title: Suppression of Methionine Oxidation of a Pharmaceutical Antibody Stored in a Polymer-Based Syringe.
abstract: Oxidation of methionine residues is one of the well-known deteriorations in monoclonal antibody (mAb) therapeutics. Because methionine oxidation may affect their efficacy and pharmacokinetic profile, oxidation levels should be strictly controlled during their storage period. In this study, we revealed that when a therapeutic antibody was filled into a cyclo olefin polymer-based syringe and stored in a blister pack with an oxygen absorber, the methionine oxidation production under thermal or light stress was suppressed because of the reduction in the concentration of dissolved oxygen. Also unexpectedly, fewer amounts of the high-molecular-weight species and the acidic variants of the antibody were generated under thermal or light stress. Although the high-molecular-weight species contains methionine oxidants at similar levels to those in a monomer species, they were likely to be constituted from a higher amount of the oxidative species of internal disulfide linkage, tyrosine, or histidine. Because the dissolved oxygen could be readily removed from the mAb solution in the polymer-based syringe owing to its high gas permeability, this study shows the advantages of the polymer-based syringe with an oxygen absorber over glass syringes in terms of the suppression of the methionine oxidation and oxidative high molecular species.
authors.affiliation: New Modality Research Laboratories, R&D Division, Daiichi Sankyo Company, Ltd., Tokyo, Japan.
authors.forename: Amano
authors.initials: A
authors.lastname: Masato
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan.
authors.forename: Fukui
authors.initials: F
authors.lastname: Kiichi
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan; Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Aichi, Japan. Electronic address: suchi@bio.eng.osaka-u.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Uchiyama
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D004356:Drug Storage / Q000379:methods* / Q000592:standards; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D008715:Methionine / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D011108:Polymers / Q000737:chemistry* / Q000592:standards*; D013594:Syringes / Q000592:standards*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011108:Polymers; D008715:Methionine
keywords: biopharmaceuticals characterization; mass spectrometry; oxidation; protein aggregation; protein formulation; stability