Evaluating Clinical Safety and Analytical Impact of Subvisible Silicone Oil Particles in Biopharmaceutical Products.

Silicone oil is a commonly used lubricant in pre-filled syringes (PFSs) and can migrate over time into solution in the form of silicone oil particles (SiOPs). The presence of these SiOPs can result in elevated subvisible particle counts in PFS drug products compared to other drug presentations such as vials or cartridges. Their presence in products presents analytical challenges as they complicate quantitation and characterization of other types of subvisible particles in solution. Previous studies have suggested that they can potentially act as adjuvant resulting in potential safety risks for patients. In this paper we present several analytical case studies describing the impact of the presence of SiOPs in biotherapeutics on the analysis of the drug as well as clinical case studies examining the effect of SiOPs on patient safety. The analytical case studies demonstrate that orthogonal techniques, especially flow imaging, can help differentiate SiOPs from other types of particulate matter. The clinical case studies showed no difference in the observed patient safety profile across multiple drugs, patient populations, and routes of administration, indicating that the presence of SiOPs does not impact patient safety.

Effect of carbon coating on the physico-chemical properties and toxicity of copper and nickel nanoparticles.

The primary aim of these interdisciplinary studies is to investigate the effect of surface carbon coating on the physico-chemical properties and toxicity of carbon-coated and noncoated copper and nickel nanoparticles (C-Cu, Cu, C-Ni, Ni NPs) in A549 alveolar epithelial cells. Compared to Cu NPs, C-Cu NPs exhibit protection against surface oxidation, tenfold higher cellular uptake, and fourfold lower release of soluble Cu. The toxicity of C-Cu NPs and Cu NPs is associated with pronounced damage to mitochondrial function and plasma membrane integrity, respectively. Compared to Cu and C-Cu NPs, Ni and C-Ni NPs are less toxic. These studies demonstrate that correlations can be drawn between physico-chemical properties and resultant toxicity of NPs as a function of surface carbon coating.