Simple method transfer from batch to continuous chromatography process to fit parameters to business needs
Abstract
Multi-column chromatography (MCC) has been proven to significantly increase throughput and productivity of biopharmaceutical continuous downstream processing.
Continuous bio-manufacturing can also greatly benefit from in-line concentration (ILC) using single-pass tangential flow filtration technique by enabling direct flow-through in-process volume reduction. Using in-line concentration to increase the load titer onto a MCC process therefore allows for a decreased load time, which consequently further boosts process productivity.
Here we demonstrate the increase in productivity and decrease in cost associated in placing ILC upstream of a MCC process. By performing process modeling we can identify the ideal product concentration with which to perform the chromatography cycle in order to maximize productivity. With this knowledge we can identify the optimum volumetric concentration factor (VCF) to operate ILC. Using this strategy we have shown that the coupled ILC-MCC productivity can be increased >3 fold over a regular multi-column process. We have established a robust continuous ILC-MCC operation for multiple cycles with stable flow rate and pressure profiles. Additionally, the HCP and aggregate content of product remained equivalent to operating in batch mode, which demonstrates no impact of the ILC-MCC process on the product quality.
A process economic study shows that coupling ILC to multi-column chromatography enables significant process cost reduction for initial titer range from 0.1 g/L to above 5 g/L, indicating this technique could be readily applied to a wide range of process operations.