Ultrafiltration of highly concentrated antibody solutions: Experiments and modeling for the effects of module and buffer conditions.

Although ultrafiltration is currently used for the concentration and formulation of nearly all biotherapeutics, obtaining the very high target concentrations for monoclonal antibody products is challenging. The objective of this work was to examine the effects of the membrane module design and buffer conditions on both the filtrate flux and maximum achievable protein concentration during the ultrafiltration of highly concentrated monoclonal antibody solutions. Experimental data were obtained using both hollow fiber and screened cassettes and in the presence of specific excipients that are known to alter the solution viscosity. Data were compared with predictions of a recently developed model that accounts for the complex thermodynamic and hydrodynamic behavior in these systems, including the effects of back-filtration arising from the large pressure drop through the module due to the high viscosity of the concentrated antibody solutions. Model calculations were in good agreement with experimental data in hollow fiber modules with very different fiber length and in screened cassettes having different screen geometries. These results provide important insights into the key factors controlling the filtrate flux and maximum achievable protein concentration during ultrafiltration of highly concentrated antibody solutions as well as a framework for the development of enhanced ultrafiltration processes for this application.