Antibody Drug Conjugates (ADCs): Analytical Considerations For QC Release, Stability Testing, Characterization And Comparability

An antibody-drug conjugate (ADC) is a complex biopharmaceutical composed of a monoclonal antibody (mAb) linked, typically via a chemical linker, to a highly potent cytotoxic agent — though new types of conjugated payloads are also being developed.

Despite the evolving nature of conjugates, the fundamental analytical approach remains consistent. Each component — the monoclonal antibody, the cytotoxin, and the chemical linker — plays a critical role in the overall efficacy of the ADC. The drug-to-antibody ratio (DAR) is another key parameter that must be precisely controlled and monitored. Thorough analytical evaluation of these elements is essential for selecting appropriate methods for release testing, stability studies, and in-depth characterization and comparability exercises.

Adding further complexity, analytical requirements extend across all stages of production, encompassing the mAb intermediate, the cytotoxic drug intermediate, the drug substance, and the final drug product. These materials are often manufactured at different sites, making a robust and coordinated analytical strategy essential for ensuring product quality and consistency throughout the supply chain.