CHMP Guidance on Unwanted Immunogenicity: Best Practice Immunogenicity Risk Management

A major concern in the development of biological therapeutics is the induction of antibodies against the biological in patients undergoing therapy. Such antibodies can adversely affect the safety and efficacy of a therapeutic product. A rigorous assessment of immunogenicity, based on state of the art measurement and characterization of antibodies, to understand the immunogenicity of the product is therefore required. A well considered strategy for immunogenicity assessment which includes a risk-level based bioanalytical testing strategy and a management plan for related adverse events is essential. The CHMP of the EU has produced a general guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins and also a draft guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use. Other CHMP guidelines also contain advice on specific aspects of unwanted immunogenicity. These will be discussed during the presentation.

Robin Thorpe PhD, FRCPath, is Head of the Biotherapeutics Group at the National Institute for Biological Standards and Control (NIBSC). Recent interests include the unwanted immunogenicity of biologicals, development of improved bioassays for cytokines, the immunology of monoclonal antibodies and cytokine contamination of biological products. He attends meetings of the Biologicals Working Party & Biosimilars Working Party of the CHMP at the EMEA. He is a member of the British Pharmacopoeia Commission (MHRA) Expert Advisory Group NOM, the British Pharmacopoeia Panel of Experts on Biological and Biotechnological Products and chairman of the Working Group on Monoclonal Antibodies of the European Pharmacopoeia. Dr. Thorpe is a member of the Biologicals & Vaccines Expert Advisory Group of the CHM. He is the Chairman of the IUIS nomenclature subcommittee for chemokines and the standardisation and nomenclature committee of the International Cytokine Society. He is a biologicals advisor to the WHO INN programme. Dr. Thorpe is an author on over 200 publications in scientific journals and books. He is an associate editor for the journal Cytokine, Biotherapeutics section editor for Biologicals and editorial board member of the Journal of Immunological Methods & Current Analytical Chemistry.