Sustaining an efficient and effective CHO cell line development platform by incorporation of 24‐deep well plate screening and multivariate analysis

• Published in: Biotechnology progress Vol. 34; no. 1; pp. 175 - 186
• Main Authors: Mora, Alessandro, Zhang, Sheng (Sam), Carson, Gerald, Nabiswa, Bernard, Hossler, Patrick, Yoon, Seongkyu
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-01-2018
• Subjects: 24‐deep well plate; Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - isolation & purification; Batch Cell Culture Techniques - methods; Bioreactors; Cell culture; cell line development; Cell lines; Cell Proliferation; Chinese Hamster Ovary; CHO Cells; Cricetinae; Cricetulus; Data analysis; Data processing; Flasks; Glycan; High-Throughput Screening Assays - methods; Mannose; Mannose - chemistry; Monoclonal antibodies; Multivariate analysis; Polysaccharides - chemistry; Process parameters; scale‐down; Scaling; Screening; Species; Viability; Chinese Hamster Ovary; cell line development; 24-deep well plate; cell culture; scale-down
• ISSN: 8756-7938; 1520-6033
• DOI: 10.1002/btpr.2584

Efficient and effective cell line screening is paramount toward a successful biomanufacturing program. Here we describe the implementation of 24‐deep well plate (24‐DWP) screening of CHO lines as part of the cell line development platform at AbbVie. Incorporation of this approach accelerated the identification of the best candidate lines for process development. In an effort to quantify and predict process performance comparability, we compared cell culture performance in and in shake flasks, for a panel of Chinese Hamster Ovary cell lines expressing a monoclonal antibody. The results in 24‐DWP screening showed reduced growth profiles, but comparable viability profiles. Slow growers in 24‐DWP achieved the highest productivity improvement upon scaling‐up to shake flasks. Product quality of the protein purified from shake flasks and 24‐DWP were also compared. The 24‐DWP culture conditions were found to influence the levels of acidic species, reduce the G0 N‐glycan species, and increase the high‐mannose N‐glycan species. Nevertheless, the identification of undesirable profiles is executed consistently with the scaled‐up culture. We further employed multivariate data analysis to capture differences depending on the two scales and we could demonstrate that cell line profiles were adequately clustered, regardless of the vessel used for the development. In conclusion, the 24‐DWP platform was reasonably predictive of the parameters crucial for upstream process development activities, and has been adapted as part of the AbbVie cell line development platform. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:175–186, 2018