ABSTRACT
The risk to patients of mounting an immune response to a therapeutic protein product will vary with the product. Food and drug administration recommends that the sponsor direct initial screening tests against the whole therapeutic protein product and, when relevant, its endogenous counterpart. The cut point of the assay can be influenced by a myriad of interfering factors, such as pre-existing antibodies, rheumatoid factor, human anti-mouse antibodies, and the levels of product-related material or homologous proteins in the matrix. Assay sensitivity represents the lowest concentration at which the antibody preparation consistently produces either a positive result or readout equal to the cut point determined for that particular assay. An important consideration is how interference from the assay matrix, which is composed of the sample and the diluent, can affect assay performance. The matrix can cause interference with neutralization assays, particularly as serum or plasma components may enhance or inhibit the activity of a therapeutic protein product in bioassays.
