Increasing batch-to-batch reproducibility of CHO cultures by robust open-loop control

Area of Science:

• Biotechnology
• Bioprocess Engineering
• Mammalian Cell Culture

Background:

• Ensuring recombinant therapeutic protein quality relies on reproducible mammalian cell culture processes.
• Current industrial processes exhibit significant deviations when initial cell density varies, impacting biomass trajectory.
• Variations in initial cell mass can lead to severe disruptions in desired biomass development.

Purpose of the Study:

• To design a fed-batch production process robust against viable cell density variations.
• To demonstrate a novel open-loop control strategy for enhanced process consistency.
• To validate the proposed method in Chinese hamster ovary (CHO) cell cultures.

Main Methods:

• Implementation of an open-loop control strategy.
• Utilizing an optimized glutamine feed rate profile F(t).
• Maintaining cells at a predefined specific growth rate below the maximum (μmax) while preserving high viability.

Main Results:

• Demonstrated for the first time in CHO cell cultures that the proposed strategy leads to converging viable cell count profiles.
• Achieved robustness against initial viable cell density variations.
• Successfully controlled CHO cells at specific growth rates below μmax with high viability.

Conclusions:

• The proposed glutamine feed rate strategy ensures robust fed-batch processes for recombinant protein production in CHO cells.
• This method mitigates the impact of initial cell density fluctuations on biomass trajectory.
• The strategy allows for precise control over cell growth rates, enhancing process predictability and quality.