Model-based evaluation and model-free strategy for process development of three-column periodic counter-current...

Area of Science:

• Biopharmaceutical Process Development
• Chromatographic Separations
• Chemical Engineering

Background:

• Multi-column counter-current chromatography (MCC) offers enhanced productivity and resin utilization for continuous capture processes.
• Process development for MCC, particularly three-column periodic counter-current chromatography (3C-PCC), is challenging due to its complexity.

Purpose of the Study:

• To develop general and convenient guidances for 3C-PCC process development.
• To clarify operating windows and understand interactive effects of key parameters on productivity.
• To establish a model-free strategy for optimizing 3C-PCC performance and resin screening.

Main Methods:

• Model-based predictions were used to define boundaries and distributions of operating windows for 3C-PCC.
• Evaluation of interactive effects between feed concentration, resin properties (qmax, De), and cycle times (tRR) on maximum productivity (Pmax).
• Development and validation of a model-free strategy using breakthrough curves for process optimization and resin screening.

Main Results:

• Operating windows and parameter interactions influencing maximum productivity (Pmax) in 3C-PCC were clarified.
• Plateau Pmax was determined by resin capacity (qmax) and regeneration time (tRR), while operating conditions depended interactively on qmax, tRR, and feed concentration (c0).
• A critical concentration threshold was identified for Pmax under constraint factors like capacity utilization and flow rate limitations.

Conclusions:

• A comprehensive model-based understanding of 3C-PCC is crucial for improving process development.
• A novel model-free strategy enables convenient determination of optimal operating conditions and resin screening.
• The proposed approach was successfully validated for monoclonal antibody (mAb) capture, demonstrating its practical applicability.