Dissolution of Polysorbate 20 Degradation Related Free Fatty Acid Particles in Intravenous Bag Solutions.

Abstract

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.