Physical Stability Studies of Antibody-Drug Conjugates (ADCs) Under Stressed Conditions

The conjugation of cytotoxic drugs to monoclonal antibodies (mAbs) generates heterogeneous drug load distribution. Antibody-drug conjugates (ADC) are physically less stable as compared to their parent molecule due to modifications made in order to link drugs to the interchain sulfhydryl groups of monoclonal antibodies. The conjugation of small molecule drugs to mAbs alters the physicochemical properties of mAbs and also impacts their degradation profile. The use of appropriate analytical tools to monitor physical stability changes is necessary to identify key product quality attributes such as aggregation. This chapter discusses suitable stress conditions and the use of stability indicating analytical methods to detect degradation products.