Enhancing protein A productivity and resin utilization within integrated or intensified processes

Area of Science:

• Biopharmaceutical Manufacturing
• Chromatography
• Process Intensification

Background:

• Continuous manufacturing of biologics is gaining interest to reduce costs.
• Multicolumn chromatography systems are being developed to improve resin utilization and productivity, particularly for Protein A capture.
• Single-pass tangential flow filtration can enhance capture step productivity by reducing harvest volume.

Purpose of the Study:

• To evaluate multicolumn chromatography systems for cost reduction in biologics manufacturing.
• To determine practical limits for capture step productivity based on manufacturing parameters.
• To compare an intensified batch capture process ('super-batch') against multicolumn chromatography.

Main Methods:

• Evaluation of multicolumn chromatography systems.
• Application of single-pass tangential flow filtration to perfusion harvests.
• Comparison of 'super-batch' intensified capture with multicolumn chromatography.

Main Results:

• Intensified capture processes can reduce resin consumption by up to 82% for short campaigns.
• For longer campaigns, lower productivity may be optimal for column lifetime and cost savings.
• The 'super-batch' process is presented as a simpler alternative for high productivity and resin utilization.

Conclusions:

• Process intensification strategies, including multicolumn chromatography and 'super-batch', can significantly reduce resin costs in biologics manufacturing.
• The optimal strategy depends on manufacturing campaign duration and frequency.
• Careful consideration of productivity limits is necessary to balance efficiency with column lifetime and process risk.