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

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.

Automated summary

From an industrial perspective, this article discusses chemical conjugation strategies for ADCs and compares three promising technologies. The majority of commercially approved ADCs currently have relatively broad drug distributions, limiting their therapeutic indices. The industrial interest in the ADC field is shifting towards site-specific conjugation technologies.