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.