The Diffusion of Hydrogen Peroxide Into the Liquid Product During Filling Operations Inside Vaporous Hydrogen...

Isolators are commonly used in filling operations of pharmaceutical products. To ensure an aseptic inner environment, isolators are regularly sterilized with vaporized hydrogen peroxide. However, despite extensive purging with air, some residual H₂O₂ remains within the isolator atmosphere and may thus end up in the liquid pharmaceutical drug product, which subsequently may cause oxidation and impact the product's safety and efficacy. We aimed to evaluate the extent of this phenomenon and to model it. For that purpose, we studied the diffusion of H₂O₂ into water contained in small recipients exposed to the atmosphere of a H₂O₂-sterilized small-scale test isolator. Based on the results, a mechanistic model was proposed to estimate the quantity of H₂O₂ in the product, taking into account the time, filling volume, H₂O₂ concentration, and a configuration factor. Afterward, this model was challenged by filling water at a manufacturing scale, and we observed that the diffusion model could predict the trend of increasing H₂O₂ concentration. However, a consistent difference in H₂O₂ concentration between the model and the experimental results was observed, suggesting the contribution of another parameter. Our results can be used to predict more accurately H₂O₂ concentration in a pharmaceutical product at the manufacturing level.