Unlocking the Secrets of ADC Purification: Insights into Ultrafiltration/Diafiltration Techniques in Cancer Treatment Innovations

Introduction to the Research and Authors

Antibody−drug conjugates (ADCs) are prominent cancer treatments. The research, “Strategies for UF/DF-Based Impurity Removal in the Post-conjugation Purification of Antibody−Drug Conjugate”, conducted by Lara Fernandez-Cerezo, Melissa Holstein, and their team, seeks to address purification challenges in ADCs.



Understanding ADCs and Their Importance

ADCs combine a small-molecule drug with a monoclonal antibody, offering targeted cancer treatment. Despite their potential, ADCs present manufacturing and purification challenges. Ultrafiltration/diafiltration (UF/DF) emerged as a critical step in ADC purification. However, literature detailing UF/DF’s application to ADCs is scanty.


The Role of the IQ Consortium in ADC Development

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) has over 2300 scientists and focuses on advancing drug development standards. A subgroup within this consortium specifically concentrates on ADC development, ensuring that small-molecule impurities from ADCs meet regulatory guidelines.


Key Insights from the Research

All responding companies used UF/DF for ADC purification. 73% of these companies exclusively relied on UF/DF, underscoring its universal application. This research delves deeper into UF/DF’s application, showcasing industry practices, challenges, and future potential in ADC purification.

While UF/DF is a common method in biopharmaceutical processing, ADCs present unique challenges due to their complex structure. The efficiency of the UF/DF process, especially in removing cytotoxic small molecule impurities, is crucial. The research aims to categorize impurities based on their ease of removal, thereby aiding in designing effective purification strategies.


Conclusion and Forward Path

UF/DF stands as a pivotal step in ADC manufacturing. The research provided a thorough analysis of UF/DF’s application in ADC purification. By highlighting impurity classification, operational parameters, and challenges, the research offers valuable insights and suggests practical strategies for impurity removal. The team hopes their findings will fuel future discussions and advancements in the ADC domain.


Lara Fernandez-Cerezo, Melissa Holstein, Srinath Thirumalairajan, Dante Romanini, Pavlo Kos, Thomas Raglione, and Paul G. Bulger
Organic Process Research & Development 2023 27 (7), 1258-1268

DOI: 10.1021/acs.oprd.3c00137