In this webinar, the presenters covered two specific applications of advanced Mass Spectrometry (MS) for the development of complex biologics. These applications include mapping of disulfide linkages of complex biologics and the application of advanced MS for Critical Quality Attribute (CQA) mapping of a biologic in vivo.
With the increasing development of complex proteins such as certain enzymes, membrane-bound proteins, and growth factors, many of which contain a high number of disulfide bonds (DSBs), it is important to confirm the correct disulfide linkages and to verify the presence, or absence, of disulfide bond variants. Correct disulfide linkages are critical in ensuring the structure, function, stability, and efficacy profiles of a biopharmaceutical throughout its clinical development. Furthermore, a molecule’s arrangement of disulfides, essentially its conformation, is integral to its higher order structure (HOS), which is increasingly regarded throughout the industry as a part of the CQA profile. These structural CQAs must be monitored closely during the biotherapeutics’ development. For those molecules of moderate to high complexity, disulfide bond analysis is challenging, and advanced application of mass spectrometry is necessary for detailed DSB confirmation/characterization, an essential component of CQA reporting.
Advanced MS is also of great advantage in preclinical and clinical in vivo studies. The product’s MS mapping data obtained through a well-designed MS study can be used to understand the relationship between specific drug structures and clinical parameters, to accelerate and de-risk the biologic drug development program. A product’s in vivo structural integrity/similarity to theoretical in vivo can support regulatory filings and approval while evaluating potential clinical impact (safety and efficacy). This in vivo structural analysis may include disulfide mapping as well, as noted above. Complex biologics can benefit from detailed characterization in vitro and in vivo to better understand the production/platforms and structure/behavior of the molecule itself from development through clinical studies.
Dr. Mreyen holds a PhD in chemistry and has spent two years in the protein analytical field at Macquarie University and at the Australian Proteome Analysis Facility (APAF). Starting at Protagen AG in 2000 he successfully worked as a Project Manager and supported multiple customer projects in the various fields of protein characterization. He transferred and deepened his technical understanding during a time working for Shimadzu Europe, as a Product Manager for Mass Spectrometry and Life Science products. During this time, he assisted customers in pharma and biotech in Europe and Russia, before returning 2013 to Protagen Protein Services as a Head for Business Development. Since then, he has supported a large variety of international companies in their Biosimilar or NBE developments from early phases of development to Phase 3, as well as for GMP release and stability testing.
Chen Li, PhD
Dr. Li is Director of Analytic Sciences at BioAnalytix. She mainly focuses on applying advanced mass spectrometry-based approaches to help the development of complex biologic drugs. Her work has been published in over 10 peer-reviewed publications and industry papers. Prior to joining BioAnalytix, she worked at ImmunoGen for antibody-drug conjugates development. Dr. Li received her PhD from Northeastern University at the Barnett Institute, where she developed LC-MS methods for biosimilar comparison and transmembrane protein characterization.
Dr. Zhang is currently the Associate Director of Analytic Sciences at BioAnalytix. She was one of the first analytical scientists hired to apply advanced mass spectrometry-based techniques to help accelerate the development of complex biologic drugs. Her work has been published in over seven peer-reviewed publications and industry papers. Before joining BioAnalytix in 2014, she served as a Scientist at Sanofi where she focused on enzyme kinetics studies. Dr. Zhang received her PhD from Northeastern University at the Barnett Institute.