Optimal loading flow rate trajectory in monoclonal antibody capture chromatography

Area of Science:

• Biotechnology
• Chemical Engineering
• Biopharmaceutical Manufacturing

Background:

• Optimizing monoclonal antibody (mAb) purification is critical for biopharmaceutical production.
• Current mAb capture processes often utilize constant flow rates, potentially limiting efficiency.
• Improving resin utilization and productivity are key economic drivers in chromatography.

Purpose of the Study:

• To determine optimal flow rate trajectories for mAb capture column loading.
• To enhance process economics by maximizing productivity and resin utilization.
• To evaluate the generalizability of optimized flow trajectories across scales.

Main Methods:

• Development of a multi-objective function balancing productivity and resin utilization.
• Simulation and experimental evaluation of constant, stepwise, and linear flow rate trajectories.
• Utilizing protein A resin (mAb Select PrismA™) in batch mode with purified mAb and clarified supernatant.
• Model calibration at constant flow for simulation of dynamic flow trajectories.

Main Results:

• Optimized flow trajectories improved productivity by up to 12% and resin utilization by up to 9% compared to constant flow.
• Yields consistently exceeded 99% across tested trajectories.
• Achieved productivity ranged from 0.23 to 0.35 mg/min/mL resin, comparable to continuous multi-column processes.
• Model calibration at constant flow successfully predicted performance for optimized trajectories.

Conclusions:

• Programming volumetric flow rate trajectories offers a simple yet effective method to improve mAb capture economics.
• The developed flow strategies are scalable and generalizable for protein A resin-based chromatography.
• This approach provides a viable alternative to enhance bioprocess efficiency and reduce manufacturing costs.