May 8-13, 2016
The lack of an adequate scale-down model for the cell culture stages of legacy processes is an ongoing issue across the industry. This presentation will describe an existing scale-down model, the modifications made to it, and an example of the utility of the new model. The scale-down model for Process X was originally developed based on power per unit volume, with minimal modification to accommodate other input parameters. This scale-down model performed significantly differently from the manufacturing-scale process with respect to cell growth, metabolites, and productivity. For example, the productivity in the scale-down model was 3 to 4 times higher than at the manufacturing scale, and the peak viable cell density (PVCD) for the scale-down model was two times the PVCD of the manufacturing scale, while cell viability was also consistently higher in the scale-down model. There was a clear need to develop a scale-down model that takes into account additional scaling parameters and better mimics manufacturing scale to increase understanding of the manufacturing-scale process. Analysis of mixing and sparging parameters indicates that the manufacturing scale results differed significantly from the model. The scale-down model was therefore modified to reduce air flow rates, increase the total volume, and to over-sparge air early in the process to better mimic the manufacturing-scale behavior and trends. These changes resulted in a scale-down model which closely matches the large-scale growth, viability, and metabolite profiles. This scale-down model has been used to successfully screen raw materials which are known to impact the manufacturing-scale process. This improved scale-down model will enable process improvement studies, effective satellite runs, improve understanding of manufacturing-scale results, address deviations, and will help ensure robust production.
Angela Au, Davanna Marks, and Hugh Graham, "Improved scale-down model development case study for raw materials screening" in "Cell Culture Engineering XV", Robert Kiss, Genentech Sarah Harcum, Clemson University Jeff Chalmers, Ohio State University Eds, ECI Symposium Series, (2016). http://dc.engconfintl.org/cellculture_xv/125