Antibody–Drug Conjugates: An Overview of the CMC and Characterization Process

Antibody-drug conjugates (ADCs) are a rapidly growing class of drugs covering a vast technical space from the perspective of process and analytical development. This chapter focuses on processes used for development of first-generation ADCs and extension of these processes to next-generation ADCs. The conjugation process must be kept free of reactive nucleophiles and provide appropriate pH control to support chemical reactivity without chemical or physical monoclonal antibody (mAb) destabilization. Characteristics of the linker or cytotoxin will determine the types of stationary and mobile phases used, much of this method development should be transferrable at the preconjugation phase from linker-drug CMC data. Production of an ADC combines many of the complexities of cytotoxic small molecule and mAb drug development, with the potential benefit being improved patient outcomes. Technologies for characterization of ADCs are advancing at a similar pace to innovations that offer to provide improved next-generation ADCs.