Polysorbate in biopharmaceuticals—an overview including in vivo fate and safety perspective

Surfactants are commonly added to biotherapeutic product formulations (including vaccines) to stabilize the active moiety against interfacial stresses commonly encountered during manufacturing, shipping, and storage. Polysorbates are the primary surfactant used in biopharmaceuticals, usually at small concentrations compared to the larger amounts used with small molecule (parenteral) products, where the objective is the solubilization of the active agent. Excipients are intended to be inactive, but they may not be pharmacologically inert as is the case with polysorbates. There are an increasing number of reports about injection site reactions, sensitization, anaphylactoid reactions, etc. from healthcare practitioners administering biopharmaceutical products, with the polysorbate component being generally implicated. This chapter provides a perspective on the in vivo impact of polysorbates and the safety aspects of this excipient including learnings from use in small molecule parenteral products and in biotherapeutics. While biotherapeutics avoid the significant adverse events associated with their use in small molecules, the importance of quality of this excipient both as raw material and in the biopharmaceutical is reemphasized, to minimize adverse events and improve tolerability.