帕利珠单抗生物类似药的细胞培养工艺优化及纯化工艺考察
Investigation on Optimization of Cell Culture Process and Purification Process of Palivizumab Biosimilars
杨鸿山 1韩姝 1张伟 1胡又佳 1谢丽萍1
作者信息
- 1. 上海医药工业研究院,上海 201203
- 折叠
摘要
帕利珠单抗(Synagis)是用于预防呼吸道合胞病毒的经典药物,但由于价格昂贵,限制了其应用范围.该研究采用中国仓鼠卵巢细胞(CHO细胞)表达帕利珠单抗类似药,并以响应面设计法对培养关键参数进行优化,筛选培养基组合以提高产量.研究结果显示,优化工艺参数为以AM01-AF02为基础-补料培养基,每1 mL含5.0×106个细胞的密度接种,37℃培养7d后,降温至33.0 ℃,培养至d16.该工艺条件下,可将帕利珠单抗类似药的产量在摇瓶和3 L生物反应器中分别提升69.3％和30.0％.随后,对生物反应器上发酵生产的抗体进行了纯化工艺研究,为帕利珠单抗类似药的后续工艺开发提供了参考.
Abstract
Palivizumab(Synagis)is a classic drug used to prevent respiratory syncytial virus(RSV).Its application is limited due to its high price.In this study,a Chinese hamster ovary cell line(CHO cells)was engineered to produce palivizumab biosimilars.The key parameters of cell culture were optimized by response surface methodology,and media combinations were screened to increase yield.The results showed that a 16-days cell culture process using AM01-AF02 medium as the basal-feed combination,seeding at 5.0× 106 cells per milliliter,and temperature shift from 37 ℃ to 33.0 ℃ on day 7 improved palivizumab production by 69.3％in shake flask and 30.0％in 3 L bioreactor.The purification process at a 3 L bioreactor scale was also studied,which provided a reference for the subsequent process development of palivizumab biosimilars.
关键词
帕利珠单抗/中国仓鼠卵巢细胞/细胞培养/响应面法/纯化Key words
palivizumab/Chinese hamster ovary cell/cell culture/response surface methodology/purification引用本文复制引用
出版年
2023
NETL
NSTL
万方数据