Excipients: Characterization, Purpose, and Selection

Protein drugs are subject to chemical, conformational, and colloidal instability throughout the manufacturing process through fill/finish to the final container. Instability can manifest itself as protein unfolding and aggregation, sticking to surfaces, and chemical modification to an inactive form (deglycosylation, deamidation, etc.) leading to loss of efficacy and/or immunogenic responses. Several stressors have been identified as contributing to protein instability, including agitation, temperature excursions, and impurities. For some protein drugs, instability is caused by a lack of solubility (e.g., antibody-drug conjugates) in the final formulation. Excipients such as salts, sugars, solubilizers, and surfactants are often added in final formulations to help protect proteins from these stressors and to increase stability. This chapter will review the types of instabilities, the stressors that cause them, and the excipients currently available to improve stability of protein formulations. The proposed mechanisms of protection of excipients for both dry powders and liquid formulations will be discussed. Emerging excipient technologies and stabilizing process additives will also be explored.