Immunogenicity
Immunogenicity, typically assessed by anti-drug antibody (ADA) analysis is a major feature of the analytical arm of biopharmaceutical drug development. Alderley Analytical offer anti-drug antibody (ADA) screening, confirmation and titre analysis. The importance and inherent challenges of ADA testing have evolved over time and now typically employ a routinely tiered approach – screening, confirmation and further characterisation by titration/neutralising antibody assays.
Screening
A number of immunoassay configurations can be used for the screening assay, the typical approach engaging a bridging immunoassay. Complications in assessment of ADA is the presence of circulating drug – the very target of ADA. On board drug interference is a major parameter to characterise in ADA assays and has to be considered early in development. Flexible and adaptive strategies are needed to establish the degree of interference. Assay formats can involve a more direct binding assay, acid dissociation of drug from ADA, capture of ADA bound drug and release of ADA amongst other approaches. Due to the importance of drug interference and other potential binding interference, Alderley Analytical have begun to enable analysis of such binding events by SPR (surface plasmon resonance): a very powerful and informative technique.
Confirmation
A potentially positive screening result will be confirmed in a confirmation assay. This can be a different immunoassay format, or typically an inhibition assay to show specificity of the ADA.
Titration
Having established the presence of ADA, an estimate of the quantity of ADA can be made. As ADA are polyclonal and also vary between individuals, a semi-quantitative/quasi quantitative approach is taken by using a titration assay. The ADA sample is titrated to a response close to the assay sensitivity (assay cut point) and the titre used to estimate ADA concentration.
See the relation between Immunogenicity and Biomarker Analysis.