IgG1 aggregation and particle formation induced by silicone-water interfaces on siliconized borosilicate glass beads: a model for siliconized primary containers.

Understanding and mitigating particle formation in prefilled syringes are critical for ensuring stability of therapeutic proteins. In the current study, siliconized beads were used as a model for the silicone-water interface to evaluate subvisible particle formation and aggregation of a monoclonal antibody (IgG(1)). Agitation with siliconized beads greatly accelerated the formation of protein aggregates and particles, an effect that was enhanced at pH 7.4 relative to pH 5 and in the presence of 0.5 M sucrose or 150 mM NaCl. Aggregation and particle formation were minimal in samples agitated without siliconized beads or in quiescent samples with siliconized beads. At pH 5, 0.01% (w/v) polysorbate 20 substantially inhibited aggregation during agitation with siliconized beads, but had minimal protective effect at pH 7.4. Transient exposure of IgG(1) formulations to the silicone-water interface by flowing formulations through a column packed with siliconized beads led to the formation of subvisible particles, with increased levels observed at pH 7.4 compared to pH 5. Agitation of protein formulations in the presence of siliconized glass beads provides a model for baked-on silicone oil-water interface in prefilled syringes and a means by which to evaluate particle formation and aggregation during formulation screening.