The Diffusion of Hydrogen Peroxide Into the Liquid Product During Filling Operations Inside Vaporous Hydrogen Peroxide-Sterilized Isolators Can Be Predicted by a Mechanistic Model.

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 H ₂ O ₂ 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 H ₂ O ₂ into water contained in small recipients exposed to the atmosphere of a H ₂ O ₂ -sterilized small-scale test isolator. Based on the results, a mechanistic model was proposed to estimate the quantity of H ₂ O ₂ in the product, taking into account the time, filling volume, H ₂ O ₂ 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 H ₂ O ₂ concentration. However, a consistent difference in H ₂ O ₂ 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 H ₂ O ₂ concentration in a pharmaceutical product at the manufacturing level.
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