On-Demand Presentation: Analytical Strategy & Challenges for ADC
Global Vice President of Analytical & Research Development, Scott Zugel, spoke at Veranova’s SCALE Symposium, where he outlined key analytical strategies and challenges in ADC manufacturing in the pharmaceutical industry. During his presentation, Scott highlighted critical topics including regulatory expectations, method development best practices, impurity control approaches, and advanced characterization techniques. Watch the presentation now to learn more.
Presenter: Scott Zugel, Global VP of Analytical & Research Development, Veranova
ABSTRACT
Antibody-drug conjugates (ADCs) are a rapidly growing therapeutic class, combining the specificity of biologics with the potency of cytotoxic small molecules. However, their hybrid nature introduces unique analytical and regulatory challenges. Drawing on Veranova’s 19 years of experience with multiple ADC linker-payload systems, we highlight key strategies in the analysis of ADCs, particularly in linker-payload impurity control. Case studies illustrate common analytical challenges encountered during linker-payload development, such as the introduction of new impurities with process scale-up, analyte peak shifts during process modification, and fit-for-use method updates for in-process control. Finally, we present proof-of-concept studies of ADC characterization, demonstrating the use of UV-Vis spectroscopy and the optimization of hydrophobic interaction chromatography (HIC) to determine the drug-antibody ratio (DAR), establishing a foundation for future bioanalytical capabilities.
KEY LEARNINGS
1) Companies and regulators increasingly treat linker-payload and antibody components as starting materials, with the ADC as the drug substance, enabling higher upstream impurity levels to translate to lower levels in the final ADC due to molecular weight differences, DAR, and purification.
2) Early identification and classification of conjugatable versus non-conjugatable impurities is critical to establishing scalable control strategies, as most non-conjugatable impurities can be removed during downstream purification.
3) Analytical techniques such as UV-Vis and HIC provide practical approaches for DAR determination during early-stage ADC development.
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