Bastiaan Duivelshof

Looking beyond current techniques to debate the next frontier in characterization, from continuous manufacturing control to analyzing single molecules. This panel discussion will challenge the status quo on what is “good enough” and explore the technologies that will redefine our understanding of ADC structure by:

• Speculate on the potential of single-molecule sequencing and mass spectrometry to fully resolve ADC populations, and whether this ultimate level of characterization is a necessary future standard or an analytical fantasy
• Debate the hurdles and rewards of implementing real-time PAT and in-line analytics for continuous ADC manufacturing, moving from batch release to a state of perpetual verification
• Explore the role of computational models and AI in predicting ADC biophysical behavior and long-term stability from early structural data, potentially rendering months of stability studies obsolete

• Compare the resolution and denaturing conditions of HIC versus reversed-phase LC-MS for DAR species separation to select the optimal stability method
• Implement native mass spectrometry for intact DAR analysis to provide a direct measurement without disrupting the native protein structure, gaining a true representation of drug distribution and identifying critical low-abundance species
• Develop orthogonal methods to overcome HIC’s poor resolution and HPLC RP’s denaturation, to understand DAR distribution, providing a robust package for regulatory filings, andensure consistent product quality