title: Chinese hamster ovary cell performance enhanced by a rational divide-and-conquer strategy for chemically defined medium development.
abstract: Basal medium design is considered one of the most important steps in process development. To optimize chemically defined (CD) media efficiently and effectively for the biopharmaceutical industry, a two-step rational strategy was applied to optimize four antibody producing Chinese hamster ovary (CHO) cell lines. In the first step, 48 of 52 components of our in-house medium were divided into three groups according to their characteristics. In the next step, these groups were optimized by spent medium analysis, response surface methodology and mixture design. Because these steps in our strategy involved dividing medium components into groups and subsequently adjusting the concentration of the components, we termed this medium development strategy "divide and conquer". By applying the strategy, we were able to improve the titers of CHO-S, CHO-DG44 and two CHO-K1 cell lines 1.92, 1.86, 2.92 and 1.62-fold, respectively, in 8 weeks with fewer than 60 tests. This divide-and-conquer strategy was efficient, effective, scalable and universal in our current study and offered a new approach to CD media development.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Yaya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Hisun Pharmaceutical (Hangzhou) Co., Ltd., Xialiancun, Xukou, Fuyang, Hangzhou, Zhejiang 311404, China.
authors.forename: Xiancun
authors.initials: X
authors.lastname: Deng
authors.affiliation: Hisun Pharmaceutical (Hangzhou) Co., Ltd., Xialiancun, Xukou, Fuyang, Hangzhou, Zhejiang 311404, China.
authors.forename: Hong Fai
authors.initials: HF
authors.lastname: Poon
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Xuping
authors.initials: X
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Tan
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, PR China. Electronic address: fanli@ecust.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Fan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D003470:Culture Media
keywords: Basal medium design; Chemical-defined; Chinese hamster ovary; High-yielding; Monoclonal antibody