Highly concentrated (&gt; 200 mg/mL) protein formulations with low viscosities, particularly of monoclonal antibodies, are strongly desired for subcutaneous drug delivery for the treatment of diseases such as cancer. However, production of concentrated antibody formulations by tangential flow ultrafiltration (TFF) is challenging due to high solution viscosities and protein aggregation that lead to significant membrane fouling and flux decay. Herein, we demonstrate the ability to mitigate aggregation and membrane fouling by the combined addition of high concentrations of viscosity-reducing co-solutes and selection of hollow fiber filter geometries, resulting in a high transmembrane flux even at mAb concentrations of 250 mg/mL and higher. The reduced solution viscosity and hollow fiber geometry will both be shown to independently minimize the axial pressure drop in the filter module. The combination of the smaller pressure drop and straight flow path in the filter module minimizes the wall shear stress and allows for a more uniform axial TMP and shear profile. As a result of the low viscosity and more uniform TMP and shear profiles, the high co-solute formulations will be shown to achieve a high-concentration membrane flux three-fold higher than that of conventional low co-solute buffer formulations. The concentrated mAb will also be shown to be stable by SEC after ultrafiltration.<br/>

Production of stable high concentration monoclonal antibody solutions with low viscosity by tangential flow ultrafiltration

251st National Meeting (2016)

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