Optimization of Tangential Flow Ultrafiltration Processing Step with High Concentration Self-Buffering Proteins

High protein concentration biopharmaceuticals are becoming more common due to the increased viability of these formulations for subcutaneous administration. Formulation of a biopharmaceutical product is most often performed using tangential flow ultrafiltration (TFUF) to concentrate the product to the desired level and, then exchange buffer components into a more stable formulation.  As protein concentrations increase, self-buffering becomes a contributing factor in achieving the targeted formulation conditions.  This case study will examine methods to formulate a self-buffering protein at commercial scale. The developed process demonstrates both robustness to manage expected parameter variation, as well as flexibility to allow potential future changes that may be deliberately implemented upstream of the step.