ABSTRACT
Polysorbate 80 (PS80) is a commonly used surfactant in therapeutic protein formulations to mitigate adsorption and interface-induced protein aggregation. Several PS80 grades and qualities are available on the market for parenteral application. The role of PS80 grade on protein stability remains debatable, and the impact of (partially) degraded PS on protein aggregation is not yet well understood. In our study, a monoclonal antibody (IgG) was subjected to 3 different mechanical stress conditions in the presence of multicompendial (MC) and Chinese pharmacopeia (ChP) grade PS80. Furthermore, IgG formulations were spiked with (partly) hydrolyzed PS80 to investigate the effect of PS80 degradants on protein stability. PS80 functionality was assessed by measuring the extent of protein aggregation and particle formation induced during mechanical stress by using size-exclusion chromatography, dynamic light scattering, backgrounded membrane imaging, and flow imaging microscopy. No distinguishable differences in PS80 functionality between MC and ChP grade were observed in the 3 stress tests. However, with increasing degree of PS80 hydrolysis, higher counts of subvisible particles were measured after stress. Furthermore, higher levels of PS80 degradants at a constant PS80 concentration may destabilize the IgG. In conclusion, MC and ChP grade PS80 are equally protective, but PS80 degradants compromise IgG stability.
