Single Pass Tangential Flow Filtration (SPTFF) of monoclonal antibodies: Experimental studies and theoretical analysis

Abstract

Single Pass Tangential Flow Filtration (SPTFF) enables continuous ultrafiltration and diafiltration for inline concentration and buffer exchange in downstream bioprocessing of monoclonal antibody (mAb) products. However, the high conversion in SPTFF modules leads to large variations in local flow rate, protein concentration, and transmembrane pressure drop, significantly complicating the design of effective SPTFF modules/processes. In this study, a recent concentration polarization model for the filtrate flux in protein ultrafiltration that accounts for protein-protein interactions has been extended to the analysis of SPTFF, specifically including the effects of the mAb and membrane properties as well as the long path-length. Model calculations are in good agreement with experimental data for the filtrate flux and pressure drop in two commercial SPTFF systems with very different module geometries. The model was then used to analyze the design of SPTFF processes for inline mAb concentration, providing additional insights into the underlying physical phenomena governing the performance and optimization of SPTFF modules for bioprocessing.