Continuous bind-and-elute protein A capture chromatography: Optimization under process scale column constraints and...

Area of Science:

• Chemical Engineering
• Biopharmaceutical Manufacturing
• Process Optimization

Background:

• Continuous downstream processing is gaining attention but lacks industrial applications.
• Protein A capture is a critical step in biopharmaceutical purification.
• Simulated Moving Bed (SMB) chromatography offers potential for continuous operation.

Purpose of the Study:

• To evaluate the process behavior of continuous Protein A capture using SMB mode.
• To analyze the impact of pressure drop constraints on compressible media in packed columns.
• To determine optimal system design points for varying feed concentrations, bed heights, and residence times.

Main Methods:

• Modeling and simulation of a continuous Protein A capture column cycling operation.
• Consideration of pressure drop limitations for compressible media.
• Comparison of SMB mode performance against traditional batch processing.
• Analysis of system design points for achievable productivity.

Main Results:

• Continuous SMB operation can significantly increase the productivity of Protein A capture.
• Shorter columns operated at higher flow rates reduce product residence time without substantial capacity loss.
• Physical limitations of packing short columns and pressure drop were considered.
• Achievable productivity was determined for various feed concentrations and column bed heights.

Conclusions:

• Continuous downstream processing via SMB is a viable strategy for enhancing biopharmaceutical manufacturing efficiency.
• SMB mode offers a pathway to reduce resin requirements and increase throughput for Protein A capture.
• The study provides a framework for optimizing continuous chromatography systems under realistic operational constraints.