Abstract：
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.
摘要：
硅油是预填充注射器(PFS)中常用的润滑剂,并且可以随着时间的推移以硅油颗粒(SiOPs)的形式迁移到溶液中。这些SiOP的存在可导致PFS药物产品中的亚可见颗粒计数与其他药物呈现(例如小瓶或药筒)相比升高。它们在产品中的存在带来了分析挑战，因为它们使溶液中其他类型的亚可见颗粒的定量和表征复杂化。先前的研究表明，它们可能作为佐剂，从而给患者带来潜在的安全风险。在本文中，我们介绍了几个分析案例研究，描述了生物治疗剂中SiOPs的存在对药物分析的影响，以及临床案例研究，研究了SiOPs对患者安全性的影响。分析案例研究表明，正交技术，尤其是流动成像，可以帮助区分SiOPs与其他类型的颗粒物。临床案例研究表明，在多种药物中观察到的患者安全性没有差异，患者群体，和管理路线，表明SiOPs的存在不会影响患者安全。
