Polysorbates, Biotherapeutics, and Anaphylaxis

摘要

Rapidly increasing use of monoclonal antibodies (MAbs) in the treatment of neoplastic, autoimmune, and inflammatory diseases has led to a dramatic increase in hypersensitivity reactions worldwide, complicating the use of MAbs as first-line therapies and limiting patient survival and quality of life (l). The origins of anaphylaxis are not well understood, though its mechanism is fairly straightforward (Figure 1). It is usually attributed to some undefined intrinsic property or properties of a biotherapeutic — despite the fact that biotherapeutic formulations are necessarily complex and include a host of functional excipients. Those help drug products meet the stringent challenges of shelf-life, stabilization, solubility, reconstitution following lyophilization, and the propensity of proteins to aggregate — especially at the high concentrations typically used to reduce MAb administration volume and time.