Recent Advances in Drug-Antibody Ratio Determination of Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are biopharmaceuticals produced by chemically linking small molecules (payloads) to antibodies that possess specific affinity for the target cell. The ADCs currently on the commercially market are the result of a stochastic conjugation of highly-potent payloads to multiple sites on the monoclonal antibod, resulting in a heterogeneous drug-antibody ratio (DAR) and drug distribution. The heterogeneity inherent to ADCs not produced site-specifically may not only be detrimental to the quality of the drug but also is less-desirable from the perspective of regulatory science. An ideal method or unified approach used to measure the DAR for ADCs, a critical aspect of their analysis and characterization, has not yet been established in the ADC field and remains an often-challenging issue for bioanalytical chemists. In this review we describe, compare, and evaluate the characteristics of various DAR determination methods for ADCs featuring recently reported technologies. The future landscape of bioconjugate DAR analysis is also discussed.

Automated summary

ADCs are biopharmaceuticals made by linking small molecules to antibodies that target specific cells, resulting in heterogeneous drug-antibody ratios. The lack of a standardized method to measure the DAR for ADCs is a challenging issue that affects the quality and regulatory perspective of these drugs. The review explores various DAR determination methods and discusses the future landscape of bioconjugate DAR analysis.