Simple and efficient control of CHO cell cultures

Area of Science:

• Biotechnology
• Cell Culture Engineering
• Bioprocess Control

Background:

• Maintaining consistent cell culture conditions is crucial for reproducible protein product quality.
• Chinese Hamster Ovary (CHO) cells are widely used in biopharmaceutical production, requiring precise control.
• Variability in cell count and growth rate can significantly impact yield and quality.

Purpose of the Study:

• To develop and validate a simple, efficient closed-loop control strategy for CHO cell cultures.
• To maintain viable cell count (Xv) and specific growth rate (μ) on predefined trajectories.
• To improve batch-to-batch reproducibility in biopharmaceutical manufacturing processes.

Main Methods:

• Indirect control of viable cell count and specific growth rate using oxygen consumption.
• Online estimation of oxygen consumption from off-gas analysis (O₂ volume ratio and air flow rate).
• Manipulation of glutamine feed rate in fed-batch cultivations to guide cell growth profiles.

Main Results:

• The developed control technique successfully maintained CHO cells on predefined viable cell count and specific growth rate profiles.
• Cell viability remained unaffected by the closed-loop control actions.
• High batch-to-batch reproducibility was demonstrated in a 2.5-L bioreactor over 140 hours of cultivation.

Conclusions:

• The presented indirect control strategy offers a robust and reproducible method for CHO cell culture.
• This technique enables precise control over critical process parameters, leading to consistent product quality.
• The findings have significant implications for optimizing biopharmaceutical manufacturing processes.