Vaporized hydrogen peroxide uptake by tubing used for aseptic fill-finish manufacturing of biopharmaceutical drug products

Abstract

Aseptic filling of biopharmaceutical products requires a grade A cleanroom environment, preferably ensured by isolators in grade C surroundings. Isolators are decontaminated before the start of filling processes using vaporized hydrogen peroxide (VHP) and filling starts at pre-defined residual VHP levels (e.g., below 0.5 ppm) depending on product sensitivity towards VHP oxidation. Manufacturing equipment and consumables, including filling assemblies, are exposed to VHP during or after the decontamination cycle or after line interruptions. We studied the VHP uptake by tubing in a lab-scale model isolator to evaluate the impact of tubing properties including contact material, tubing dimensions, suppliers, and VHP exposure (concentration and exposure time). Quantifying the release of H2O2 from the tubing into solution using an Amplex Red Hydrogen Peroxide Assay, showed that H2O2 concentrations decreased linearly with an increase in wall thickness and increased with higher surface to volume ratio. We further conclude that thermoplastic elastomer and thermoplastic vulcanizate tubing did not show any measurable VHP uptake for the tested conditions, whereas significant VHP uptake occurred in different platinum cured silicone tubing depending on tubing material and supplier. We further verified the results in a GMP manufacturing isolator setting. Based on our findings, we recommend to evaluate VHP uptake of filling tubing used for fill-finish manufacturing in isolators, to reduce the risk of oxidation for active pharmaceutical ingredients or excipients.