Miguel Saggu, Stanley C. Kwok, Linda O. Narhi, Bin Zhang, Shalini Minocha, Monica Pombo, Desmond G. Hunt
Correspondence should be addressed to: Desmond G. Hunt, Principal Scientific Liaison, US Pharmacopeial Convention, 12601 Twinbrook Parkway, Rockville, MD 20852-1790; tel: +1.301.816.8341; email: dgh@usp.org.
Subvisible particles are a Critical Quality Attribute (CQA) of a drug product, requiring stringent control. Silicone oil, used in prefilled syringes, can form subvisible silicone oil particles, posing unique analytical and clinical challenges. This article discusses industry challenges, analytical strategies, and the rationale for a new informational chapter on subvisible silicone oil particles (SiOPs).
The complexity of subvisible particles (SbVPs) has increased with advanced drug delivery systems. Silicone oil droplets impact SbVP counts, complicating differentiation from other particles. Analytical methods like flow imaging and light obscuration are explored for SiOP characterization, despite limitations.
The absence of reported adverse events following intravenous and subcutaneous administration—routes most commonly associated with device use—suggests that SiOPs have low toxicity and are not inherently immunogenic. However, their interactions with protein particles may influence immunogenic responses (1). The intravitreal route of administration is out of scope for this article. Strategies to minimize SiOP formation during development and manufacturing are proposed.
Orthogonal analytical techniques are essential for SiOP characterization and establishing product-specific specifications. Regulatory perspectives emphasize control strategy and patient safety, advocating comprehensive risk assessments and clinical trials.
Emerging technologies, such as holographic microscopy and artificial-intelligence-based image analysis, offer advancements in SiOP characterization and classification. The proposed USP chapter aims to guide SiOP analysis, safety assessment, and control strategies, ensuring consistency and patient safety across biopharmaceutical products.