Effect of Polysorbate 80 Quality on Photostability of a Monoclonal Antibody

Abstract

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 polysorbate80 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.

Effect of Polysorbate 80 Concentration on Thermal and Photostability of a Monoclonal Antibody

“…Investigation of protein oxidation is complicated not only by the unique structure of each individual protein but also by the existence of different oxidation mechanisms under various oxidative stresses (18). Quality of surfactants such as Polysorbate 80 can also significantly influence the photostability of a protein (19).…”

Impact of Residual Impurities and Contaminants on Protein Stability

“…A major degradation pathway in these materials is autoxidation, especially at high temperatures . Both neat polysorbate 80 and its diluted solutions easily generate peroxides, catalyzed by light, and in the presence of metal . Because of these influencing factors, the peroxide levels in different lots from the same vendor may vary significantly .…”

“…Because of these influencing factors, the peroxide levels in different lots from the same vendor may vary significantly . Accordingly, peroxide‐induced degradation in protein solutions containing PS 80 of different grades from different vendors can vary significantly . Different types of polysorbates are expected to have varying degrees of deleterious effect because of the structural variations …”

“…Examples include oxidation of sulfhydryl groups in membrane proteins and oxidation of recombinant human granulocyte colony‐stimulating factor during storage . Other oxidation‐derived degradation products can also be observed such as high‐molecular weight and low‐molecular weight species . Even in a solid state, a protein can be oxidized by a low level of peroxides in polysorbate 80 during storage …”

“…13 Both neat polysorbate 80 and its diluted solutions easily generate peroxides, catalyzed by light, and in the presence of metal. 32,99,136 Because of these influencing factors, the peroxide levels in different lots from the same vendor may vary significantly. 137 Accordingly, peroxide-induced degradation in protein solutions containing PS 80 of different grades from different vendors can vary significantly.…”