After 4 years of the MAH pilot program, the country will implement policy dividends with heavy responsibilities.

After 3 + 1 years of pilot, the market authorization holder (MAH) system, which is known as bringing a "timely rain" to innovative enterprises in China, will be fully implemented in December this year In the past four years, both the industry and regulators have hoped to break the ecological pattern of innovative drug R & D and production with MAH system Now, the pilot is over, how to judge the future development direction of innovative drugs in MAH pilot cases? What opportunities and challenges will it face in the future? Among the many innovative drugs in MAH pilot, fuquitinib is undoubtedly a typical representative This is not only a major and landmark success of Hutchison Whampoa pharmaceutical in its 16-year innovation and research, but also one of the first varieties in Shanghai pilot since the implementation of MAH pilot The new drug can go on the "green channel" and quickly bring good news to patients with advanced colon cancer in China, undoubtedly benefiting from this policy dividend For this reason, recently, Sina pharmaceutical has made a special dialogue to deeply analyze the current situation and practical operation of MAH in China Mah system refers to the management mode of separating listing license and production license Under this mechanism, marketing license and production license are independent of each other The holder of the marketing license may entrust the products to different manufacturers for production The safety, effectiveness and quality controllability of the drugs shall be the responsibility of the marketing license to the public In a word, according to Dr Wu Zhenping: In China, pharmaceutical enterprises are mainly divided into the above three categories Before 2016, China's drug registration system was that if the R & D party wants to keep the drug approval number in its own hands, it needs to build a production line and obtain the production license Therefore, many new drug R & D teams are deterred by the threshold of "investing in the establishment of a factory", and only transfer the relevant drug technology to the manufacturer! In Dr Wu Zhenping's view, MAH's management mode is undoubtedly a "timely rain" for many innovative enterprises The main advantages are as follows: In this pilot process, MAH pilot varieties have been approved one after another, which can be described as flowering all over the country As of the end of July 2019, the State Drug Administration announced that the database of drug listing license holders indicated that there were 3239 varieties of listed license holders (calculated by drug approval number) and 156 listing license holders According to the statistics of China Journal of new drugs earlier, by the end of September 2018, 1118 applicants for drug registration in 10 pilot provinces (cities) had applied for the holder, covering the administrative region, subject type and pilot drug scope specified in the pilot program In the coverage of pilot drugs, new drugs accounted for 42.6%; generic drugs developed according to the new standards consistent with the quality and efficacy of the original drugs accounted for 44.8%, while in terms of regional distribution, Jiangsu, Guangdong and Shandong accounted for more than half of the total It can be seen that MAH has brought multiple choices to major innovative pharmaceutical enterprises and further released the innovation vitality of China's pharmaceutical industry "At the beginning of the trial implementation of the MAH system, we found in our communication with the regulatory authorities that under the new regulatory mode, the regulators are most worried about the holders." According to Dr Wu Zhenping, the process of drug research and development is complex, involving many professional fields, as well as barrier filled patent application, drug application and other work, which should not only bear unexpected drug quality risks but also bear significant liability for compensation The third chapter "drug marketing license holders" is specially set up in the new drug administration law, which makes a comprehensive and systematic regulation on the holders It is clearly pointed out that MAH refers to "the enterprise or drug development institution that has obtained the drug registration certificate" In short, it is In his view, proving the strength of enterprises may be a problem that every enterprise that wants to go through MAH channel will encounter The capacity requirements of the new deal for the holders are as follows: In addition, in addition to the major responsibility accident, with MAH to be launched nationwide, a series of troubling phenomena have also emerged during the pilot process, which need to be paid attention to: 1 For example, MAH quality assurance system for licensed drugs has not yet had a model for reference Under the MAH system, the product quality problem is actually closely related to each link of the industrial chain, but if only MAH takes the main responsibility, is it appropriate? 2 : with the increasing number of cross province commissioned production, but the different understanding of MAH in each province leads to different policies in each province, and the cross region supervision problem is gradually spreading At the same time, due to the difference of development level and attraction policy in each region, the inclined distribution of scientific researchers may also aggravate the imbalance of development of pharmaceutical industry between regions 3 : in the pilot scheme of MAH system and subsequent policy interpretation documents, the words carefully stipulate that the holder can entrust the sale of drugs, and then the policy is relaxed to that the holder can sell his own varieties Later, through further policy interpretation, drug "sales" is not the narrow sense "sales" of "hand in money and hand in delivery" in the process of commodity exchange in the usual sense Its original meaning refers to drug business behavior, not only including logistics, ticket flow, capital flow, information flow and other processes, but also a series of activities of drug business quality management From the legal point of view, the pilot scheme not only gives the holder the right to produce drugs, but also naturally gives the holder the right to sell drugs and obtain profits Its production and operation rights should be jointly owned, but if the holder does not have the content of drug production and sales in his business or business scope, he will not be able to issue an invoice to the drug buyer through the tax control system, and he will not be able to complete the actual sales This is the drug sales problem encountered by a few pure R & D institutional holders in the pilot 4 Because drugs sold to public medical institutions need to implement the "two vote system", in the pilot, some holders can only bill and sell to a drug handling enterprise as the general agent, and then sell to the downstream because they do not have the ability of drug trading or market operation However, the general agent often does not have the national distribution capacity, and must open one more ticket to sell to regional distributors, and then sell and distribute to public medical institutions, which violates the "two ticket system", which is also a problem .. "It's all crossing the river by feeling the stones, and the road will come out." Although there are some perplexing phenomena in the experimental process of MAH, these problems do not affect the enthusiasm of enterprises for MAH system.