Optimization study on periodic counter-current chromatography integrated in a monoclonal antibody downstream process

Area of Science:

• Biopharmaceutical Manufacturing
• Chromatographic Separations
• Process Optimization

Background:

• Monoclonal antibody (mAb) purification is critical in biopharmaceutical manufacturing.
• Periodic counter-current chromatography (PCC) offers potential for improved efficiency in downstream processing.
• Lab-scale optimization of integrated PCC processes requires detailed mechanistic modeling.

Purpose of the Study:

• To optimize an integrated periodic counter-current chromatography (PCC) process for monoclonal antibody (mAb) downstream processing.
• To investigate the trade-offs between productivity and resin utilization.
• To evaluate the impact of feed concentration and yield on PCC performance.

Main Methods:

• Optimization study based on a mechanistic model of the protein-A capture step's breakthrough curve.
• Analysis of different integration approaches for PCC.
• Evaluation of feed concentration, yield, and protein-A resin effects on process scheduling and performance.

Main Results:

• Pareto optimal solutions were identified, balancing productivity and resin utilization.
• Maximum productivity of 0.38 mg/mL/min was achieved at 0.5 mg/mL feed concentration and 99% yield, with 60% resin utilization.
• Maximum resin utilization of 95% resulted in a productivity of 0.10 mg/mL/min.
• Higher feed concentrations and longer recovery times negatively impacted productivity due to process scheduling constraints.

Conclusions:

• A holistic approach considering all purification steps is necessary for effective PCC process design.
• Process scheduling significantly influences the achievable productivity and resin utilization in PCC.
• The study provides valuable insights for optimizing mAb downstream processing using PCC.