Evaluation of Super Refined™ Polysorbate 20 With Respect to Polysorbate Degradation, Particle Formation and Protein Stability

Super Refined (TM) and Tween (TM) 20 HP polysorbate 20 (PS20) are two commercially available compendial grades of PS20 frequently used in biopharmaceutical formulations as protein stabilizing surfactants. PS20 degradation has been a major concern recently for potentially limiting drug product shelf life due to free fatty acid particle formation. This work is a side-by-side comparison of SR and HP PS20 in terms of PS20 degradation, particle formation and protein stability. The use of SR grade PS20 results in higher levels of oxidative PS20 degradation, protein oxidation, peroxides and protein aggregation, and therefore requires addition of methionine as an antioxidant to mitigate these issues. No clear root cause was identified as to why SR PS20 is more prone to oxidative degradation. This work also suggests that SR PS20 is less prone to particle formation than HP PS20 when there is preferential degradation of mono-esters of PS20, while more susceptible to particle formation when there is preferential degradation of higher order esters of PS20. Overall, this publication summarizes the potential risks and benefits of SR PS20 compared to HP PS20 to enable a formulator to make an informed decision when choosing between the two surfactant grades in their drug product formulations. (C) 2020 Published by Elsevier Inc. on behalf of the American Pharmacists Association.