| Mammalian cell-culture processes require close monitoring of process and operating parameters to ensure reproducibility of the harvested product. Quality by design (QbD) with process analytic technology (PAT) is a paradigm encouraged by the FDA to shift biopharmaceutical focus from off-line sample analyses to on-line and at-line analyses for data collection and process validation. Using off-line analysis technologies, a design of experiments (DOE) was utilized to obtain measurements associated with different initial nutrient concentrations and operating temperature shifts. Investigation into the design space for a small-scale cell-culture process and optimization of that defined design space was performed to gain further process understanding. The optimal degree of mid-course temperature reduction after sufficient cell growth was determined to be between 3 and 6°C. Predictive models were built from near-infrared spectroscopy (NIRS) to actively and accurately monitor the metabolite concentrations however the harvested antibody titer measurement models require a larger dataset. |
