Recent advances in the development and regulatory pharmaceutical evaluation of dual-payload antibody-drug conjugates
CHEN Hao
LI Qian
WEI Wei
Abstract：Antibody-drug conjugate(ADC)are targeted therapeutics composed of monoclonal antibodies chemically linked to small-molecule payloads via specialized linkers.In recent years,ADC development has grown rapidly,with more than a dozen products approved globally.With advancing technologies,next-generation ADC are evolving toward increasingly complex designs,such as dual-payload ADC,which conjugate two distinct payloads to a single antibody molecule.Dual-payload ADC are expected to enhance anti-tumor efficacy by delivering two active agents simultaneously,thereby improving the killing of heterogeneous tumor cell populations and overcoming drug resistance.However,their structural complexity and increased challenges in controlling product homogeneity and impurity levels pose new difficulties for pharmaceutical development and regulatory evaluation.This article discusses the key considerations in the development and pharmaceutical review of dual-payload ADC,including raw material selection,manufacturing processes,structural characterization,impurity profiling,analytical methodology,quality control,and stability assessment.Based on issues observed in actual regulatory submissions,the paper highlights pharmaceutical development trends and review challenges specific to dual-payload ADC,aiming to provide practical references for their development and quality research.
Keywords：dual-payload antibody-drug conjugatestructural heterogeneitypharmaceutical development
Publication Date：2025-12-30
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：6( 2668-2673 )