Chapter 13. Assessing the Impact of Functional Excipients on Peptide Drug Product Attributes During Pharmaceutical Development

Achieving market approval of a new peptide therapeutic requires phase-appropriate demonstration of product safety, efficacy and quality across all stages of development, including raw materials, drug substance and drug product manufacture, product distribution and shelf-life. Of particular importance is the definition of a drug product formulation that meets requirements as defined by the Quality Target Product Profile (QTPP) and mitigates peptide-specific Chemistry, Manufacturing and Controls (CMC) liabilities. Peptide drug product formulations can range widely in complexity, but often require the inclusion of excipients that are selected to perform a number of functions, such as buffering pH, preserving sterility, mitigating chemical and/or physical instabilities of the peptide active substance or controlling the rate of peptide drug release upon administration in people. The choice of excipient(s) and composition(s) can impact multiple drug product attributes, which necessitates appropriate formulation characterization and data-driven decision-making regarding excipient use throughout development and ultimately in the final drug product. This chapter briefly surveys categories of excipients employed in therapeutic peptide formulation development, highlights guidance and regulations related to the selection and evaluation of such excipients and discusses the assessment and justification of excipient use in formulations, from discovery through development, with a focus on peptide-specific challenges in parenteral formulations.