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Implementation of a 10-Factor Definitive Screening Design for the Identification of Key Parameters Controlling a Two-Step Chemical Reaction

Sandrine Garcia, Synthetic Chemist, GlaxoSmithKline

The last stage of the synthesis of a pharmaceutical drug is a complex process involving two sequential chemical transformations resulting in a large number of parameters that may affect the chemistry. Ten critical parameters were identified as potentially having an effect on the reaction and studied in a definitive screening design (DSD) to determine their impact on the formation of the desired product. The DSD was chosen over a classical design because, for a similar number of experiments, the main effects can be unambiguously identified and curvature can be estimated. This approach minimised the resources required for a rapid understanding of the critical few effects controlling the chemical process. The setup and analysis of the design will be discussed to demonstrate how this enabled the identification of two parameters as having a significant impact on the outcome of the process. This provided the project team with the confidence to determine the operating ranges for those parameters and specify key control points.

Discovery Summit Europe 2015 Resources

Discovery Summit Europe 2015 is over, but it's not too late to participate in the conversation!

Below, you'll find papers, posters and selected video clips from Discovery Summit Europe 2015.