title: An ultra scale-down approach identifies host cell protein differences across a panel of mAb producing CHO cell line variants.
abstract: During the manufacture of biopharmaceutical products, the final product must lie within strict pre-set specifications, for example the host cell protein (HCP) content. A number of specific HCPs have been identified in particular products and the interactions between product/HCPs have also been recently investigated; however, a comparison of the HCP dynamics between related cell lines and their response to early downstream processing to aid process development and cell line selection has not been published. We have utilised a proteomic approach coupled with an ultra scale-down study to determine the HCP profile dynamics, at harvest and during early downstream processing, across a panel of recombinant GS-CHOK1SV antibody producing cell lines. The results reveal that cell culture viability upon harvest has the greatest impact upon shear sensitivity and HCP concentration. Whilst the general HCP population/profile was broadly similar across the cell lines, the actual amounts of some specific HCPs in the supernatant differed and a number of cell line specific differences in the response to early downstream processing were observed. We anticipate that such knowledge can now be applied to cell line selection and downstream processing development to target reduction/removal of general and specific problematic HCPs before and during downstream processing.
authors.affiliation: Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury, Kent, UK. c.e.m.hogwood@kent.ac.uk.
authors.forename: Catherine E M
authors.initials: CE
authors.lastname: Hogwood
authors.affiliation: Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, London, UK.
authors.forename: Shahina S
authors.initials: SS
authors.lastname: Ahmad
authors.affiliation: Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, London, UK.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Tarrant
authors.affiliation: Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, London, UK.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bracewell
authors.affiliation: Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury, Kent, UK. c.m.smales@kent.ac.uk.
authors.forename: C Mark
authors.initials: CM
authors.lastname: Smales
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D040901:Proteomics / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal
keywords: Chinese hamster ovary cells; Host cell protein; Mammalian cell culture; Monoclonal antibody; Ultra scale-down