Bioanalytical Challenges and Strategies for Antibody–Drug Conjugates

ADCs are typically mixtures with varying drug-to-antibody ratios (DARs) due to deconjugation and biotransformation. In ADC PK assay, the used reference standard may not be identical to the ADCs in the subject matrix. It is not uncommon to obtain unexpected results that the measured ADC concentration exceeds that of total antibody, or conformational changes of ADC products, non-specific interference, and DAR sensitivity issues leading to inaccurate measurement. Immunogenicity assessment of ADCs is more complex than that of mAb therapeutics since immunogenicity can occur to any component of an ADC. Thus, domain specificity characterization is required. Moreover, ideal drug tolerance and assay sensitivity are hard to achieve due to the non-specific interference. These issues present significant challenges in ADC clinical studies. In this presentation, we will share strategies and solutions to the above challenges, providing comprehensive insights into ADC bioanalysis with the goal of accelerating the progress of ADC clinical studies.