Analytical Development and Testing Strategy of Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) have gained significant successes in the cancer treatment and are expanding rapidly into other therapeutic areas. This review outlines the integration of the analytical development and process development based on the technical challenges and control strategy of different process stages from the antibody intermediate, drug-linker intermediate, ADC drug substance (DS) to drug product (DP). The priority of analytical method development should be tailored to support the cascades of process development decision-making at early-stage, while additional analytical development for process characterization and product understanding should be planned to deliver a comprehensive analytical control strategy at late-stage for licensure. The development strategy of a few unique ADC methods including drug-antibody ratio (DAR), residual free drug quantitation, and cytotoxicity assay (bioassay) are discussed. Furthermore, the QC testing network should be strategized to allow fast speed to IND and clinical trial; the approaches including consolidated QC testing, central QC lab, one-stop shop, and conditional release may be considered and adjusted from early to late-stage product development.