title: Effect of polysorbate 80 quality on photostability of a monoclonal antibody.
abstract: Polysorbate 80 is one of the key components of protein formulations. It primarily inhibits interfacial damage of the protein molecule due to mechanical stress during shipping and handling. However, polysorbate 80 also affects the formulation photostability. Exposure to light of polysorbate 80 aqueous solution results in peroxide generation, which in turn may result in oxidation of the susceptible amino acid residues in the protein molecule. The purpose of this study was to determine if the photostability of our proprietary IgG(1) monoclonal antibody formulation containing polysorbate 80 is affected by the quality (grade/vendor) of polysorbate 80. Following four types of polysorbate 80 were tested: (1) Polysorbate 80 Super-Refined, Mallinckrodt Baker, (2) Polysorbate 80 NF, Mallinckrodt Baker, (3) Polysorbate 80 NF, EMD Chemicals, and (4) Ultra-pure Polysorbate 80 (HX), NOF Corporation. The samples were exposed to light as per ICH guidelines Q1B. The results of the study show that photostability of the antibody formulation is indeed affected by the quality of polysorbate 80. This study underscores the importance of carefully choosing the quality of polysorbate 80 to ensure the robustness of formulation.
authors.affiliation: ImClone Systems, Branchburg, New Jersey 08876, USA. swita.singh@imclone.com
authors.forename: Swita R
authors.initials: SR
authors.lastname: Singh
authors.forename: Jingming
authors.initials: J
authors.lastname: Zhang
authors.forename: Courtney
authors.initials: C
authors.lastname: O'Dell
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Hsieh
authors.forename: Joel
authors.initials: J
authors.lastname: Goldstein
authors.forename: Joseph
authors.initials: J
authors.lastname: Liu
authors.forename: Arvind
authors.initials: A
authors.lastname: Srivastava
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000528:radiation effects; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D004355:Drug Stability; D015180:Electrophoresis, Gel, Two-Dimensional; D005079:Excipients / Q000737:chemistry* / Q000592:standards; D008027:Light; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010449:Peptide Mapping; D010545:Peroxides / Q000737:chemistry; D010782:Photolysis; D011136:Polysorbates / Q000737:chemistry* / Q000592:standards; D055550:Protein Stability; D011786:Quality Control; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D005079:Excipients; D010545:Peroxides; D011136:Polysorbates