Biopharmaceutical drugs are mainly recombinant glycoproteins produced in cell culture. These macromolecules are inherently heterogeneous structurally, most notably in terms of glycosylation. Certain structural attributes have detrimental effect on drug safety profile and therapeutic performance, and therefore, should be routinely monitored for safety and quality assurance of therapeutic proteins.
The assessment of product safety and quality through product and process analysis is the major task of the Analytics Group. The Group has anchored technologies in monitoring vital components involved in cell culture, especially amino acids, to assist medium design and optimization of the operating strategy in running bioprocesses.
Extensive biopharmaceutical product characterization is also routinely carried out at Analytics for protein aggregation, conformation and glycosylation analysis utilizing a suite of technologies consisting of MALDI-TOF mass spectrometry (MS), High Performance Liquid Chromatography (HPLC), Capillary Electrophoresis (CE), and Multi-Angle Light Scattering device (MALS) and other established biochemical assays.
In particular, a comprehensive glycan analytical platform has been built up based on the MALDI-TOF and HPLC systems for both N- and O-glycan profiling of recombinant glycoprotein drugs (IgG, EPO, IFN-γ, etc.). Additionally, the glyco-analytics platform has been applied to the study of glycosylation status of host cell lines and tissues. This enabling analytical platform now allows us to monitor many glycosylation-associated critical quality attributes (gCQAs) such as site occupancy, sialic acid types and their levels, as well as relative abundance of glycan species, to ensure the safety and efficacy of biopharmaceutical products.
The group is also developing new methods and platforms for rapid, more detailed glycosylation characterization at higher throughput to strengthen the glycomics and glycoproteomics capabilities for the development of novel drugs and biosimilars in Singapore.