Performance Guarantees and Optimal Purification Decisions for Engineered Proteins

• 成果类型: Article
• 署名作者: Martagan, Tugce; Krishnamurthy, Ananth; Leland, Peter A.; Maravelias, Christos T.
• 署名单位: Eindhoven University of Technology; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
• 刊物名称: OPERATIONS RESEARCH
• ISSN/ISSBN: 0030-364X
• DOI: 10.1287/opre.2017.1661
• 发表日期: 2018
• 页码: 18-41
• 关键词: biopharmaceutical manufacture; optimization; methodology; ECONOMICS; purity

摘要

We investigate protein purification operations conducted by biomanufacturers and pharmaceutical companies as part of their research and development efforts. Purification of these proteins involves unique challenges such as balancing the yield and purity trade-offs, dealing with uncertainty in the starting material, and estimating the impact of several interlinked decisions. We develop a Markov decision model and partition the state space into decision zones that provide managerial insights to optimize purification operations. We develop practical guidelines to quantify financial risks, and we characterize the optimal operating decisions based on specific production requirements. The optimization framework has been implemented at Aldevron, a contract biomanufacturer specializing in proteins, and has resulted in 25% reduction in the total lead times and 20% reduction in the costs of protein purification operations on average.