Fu, Z, et al. Exometabolome analysis reveals hypoxia at the up-scaling of a Saccharomyces cerevisiae high-cell density fed-batch biopharmaceutical process. Microb Cell Fact, 2014. 13(1):32.
The scale-up of processes is often accompanied by “scaling pains” whereby the process at large scale fails to adhere to the predictable performance observed at smaller scales. Researchers at GlaxoSmithKline observed that, despite a myriad of process adaptations that ensured that a scaled-up process was still able to produce sufficient quantity and quality product, viscosity differences between scales persisted. Thus, they sought to understand the basis of these physiological differences using metabolomics. The results identified striking metabolic differences with scale-up. These differences all pointed back to a single cause - reduced oxygen availability. The insights provide a strong example of how divergent a cells metabolism can be from laboratory to industrial scale. Further, the results provide targets for more effectively mitigating these differences to achieve successful scale up.
Metabolon results led to:
• A deeper understanding of the metabolic demands imposed by scale-up
• Specific pathways (i.e. targets) for amending/supporting scaling-up