文献类型：期刊文献

中文题名：CHO细胞培养生产抗体产量的稳定性

英文题名：Titer Stability of Antibody Produced by CHO Cell Culture

作者：张进[1];王星懿[1];范里[1];谭文松[1]

机构：[1]华东理工大学生物工程学院生物反应器工程国家重点实验室,上海200237

年份：2017

卷号：43

期号：6

起止页码：806

中文期刊名：华东理工大学学报（自然科学版）

外文期刊名：Journal of East China University of Science and Technology

收录：北大核心:【北大核心2014】；CSCD:【CSCD_E2017_2018】；

语种：中文

中文关键词：细胞培养技术;QbD;FMEA;设计范围;过程控制

外文关键词：cell culture technology;QbD;FMEA;design space;process control

摘要：实现了中国仓鼠卵巢(CHO)细胞高密度培养过程的稳定。以表达IgG抗体的流加培养过程为研究对象,首先通过"鱼骨图"分析、FMEA风险评估剖析潜在的关键控制参数,其次通过DOE(实验设计)方法确定和优化关键控制参数及其范围。结果表明,在99个培养过程参数中搜寻并确认了8个关键控制参数及其范围。经优化控制后,表达IgG抗体的流加培养过程批次间抗体产量差异从200%下降至10%。基于QbD理论,能快速有效地实现CHO细胞培养生产抗体产量的稳定性,有利于保证抗体药物生产的安全性以及保障企业的经济效益。
The stability of Chinese hamster ovary(CHO)cells during high density cultivation process was realized.The fed-batch culture process expressing IgG antibody was studied based on QbD theory.Firstly,potential critical control parameters were dissected by using "fishbone diagram"analysis and Failure Mode and Effect Analysis(FMEA).Secondly,key control parameters were determined and their design ranges were optimized by DOE(Design of experiment)method.Results show that eight key control parameters and their scope were searched and confirmed within 99 cell culture process parameters.Through optimization and control,difference of antibody titer between batches of fed-batch culture process decreases from 200% to 10%.Based on QbD theory,it can rapidly and effectively achieve process stability of antibody production by CHO cell culture which is benefit for the safety of antibody drug production and the economic benefits of enterprises.