Beyond Efficacy: Ensuring Safety in Peptide Therapeutics through Immunogenicity Assessment.

Peptides are gaining remarkable popularity in clinical diagnosis and treatment due to their high selectivity and minimal side effects. Over 11% of all new pharmaceutical chemical entities authorised by the FDA between 2016 and 2024 were synthetically manufactured peptides. A critical factor that can potentially limit the efficacy and safety of peptide-based therapeutics or biologics is immunogenicity, defined as an unintended or adverse immune response to a protein or peptide therapy. This response may be triggered by the peptide itself or by impurities in the production or formulation steps, leading to the production of antidrug antibodies (ADAs). To address this, current regulatory guidelines require the assessment of risks in market authorization applications, which include identifying drug impurity levels and immunogenicity. The development and critical evaluation of appropriate immunogenicity assays is therefore highly warranted. Such assays must consider the fine complexities of the immune response, as well as its variation within the human population. Moreover, immunogenicity testing is expected to remain a priority as the shift toward greener chemistries in peptide synthesis may require reassessment of novel impurities in peptide formulations.