Consistency evaluation of injection: Chinese medicine is coming

Source: e drug manager 2018-02-05 after the consistency evaluation of oral solid preparations, the greater impact on the industry of chemical injection consistency evaluation was officially put on the work schedule by CFDA In 2016, China's injection scale reached 757.7 billion yuan, an increase of 8.1% year on year, of which chemical injection accounted for 72% of the market share On December 22, 2017, CDE issued technical requirements for conformity evaluation of listed chemical generic drugs (injections) (Draft for comments) (hereinafter referred to as "draft for comments"), which specifically stipulated the technical requirements for the selection of reference preparation, prescription process requirements, original auxiliary package and conformity evaluation of special injections for conformity evaluation of chemical injections This means that after the consistency evaluation of oral solid preparations, the consistency evaluation of chemical injection, which has a greater impact on the industry, has been formally put on the work schedule 1 A larger scale of consistency evaluation will undoubtedly have a greater impact on the industry China's injection industry has developed rapidly, accounting for more than 50% of the end market share Specifically, in the field of Western medicine, more than 70% of the clinical use is injection type, which has a wider coverage compared with oral solid preparations and more related enterprises According to the monitoring data of Zhongkang CMH, in 2016, the scale of injection in China reached 757.7 billion yuan, an increase of 8.1% year on year, of which chemical injection accounted for 72% of the market share The specific range of varieties to be evaluated was not specified in the opinion draft According to the content of the opinion draft, the general injection should be studied and verified from the aspects of prescription, production process, etc., and at the same time, the quality control of APIs, excipients, packaging, etc should follow the corresponding requirements, without be test, more re evaluation of impurities, heat source reaction and safety For liposomes, intravenous milk and other special injections, they need to refer to the technical requirements of special injections issued by FDA and EMA, and they need to be tested Before 2007, from a commercial point of view, the phenomenon of changing the dosage form in order to change the dosage form was very common, resulting in many exclusive dosage forms and specifications In this opinion draft, the regulations on changing the dosage form, specification and base injection were stipulated The consistency evaluation should fully demonstrate the scientificity, rationality and necessity of the "three changes", and the modified injection should have obvious clinical advantages This indicates that some varieties will fail to pass the consistency evaluation According to the opinions on deepening the reform of the review and approval system and encouraging the innovation of medical devices issued by the two offices, the review and approval of drug injections shall be strictly carried out, "the application for changing the dosage form between large volume injection, small volume injection and sterile powder injection shall not be approved if there is no obvious clinical advantage." From this point of view, the injection market will also usher in a round of integration period Those products that can't prove the safety and effectiveness of their own products, as well as those enterprises that don't have the technical and financial strength to do the consistency evaluation, will face the delisting outcome Although the opinion draft has not yet clearly defined the consistency evaluation and time axis, the opinions on deepening the reform of the review and approval system and encouraging the innovation of pharmaceutical and medical devices issued by the two offices on October 8, 2017 said, "strive to basically complete the re evaluation of injections in 5-10 years" 2 more than 52 enterprises have been put on the market As of December 26, 2017, there are 31289 chemical generic injections approved by CFDA for listing, involving 820 varieties and 748 enterprises, according to the database of minenet at the beginning of the new race The top 5 chemical injection approval companies are China Resources Shuanghe, Chenxin pharmaceutical, Ruiyang pharmaceutical, Southwest Pharmaceutical and Hunan Kelun pharmaceutical However, according to the statistics of Xinkangjie, the top 5 domestic injection market share enterprises are China Resources, Qilu pharmaceutical, Kelun pharmaceutical, Fosun Pharmaceutical and Shanghai Pharmaceutical Group Among them, China Resources has the largest share in the domestic injection Market, with hundreds of injection varieties, including cefazolin, sodium chloride, Shenfu injection, etc with large sales volume; Qilu pharmaceutical, with the first three varieties of monosialotetrahexosylganglioside sodium, heavy group human granulocyte stimulating factor and docetaxel; Kelun pharmaceutical, with the share of sodium chloride and glucose varieties The largest manufacturer The top three sales volume of domestic injection varieties are sodium chloride, omeprazole and monosialotetrahexosylganglioside sodium Sodium chloride is the largest variety of injections in China There are hundreds of manufacturers, and the top three manufacturers are Kelun pharmaceutical, China Resources and Shijiazhuang Pharmaceutical; the leading manufacturers of omeprazole are Jiangsu aosaikang, AstraZeneca pharmaceutical, Wuhan Pusheng pharmaceutical, Shandong Luoxin, etc.; the main manufacturers of monosialotetrahexosylganglioside sodium are Qilu pharmaceutical and Harbin medical Big and fourth ring medicine, etc At present, more than 52 enterprises have put forward the filing of injection reference preparation, and 66 injection varieties are to be evaluated The treatment category of the recorded varieties was mainly anti infective drugs, followed by nervous system drugs and digestive system drugs, and the total of the three accounted for 51.5% With reference to the experience of consistency evaluation of oral solid preparations, the varieties approved and listed by foreign drug inspection agencies may be exempt from the consistency evaluation of injections, and will benefit from the reconstruction of industry pattern as soon as possible For example, Hengrui pharmaceutical, Puli pharmaceutical, Qilu pharmaceutical, Haizheng pharmaceutical and other products are listed abroad Leading domestic injection enterprises, or high-quality injection R & D and production enterprises with strong capital strength, such as Kelun pharmaceutical, Fosun Pharmaceutical, Lizhu group, etc., will also be strong Hengrui medicine: many injection varieties are listed in the United States and the traditional advantages of Hengrui medicine are concentrated in the anti-tumor and narcotic drug product line, and the injection is the main one At present, docetaxel, irinotecan, cisatracurium, dexmedetomidine, cyclophosphamide, oxaliplatin and other products have been listed in the United States and made profits In 2016, the operating revenue of Hengrui's export business reached 430 million yuan, of which the key products are cyclophosphamide and oxaliplatin, both of which are injection varieties In the international market, the supply of injection is a little insufficient compared with oral preparations, and its production requirements for sterility are more stringent, far higher than oral preparations The construction and maintenance of the production line need to invest more costs, and the entry threshold is higher These objective reasons lay a special competitive advantage for high-end injection export enterprises in the world Hengrui is one of these enterprises In the domestic market, docetaxel injection, oxaliplatin for injection, irinotecan hydrochloride for injection and other varieties were purchased at the end of over 100 million in 2016 Among them, the market space of docetaxel and oxaliplatin is over 100 million, and there is still a huge space for substitution At present, the terminal purchase amount of Hengrui is stable, but the opportunity for further growth comes because of the injection consistency evaluation Capecitabine's domestic market structure is composed of Roche's imported product Xeloda and three domestic products Xeloda's market share in 2016 was 67%, and the import substitution is gradually going on Zhejiang medicine: the leading global technology platform, Zhejiang medicine has submitted 505 (b) (2) applications for two varieties of dtomycin and vancomycin in FDA, and is expected to be listed in 2018 Its "aseptic spray drying" technology platform is the world leader Under the technology platform, products are expected to enter the US market in 505 (b) (2) way And has established a systematic drug research and development, registration and production system in line with FDA cGMP certification 505 (b) (2) the application way can obtain a long period of market monopoly, which will benefit the domestic market and the injection consistency evaluation while the US market is profitable According to IMS data, in 2015, the sales volume of metomycin in the U.S market was US $1.26 billion, and that of vancomycin in the U.S market was about US $500 million Jianyou: the leading injection export enterprise in the future In 2013, Chengdu Jianjin exported the first batch of sterile injections to the United States, becoming the first Chinese enterprise that directly sold injections to the United States; in 2016, Chengdu Jianjin R & D center passed the U.S FDA certification and inspection for zero defects, becoming the first Chinese R & D institution of sterile injections that passed the U.S FDA certification, and successfully built an integrated industrial chain of injection export research and production At present, three production lines of Jianyou have passed FDA certification According to Jianyou's announcement, it is in the stage of R & D / anda application for more than 10 injection products Bloomberg terminal data shows that the market capacity in the United States is more than 5 billion US dollars, and anda will be approved from 2018 Enoxaparin injection, a heavyweight product, is expected to be approved by the end of 2018 in the European Union (with a market capacity of EUR 1 billion) and in the United States in early 2019 (with a market capacity of USD 2 billion) Puli Pharma: after ten years of investment, Puli Pharma has established a complete R & D, registration and production system, applying for about five varieties every year, focusing on injection, expanding the field of polypeptide and tumor In September 2016, three varieties were included in the priority review Azithromycin for injection has been temporarily approved by the FDA of the United States It has been approved for listing through priority review in China The global market is 387 million US dollars, and the domestic market is 1.5 billion yuan Ganciclovir Sodium for injection has passed the on-site inspection of Anda in the United States, and is under technical review in China, with a domestic market size of 760 million Injection varieties that have been listed abroad The data is from Mino database, and the pictures are from medical economic newspaper In fact, the more severe re evaluation of traditional Chinese medicine injections, compared with the consistency evaluation of injections, makes the industry feel a big reshuffle, more is the re evaluation of traditional Chinese medicine injections Traditional Chinese medicine injections are affected by historical reasons, poor technology, lack of standards in quality supervision, as well as nonstandard drug use, obvious abuse and large dosage The new national medical insurance catalog restricts traditional Chinese medicine injections Provinces and hospitals continue to flow out of the key monitoring catalog, as well as restrictions on auxiliary drugs, outpatient infusion and other reasons The whole traditional Chinese medicine injection industry continues to bear pressure On February 27, 2017, Bi Jingquan, director of the State Food and drug administration, formally proposed to start the reevaluation of the safety and effectiveness of traditional Chinese medicine injections The reevaluation of traditional Chinese medicine injections has been arranged in September 2015 within the scope of responsibilities and tasks of CFDA departments and bureaus However, the re evaluation of traditional Chinese medicine injection is lack of reference experience, working rules and special complex reasons of traditional Chinese medicine itself, so it is very difficult to carry out the re evaluation In 2009, China's old attempt to start the re evaluation of traditional Chinese medicine injections did not really land There are 112 varieties involved in the re evaluation of traditional Chinese medicine injections, and the top 10 varieties involving the most manufacturers are Chaihu Injection (101), Xiangdan injection (87), Danshen injection (58), Banlangen injection (52), pilose antler essence injection (25) and Andrographis injection (23), Breviscapine Injection (22), Shuanghuanglian infusion (18), Shuanghuanglian injection (18), Honghua injection (16) According to the Research Report of Soochow securities, there are more than 140 varieties of traditional Chinese medicine injections, with 1252 approvals in total The product competition is disordered But at the same time, the market concentration of traditional Chinese medicine injection is very high, the cumulative proportion of the top 10 products is about 45%, and the cumulative proportion of the top 20 products is more than 70% This indicates that through a round of re evaluation, the market of traditional Chinese medicine injection will further shrink, and a large number of small and scattered traditional Chinese medicine injection enterprises will withdraw from the market According to the trend analysis of various kinds of limited auxiliary and limited outpatient infusion in the near future, even though the work of traditional Chinese medicine injection is difficult to carry out, the market will gradually choose the products with good quality and strong sales ability, and actively carry out clinical re evaluation and basic research