation should be implemented to people In addition, we need to strengthen the connection between clinical trials and research and development, so that clinical doctors can understand drug research and development, and drug developers can understand clinical needs and laws "Open the door to make good use of some good systems to attract good things from outside." For example, support domestic and foreign innovative pharmaceutical companies to carry out clinical trials at home, Song said In this respect, foreign experience is worth learning It is understood that Japan can maintain a premium when adjusting the price of drugs that carry out Ⅱ - Ⅳ clinical trials in its own country; Taiwan can enjoy a premium of up to 10% for drugs that carry out Ⅰ - Ⅲ clinical trials in its own country Why are new drugs so expensive? The most important factor that constitutes the "sky high price" is the high research and development cost of new drugs Tufts Medical Center concluded that the total cost of developing a new drug is about 2.6 billion US dollars, and the success rate of new drug research and development is very low Successful new drugs on the market also need to pay for the failed drugs According to industry insiders, the cost of new drug research and development in China is relatively low, spending about 1 billion yuan and 10 years "If a country cannot tolerate the price of innovative drugs, it will not go far on the road of innovation." Song Ruilin said that at present, there are still defects in the price formation mechanism and payment system of domestic innovative drugs, which need to be speeded up and improved According to public information, the sales volume of new drugs in the first five years after they are put on the market in China is 1 / 6 of that in Japan and 1 / 30 of that in the United States "No matter whether the medical insurance can enter or not, no matter how many drugs are approved by the medical insurance, this leads to a serious phenomenon of low-level duplication, and real innovative drugs are difficult to be supported." Song Ruilin suggested that we should establish an effective linkage mechanism between drug supervision and medical insurance access, and shorten the distance between government approval and patients' drug reimbursement For example, Japan started the pricing process two months before the approval of the drug, and the time difference between the time when the drug is on the market and the time when it can be reimbursed is only 60-90 days Specifically, he suggested that the approval of innovative drugs should be based on clinical urgent needs and fill in gaps, while the approval of generic drugs should be based on reducing the cost of drugs and reducing the pressure of medical insurance fund; while the medical insurance department should establish a dynamic adjustment mechanism according to the clinical needs and fund bearing capacity to provide stable market expectations for approved drugs, provide market support for innovative drugs, and support domestic generic drugs to achieve excellence Replace first Song Ruilin said that more efforts should be made to establish and improve the withdrawal mechanism of the medical insurance catalog, remove the safe and invalid magic medicine and re evaluation varieties from the catalog, and save medical insurance funds It is also crucial to implement the patent term compensation system for innovative drugs to obtain returns According to the regulations of WTO, new drugs have a patent protection period of 20 years Due to the need of government approval, it takes about 10 years from application to listing, so the average patent period is about 10 years Different countries have different evaluation policies and patent periods for new drugs The average patent protection period in the United States is 13.2 years, while in China it is 8 years Generally speaking, it takes five years to cultivate innovative drugs from being listed to market maturity According to the 10-year patent protection period, only five years can really make money, song Ruilin said by