Modeling the Impact of Holdup Volume from Chromatographic Workstations on Ion-Exchange Chromatography

Chromatographic workstations can significantly impact column chromatography performance by altering the peak shape and retention time. Inclusion of system contributions can help prevent misinterpretation of process data during column qualification, process scale-up, tech transfer to a different facility, or the implementation of equipment changes over the product life cycle. Holdup volumes, not usually considered, can pose significant risks during process development. Using bench-scale and pilot-scale AKTA chromatography systems, we investigated the impact of individual units within the flow path on ion-exchange chromatography operation. Experimental data was used to build a comprehensive model comprising of dispersive plug flow and ideal continuous stir tank reactors to mimic the holdup volume. Our models, which include a column model and a system model, demonstrate the importance of accounting for system holdup volume in chromatography modeling. These comprehensive models can also predict the impact of foreseeable system variations.