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Degradation of Polysorbate 20 (PS20), a commonly used surfactant in drug product (DP) formulations, is a phenomenon of increasing concern to the biopharmaceutical industry. One of the most prevalent modes of PS20 degradation is enzymatic hydrolysis resulting from co-purified hydrolases that make their way into biologic DP formulations at trace levels. Enzymatic PS20 degradation results in generation of free fatty acids (FFAs) that have limited solubility in aqueous formulations and can form visible and/or sub-visible particles which is undesirable for parenteral DP stability and administration. Many therapeutic monoclonal antibodies are administered intravenously after first diluting the DP into an infusion solution (e.g., 0.9% normal saline, 0.45% half normal saline or 5% dextrose). The purpose of this work is to understand if FFA particles in the DP dissolve in intravenous solutions prior to administration. Our assessment indicates that visible and/or sub-visible particles that contain high levels of lauric, myristic and palmitic acids dissolve immediately upon dilution (at or exceeding two fold) regardless of the intravenous bag or solution type. Therefore, the risk is low of visible and/or sub-visible particles, comprised of FFAs in biopharmaceutical DPs, being intravenously administered to a patient. [ABSTRACT FROM AUTHOR]

Super Refined™ and Tween™ 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. [ABSTRACT FROM AUTHOR]