Integrated continuous bioprocessing is steadily gaining popularity in the biopharma industry, chiefly due to its high productivity and smaller footprint when compared to traditional batch processes. These benefits can be realized through single-use technologies and simple but accurate control strategies. Inline continuous viral inactivation (cVI) requires the accurate control of pH to ensure the complete inactivation of enveloped viruses. Therefore, it is important to develop an effective inline adjustment strategy capable of titrating diverse incoming protein streams. Here, we discuss a modeling workflow for the development of a robust inline titration strategy for cVI. High-throughput experiments were performed to generate statistical and hybrid models to identify key control factors. The models were validated for their ability to predict titration within a narrow target pH range and were subsequently successfully validated on an automated scale-down inline adjustment setup. This has led to a standardized approach for developing and evaluating inline adjustment and cVI for new molecules. Finally, this control strategy will be evaluated for effectiveness in cVI at the pilot scale. Not only does this workflow enable the quick development of efficient model-based control for integrated continuous processes, but it can also find applicability in a wide range of inline adjustment operations across diverse purification processes.

Modeling titration for effective inline adjustment in continuous viral inactivation processes

ACS Fall 2021

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