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

• Published in: Journal of pharmaceutical sciences Vol. 101; no. 12; pp. 4569 - 4583
• Main Authors: Felsovalyi, Flora, Janvier, Sébastien, Jouffray, Sébastien, Soukiassian, Hervé, Mangiagalli, Paolo
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.12.2012; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: Biological and medical sciences; biotechnology; Chemistry, Pharmaceutical; Cross-Linking Reagents - chemistry; Drug Delivery Systems; drug interactions; Drug Packaging; excipients; Excipients - chemistry; General pharmacology; injectables; Medical sciences; parental solutions; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; prefillable systems; prefilled syringes; silicone oil; Silicone Oils - chemistry; subvisible particles; Syringes; injectables; drug delivery systems; biotechnology; drug interactions; subvisible particles; prefilled syringes; parental solutions; silicone oil; excipients; prefillable systems; Biotechnology; Vehicle(excipient); Drug carrier; Prefilled syringe; Particle; Parenteral form; Conditioning; Solution; Drug; Pharmaceutical technology; Silicone oil; Container content interaction; Biopharmaceuticals; Lubricant; Syringe; Particle interaction; Regulation; Detection
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23328

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