Vaporized Hydrogen Peroxide Sterilization in the Production of Protein Therapeutics: Uptake and Effects on Product Quality.

The aseptic filling of drug products is carried out in pharmaceutical isolators that have been sterilized. A commonly used method for achieving a high level of sterility assurance is vaporized hydrogen peroxide (VHP) sterilization, which is favorable to other methods, such as ethylene oxide sterilization, due to its low cycle times and nontoxic residuals. While VHP cycles are often employed to create a sterile environment within an isolator, they can leave residual levels of hydrogen peroxide behind that can enter the product during fill-finish operations. Due to the oxidizing potential of hydrogen peroxide and the multiple possible sources of uptake along filling lines, the extent of the potential impact on product quality needs to be understood during pharmaceutical development. Herein, different factors affecting hydrogen peroxide uptake, points of entry along the filling line, and possible impacts on product quality are reviewed.