LAUSR

Silicone oil is a lubricant for pre-filled syringes (PFS), a common primary container for biotherapeutics. Silicone oil particles (SiOP) shed from PFS are a concern for patients due to their potential for increased immunogenicity and therefore also of regulatory concern. To address the safety concern in a context of manufacturing and distribution of drug product (DP), SiOP was increased (up to ∼ 25,000 particles/mL) in PFS filled with mAb1, a fully human antibody drug, by simulated handling of DP mimicked by drop shock. These samples are characterized in a companion report (Jiao et al). The risk of immunogenicity was then assessed using in vitro or in vivo immune model systems. The impact of a common DP excipient, polysorbate 80 (PS80), on both the formation and biological consequences of the SiOP was also tested. SiOP was found associated with (1) minimal cytokine secretion from human peripheral blood mononuclear cells, (2) no response in cell lines that report the NF-κB/AP-1 signal, and (3) no anti-drug antibodies or significant cytokine production in transgenic Xeno-het mice, whether or not mAb1 or PS80 was present. These results suggest that SiOP in mAb1 representative of real-world DP in PFS poses no increased risk of immunogenicity.