title: Oxidation of protein by vaporized sanitizing agents.
abstract: For the first time, it has been demonstrated that a protein product can be oxidized readily by certain sanitizing agents through vapor transfer not only in a closed system but also in an open environment. The effect of several sanitizing agents on the oxidation of a model protein, IL-2 mutein, was investigated under different processing conditions. Reversed phase-high performance liquid chromatography (RP-HPLC) was used to separate and quantitate both intact and oxidized IL-2 mutein. It was found that peracetic acid or NaOCl oxidizes IL-2 mutein instantaneously, while H2O2-induced oxidation of IL-2 mutein is much slower in solution. The amount of protein oxidation product is proportional to the duration of sample exposure and the type and concentration of the sanitizing agent. In addition, sanitizing agents can accelerate protein oxidation during lyophilization, and the residual amount can promote oxidation of the lyophilized product during storage. These results strongly suggest that the sanitization process needs to be properly controlled and closely monitored during manufacturing of drug products that are sensitive to oxidation.
authors.affiliation: Analytics & Formulation, Biotechnology Division, Bayer Healthcare, Berkeley, CA 94701, USA. wei.wang.b@bayer.com
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Cui
authors.forename: Y John
authors.initials: YJ
authors.lastname: Wang
authors.forename: Sheryl
authors.initials: S
authors.lastname: Martin-Moe
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004202:Disinfectants / Q000737:chemistry*; D004339:Drug Compounding; D004340:Drug Contamination; D005612:Freeze Drying; D007376:Interleukin-2 / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D019999:Pharmaceutical Solutions; D011506:Proteins / Q000737:chemistry*
chemical_list: D004202:Disinfectants; D007376:Interleukin-2; D016877:Oxidants; D019999:Pharmaceutical Solutions; D011506:Proteins