Advancement in the modeling of pressure-flow for the guidance of development and scale-up of commercial-scale biopharmaceutical chromatography.

This paper details the advancements made in the modeling of open column and packed bed pressure-flow. The theoretical description is a one-dimensional elasticity model. By accounting for the loss of intra-particle porosity through empiricism, and by systematically selecting the functional form of the elastic modulus from stress-strain data, this model can accurately predict several kinds of large-scale behavior from small-scale data: packed pressure-flow, open column pressure-flow, and critical velocity.

Toward a robust model of packing and scale-up for chromatographic beds. 2. Flow packing.

We developed and evaluated a model for predicting the flow packing of nonrigid chromatographic resins. The model is based on elasticity theory and accounts for resin rigidity and column diameter. When a modulus determined from a standard mechanical compression (consolidation) test is used, the model captures the primary phenomena of the scale-up process.

Toward a robust model of packing and scale-up for chromatographic beds. 1. Mechanical compression.

The packing of compressible biochromatographic resins at large scale suffers from a poor understanding of how column packing method, resin properties, and column geometry impact column performance. To improve understanding, we develop and evaluate a one-dimensional, continuum mechanics model of column packing by mechanical compression. We show that the model can quantitatively predict the change in bed height, applied stress, and internal axial porosity profile without adjustable parameters when the modulus and wall friction coefficients are determined independently.