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Using a Definitive Screening Design to Increase Antibody Expression and Quality in Yeast Fermentation


Patricia Dianne McNeill, Head of Research Fermentation, Alder Biopharmaceuticals pattidimcneill
Kathy Stein, Research Associate, Alder Biopharmaceuticals
Barbara Bengtsson, Research Associate, Alder Biopharmaceuticals
Shaun Barnett, Research Associate, Alder Biopharmaceuticals
Dan Allison, Senior Director Antibody Technologies, Alder Biopharmaceuticals

The definitive screening design is a powerful tool for screening multiple factors in a cost-effective manner. The Research Fermentation team at Alder Biopharmaceuticals attempted to use this powerful DOE tool to increase antibody production in yeast by modifying fermentation media components. This presentation will show how we used JMP 11 to create the design and analyze the results of a media formulation study focusing on six individual trace metals and their impact on antibody quality and yield over time in yeast fermentations. One of the six metals studied had a strong significant impact on both quality and expression. Another metal had no significant impact, leaving four metals with varying degrees of impact. The Fit Model feature of JMP was used to create a response surface model for expression, and a different response surface model for quality. Model evaluation is critical for determining predictability. A sampling of our studies will be described to highlight correlation and the data visualization we conducted with our current working model.

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