Challenges in surfactant removal from biopharmaceutical formulations using tangential flow filtration (TFF) and spin columns

This is the authors' abstract. We don't add key points for this paper.

Surfactants such as polysorbate 20 (PS20), polysorbate 80 (PS80), and poloxamer 188 (P188) are integral to the stabilization of protein therapeutics, yet their removal is often required during formulation development and analytical characterization. This work investigates the efficiency of surfactant removal by commercial spin columns and tangential flow filtration (TFF), using liquid chromatography with charged aerosol detection (LC-CAD) to evaluate subspecies specific behavior. Spin column experiments demonstrated effective PS20 clearance from monoclonal antibody formulations, while PS80 removal was limited, particularly for PS80 polyester species. TFF enabled selective removal of unesterified and monoester species for both polysorbates, with PS20 showing the highest overall clearance, especially when processed below its critical micelle concentration (CMC). PS80 removal was ineffective again due to retention of polyester species, while P188 exhibited slower and incomplete removal kinetics. These findings underscore the need for improved surfactant removal strategies and the importance of subspecies profile analysis in surfactant quantification.