title: Unwanted immunogenicity: lessons learned and future challenges.
abstract: All biological therapeutics have the potential to induce an immune response in recipients of these products. Elicitation of an immune response can result in variable clinical impact, ranging from benign to severe adverse effects, a diminution in clinical efficacy or, in some cases, hypersensitivity or allergic reactions. Consequently, assessment of unwanted immunogenicity is an important element of the data required for regulatory submission for product approval. However, issues relating to immunogenicity occur throughout the life-cycle of a biotherapeutic and need to be considered appropriately when introducing any product change(s). Evaluation of immunogenicity of a product requires a well-considered strategy and a panel of appropriately validated (or 'fit-for-purpose') assays for antibody detection and characterization in clinical samples. An overview of the bioanalytical methods that are currently being used for assessment of immunogenicity of biotherapeutics and the guidance available along with some of the challenges facing the industry are discussed in this review.
authors.affiliation: Biotherapeutics Group, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK. Meenu.Wadhwa@ nibsc.hpa.org.uk
authors.forename: Meenu
authors.initials: M
authors.lastname: Wadhwa
authors.forename: Robin
authors.initials: R
authors.lastname: Thorpe
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001681:Biological Assay; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007118:Immunoassay; D018570:Risk Assessment
chemical_list: D000906:Antibodies