聚山梨酯对单克隆抗体药物稳定性的影响  

Effects of polysorbates on stability of monoclonal antibody drugs

作　　者：朱圣婴 曹嘉炜 徐进 陈晨辉 郭清城 李军 张大鹏 钱卫珠 侯盛 郭怀祖 ZHU Sheng-ying;CAO Jia-wei;XU Jin;CHEN Chen-hui;GUO Qing-cheng;LI Jun;ZHANG Da-peng;QIAN Wei-zhu;HOU Sheng;GUO Huai-zu(不详;Shanghai Zhangjiang Biotechnology Co.,Ltd,State Key Laboratory of Antibody Medicine and Targeted Therapy,Shanghai 201203,China)

机构地区：[1]上海张江生物技术有限公司抗体药物与靶向治疗国家重点实验室,上海201203 [2]国家药品监督管理局治疗类单抗质量控制重点实验室,上海201203 [3]聊城大学药学院,山东聊城252059 [4]泰州迈博太科药业有限公司,江苏泰州225316

出　　处：《中国生物制品学杂志》2023年第2期172-177,共6页Chinese Journal of Biologicals

基　　金：上海市科技创新行动计划科技支撑项目生物医药专题(19431907500);上海技术带头人项目(18XD1422300);上海启明星项目(19QB1400700);山东省抗体制药协同创新中心开放课题(CIC-AD1802)。

摘　　要：目的评估不同种类聚山梨酯(polysorbate,PS)对不同类型单克隆抗体(简称单抗)药物稳定性的影响。方法以单抗A(mAbA,IgG1前抗体药物)、单抗B(mAbB,IgG1单抗)和单抗C(mAbC,IgG1单抗,Fc N297A突变)3种单抗药物作为模型蛋白,分别在其各自的制剂处方中添加不同种类及含量的PS,并进行影响因素研究,通过考察蛋白聚集体、不溶性微粒等质量属性的变化,综合评估PS对单抗药物稳定性的影响。结果PS20和PS80对于抑制3种单抗中聚集体及电荷异质体生成的作用差异均无统计学意义(P>0.05),而mAbB中加入PS80,mAbC中加入PS20分别能起到更显著地抑制不溶性微粒增加的效果(P<0.05);PS20含量的高低对于mAbC中电荷异质体及不溶性微粒的检测指标影响显著(P<0.05)。结论不同类型的单抗对于不同种类、不同含量PS的敏感度不同,因此在进行单抗制剂处方设计时,需选择适合的PS种类及含量,以进一步提高单抗制剂的稳定性。Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.

关 键 词：聚山梨酯 单克隆抗体 稳定性 聚集体 不溶性微粒 

分 类 号：Q816[生物学—生物工程]