Pressure-Flow experiments, packing, and modeling for scale-up of a mixed mode chromatography column for...

To obtain consistent chromatographic behavior, it is important to develop resin packing methods in accordance with the characteristics of each resin. Resins, particularly those with a significant level of compressibility, require proper knowledge of the packing methodology to ensure scalable performance. The study demonstrates the applicability of pressure-flow modeling based on the Blake-Kozeny equation for cellulose based resins, using the MEP HyperCel (Pall) resin as a case study. This approach enabled the understanding of the appropriate bed compressibility and the determination of the minimum column diameter that can predict bed integrity during commercial manufacturing scale operation. Studies suggested that scale-dependent wall effects become negligible for column diameters exceeding 20 cm. Pressure-flow modeling produced a minimum compression recommendation of 0.206 for the MEP HyperCel resin. Columns with diameters up to 80 cm packed with this bed compression yielded incompressible beds with pressure-flow curves consistent with model predictions. Model parameter (particle diameter, viscosity, porosity) values were then varied to demonstrate how changing operating conditions influence model predictions. This analysis supported the successful troubleshooting of unexpected high pressures at the commercial manufacturing scale using MEP HyperCel resin, further supporting the applicability of this approach.