Bioassays for the measurement of neutralizing antibodies in serum (SNFs)

Bioassays to measure serum neutralizing factor (SNF) activity against therapeutic biological products are an important tool for assessment of the immune status of patients on a dosing regimen. Because of the large diversity of bioanalytical methodology currently available to measure neutralization of a biological response, approaches to assay development and validation can create a considerable challenge. Assay design can take on many forms depending on the biological response to be monitored and the severity of complicating serum effects. In addition, the manner in which assay results are reported should have clinical relevance, (e.g. related back to the amount of analyte neutralized per volume of serum, etc.). Although ICH/FDA assay validation guidelines exist, they were not created with biotechnology-based bioassays in mind. Therefore, a thorough assessment of the analytical method and proper interpretation of current guidelines is critical for a meaningful validation effort. Several assay development strategies and approaches to assay validation will be discussed.