Characterization of complex drug products

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Since 2012, our research activities have expanded to the development of innovative strategies for characterizing new and complex modalities of particular relevance to the (bio)pharmaceutical industry. These include monoclonal antibodies, antibody–drug conjugates, fusion proteins, oligonucleotides (ASOs, siRNAs), gene therapy products (rAAV), mRNA, and lipid nanoparticles.

Our goal is to design advanced analytical strategies, primarily based on LC, CE and MS, to effectively separate and identify synthesis-related impurities, degradation products, and post-translational modifications. We try to maintain a good balance between fundamental research and practical application.

A wide range of chromatographic modes has been investigated to tackle the challenges posed by these complex molecules, including RPLC, HILIC, SEC, IEX, HIC, IP-RPLC, and affinity LC. Below are some key research topics we have recently explored in our research:

  • Achieving ultra-fast separations of large biomolecules using ultra-short LC columns
  • Enhancing selectivity between closely related species by exploiting on–off retention mechanisms in LC
  • Developing pH-gradient and salt-mediated pH-gradient elution techniques in IEX
  • Demonstrating the benefits of bioinert columns for biopharmaceutical analysis
  • Employing capillary electrophoresis as a complementary strategy for biopharmaceutical characterization
  • Utilizing IEX to assess the encapsulation efficiency of mRNA in lipid nanoparticles
  • Evaluating next-generation sub-3 µm SEC columns for improved separation performance
  • Investigating HILIC as an alternative to IP-RPLC for oligonucleotide analysis
  • Understanding the separation of diastereoisomers in phosphorothioate-modified oligonucleotides
  • Assessing phenyl-based RPLC columns for oligonucleotide analysis without the need for ion-pairing reagents

For our research on biopharmaceutical products, we collaborate extensively with pharmaceutical companies to access challenging reference samples that serve as benchmarks for our methodologies. If you are interested in such collaborations, please feel free to contact us at davy.guillarme@unige.ch