Abstract:
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.