Synthetic-Biologics Fusion Cuisine: Innovation in Analytical Characterisation of Novel Drug Modalities
Key Learning Outcomes
- Gain insight into how the therapeutic landscape has broadened beyond the traditional small molecule versus biologic divide, now including oligonucleotides, peptides, antibody fragments, fusion proteins, ADCs, and cell therapies. Understand why this diversity necessitates hybrid development and control strategies.
- Learn how oral biologic development integrates large and small molecule processes, quality attributes, and release testing into a unified control strategy, exemplified by a real-world single-domain antibody tablet programme from drug substance to final dosage form.
- Discover how novel analytical technologies, such as solid-state hydrogen-deuterium exchange combined with mass spectrometry, Raman microscopy imaging, molecular dynamics simulation, and accelerated stability assessment programme modelling, are employed to explore protein-excipient interactions and forecast degradation in solid-state protein formulations.
- Explore two innovative analytical techniques for antibody-drug conjugate characterisation: enzymatic digestion for stereospecific drug-linker quantitation, and online hydrophobic interaction chromatography combined with native mass spectrometry for swift, high-resolution drug-to-antibody ratio profiling.
Event Overview
This session by Dr Bingchuan Wei, MBA, explores the evolving comparison between small molecules and biologics, a shift that is rapidly becoming the new norm in pharmaceutical development. It focuses on the expanding class of novel modalities at the intersection of these two areas and the analytical and control-strategy challenges they pose. Oriented from the perspective of a scientist experienced in both small molecule chemistry and protein biology, the presentation uses two real development programmes at Genentech to illustrate what happens when traditional disciplinary boundaries are no longer applicable.
The first case study follows the development of an oral single-domain antibody (VHH) tablet, a product that must withstand gastric pH and proteolytic degradation, achieve meaningful GI absorption, and ultimately be manufactured through a process that begins with cell culture and ends with a tablet press. The presentation explores the evolution of the formulation from a protein solution to enteric-coated mini-tablets encapsulated in capsules, then unpacks the control strategy that results: three release points, each requiring a different blend of large molecule and small molecule testing, with conventional biologic quality attributes such as host cell protein and endotoxin appropriately de-scoped for the non-parenteral route. Two advanced analytical tools are highlighted: solid-state HDX-MS with molecular dynamics to elucidate protein aggregation at the formulation level, and ASAP modelling to predict the degradation of critical quality attributes in the solid state over shelf life.
The second case study shifts focus to antibody-drug conjugates, where the challenge lies in characterising a molecule that is both a biologic and a small molecule, with critical quality attributes including stereochemical purity of the drug-linker and drug-to-antibody ratio that demand specialised analytical solutions. The session introduces two innovations: a cathepsin-based enzymatic digestion assay that utilises the molecule’s own cleavage mechanism to quantify chiral impurities in a manner independent of the modality, and a thermally decomposable salt-based HIC-native MS workflow that profiles all DAR species, glycoforms, and minor variants in less than an hour.
Who Should Attend?
Scientists and development professionals working on novel modalities, or anyone seeking to expand their analytical and development toolkit beyond traditional small molecule or biologic frameworks.
- Analytical Scientists and Chemists working on novel modalities, ADCs, or oral biologics
- Protein and Formulation Scientists in biopharmaceutical development
- Quality Control and Quality Assurance Professionals in biologics and hybrid modality settings
- CMC and Regulatory Affairs Specialists for novel therapeutic formats
- Mass Spectrometry and Bioanalytical Scientists
- Drug Discovery and Early Development: Scientists exploring new therapeutic formats
- R&D Managers overseeing cross-modality or emerging modality programmes
Unlock Additional Educational Resources
Register today for Bingchuan’s presentation and gain access to exclusive bonus content, such as the insightful panel discussion on “Understanding The Difference Between Small-Molecule Drugs And Biotherapeutics”.
Dr. Bingchuan Wei, MBASenior Principal ScientistGenentech (USA)Bingchuan worked on the analytical development and characterisation of various drug modalities including both synthetic and biologics from early-stage discovery through to marketed products for 15 years. His scientific research is centered on leveraging advanced analytical technologies in drug development, understanding the structural-functional relationship of therapeutics, and fostering entrepreneurial spirit in the biopharmaceutical industry. He has a PhD in analytical chemistry from Purdue University, MBA from Penn State University and BS in chemistry and mathematics from Peking University.
| Presenter |
|
Brought to you by:
