The propensity of protein-based biologics to form protein particles during bioprocessing can be related to their interfacial properties. In this study, we compare the surface activity and interfacial film properties of two structurally different biologics, an IgG and Fc-fusion, in the absence and presence of interfacial dilatational stresses, and correlate these differences to their tendency to form interface-induced protein particles. Our results show that interface-induced particle formation is protein-dependent, with the Fc-fusion demonstrating greater interfacial stability. This observation can be correlated with faster adsorption kinetics of the Fc-fusion protein, and formation of a less incompressible film at the air-liquid interface. The addition of polysorbate 80 (PS80), commonly added to mitigate protein particle formation, led to a surfactant-dominant interface for quiescent conditions and coadsorption of protein and surfactant for the Fc-fusion when exposed to interfacial stress. On the other hand, for the IgG molecule, the surface always remained surfactant dominant. Image analysis demonstrated that PS80 was more effective in mitigating particle formation for the IgG than Fc-fusion. This suggests that a surfactant-dominant interface is necessary to prevent interface-induced protein particle formation. Further, while PS80 is effective in mitigating particle formation in the IgG formulation, it may not be the best choice for other protein modalities.
Keywords: Fc-fusion protein; dilatational stress; interfacial stability; monoclonal antibody; polysorbate 80.