Standardization of antibody preparations for use in immunogenicity studies: a case study using the World Health Organization International Collaborative Study for Islet Cell Antibodies.

The immunogenicity of biological therapeutic products is currently a high profile regulatory and biotechnology industry issue. The immune responses raised against biotechnology products range from the benign, to affecting product efficacy, to those that have serious deleterious clinical impact. The most widely used marker of immunogenicity is the detection and measurement of antibody responses induced in vivo to a product. This relies on assays that are sensitive and robust. In order to assess the parameters of an assay during its design, development and validation, it is extremely useful to have a reference standard to compare assay results. However, immune responses lead to polyclonal antibody preparations that can vary by affinity and avidity. This makes it extremely difficult to select a preparation that will behave similarly in different test systems and against different antibody samples. The case example of the WHO standardization of islet cell antibodies illustrates the difficulties in the process and the mechanisms required to produce a suitable antibody standard.