Continuous multicolumn chromatography (MCC) has enabled process intensification of key chromatography steps through increased resin capacity utilization. However, transferring a process from batch to continuous presents more degrees of freedom that can be optimized. These include load configuration and number of columns. Here we evaluate four MCC load configurations; two column multiphase, where the columns that are connected intermittently, two (1+1) and three (1+1+1) columns in series and a three column scenario where one column is loaded directly and the flowthrough of that column is directed to two subsequent columns (1+2). The total number of columns was constrained to 8 or less. To evaluate the effect that these parameters have on process performance and economics, a computational chromatography model was generated and validated experimentally. Then, by using the predictive abilities of the model, the four different MCC loading configurations were assessed for operating binding capacity, productivity, and consumable costs at a multitude of load residence times and concentrations. At 1 g/L, the 2 column multiphase process is the most cost effective loading scenario. However, at 5 and 8 g/L, the most cost effective processes are both single phase loading scenarios: 1+1 configuration for 5 g/L and the 1+2 configuration for 8 g/L. The 1+1 and 1+2 single phase loading processes use significantly more columns (5 and 7 respectively) which results in a reduction of both total sorbent consumed as well as a reduction in pre-packed column diameter. This highlights the advantages of operating multicolumn chromatography with more columns as higher feed concentrations become available from intensified upstream fed-batch processes.<br/>

Optimized continuous multicolumn chromatography enables increased productivities and cost savings by employing more columns

2019 Spring National Meeting

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