Dynamic pH profiles drive higher cell-specific and volumetric productivity.

Area of Science:

• Biotechnology
• Bioprocess Engineering
• Mammalian Cell Culture

Background:

• Critical process parameter control is vital for mammalian cell cultures in bioreactors to optimize recombinant therapeutic protein production.
• Culture pH significantly impacts cell growth, productivity, and critical quality attributes.
• Traditional pH control methods (set-point or single shift) can lead to detrimental CO2 accumulation.

Purpose of the Study:

• To investigate the efficacy of a dynamic pH profile in mammalian cell cultures.
• To mitigate CO2 accumulation and enhance productivity in bioreactors.
• To evaluate the impact of dynamic pH control on product quality attributes.

Main Methods:

• A dynamic pH profile, mimicking shake flask conditions, was implemented in a bioreactor.
• Multiple pH shifts were applied during the exponential growth phase.
• Chinese Hamster Ovary (CHO)-K1 cell line producing IgG1 was used.
• Impacts on cell-specific productivity, overall productivity, glycosylation, and charge variants were assessed.

Main Results:

• The dynamic pH profile successfully alleviated carbon dioxide accumulation.
• Significant increases in both cell-specific and overall culture productivity were observed.
• Product quality attributes showed mixed impacts on glycosylation and a positive impact on charge variants.

Conclusions:

• Dynamic pH control is a viable strategy to improve productivity in mammalian cell bioreactors.
• This approach effectively manages CO2 levels, benefiting cell growth and protein yield.
• Product quality requires careful evaluation on a per-process basis due to varied impacts on attributes like glycosylation.