As anyone in the pharmaceutical industry knows, antibody based therapeutics are seeing tremendous growth in the field with more drugs entering the pipeline each day.  With this comes the need for analytical instrumentation that supports all stages of development, but particularly once a drug candidate has made it to large-scale production. Once in production, analytical tools to support this effort should be simple, rapid, and capable of directly measuring the drug product. However, at-line or in-line approaches to analysis are often hindered by the extensive sample prep required when directly sampling cell culture harvest material. Therefore, there remains a need for simple methods that can support product manufacturing.

Recently, researchers a Biogen Inc. reported a method that does just that. Using ZipChip™, a separations platform that uses cutting-edge microfluidic technology with capillary electrophoresis (CE) and electrospray ionization (ESI) to optimize mass spec analysis, they assessed protein isoforms and glycosylation profiles of their drug product in addition to protein titer. After sampling directly from the cell culture supernatant, the drug molecule was reduced and both light and heavy chains of the antibody were separated via microfluidic CE-ESI. The extent of glycosylation was assessed from the heavy chain and protein titer was determined from the light chain using heavy isotope controls. They obtained both pieces of information using one quick method and both results agreed with their established LC-MS and ProA titer methods!

So, what are the benefits of using the ZipChip platform for production support?

• Direct monitoring of the drug product as it is being produced. By sampling over multiple timepoints, a clear picture of how glycosylation is changing in the bioreactor can be obtained.
• Easier sample prep. By using ZipChip, an entire purification step was eliminated from the front-end sample prep saving time and money.
• It’s fast! The ZipChip separations only took about two minutes to complete and returned two pieces of information about the production process.
• It’s simple. ZipChip methods are easy to create and use in the control software. Additionally, pre-mixed reagent kits are available for target applications that eliminate the need for time-consuming method development. Together, these elements help to reduce the time between sample prep and having data in hand.

You can read about Biogen’s method for using ZipChip to monitor key quality attributes during monoclonal antibody production in a recently published article titled “Monitoring Glycosylation Profile and Protein Titer in Cell Culture Samples Using ZipChip CE-MS” in the Journal of Analytical & Bioanalytical Techniques.

Also, join us on Thursday, August 31, 2017 at 11am EDT | 8am PDT | 4pm BST | 5pm CEST to hear Dr. Seth Madren, a scientist at Biogen, discuss how they are using the ZipChip platform in their lab to characterize biotherapeutics.

By: Erin Redman, Senior Research Scientist