Raman-Based Nutrient Control in Bioprocessing Optimizes Viable Cell Density and Protein Glycation

Critical process parameters in bioprocessing include pH, dissolved oxygen (DO), temperature and agitation rate. Glucose is a critical process parameter because it affects the cell’s metabolic profile, production of waste products and post-translational non-enzymatic glycation of proteins. Glycation can also lead to generation of advanced glycation end products, which results in binding inhibition, loss of therapeutic function and, in some cases, can generate an unwanted immunogenic response. Glycation can be minimized through careful control of glucose concentration in the process. Recent research has shown that online measurements of glucose can optimize fed-batch strategies to improve cell density and titer, and increase process robustness. Continuous glucose measurements offer important bioprocess information for process understanding and enables feedback control feed conditions from process development (PD) to manufacturing.