Clean Batch Manufacturing with Uncertainty Management (TSE03-K)

这个NSF/EPA TSE项目解决了制药行业中新药设计和批准的环境和经济影响之间的权衡问题。药品生产决策者面临的关键问题对设计过程提出了许多要求。例如，批量操作程序应该在概念设计阶段进行优化，因为后期的改进需要昂贵的FDA重新批准。此外，性质和操作的不确定性不得降低阶段中间体的纯度，严格的纯度要求使内部回收到下一批的习惯减少。预期该项目将制订一种计算机辅助批处理发展方法，具有两个显著特点：一是旨在统一公司生产目标和环境目标的全厂问题表示；并生成数学算法来量化有关工艺和材料的不确定信息的影响。设计模型将利用概率方法来量化不确定性的影响和成本。计划在经济和生态目标之间进行最佳权衡的多时期规划框架，以促进五年规划范围内的投资决策，并为参与许可交易市场创建可持续的工厂管理方案。该项目有望显著提高一大批制药和特种化学品制造商的技术和生态能力。人们还期望，为制药业设计的框架将被发现适用于经济和环境之间的权衡被视为规范的其他工业部门。工程课程将受益于具有生态考虑的批处理过程设计课程的改进，以及通过不确定性下的过程“环境设计”的新方法，将概率方法和绿色工程的基本原理引入本科和研究生水平的设计培训。

This NSF/EPA TSE project addresses trade-off issues between environmental and economic impacts in the pharmaceutical industry for new drug design and approval. Key issues facing the decision-makers in drug manufacture place numerous demands upon the design process. For example, batch operating procedures should be optimized at the conceptual design phase, since later improvements require expensive, FDA re-approval. In addition, uncertainty in properties and operations must not deteriorate the purity of the stage intermediates, and stringent purity requirements make internal recycles to the next batch less customary. This project is expected to make a computer-aided batch process development methodology with two salient features, a plant-wide problem representation aimed at unifying the corporate production targets and the environmental objectives; and the generation of mathematical algorithms to quantify the impact of uncertain information about the process and the materials. Design models will make use of probabilistic methods for quantifying the impact and cost of uncertainty. A multi-period planning framework with optimal trade-off between economic and ecological targets is planned, to facilitate investment decisions over a five-year planning horizon, and to create a sustainable plant management scheme for participation in permission trading markets. This project is expected to make significant improvements in technological and ecological competency of a large group of pharmaceutical and specialty chemical manufacturers. It is also expected that the framework designed for pharmaceuticals will be found to be applicable to other industrial sectors where trade-offs between economics and the environment are considered the norm. The engineering curricula will benefit from course enhancements for batch process design with ecological considerations and through new approaches to process "design for the environment" under uncertainty, bringing probabilistic methods and the fundamentals of green engineering into design training at the undergraduate and graduate level.