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The introduction of lean thinking and Six Sigma methodologies into the drug discovery process has become an important approach for ensuring efficient workflows while containing costs. For the compound management department at Bristol-Myers Squibb, this has resulted in a partnership with the research community to evaluate and streamline processes to enable cost-disciplined science. The authors describe the results of Lean Six Sigma approaches in the automation and informatics environment that have been optimized to support parallel processing of compounds. This new platform facilitates the rapid and simultaneous data generation from structure activity and structure liability assays. As a result of these compound management improvements, reduction of timelines and quicker decision making has been achieved in the lead optimization process.