Antibody-Drug Conjugate Overview: a State-of-the-art Manufacturing Process and Control Strategy.

Antibody-drug conjugates (ADCs) comprise an antibody, linker, and drug, which direct their highly potent small molecule drugs to target tumor cells via specific binding between the antibody and surface antigens. The antibody, linker, and drug should be properly designed or selected to achieve the desired efficacy while minimizing off-target toxicity. With a unique and complex structure, there is inherent heterogeneity introduced by product-related variations and the manufacturing process. Here this review primarily covers recent key advances in ADC history, clinical development status, molecule design, manufacturing processes, and quality control. The manufacturing process, especially the conjugation process, should be carefully developed, characterized, validated, and controlled throughout its lifecycle. Quality control is another key element to ensure product quality and patient safety. A patient-centric strategy has been well recognized and adopted by the pharmaceutical industry for therapeutic proteins, and has been successfully implemented for ADCs as well, to ensure that ADC products maintain their quality until the end of their shelf life. Deep product understanding and process knowledge defines attribute testing strategies (ATS). Quality by design (QbD) is a powerful approach for process and product development, and for defining an overall control strategy. Finally, we summarize the current challenges on ADC development and provide some perspectives that may help to give related directions and trigger more cross-functional research to surmount those challenges.