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Level II

Industrial Biotech Case Study: Customized DOE for Process Optimization in Small-Scale Bioreactors (2020-EU-EPO-473)

Level: Intermediate


Andreas Trautmann, R&D Scientist, Lonza AG
Claire Baril, Scientist USP Development, Lonza AG


Design of Experiments (DOE) is a frequently used and time-saving tool in industrial biotechnology for optimizing microbial cultivation process parameters. Developing standard approaches for such experiments facilitate the transferability to customers as well as the comparability between similar projects.


In this case study, we show a general approach for the optimization of process parameters in small-scale bioreactors including a subsequent DOE model validation in pre-pilot scale. The software tool Custom Design in JMP was applied to generate an I-optimal response surface design with three center points. In total four continuous factors were chosen based on empirical knowledge and preliminary data from disposition runs.


One major goal of DoE approaches in industrial biotechnology is to increase yield, e.g. concentration or titer, of the final product. By applying the Custom Design in JMP we were able to increase product titer significantly. The generated model was able to accurately predict the output variable within the characterized range, even though three out of the twenty-four experimental runs were not successful. In addition, the JMP Data Exploration tools enabled a fast evaluation of the data quality as well as time-dependent factor correlations, which contributed to enhancing the DOE model.