Impact of dynamic online fed-batch strategies on metabolism, productivity and N-glycosylation quality in CHO cell cultures

• Published in: Biotechnology and bioengineering 2005-01, Vol.89 (2), p.164-177
• Main Authors: Chee Furng Wong, Danny, Tin Kam Wong, Kathy, Tang Goh, Lin, Kiat Heng, Chew, Gek Sim Yap, Miranda
• Format: Article
• Language: English
• Subjects: Ammonia; Animals; Batch processing; Biological and medical sciences; Bioreactors; Biotechnology; Cell culture; Cell Culture Techniques - methods; Cell Proliferation; Cell Survival - physiology; Cells; CHO; CHO Cells; Cricetinae; Cricetulus; Dynamical systems; fed-batch; Fed-batch culture; Feedback - physiology; Fundamental and applied biological sciences. Psychology; gamma -Interferon; Glucose; Glucose - metabolism; Glutamine; Glutamine - metabolism; Glycoproteins; Glycosylation; interferon gamma; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Lactic acid; low glutamine; Metabolism; Nutrients; Online Systems; Polysaccharides; Protein Engineering - methods; Q1; Recombinant Proteins - biosynthesis
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.20317

As we pursue the means to improve yields to meet growing therapy demands, it is important to examine the impact of process control on glycosylation patterns to ensure product efficacy and consistency. In this study, we describe a dynamic on‐line fed‐batch strategy based on low glutamine/glucose concentrations and its impact on cellular metabolism and, more importantly, the productivity and N‐glycosylation quality of a model recombinant glycoprotein, interferon gamma (IFN‐γ). We found that low glutamine fed‐batch strategy enabled up to 10‐fold improvement in IFN‐γ yields, which can be attributed to reduced specific productivity of ammonia and lactate. Furthermore, the low glutamine concentration (0.3 mM) used in this fed‐batch strategy could maintain both the N‐glycosylation macro‐ and microheterogeneity of IFN‐γ. However, very low glutamine (