title: Assessment of the effects of sterilization methods on protein drug stability by elucidating decomposition mechanism and material analysis.
abstract: 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.
authors: Terumo Corporation, R&D Center 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan. Electronic address: Kouji2_Nakamura@terumo.co.jp.
authors: Koji
authors: K
authors: Nakamura
authors: Terumo Corporation, R&D Center 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors: Hideaki
authors: H
authors: Kiminami
authors: Terumo Corporation, R&D Center 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors: Arisa
authors: A
authors: Yamashita
authors: Terumo Corporation, R&D Center 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors: Yoshihiko
authors: Y
authors: Abe
authors: Terumo Corporation, R&D Center 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors: Keisuke
authors: K
authors: Yoshino
authors: Terumo Corporation, R&D Center 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors: Shigeru
authors: S
authors: Suzuki
mesh_terms: D004355:Drug Stability; D004921:Erythropoietin / Q000737:chemistry*; D010084:Oxidation-Reduction; D055550:Protein Stability; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013227:Steam; D013242:Sterilization / Q000379:methods* / Q000592:standards*; D013594:Syringes / Q000592:standards*
chemical_list: D013227:Steam; D004921:Erythropoietin
keywords: Electron beam; Oxidation; Polymer based prefilled syringe; Protein stability; Radical generation; Steam sterilization