Silicone oil is utilized in pre-filled syringes to allow the plunger to move freely within the glass barrel. Silicone oil may be sprayed or baked on the inside of the pre-filled syringe. If the therapeutic protein being developed is to be marketed in a pre-filled syringe image, testing with silicone oil is essential. Incompatibility with silicone oil may result in protein aggregation or other adverse consequences (Jones et al., 2005; Thirumangalathu et al., 2009; Liu et al., 2011). Silicone oil may also interact with formulation excipients (Ludwig et al., 2010). New methods have been developed to evaluate silicone oil in protein-containing formulations, which include optics and spectroscopy, microflow imaging, flow cytometry, and other methods (Ludwig et al., 2011; Sharma et al., 2010; Wen et al., 2009). Efforts by manufacturers are being made to develop devices such as pre-filled syringes with modified amounts of silicone or devices that are silicone-free (Majumdar et al., 2011). One approach to studying the effects of silicone oil on a therapeutic protein is via spiking studies or stability studies with the syringe containing the silicone oil.