Abstract
Background Peptide drugs occupy an intermediate position between small-molecule drugs and biologics in terms of molecular size and structural complexity. Owing to their unique characteristics, they face regulatory challenges for quality assessment and control, as existing regulatory frameworks for small molecules and biologics are not fully applicable to peptide drugs. To address these challenges, regulatory agencies and pharmacopeial authorities have developed guidelines and analytical standards based on scientific considerations to ensure manufacturing consistency and reliable quality evaluation. Area covered This review examines recent regulatory trends for peptide drugs by analyzing guidelines and standards issued by major regulatory agencies and pharmacopoeias, focusing on analytical strategies for identification, impurity testing, and assay. The inherent complexity of peptides requires comprehensive and orthogonal analytical approaches to accurately characterize their structural attributes and satisfy stringent regulatory requirements. In this context, advanced analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy play complementary roles in peptide quality assessment. MS is a highly sensitive tool for sequence analysis and impurity profiling, while NMR offers unique capabilities for structural elucidation, higher-order structural assessment, and orthogonal confirmation. Expert opinion Recent advances in analytical technologies have contributed significantly to the development of science-based regulatory strategies for synthetic peptide drugs. The continued harmonization of peptide drug regulations, together with the integration of advanced analytical methodologies and industrial perspectives, is expected to facilitate efficient quality assessment and support the production of safe and effective peptide therapeutics.