Anti-drug Antibody (ADA) & Other Immunogenicity Immunoassays
With the rise of large molecule biologic drugs, the possibility of patients developing immune responses to therapeutics requires evaluation. Such immune responses can pose safety concerns, but also inform the interpretation of pharmacokinetic and pharmacodynamics data. Regulatory authorities require a comprehensive strategy for the evaluation of immunogenicity and anti-drug antibodies for any therapeutic protein. Developing and validating assays for this poses its own specific set of challenges above and beyond those associated with any other immunoassay, particularly around potential interference from the drug itself and characterisation of the nature of any response.
Example Projects
ADA standardisation issues traced to differences in antigen preparations
A client was experiencing issues with comparability of ADA responses as measured by two different approaches. Investigations by Fleet were able to ascertain that the differences were due to heterogeneity in the antigen preparations used in each assay.
Panel of 15 auto-antibody assays developed and standardised
A prototype assay had been developed to measure auto-antibodies against a panel of antigens as markers of cancer. This prototype suffered from extensive issues with non-specific binding. By re-optimising the assay Fleet was able to lower NSB considerably, whilst also reducing consumption of precious antigen. Antigen-specific control materials were developed by conjugating specific antibodies to human IgG.
ADA assay developed for CAR T-cell therapeutic
A client approached Fleet regarding development of an immunogenicity assay for a marker of of its CAR T-cell therapeutic. Fleet optimised the newly developed assay and carried out performance verification investigations to assess against predefined criteria and define acceptance limits for future bioanalytical runs. The assay was then transferred to the clients facilities for use in sample analysis.