Process Development and Manufacturing of Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are an emerging class of therapeutic that harnesses the binding specificity of an antibody to deliver a highly potent drug. There is significant diversity in the design of ADC molecules including the antibody, linkers, conjugation chemistries and drugs used. Despite this diversity in the design of ADC molecules, many ADC manufacturing processes consist of three distinct stages: the functionalization of the antibody, the conjugation reaction, and the downstream purification and formulation steps. Examples of challenges encountered and process development approaches for each of these stages are provided, as well as a discussion of how the design of an ADC molecule can directly impact both the manufacturing process and the process development requirements. Case studies from three different ADC platforms are discussed.