Development and validation of cell-based assays for the detection of neutralizing antibodies to drug products: a practical approach.

Neutralizing antibodies (NAbs) that bind to drug products and may diminish or eliminate the associated biological activity are an unintended and undesirable outcome of some drug products. Standard immunoassays can detect drug-specific antibodies but cannot distinguish NAbs, so cell-based assays are often preferred because they closely mimic the mechanism by which NAbs and drug products interact in vivo. Each cell-based NAb assay is unique and based on several factors, such as the drug product, study population and phase of development (preclinical or clinical). The type of NAb assay (direct or indirect) depends on the drug's mechanism of action. Key steps in assay development are: selecting a suitable cell line, choosing the proper cellular response (end point method), selection of proper controls and optimization of assay parameters. Once developed, the assay must be rigorously tested (validated) to ensure that it meets several important criteria and is fit for its intended purpose.