The Impact of Glycosylation on Efficacy – What Does It Mean for Cost of
Goods Sold?
Half of all human proteins and 40% of all approved therapeutic proteins are estimated to be
glycoproteins (1). There are many factors that influence protein glycosylation during
bioprocessing, including cell culture parameters, media components and cell health. In Did You
Know #7, we discuss the process of glycosylation and the factors that influence this process. In
this edition of Did You Know, we discuss the impact of glycosylation on efficacy and the effect
that glycosylation has on development and manufacturing efficiencies.
The Challenge
Many different glycosylation patterns, called glycoforms, can be produced during a single
bioproduction run. Not all glycoforms are created equal – typically, one or a few glycoforms are
associated with optimal efficacy. Glycosylation impacts protein properties such as folding,
binding, stability and solubility. Lower order glycoforms – such as G0, G0F, G1, and G1F – may
exhibit altered protein properties, which may reduce complement-dependent cytotoxicity or
increase clearance from blood when compared to higher order glycoforms (2). Further,
glycosylation patterns are particularly important during development of biosimilars, as FDA
evaluates how closely the glycosylation pattern of the biosimilar matches the innovator protein
during the drug approval process.
Considering that glycosylation can affect therapeutic efficacy, development timelines and
manufacturing efficiency can be impacted by glycosylation. For example, the current cell line or
media scheme in use might not produce the desired glycosylation profile, or desirable
glycosylation profiles might be altered when attempting to scale up or switch to single-use
systems. If the desired glycosylation profile is not achieved during these steps, additional
optimization and troubleshooting efforts might prolong the development timeline. Further,
inconsistencies between bioproduction runs can negatively impact manufacturing efficiencies.
Entire bioproduction runs might be discarded if the glycosylation profile does not meet
specifications. Extended development timelines and manufacturing inefficiencies due to
inconsistent glycosylation profiles can negatively impact cost of goods sold.
Conclusions and Solutions
Process development engineers have many different modes of optimization that can be
employed to alter glycosylation patterns. Glycosylation can be addressed upstream through
glycoengineering and clone selection, or it can be addressed later in development, through media
and feed optimization. Cell-Ess® universal titer boost and optimizer is a media component that
can be added to any system to increase titer by >20% without producing undesirable
glycosylation patterns. In addition to increasing titer, Cell-Ess has been shown to increase higher
order glycoforms, which may help shorten development time. Further, Cell-Ess has been shown
to decrease variability in the overall glycosylation from run to run, which may help improve
manufacturing efficiency. Shortened development time and improved manufacturing efficiency
combined with the increase in protein output may lead to improved cost of goods sold, which is
especially critical for biosimilars.
Contact us and learn more about Cell-Ess and the benefits it provides to the bioprocessing
industry by email [email protected] or phone 1-844-Ess-Prod (377-7763).
References
1Steger
K, Brady J, Duskin M, Donato K. Literature Review: CHO versus HEK Cell Glycosylation.
MaxCyte® application note. www.maxcyte.com.
2Goetz
AM, Liu DY, Zhang Z, Shah B, Lee E, Bondarenko PV, Flynn GC. High-mannose glycans on
the Fc region of therapeutic IgG antibodies increase serum clearance in humans. Glycobiology.
2011. 21(7):949-959.