Silicone-Oil-Based Subvisible Particles: Their Detection, Interactions, and Regulation in Prefilled Container Closure Systems for Biopharmaceuticals

ABSTRACT

Recent increased regulatory scrutiny concerning subvisible particulates (SbVPs) in parenteral formulations of biologics has led to the publication of numerous articles about the sources, characteristics, implications, and approaches to monitoring and detecting SbVPs. Despite varying opinions on the level of associated risks and method of regulation, nearly all industry scientists and regulators agree on the need for monitoring and reporting visible and subvisible particles. As prefillable drug delivery systems have become a prominent packaging option, silicone oil, a common primary packaging lubricant, may play a role in the appearance of particles. The goal of this article is to complement the current SbVP knowledge base with new insights into the evolution of silicone‐oil‐related particulates and their interactions with components in prefillable systems. We propose a "toolbox" for improved silicone‐oil‐related particulate detection and enumeration, and discuss the benefits and limitations of approaches for lowering and controlling silicone oil release in parenterals. Finally, we present surface cross‐linking of silicone as the recommended solution for achieving significant SbVP reduction without negatively affecting functional performance. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4569–4583, 2012