Full title: Addressing Subvisible Silicone Oil Droplets-Industry Challenges, Analytical Strategies, and USP's Rationale for a New General Informational Chapter
Subvisible silicone oil droplets (SiOPs) originating from siliconized prefilled syringes have become a significant contributor to subvisible particulate matter (SbVP) in biopharmaceutical products. While silicone oil is essential for device functionality, dispersed droplets complicate compendial particle measurements, challenge method specificity, and may interact with therapeutic proteins. This presentation synthesizes insights from a recent Pharmacopeial Forum Stimuli article titled and “Addressing Subvisible Silicone Oil Droplets—Industry Challenges, Analytical Strategies, and USP's Rationale for a New General Informational Chapter”.
We will examine the industry context of subvisible silicone oil droplets (SiOPs) across evolving delivery systems, including prefilled syringes and autoinjectors, and various administration routes except intravitreal use. This overview will compare analytical strategies such as light obscuration, flow imaging with morphology filters, orthogonal methods like NMR/ICP-MS and Raman/FTIR, and emerging tools such as holographic microscopy and AI-enabled image analysis, focusing on their limitations, variability, and fit-for-purpose application. Clinical and safety data will be discussed, emphasizing the low intrinsic toxicity of silicone oil and the context-dependent nature of immunogenicity risks. We will also outline development and lifecycle control strategies—covering siliconization processes, container selection, formulation factors, and manufacturing controls—and present a risk-based framework for product-specific specifications and regulatory engagement when SiOPs impact apparent SbVP levels.
