Rapid Polysorbate 80 Degradation by Liver Carboxylesterase in a Monoclonal Antibody Formulated Drug Substance at Early Stage Development

Polysorbates (PS) are surfactants commonly added in a therapeutic protein drug product to protect proteins from denaturation and aggregation during storage, transportation, and delivery. Significant degradation of PS in drug products could lead to particulate formation with shortened drug shelf life, and one of the major root causes of PS degradation is the host cell protein (HCP) derived lipase/esterase, which belong to the serine hydrolase family. Typically, PS degradation can only be observed in drug products after a long time of storage if very low levels of host cell protein impurity with PS degradation activities are present. In this study, PS80 degradation was observed in a monoclonal antibody (mAb) within 18 h at 5 °C with a low level of HCP presented (