BioOutsource

Measuring Drug Induced Immunogenicity
(Anti-drug Antibodies)

Drug immunogenicity refers to the ability of a drug to induce an immune response. Large Polypeptides and protein drugs are usually immunogenic if administered to a mammalian species in which the molecule does not naturally occur or if the molecule is presented in an unnatural form. Immunogenicity is unpredictable and is dependant on a number of factors. There are two major concerns associated with drug immunogenicity: (1) drug allergy, and (2) the ability of anti drug immune responses to alter the biological activities of the drug or the native protein.

BioOutsource offer 3 types of assay to measure anti-drug antibodies.

  1. Screening Assays
  2. Confirmatory and Specificity Assays
  3. Neutralisation Assays

We normally recommend a screening bridging ELISA assay to identify potentially positive samples and then use a cell based neutralisation bioassay to investigate the anti-drug neutralisation potential of the sample. For the most efficient development of such screening procedures we recommend initiating the validation of both assays at the earliest opportunity, as today clinical trials will be delayed without an appropriate means of measuring anti-drug responses in clinical samples.

Assay Validation

All assays are required to be validated for their intended purpose. At BioOutsource the assays are validated to show linear responses to the analyte as well as to the ICH guidelines for accuracy, precision, sensitivity, specificity and robustness. Assays are also validated to clearly define the background response of negative samples and to ensure the matrix effects of substances present in the intended samples do not interfere or that steps are taken to ensure these issues are accounted for. BioOutsource normally use spiking experiments with control samples to investigate these matrix effects. The issue of drug product interference is also accounted for in our validation studies from the pharmacodynamic data available.