Essential Analytical Measurements and Quality by Design for Bioconjugates

Sponsored by Waters Corporation

Selecting which analytical measurements matter most for a bioconjugate program is complicated by the sheer number of attributes that could be tracked from preclinical development through commercialization. Lance Cadang, Scientist, Synthetic Molecule Analytical Chemistry at Genentech, explains how his team approaches this challenge by identifying the technical pitfalls that have caused other programs to fail. He then explains a measurement strategy that anticipates a molecule’s full development life cycle. He outlines the CQAs prioritized in this approach, including drug-to-antibody ratio (DAR), drug-load distribution, conjugation site occupancy, aggregation, charge heterogeneity, free payload, linker stability, and higher-order structure. Deanna Hunt, Senior Director of Business Development at KBI Biopharma, explains how increasing DAR raises a molecule’s hydrophobicity and can complicate purity assessment, since purity for an ADC depends on which method is used to measure it. The approach centers on selecting measurements that explain biological performance, rather than defaulting to whichever technique is most familiar.