Synergistic effect of plunger insertion and siliconization methods on particle formation of an antibody formulation

Prefilled syringes are becoming an industry standard for administering protein therapeutics due to their numerous clinical and economic benefits. However, prefilled syringes that contain silicone oil as a lubricant can leach silicone oil into the injectable solution, promoting protein aggregation and particle formation. These effects are undesirable due to their potential to compromise drug safety and efficacy. The development of optimal practices that minimize particle formation and maintain protein stability, quality, and safety is crucial to patient health and drug efficacy. This study evaluated the particle formation and aggregation of a model therapeutic antibody in prefilled syringes lubricated with different siliconization methods and fill/finished with either vacuum or vent tube plunger insertion methods. Particle content and protein aggregation were measured using a combination of micro-flow imaging, light obscuration, size-exclusion chromatography, multi-angle light scattering, and analytical ultracentrifugation. Additionally, we investigated how syringes prepared with each insertion-siliconization pairing were affected by thermal and mechanical stress to simulate real-world shipping and handling practices. Our results showed that syringes prepared with a combination of cross-linked silicone coating and mechanical plunger insertion exhibited significantly reduced particle concentrations when compared to syringes prepared with vacuum plunger insertion or sprayed-on siliconization. These findings suggest that the plunger insertion and siliconization methods can have a synergistic effect on aggregate formation during the fill/finish process of antibody formulations.