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.