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Purification and Analytics of a Monoclonal Antibody from Chinese Hamster Ovary Cells Using an Automated Microbioreactor System
Published on: May 1, 2019
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Tuning monoclonal antibody galactosylation using Raman spectroscopy-controlled lactic acid feeding
Thomas W Eyster1, Sameer Talwar1, Janice Fernandez1
1Microbial & Cell Culture Development, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
Biotechnology Progress
|September 25, 2020
Summary
Raman spectroscopy enables real-time control of glucose and lactate in cell cultures. This advanced process analytical technology improves monoclonal antibody production by reducing ammonium levels and enhancing product quality.
Area of Science:
- Biotechnology
- Bioprocess Engineering
- Analytical Chemistry
Background:
- Upstream cell culture is critical for biotherapeutic production.
- Process analytical technology (PAT) enhances monitoring and control.
- Raman spectroscopy offers real-time process attribute monitoring.
Purpose of the Study:
- Develop a Raman spectroscopy-based strategy for dual glucose and lactate control.
- Optimize fed-batch Chinese Hamster Ovary (CHO) cell culture for monoclonal antibody (mAb) production.
- Investigate the impact of lactic acid feeding on cell metabolism and mAb quality.
Main Methods:
- Developed partial least squares chemometric models for real-time glucose and lactate prediction.
- Implemented feedback control loops using Raman spectroscopy data.
- Assessed three feeding strategies: bolus glucose, glucose control, and simultaneous glucose/lactate control.
Main Results:
- Simultaneous glucose and lactate control significantly reduced ammonium levels by 68%.
- mAb galactosylation levels increased by approximately 50% under dual control.
- Demonstrated effective real-time, multi-attribute control using Raman spectroscopy.
Conclusions:
- Raman spectroscopy is effective for simultaneous control of multiple nutrient feeds in cell culture.
- Lactic acid feeding positively impacts cell metabolism and mAb product quality.
- This PAT approach supports consistent bioprocess execution and product quality.
