Principal Scientist, Regulated Bioanalytics Merck & Co., Inc. Collegeville, Pennsylvania
Electrochemiluminescence (ECL) bridging assay is the most used format to detect anti-drug antibodies (ADA) in drug development for biologics. A challenge often encountered with this assay format is target interference, where a soluble target can bridge the capture and detection reagents and generate a false positive signal. During ADA assay development, target interference is often assessed. However, it can be challenging to assess the likelihood of target-induced ADA positivity in actual patient samples. This is for several reasons. Firstly, the target level reflecting the relevant study population and treatment may not be available or may be unknown. Secondly, the physiologically relevant form of the target may not be known or available for experimental testing, particularly if the target exists in multiple forms. Finally, assessment with recombinant target protein spiked samples may not reflect the actual study samples in composition and dynamics of target, drug and ADA. Therefore, it is critical to assess the true impact of target on the ADA assay or ADA data during the clinical stage. Here, two case studies will be discussed applying a novel approach to assess if target induced false ADA positive was of concern and confirm if soluble targets were attributable to clinical ADA positive result in the absence of soluble target level information for clinical stage programs.
Learning Objectives:
How to identify drug competitive target binding antibodies
How to assess if target – induced false ADA positive was a real concern in the absence of target level information