Chapter 8: Higher-order Structure Characterization and Comparability Assessments for Peptides

There is increased interest in peptides in pharmaceutical research and development owing to their superior characteristics over small molecules in terms of high selectivity, efficacy and safety and also over large biomolecules in terms of less complexity and the associated cost. However, peptides sit between these two well-studied and understood groups of therapeutics, challenging scientists in designing characterization and comparability studies to cover all analytical aspects. There is a vital part of chemistry, manufacturing and control (CMC) in peptide drug development describing the structure and characterization of the molecule itself and in the case of a generic development comparing its structure with that of a reference product. Considering the complexity in terms of multiple structural elements of peptides, similarly to proteins, these sections highlight the higher-order structure of peptides during development. This chapter focuses on the description of the higher-order structure elements of peptides and the potential analytical methodologies for characterization and to present the main differences and challenges when studying peptides compared with large proteins. At the end of the chapter, a recommended study design of higher-order structure characterization and comparability of generic peptides is presented. Note that in this chapter peptides are considered to be, by definition, to contain fewer than 100 amino acid residues and are well distinguished from proteins.