Recent Advances in Biologic Therapeutic N-Glycan Preparation Techniques and Analytical Methods for Facilitating Biomanufacturing Automation

Post-translational modification such as N-Glycosylation on biologics during the production of monoclonal antibody (mAb) based therapeutics is a critical quality attribute that dictates safety and efficacy. Variability is introduced in the cell culture process which influences, the glycosylation pattern which is known to be highly heterogenous and must be tightly controlled during the manufacturing process. Techniques have been developed for glycan screening through the use of new denaturation techniques; deglycosylation, fluorescent labeling, and analysis coupled to state-of-the-art tools consisting of multi attribute methods and multi attribute chromatography. In this review, we delve into advances within sample preparation techniques that allow for rapid and robust sample preparation as well as how these techniques are being used for innovative at-line high-throughput screening and PAT focused systems. Finally, we foresee how these advances will influence current manufacturing practices and enable bioprocess automation. The future state of biomanufacturing looks to decrease process costs while increasing process understanding and quality for novel biologic candidates and biosimilars