There’s been a lot of interest recently in the study of glycans and glycoforms, such as proteins and peptides that have glycans attached to them. The analysis of glycans (also known as carbohydrates, or sometimes simply sugars) is of growing importance to sciences as diverse as pharmaceutical drug development, cancer research, stem cell research and biofuels development.In the biotechnology industry, which is of special interest to me, it’s now widely accepted that biotherapeutic protein-based drug efficacy is strongly affected by glycosylation, with scholarly articles making it as far as Nature, as this article, titled, Acceptable changes in quality attributes of glycosylated biopharmaceuticals, (viewing the abstract is free) demonstrates. There are now a number of glycoprotein therapeutics with over 30 approved glycoprotein‐based biodrugs on the market and that number is rapidly increasing. The techniques that are used in the characterization of these biomolecules are many and varied, from HPAE-PAD (Thermo Scientific Dionex CarboPac Analytical Columns) for the analysis of monosaccharides to accurate mass spectrometry (Thermo Scientific Orbitrap Fusion Tribrid Mass Spectrometer) for the ultimate in structural elucidation. One of my colleagues, Timothy Cross, recently published an excellent a nice blog post, titled, Why I Turned from Phosphorylation to Glycan Analysis, (link to post), about the techniques involved; it’s really worth a read.
This got me thinking, who can we turn to for guidance in the biotechnology field? Typically, regulatory bodies are pretty helpful; for example the European Medicines Agency has a good document that details monoclonal characterization, including glycosylation, in this downloadable PDF, titled, Pre-authorisation Evaluation of Medicines for Human Use. Furthermore, there was a recent updated guidance from the U.S. FDA for characterization of biosimilar therapies which suggests that the oligosaccharide content of glycoprotein products should be understood and monitored to ensure that it is consistent from one lot of therapeutics to another. It gets even trickier for biosimilars, as indicated by this presentation by Dr. Steven Koziowski, titled, Biosimilars – An Update Focused on Quality Considerations, (downloadable PDF), but that’s for another blog post!
I decided to identify a few of the specialist organizations that we can turn to for guidance through this analytical minefield. The first is the National Institute for Bioprocessing Research & Training (NIBRT) in Ireland and it is clear they have immense capability in this field; I visited their site which contains a fabulous bioproduction facility in miniature and my contact there, Dr. Jonathan Bones, one of the principal investigators, was an excellent host. I thought their brochure, titled, Biopharmaceutical Gylcosylation Analysis, (downloadable PDF), an excellent read of their capabilities. Another organization that has struck a chord with me is Ludger, in the UK. Unlike NIBRT, they are a commercial entity, but their specialism in glycoprofiling is somewhat similar. Furthermore, Daryl Fernandes, their Managing Director, has written a fantastic glycan overview, described in this document, titled, Demonstrating Comparability of Antibody Glycosylation during Biomanufacturing, (downloadable PDF). It’s a few years old but still really relevant and interesting.
Of course, our own in-house specialists are a great source of knowledge as in this 2.5 min video in which Julian Saba gives a great introduction to glycans in the biopharmaceutical industry.
We try to keep ahead of the analytical requirements in this community, and we even tailor products specifically to glycoscience, a great example being the recently-introduced HPLC columns for glycan analysis (Thermo Scientific GlycanPac AXR-1 columns). No doubt we’ll see more products of this type in the coming years as glycosylated proteins become an ever greater part of our lives.
The image is of an ebola virus glycoprotein.
Are you aware of other organizations within the glycoscience community that can improve the analytical experience? If so, please let us know using the comments box below.
Steve Guilfoyle, a former research physicist, is now a biopharmaceutical and pharmaceutical market development manager with a focus on customer needs in the Chromatography and Mass Spectrometry Division at Thermo Fisher Scientific Inc. Steve strives to ensure that the company better serve the chromatography consumable needs of customers in this challenging market. Following the completion of his Ph.D. from University of Salford (UK), Steve has worked in a number of roles, mostly in analytical instrumentation, from installation engineer and application scientist to sales manager. In all his roles, Steve has always strived to represent the voice-of-customer; his marketing and selling efforts have always been driven by this particular focus.
Thermo Fisher Scientific
United States
