Vapor Phase Hydrogen Peroxide Uptake by Silicone Tubing and Primary Packaging Components during Protein Drug Product Aseptic Filling: Impact by Pre-treatment and Sterilization Process

In the vapor phase hydrogen peroxide (VPHP)-sanitized environment, VPHP uptake by product-contacting components could eventually lead to undesired oxidation of biological drug products. Silicone tubing and primary packaging materials are prominent examples of such product-contacting surfaces that are typically processed/sterilized prior to use. This study investigated the VPHP-uptake tendency of these components and how their respective processing/sterilization methods affect uptake behaviors. Silicone tubing that was sterilized via autoclave or gamma irradiation exhibited different VPHP uptake patterns; decreased uptake rates post autoclaving vs. increased uptake rates post gamma irradiation. The reduced uptake tendency of autoclaved tubing is maintained 14 days after sterilization while the uptake tendency of irradiated tubing was mostly reversed to normal levels 1 month after irradiation. Empty glass vials adsorbed hydrogen peroxide via the diffusion of VPHP into the vial with high vial-to-vial variability. Vial pre-treatment (i.e., depyrogenation) and surface hydrophilicity/hydrophobicity impacted uptake tendency. Stoppers and empty syringes also adsorbed hydrogen peroxide but at a relatively low level. The uptake behavior of these components appeared to correlate with water levels at the surface (i.e., hydrophilicity). This study would provide process development scientists and engineers an in-depth understanding of VPHP uptake by critical product-contacting surfaces to mitigate the impact on drug product quality.