药学学报, 2019, 54(11): 2118-2125
引用本文:
刘伯宁, 阚红金, 白玉, 罗建辉. 关于利妥昔单抗生物类似药“质量相似性”评价标准的探讨[J]. 药学学报, 2019, 54(11): 2118-2125.
LIU Bo-ning, KAN Hong-jin, BAI Yu, LUO Jian-hui. The discussion on a proposed quality similarity assessment criteria of rituximab biosimilar[J]. Acta Pharmaceutica Sinica, 2019, 54(11): 2118-2125.

关于利妥昔单抗生物类似药“质量相似性”评价标准的探讨
刘伯宁, 阚红金, 白玉, 罗建辉
国家药品监督管理局药品审评中心, 北京 100022
摘要:
单抗生物类似药是目前我国生物制品研发的热点。确保候选药与原研药具有“质量相似性”(分析可比性)是此类产品药学开发与评价的核心。但是,由于原研药物的质量漂移及可获得性等原因,通过测定有限批次原研药物的表征数据难以准确定义产品“目标质量属性”,这就为生物类似药的开发与评价提出了挑战。本文以利妥昔单抗为例,分析了利妥昔原研药物及生物类似药候选药在国内的注册与研发现状,通过对原研厂及18家生物类似药研发企业累计的123批原研药表征分析数据进行统计分析,提出了利妥昔单抗关键质量属性及限度要求的参考区间。为此类生物类似药的药学开发与评价提供依据。
关键词:    利妥昔单抗      生物类似药      质量相似性      分析相似性      药学评价      关键质量属性     
The discussion on a proposed quality similarity assessment criteria of rituximab biosimilar
LIU Bo-ning, KAN Hong-jin, BAI Yu, LUO Jian-hui
Center for Drug Evaluation, National Medical Products Administration, Beijing 100022, China
Abstract:
Recently, biosimilar antibodies have become a mainstream component of the biopharmaceutical industry in China. The principle requirements for the development and evaluation of biosimilars are based on proving similarity in product quality (analytical similarity) between a proposed biosimilar candidate and the originator reference drug. However, because the quality of a reference drug often varies during the life cycle and not all reference drug samples are able to collected by a biosimilar sponsor, it has not been practical to accurately determine the critical quality attributes as well as an accurate control range through the characterization of the limited number of reference drug lots that are typically collected. Therefore, the development and evaluation of biosimilars has been challenging both for industry and regulatory agencies. In this article, The Chemistry, Manufacturing and Control (CMC) dossier of the rituximab originator company and the dossiers of 18 biosimilar companieswere retrospectively analyzed. Furthermore, the assessment criteria to determine quality similarity of rituximab biosimilar candidates have been proposed, which criteria have been used by reviewing the physicochemical and biological properties data obtained from 123 lots of the reference drug. Moreover, some case studies have been provided that illustrate the application of the proposed analytical similarity criteria in the practice of drug evaluation.
Key words:    rituximab    biosimilar    quality similarity    analytical similarity    chemistry manufacturing controls review    critical quality attribute   
收稿日期: 2019-06-15
DOI: 10.16438/j.0513-4870.2019-0477
基金项目: 国家“重大新药创新”课题(2015ZX09501008).
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