Hydrophobic Interaction Chromatography (HIC) has been used in the large-scale purification of numerous biologics products. However, it routinely presents back-pressure and bed stability issues at the large-scale operation due to high viscosity of buffers and load material used in that step. Therefore, it is important to evaluate the effect of mobile phase viscosity, flow rate and packing method on the pressure drop and bed stability. In this work, a 20 cm diameter column was used to study these factors affecting the HIC column performance. Using this scale-down model, pressure-flow profiles at different packing factors and mobile phase viscosities were determined. Subsequently, the data collected was fitted using the Blake-Kozeny equation to predict the bed porosities at different packing conditions. Model predictions were in good agreement with the experimentally determined pressure drop values of the scale-down model and the 80 cm diameter large-scale column. Based on these studies, the optimal slurry determination method, packing buffer and packing factor were recommended for large-scale operation.

Modeling of hydrophobic interaction chromatography column performance using a scale-down column

247th National Meeting (2014)

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