Lessons Learned from a Scale-down Model Qualification Case Study

Cell culture process characterization studies for a protein production process were performed using a scale-down model. A Quality by Design (QbD) approach was taken in order to improve overall process understanding, with the final outcome being both univariate and multivariate acceptable ranges for each parameter tested. However, applicability of these study results to the manufacturing scale depends on the validity of the scale-down models that have been used. In this particularly complex case study, both small and pilot scale models were qualified. Evaluation of some product quality attributes required further downstream processing through scale-down purification models. As a result, qualification of the cell culture model ultimately relies on qualification with the purification scale-down model as well. The way the models were applied depends both on the product quality attribute being evaluated and the unit-operation being characterized. Our scale-down model qualification approach will be presented and challenges related to applying scale-down results to manufacturing scale will be discussed.

Key Message Bullet Points:

• A QbD approach to cell culture process characterization relies on the use of scale-down models
• Applicability of study results to manufacturing scale depends on the validity of the scale-down models that are used
• Our scale-down model qualification approach will be presented and challenges related to applying scale-down results to manufacturing scale will be discussed