| As biopharmaceuticals are becoming an increasing fraction of new therapeutic candidates, and as the scale of many of these processes continues to increase, there is a growing need for packing procedures which can be scaled while preserving column elution profiles and structural stability. Toward the development of rigorous and practical model descriptions of the column packing process, we have applied theoretical approaches from the continuum mechanics of solids to describe column packing and scale-up effects. To elucidate important factors in structural stability and elution profiles, we used magnetic resonance imaging (MRI) to provide in situ porosity maps and concentration profiles.; Our modeling efforts showed that a Cauchy elasticity based model can quantitatively describe column packing, including the effects of scale-up. The model was evaluated for both components of packing procedures: mechanical compression (e.g. by a headpiece) and flow-induced consolidation. The key factor in the model's success was accounting for dependence of media rigidity on the method of packing.; Using MRI, we found that the slope of axial porosity profiles is an important factor pertaining to the structural stability of a bed. We found that the surface chemistry and rigidity of media seem to influence the broadness and asymmetry of elution profiles. Sephadex G75, a model non-rigid resin, was prone to peak broadening as a result of gradual radial variation in porosity spanning about a column diameter. In contrast, Phenyl Sepharose 6FF, a representative hydrophobic interaction resin was prone to a leading edge feature that was related to a sharp porosity increase adjacent to the column wall. |
