"289 limit" is coming! 13 varieties pass customs, 36 are on the road, and nearly 200 "three no varieties" are out?

On July 31, CDE issued a notice that in order to accelerate the consistency evaluation of "289 varieties", it specially combed and investigated the domestic unique varieties in the 289 catalog, formed evaluation suggestions for these varieties and solicited opinions from the public Up to now, it is only 5 months before the consistency evaluation of "289 varieties" is completed According to statistics, as of July 31, 2018, only 13 "289 varieties" have passed the consistency evaluation In addition, 36 varieties are applying for the consistency evaluation, among which 6 varieties have passed the consistency evaluation According to the intranet data, nearly 200 varieties of 289 are still in the "three no states" of no be clinical trial registration, no conformity evaluation application and no conformity evaluation At the end of 2018, the big limit will come Where will these "three no varieties" go? Will they be eliminated; max-width: 100%; color: rgb(51, 51, 51); font-family: -apple-system-font, Bl inkMacSystemFont, "Helvetica Neue", "PingFang SC", "Hiragino Sans GB", "Microsoft YaHei UI", "Microsoft YaHei", Arial, sans-serif; font-size: 17px; letter-spacing: 0.544px; line-height: 27.2px; widows: 1; border-style: none none solid; text-align: center; border-bottom-width: 1px; border-bottom-color: rgb(0, 0, 0); box-sizing: border-box !im portant; word-wrap: break-word !im portant; "> as the time limit approaches, only 13" 289 varieties "have passed the consistency evaluation On May 26, 2016, the State Drug Administration issued a notice:" for those approved to be marketed before October 1, 2007 and listed in the national basic drug catalogue (2012 version), in principle, the consistency evaluation shall be completed by the end of 2018 " In 2016 No 106 document, 289 base drug varieties are listed According to the requirements of the announcement, in principle, these varieties should complete the consistency evaluation before the end of 2018, which is the "289 limit" (source: Official Website of the State Drug Administration) up to now, the State Drug Administration has released a list of 5 batches of drugs that have passed the consistency evaluation, involving 31 varieties (57 acceptance numbers), of which only 13 varieties (24 acceptance numbers) are "289 varieties" Since the State Food and Drug Administration issued the list of the last batch of drugs passing the consistency evaluation, amlodipine besylate tablets (acceptance No cyhb1840005) of China Resources SECCO Pharmaceutical Co., Ltd have also been approved and passed the consistency evaluation Therefore, as of July 31, 2018, a total of 13 varieties (25 acceptance numbers) of "289 varieties" passed the consistency evaluation All specifications of clopidogrel bisulfate tablets, cefuroxime axetil tablets, enalapril maleate tablets, alfacalcitol tablets, etc have been declared by enterprises and passed the consistency evaluation Among them, cefuroxime axetil tablets are more competitive and all specifications have passed the consistency evaluation by two enterprises; Amlodipine besylate tablets and montmorillonite powder, two kinds of single specifications, have been declared by three enterprises and passed the consistency evaluation; among the "289 varieties" that need consistency evaluation, only 0.25g of azithromycin tablets needs to pass the consistency evaluation, but Ouyi pharmaceutical group of Petrochemicals Group has declared two specifications, 0.25g and 0.5g, and both have passed the consistency evaluation From the perspective of the enterprises that have passed the consistency evaluation of "289 varieties", Zhejiang Huahai Pharmaceutical Co., Ltd., Yangzijiang Pharmaceutical Group and its subsidiaries have all passed the consistency evaluation of 3 varieties, and Shiyao group and its subsidiaries have passed the consistency evaluation of 2 varieties   none="shifuMouseDownStyle('shifu_bus_002')" style="margin: 1em auto; padding: 0px; max-width: 100%; color: rgb(51, 51, 51); font-family: -apple-system-font, Bl inkMacSystemFont, "Helvetica Neue", "PingFang SC", "Hiragino Sans GB", "Microsoft YaHei UI", "Microsoft YaHei", Arial, sans-serif; font-size: 17px; letter-spacing: 0.544px; line-height: 27.2px; widows: 1; border-style: none none solid; text-align: center; border-bottom-width: 1px; border-bottom-color: rgb(0, 0, 0); box-sizing: border-box !im portant; word-wrap: break-word !im portant; "> 10 billion varieties lead the way, 36" 289 varieties "apply for conformity assessment According to 2.0 data of midnet Med China drug review database, as of July 31, 2018, 87 acceptance numbers of 205 application for conformity assessment (excluding acceptance numbers that have passed or not approved the conformity assessment) belong to" 289 varieties ", involving 36 varieties (source: meter net database, statistics as of July 31, 2018) Among the 36 application conformity evaluation varieties, 10 belong to systemic anti infective drugs, 8 belong to digestive system and metabolic drugs, and two major categories of products occupy "half of the country" According to the data of mienei.com, systemic anti infective drugs, digestive system and Metabolic Drugs ranked first in the end-user chemical drug pattern of public medical institutions in China in 2017 with 19.95% and 16.58% market shares respectively And second In terms of the national sales volume of products in 2017, clopidogrel bisulfate tablets are the only products with a sales volume of more than 10 billion among the products applying for conformity assessment; there are 13 products with a sales volume of more than 1 billion yuan, including 10 billion varieties In terms of the number of enterprises to be evaluated and the number of approval documents, there are 7 products with more than 100 production approval documents, with a total number of 2102 approval documents In terms of the national sales volume of these products in 2017, except Amoxicillin Capsules and metformin hydrochloride tablets, the sales volume of other products is relatively low, with 383 production enterprises and 571 isoniazid tablets with drug approval documents In 2017, the national sales volume was only RMB 119 million, which reflected from the side that China's generic drug repeated construction and application, and the vicious market competition was relatively serious In terms of the number of enterprises and subsidiaries applying for conformity assessment, Sichuan Kelun Pharmaceutical Co., Ltd and its subsidiaries applied for the largest number of varieties, with a total of 6; followed by Shiyao group and its subsidiaries, with 4 varieties applied for; The competition of amlodipine besylate tablets is fierce In addition to the three enterprises that have passed the consistency evaluation, there are six enterprises that have applied for the consistency evaluation of the product From the perspective of the time of undertaking, the application for the consistency evaluation of amlodipine besylate tablets of Shanghai Novartis trade has been undertaken at the end of 2017 and is still in the "issued" state Amoxicillin capsule also has a fierce competition There are 6 enterprises applying for the conformity evaluation of the product From the perspective of the time of undertaking, amoxicillin capsule of Sinopharm (Shijiazhuang) Co., Ltd of Shiyao group was first undertaken, but it is still in the state of "review and approval" According to the number of enterprises passing the consistency evaluation, amlodipine besylate tablets and montmorillonite tablets have passed the consistency evaluation, while cefuroxime axetil tablets have passed the consistency evaluation As long as another enterprise passes the consistency evaluation, the varieties failing to pass the consistency evaluation will not be used in the centralized purchase of drugs   none="shifuMouseDownStyle('shifu_bus_002')" style="margin: 1em auto; padding: 0px; max-width: 100%; color: rgb(51, 51, 51); font-family: -apple-system-font, Bl inkMacSystemFont, "Helvetica Neue", "PingFang SC", "Hiragino Sans GB", "Microsoft YaHei UI", "Microsoft YaHei", Arial, sans-serif; font-size: 17px; letter-spacing: 0.544px; line-height: 27.2px; widows: 1; border-style: none none solid; text-align: center; border-bottom-width: 1px; border-bottom-color: rgb(0, 0, 0); box-sizing: border-box !im portant; word-wrap: break-word !im portant; "> where to go for the nearly 200" three no varieties "? Postpone or eliminate According to the data of minenet, more than 40 varieties, such as acarbose capsule, aripiprazole tablets and orally disintegrating tablets, amoxicillin and clavulanate potassium tablets, quetiapine fumarate tablets, indapamide sustained-release tablets, ondansetron hydrochloride tablets, nifedipine sustained-release tablets (Ⅱ), valsartan capsule, betahistine hydrochloride tablets, azithromycin granules, have not yet been applied for consistency evaluation by enterprises or passed the evaluation There are many enterprises that have been registered for be test, including clarithromycin tablets, omeprazole enteric coated capsules, etc Through the analysis of these varieties, it can be found that the be tests of some varieties are the ones registered by some manufacturers according to the new 4 kinds of generic drug standards Once these varieties are approved for production, they are also deemed to have passed the consistency evaluation, such as indapamide sustained release tablets of Tianjin Lisheng As of July 31, 2018, nearly 200 varieties of "289 varieties" are currently in the "three no" status of no be clinical trial registration, no application for consistency evaluation, and no conformity evaluation has passed We call these varieties "three no varieties" (source: minenet database, statistics as of July 31, 2018) analyze these "three no varieties", 19 domestic unique varieties are listed (varieties marked in red in the table) The market scale of these domestic unique varieties is relatively small, most of the drugs are sold at a relatively low price, and the profits of the manufacturers are relatively small In addition, these varieties are not available abroad, and reference preparations cannot be found, and the cost for consistency evaluation may be in the range of millions to tens of millions, and many enterprises will choose to give up directly, which also means that these domestic unique varieties may Exit the market In April 2017, CDE put forward specific regulations for the consistency evaluation of these varieties: enterprises can choose to carry out clinical trials again to prove its safety and effectiveness, and submit an application in accordance with the requirements for application materials for consistency evaluation of quality and efficacy of chemical generic oral solid preparations (Trial), and pass the consistency evaluation after the subsequent review; If the enterprise does not choose to carry out the clinical trial again, the State Drug Administration will announce the lack of effective data to the public, and it is not recommended to use According to the latest notice issued by CDE on July 31, there are 3 more unique varieties in China, 22 in total Among the evaluation suggestions for each variety, 12 varieties such as lactase shengpian, compound aluminum hydroxide Pian, prednisone acetate Pian do not need to carry out clinical effectiveness, 5 varieties such as berberine hydrochloride Pian and lactase shengpian are not recommended for reference, 7 varieties such as nystatin Pian and anisodamine hydrobromide Pian are not recommended for reference It is not recommended to carry out the reevaluation of bifendate tablets In addition, due to the lack of clinical evidence, the manual needs to be revised There are also some "three no varieties" that can be exempted or simplified human bioequivalence (be) test varieties (blue marked varieties in the table) At the end of May this year, the State Food and Drug Administration released 48 varieties that can be exempted or simplified from human body bioequivalence (be) test, including 15 varieties that can be exempted from human body be, such as oral rehydration salt powder, vitamin B2 and B6 tablets, Ferrous Succinate Tablets, ferrous sulfate tablets, potassium chloride granules, etc; The BCS classification of 7 kinds of self certification such as metoprolol tartrate tablets, propranolol hydrochloride tablets and levofloxacin tablets was applied for exemption from be; the be of 13 kinds such as tinidazole tablets, rifampin capsules, captopril tablets and indapamide tablets could be simplified Among the 48 varieties mentioned above, montmorillonite powder and captopril tablets have passed the consistency evaluation; isoniazid tablets, potassium chloride granules, polyethylene glycol 4000 powder, sodium bicarbonate tablets, lamivudine tablets, ranitidine hydrochloride capsules, terazosin hydrochloride tablets, indapamide tablets, tinidazole tablets, fluconazole tablets, propranolol hydrochloride tablets and other enterprises have applied for the consistency evaluation; tabellae paracetamol