Authors
Shengnan Xu, Pan Wang, Xiaofei Wang, Qixin Liu, Yunfei Lin, Xiaojing Liu, Qingquan He, Guohong Qin
Published in
Cytotechnology. Volume 78. Issue 6. Pages 228. Epub Nov 02, 2026.
Abstract
To reduce the operational complexity of conventional dual-feed fed-batch processes while maintaining high productivity, an intensified cell culture strategy integrating a commercial single-feed medium with N-1 perfusion-based high-density inoculation was developed using a CHO-K1 cell line expressing a bispecific antibody. Six commercially available single-feed media were first evaluated in shake-flask cultures, and the selected medium achieved cell growth, metabolic performance, antibody titer, and product quality comparable to those of a conventional dual-feed process. To further improve productivity, N-1 perfusion intensification enabled inoculation at 10 × 106 cells/mL in 2 L bioreactors. High-density cultures entered the stationary phase earlier while maintaining elevated viable cell densities throughout production. When combined with the single-feed strategy, The IFB-Single process achieved a final antibody titer of 9.4 g/L, approximately 24% higher than that of the conventional FB process (7.6 g/L). Although its titer was lower than that of IFB-Dual (10.2 g/L), IFB-Single exhibited lower culture osmolality, suggesting an opportunity for further feed optimization. Product quality attributes, including monomer content, charge variants, and N-glycan profiles, remained comparable across all conditions. These results demonstrate that combining single-feed supplementation with high-density inoculation provides a practical and scalable strategy for process intensification, simplifying operation while enhancing manufacturing performance without compromising product quality.
PMID:
42979013
Bibliographic data and abstract were imported from PubMed on 04 Nov 2026.
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