Strategies and assays for the assessment of unwanted immunogenicity.

The assessment of unwanted immunogenicity associated with biological products continues to be a major issue for the biotechnology industry. Monitoring of unwanted immunogenicity during the development of the product from pre-clinical stage through clinical trials is now a regulatory expectation with extended post-marketing commitments required for at least some of these products. Prospective planning of immunogenicity studies incorporating appropriately devised strategies is critical if valid conclusions concerning the immunogenicity profile of a product are to be derived. An important consideration of such studies is the selection of optimized, rigorously validated and standardized methodologies for detection and characterization of antibodies with emphasis on desired assay design, assay controls, and performance criteria. Binding assays with different formats and detection systems, radioimmuno-precipitation assays or surface plasmon resonance procedures are often used as the basis for a screening assay. For assessing the neutralizing capacity of the antibodies, however, a neutralization assay is an absolute requirement. Therefore, a panel of methods is usually necessary for a detailed understanding of the type(s) of antibodies induced against a therapeutic product. This manuscript considers briefly the benefits and limitations of the different techniques available for antibody detection and characterization. A strategy that can be adopted for the assessment of unwanted immunogenicity of therapeutic products is also suggested.