Perspectives on exploring hybrid LBA/LC-MS approach for clinical immunogenicity testing.

ABSTRACT

Biological drug products may elicit an antidrug antibody (ADA) response. The current widely used bridging ligand binding assay (LBA) is the gold standard for ADA assessments in drug development, which is a qualitative assay followed by a quasi-quantitative titer analysis but can be prone to interferences from biological matrices, drug targets and circulating drugs. We present our perspectives and findings in exploring a hybrid LBA/LC-MS as an orthogonal bioanalytical tool for clinical immunogenicity assessments. The hybrid LBA/LC-MS is a semiquantitative assay with acceptable specificity, drug tolerance and the capability of multiplexed detection of ADA isotypes. The assay results suggest this technology to be a promising and complementary bioanalytical tool that can provide informative immunogenicity data in drug development.