Chapter 3. Biological and Immunogenicity Evaluation Strategy for Therapeutic Peptides: Chemistry, Manufacturing and Controls Perspective

Abstract

Assessment of the immunogenicity of peptides used for therapeutic purposes along with measurement of their biological activity is essential to evaluating the safety of therapeutic peptides. Accurate determination of the potency (biological activity) and evaluation of the immunogenicity of peptide-based therapeutic drugs for use in humans are crucial to their efficacy and safety. The assays used in determining the biological activity must closely follow the mechanism of action. A panel of assays can be used for testing the activity of a molecule. Several cell-based assay methods with a wide range of readouts can be used in the evaluation. These readouts can be cellular responses, signal transduction events, gene transcription reporter assays and/or ligand–receptor-binding cell-based assays using flow cytometry. Additionally, it is important to evaluate the immunogenic potential of the biologics in an appropriate fashion using a clearly defined strategy and clinical trials. The studies must include the appropriate risk assessment procedures and evaluation of immunogenicity using validated methods. The immune responses against the therapeutic biologics can be studied using various methodologies. These include enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), chemiluminescence and flow cytometry assays for binding antibodies and cell-based assays for neutralizing antibodies. The immune responses to the biologics can vary widely in various cross-sections of the population, hence a combination of techniques is necessary to evaluate fully the immunogenic potential of the biologics. This chapter outlines various commonly used technology platforms and their merits and shortcomings.