Direct LC-MS Characterization Of Glycoform Distribution And Low Molecular Weight Impurities In mAb Process From Ambr® 15 Bioreactors

By Lindsay Morrison, Charles Proschaska, Alireza Aghayee, Clint Kukla, and Ying Qing Yu

Full characterization of Critical Quality Attributes (CQAs) in biotherapeutic proteins during upstream development is often limited to a handful of high-performing cultures due to high instrument demand and consequently long core lab turn-around times. Although protein A purification or other affinity enrichment approaches are frequently used for LC-MS characterization of biotherapeutic proteins, elimination of this step reduces sample preparation complexity and time from sampling to analysis.

In this application note, we demonstrated a streamlined and robust mAb product monitoring method. The mAb fermentation samples were collected directly from an Ambr® 15 running a CHO process. The analytical method was developed on a small bench top LC-MS system, for rapid mAb glycoform confirmations and mAb purity assessments. This developed method is high throughput capable and has the potential to be a fully automated platform for mid-process intraday monitoring of CQAs.