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脂质体药物产品的开发与质量:美国当前的经验与展望

Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

作者信息

Kapoor Mamta, Lee Sau L, Tyner Katherine M

机构信息

Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.

出版信息

AAPS J. 2017 May;19(3):632-641. doi: 10.1208/s12248-017-0049-9. Epub 2017 Feb 3.

Abstract

Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

摘要

在过去几十年中,脂质体领域的研究有了显著增长。脂质体是脂质双层结构,能够包载药物物质以改变药物的药代动力学特征,从而改善药物递送。该机构已收到400多份脂质体药物产品申报(不包括联合疗法),目前美国市场上有8种已批准的脂质体药物产品。为了确定脂质体药物产品研发和生产中的痛点,从质量角度对新的和仿制药脂质体药物产品的申报进行了回顾性分析。还对脂质体药物产品申报进行了总体分析。结果表明,96%的申报是研究性新药(IND)申请,3%是新药申请(NDA),其余1%是简略新药申请(ANDA)。盐酸多柔比星是脂质体中最常用的药物物质(31%)。大多数脂质体产品通过静脉途径给药(84%),癌症(各种类型)是最常见的适应症(63%)。从质量角度来看,脂质体药物产品研发过程中的主要挑战包括脂质体药物产品关键质量属性的识别和(适当的)表征,以及产品研发过程中合适的控制策略。通过关注这些领域,可以实现脂质体药物产品更快、更高效的研发。此外,通过这种方式,可以简化此类产品的药物审评流程。

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