Comparison of assay formats used for the detection of pre-existing anti-drug antibodies against monoclonal antibodies.

Assessment of pre-existing anti-drug antibody (preADA) reactivity at early drug development stages can be beneficial for candidate selection. We investigated the applicability of a generic immune-complex anti-drug antibody (ADA) assay for early preADA assessment as an easily available alternative to the commonly used ADA bridging assay. The results confirmed the expected assay difference regarding isotype detectability. Tested drug candidates were identified as preADA-reactive using the immune-complex ADA assay despite its limitation of not being able to detect IgM-type preADAs. We recommend a purpose-driven use of the two assay formats. For the purpose of ranking different Pro329Gly mutation-bearing drug candidates, the immune-complex ADA assay is preferred in the phase before selecting a drug for clinical development.