Comparison of batch and continuous multi-column protein A capture processes by optimal design

Area of Science:

• Biopharmaceutical manufacturing
• Chemical engineering
• Chromatographic separation science

Background:

• Batch chromatography is a standard method for monoclonal antibody (mAb) capture.
• Multi-column chromatography processes offer potential advantages over batch methods but require careful optimization.
• Determining the optimal number of columns for periodic counter-current chromatography (PCC) and simulated moving bed (SMB) chromatography is crucial for process efficiency.

Purpose of the Study:

• To numerically optimize and compare the process performance of twin-column CaptureSMB, 3- and 4-column PCC, and single-column batch capture.
• To evaluate these processes for capturing monoclonal antibodies using protein A chromatography.
• To analyze the trade-offs between productivity and capacity utilization across different multi-column configurations and feed conditions.

Main Methods:

• Numerical optimization of twin-column CaptureSMB, 3- and 4-column PCC, and single-column batch capture processes.
• Focus on maximizing productivity and capacity utilization while maintaining constant yield and purity.
• Comparison of process performance under various conditions for monoclonal antibody capture via protein A chromatography.

Main Results:

• All three multi-column processes (CaptureSMB, 3- and 4-column PCC) demonstrated similar maximum capacity utilization, significantly outperforming batch capture.
• CaptureSMB achieved optimal productivity, except at high feed titers where batch chromatography showed higher productivity but lower capacity utilization.
• CaptureSMB offered the best trade-off between capacity utilization and productivity at low and high feed titers; the 3-column process was optimal in an intermediate feed titer range.

Conclusions:

• Multi-column chromatography, particularly CaptureSMB and PCC, provides superior performance compared to batch processes for mAb capture.
• The choice between CaptureSMB, PCC, and batch chromatography depends on specific production scenarios, considering feed titer and desired balance between productivity and capacity utilization.
• Optimization findings enable informed selection of the most suitable capture process for diverse biomanufacturing applications.