Improving cultivation processes for recombinant protein production.

Area of Science:

• Biotechnology
• Process Engineering
• Bioprocess Control

Background:

• Recombinant protein production relies on stable and reproducible fermentation processes.
• Existing control strategies often struggle with long response times and process variability.
• Enhanced control is crucial for optimizing yield and consistency in biomanufacturing.

Purpose of the Study:

• To introduce and validate a novel cascade control system for bioprocess cultivation.
• To improve batch-to-batch reproducibility in fed-batch fermentation.
• To provide a simple yet effective control alternative for biopharmaceutical production.

Main Methods:

• Design and tuning of a cascade control system using a virtual plant environment (SIMATIC PCS 7).
• Direct control of carbon dioxide production rate and mass.
• Simultaneous regulation of specific biomass growth rates and biomass profiles.
• Validation through experimental application in Escherichia coli and CHO cell cultures.

Main Results:

• The cascade control system demonstrated superior performance compared to previous methods in simulations and experiments.
• Significant improvement in batch-to-batch reproducibility of fermentation processes was achieved.
• The controller effectively managed processes with long response times and delays.
• Successful application in both bacterial (E. coli) and mammalian (CHO) cell cultures.

Conclusions:

• The presented cascade control system offers a robust and reproducible method for managing fed-batch cultivations.
• It provides a straightforward and reliable alternative to complex model-supported controllers.
• This approach enhances process consistency and is suitable for various biopharmaceutical production systems.