CHAPTER 17: Current Stage of Commercially Available Glycans to Support Realization of Biologic Drugs

Glycosylation is the most visible post-translational modification of therapeutic glycoproteins and is the greatest source of their molecular heterogeneity and variability. Drug glycosylation patterns can influence their clinical performance. Given this, biopharma companies are facing increasing pressures from regulatory authorities to properly design, measure and control the glycosylation patterns of their biologic drugs. However, this is challenging. The importance of addressing these challenges is underlined by the numbers of glycosylated therapeutics being developed – in the past two years 27 of the 28 biologic drugs approved by the FDA have been glycoproteins. Fortunately, technological advances in developing better glycoanalysis methods have helped to reduce these problems over the past decade. This chapter covers the current state of commercial glycans used to support the biopharmaceutical industry. We will describe the reasons why drug glycosylation is important, give examples of serious problems with drug programs that could have been avoided through better glycoanalysis, and overview the classes, uses and manufacture of currently available glycan standards for qualitative and quantitative glycoanalysis work. Finally, we will summarize our thoughts on how glycochemists could enhance the repertoire of commercially-available glycan standards in order to aid development and manufacturing of safer and more effective biologic drugs.