Like an Olympian combining many precise steps on the journey to a gold medal, a bioprocessor develops a plan that turns substances from living cells into a therapy that raises its own accolades—saving lives. By monitoring critical metabolic parameters, Nicholas Trunfio, PhD, a research scientist at the FDA’s Center for Drug Evaluation and Research in Silver Spring, MD, and his colleagues mapped out a path to so-called “golden batches,” which meet or exceed all of the critical process parameters. Any golden-batch should produce a safe and effective product.
To test this approach, Trunfio and his colleagues used Chinese hamster ovary (CHO) K1 cells to produce an antibody. After subjecting the cultures to various conditions, the scientist measured the concentration of metabolites and cell density. Next, they calculated the rates of transport for metabolites, such as glucose and lactate. That data was used for flux balance analysis, which estimates the rate of metabolic reactions inside the cells in a culture.
Multivariant batch evolution model
Then, Trunfio’s team used partial least squares regression to model the changes in metabolites, such as ATP, being created in a culture. From this, the scientist created a multivariant batch evolution model, which was trained on data from six bioreactors. By combining all of this work, the scientist developed a batch-level model, which provides an overview of the process underway in a bioreactor.
This collection of tools can be used in various ways. For example, the scientists noted that a model of the cellular metabolism in a bioreactor can reveal the key metabolites to track during processing. As Trunfio and his colleagues emphasized, monitoring critical metabolic parameters “may result in savings during process development.”
Much like an athlete tracking her progress while training for an Olympic event, a bioprocessor can monitor key attributes on the way to producing a therapy. Picking the right attributes to assess, however, can make the difference between a failed product or achieving a gold-medal treatment.