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大品种舒更葡糖钠注射液,1500万保证生物等效了解一下?

医药魔方 医药魔方 来源:医药魔方
2018-12-04
一致性评价
原文

注射剂的一致性评价虽然说拉开了序幕,但到目前也只见CDE在2017年12月22日发布了一个征求意见稿,正式文件一直未出台。不过这也并不妨碍国内一批有实力、有远见的企业兵贵神速地递交注射剂品种的一致性评价申请。


截止目前,CDE承办的注射剂类一致性评价受理号已经有122个,但是通过一致性评价的也仅有普利制药的注射用阿奇霉素一个品种。从《中国上市药品目录集》是收录情况来看,虽然也有其他数个注射剂品种在列,但均属于“按化学药品新注册分类批准的仿制药”或“创新药”。


显然,对于注射剂一致性评价,存量老品种的审评审批标准还不甚明朗,但若按照新4类注册申报上市,获得使用“通过一致性评价”标识的资格倒是一条明路。


下面要说的是一个大品种注射剂——舒更葡糖钠注射液。


舒更葡糖钠结构式


舒更葡糖钠是一种γ-环糊精,可以与罗库溴铵或维库溴铵形成复合物,从而逆转罗库溴铵和维库溴铵的神经肌肉阻滞作用,是全球首个用于逆转神经肌肉阻滞剂的选择性松弛拮抗剂。在临床手术麻醉中,舒更葡糖钠注射液可帮助全身麻醉患者精准、快速地逆转深度和中度肌肉松弛(以下简称肌松)状态,促进患者恢复自主呼吸和肢体活动能力,帮助改善患者的术后转归。


舒更葡糖钠由默沙东开发,2008年9月在欧盟上市,2015年12月在美国上市,2017年4月在中国上市。2017年全球销售额7.04亿美元,2018年前3季度销售额6.61亿美元,接近成为重磅炸弹品种。



这样一个大品种,自然也引得国内企业的青睐。11月28日,原研在国内上市仅一年半之后,科伦药业即宣布首家提交舒更葡糖钠注射液的仿制上市申请并获得国家药品监督管理局受理。该品种的仿制药研发企业除了科伦之外,只有恒瑞、河北智恒医药2家,竞争格局比较良好。


比较有意思的是,12月3日晚间,主打中药品种的步长制药发布了一则技术开发合作公告,其子公司通化谷红、吉林步长分别与国内两家CRO公司签订了委托技术开发合同。这两项合作的合同框架结构非常类似,涉及的则是两个比较受关注的重磅大品种——注射用伏立康唑(200mg)和舒更葡糖钠注射液(2ml:200mg)。


在舒更葡糖钠注射液(2ml:200mg)这个项目上,吉林步长将向这家CRO公司支付1500万元,最终目标是获得药品批准文号。费用所包括的服务内容是:①全部药学研究费用; ②包材相容性研究费用; ③研究所需的原研药品/参比制剂购买费用; ④局部刺激性过敏性溶血性试验费用。


而且,对于这样一笔1500万元的支出,吉林步长是一种“势在必得”的姿态,因为合同做出了如下约定:合同总金额是包干价,乙方须确保项目该项目与原研药品质量和疗效一致……直至获得批准文号;如果不一致,乙方负责继续研究,直至一致。



注射剂类仿制药在开展一致性评价时,一般不涉及BE临床试验,成本主要集中在药学CMC研究上面。对于以上合同条款,只能说明吉林步长的心理底线是花费1500万元拿到舒更葡糖钠注射液这样一个新4类注射剂批文。不可能投入再多了……

毕竟,科伦药业在舒更葡糖钠注射液这个项目上的研发投入费用也才736万元……

机器翻译
Although the consistency assessment of

injections has begun, it has only been seen so far that CDE has issued a draft for comment on December 22, 2017, and official documents have not been issued.However, this does not prevent a group of powerful and far-sighted enterprises in China from promptly submitting applications for consistency assessment of injection varieties.

Up to now, there have been 122 acceptance numbers for the consistency evaluation of injections undertaken by CDE, but only one variety of azithromycin for injection of Puli Pharmaceutical has passed the consistency evaluation.From the point of view of the "Catalogue of Listed Drugs in China", although there are several other types of injections listed, they all belong to "approved generic drugs according to the new registration category of chemical drugs" or "innovative drugs".

Obviously, for the consistency evaluation of injections, the review and approval criteria for the stock of old varieties are not yet clear, but if according to the new category 4 registration application, it is a clear way to obtain the qualification to use the "pass the conformity assessment" logo.

The following is a large variety of injections - Shugan Sodium Glucose Injection.

Shugengu Sodium Structural Formula

Shugengu Sodium is a γ-cyclodextrin that can form complexes with rocuronium or vecuronium, thereby reversing the neuromuscular blocking effects of rocuronium and vecuronium, and is the world's first selective relaxant antagonist for reversing neuromuscular blockers.In clinical surgical anesthesia, Shugan Sodium Injection can help patients with general anesthesia to accurately and quickly reverse the deep and moderate muscle relaxation (hereinafter referred to as muscle relaxation) status, promote the patient's ability to resume spontaneous breathing and limb mobility, and help improve the patient's Postoperative outcome.

Shugan Sodium Glucose was developed by Merck and listed in the European Union in September 2008, listed in the United States in December 2015, and listed in China in April 2017.2017 global sales 7.$04 billion, sales in the first three quarters of 2018 6.$6.1 billion, close to becoming a blockbuster variety.

Such a large variety naturally attracts the favor of domestic companies.On November 28th, only one and a half years after the original research was listed on the domestic market, Kelun Pharmaceutical announced that it was the first to submit a generic listing application for Shugan Sodium Glucose Injection and was accepted by the State Drug Administration.In addition to Kelun, there are only Hengrui and Hebei Zhiheng Pharmaceuticals, and the competitive landscape is relatively good.

Interestingly, on the evening of December 3, Buchang Pharmaceutical Co., Ltd., the main Chinese medicine variety, issued a technology development cooperation announcement. Its subsidiaries Tonghua Guhong and Jilin Buchang signed commissioned technology development contracts with two domestic CRO companies.The contract frame structure of the two cooperatives is very similar, involving two of the most important varieties of concern — voriconazole for injection (200 mg) and Shugan Sodium Glucose Injection (2 ml: 200 mg).

In the project of Shugan Sodium Glucose Injection (2ml: 200mg), Jilin Step will pay 15 million yuan to this CRO company, and the ultimate goal is to obtain the drug approval number.The services included in the cost are: 1 all pharmaceutical research costs; 2 package compatibility research costs; 3 the original research drug/reference preparation purchase costs required for the study; 4 local irritant allergic hemolytic test costs.

Moreover, for such a expenditure of 15 million yuan, the Jilin step is an "imperative" attitude, because the contract made the following agreement: The total amount of the contract is the contract price, and Party B must ensure that the project is consistent with the quality and efficacy of the original research drug...Until the approval number is obtained; in case of inconsistency, Party B is responsible for continuing the study until it is consistent.

Injectable generic drugs generally do not involve BE clinical trials when conducting conformity assessments, and the costs are mainly focused on pharmaceutical CMC research.For the above terms of the contract, it can only be explained that the psychological bottom line of Jilin Buchang is to spend 15 million yuan to get a new type 4 injection approval such as Shugan Sodium Glucose Injection.There's no way to put more...

After all, Kelun Pharmaceutical's R & D investment in the Shugan Sodium Glucose Injection project was only 7.36 million yuan...

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