An overview of process development for antibody-drug conjugates produced by chemical conjugation technology

Abstract

ABSTRACT Introduction: We discuss chemical conjugation strategies for antibody-drug conjugates (ADCs) from an industrial perspective and compare three promising chemical conjugation technologies to produce site-specific ADCs. Areas covered: Currently, nine ADCs are commercially approved and all are produced by chemical conjugation technology. However, seven of these ADCs contain a relatively broad drug distribution, potentially limiting their therapeutic indices. In 2019, the first site-specific ADC was launched on the market by Daiichi-Sankyo. This achievement, and an analysis of clinical trials over the last decade, indicates that current industrial interest in the ADC field is shifting toward site-specific conjugation technologies. From an industrial point of view, we aim to provide guidance regarding established conjugation methodologies that have already been applied to scale-up stages. With an emphasis on highly productive, scalable, and synthetic process robustness, conjugation methodologies for ADC production is discussed herein. Expert opinion: All three chemical conjugation technologies described in this review have various advantages and disadvantages, therefore drug developers can utilize these depending on their biological and/or protein targets. The future landscape of the ADC field is also discussed.