Assessment of the effects of sterilization methods on protein drug stability by elucidating decomposition mechanism and material analysis.

The effects of different sterilization methods on the stability of highly sensitive protein drugs were assessed by elucidating mechanism involved in the process of protein decomposition. Results demonstrated that the steam sterilized syringes produced less protein oxidation compared with sterilization by the electron beam method. Electron spin resonance analysis showed that while considerably high levels of radicals were observed in the electron beam-sterilized syringes, no radicals were detected with steam sterilization. To identify the factor involved in protein oxidation, stability of the chemical composition of the syringe material was investigated using various analytical methods. Results showed that the syringe material itself was oxidized and two forms of oxidation products were identified with electron beam sterilization. Protein oxidation was shown to increase over time, and this was thought to be as a result of persistent exposure to the oxidized syringe barrel surface, which induced further protein oxidation. These results suggest that compared to electron beam sterilization, steam sterilization is a preferable method for the plastic prefilled syringe system, particularly for biopharmaceutical drug products that are highly sensitive to oxidization.