活性成分
设定值
设计质量
工艺工程
工艺优化
过程分析技术
过程开发
过程(计算)
质量(理念)
生化工程
操作点
医药制造业
过程控制
关键质量属性
灵敏度(控制系统)
先进过程控制
过程建模
计算机科学
在制品
新产品开发
工程类
业务
人工智能
哲学
营销
电气工程
运营管理
操作系统
认识论
环境工程
生物
生物信息学
电子工程
作者
Samir Diab,Charalampos Christodoulou,George M. Taylor,Philip Rushworth
标识
DOI:10.1021/acs.oprd.2c00208
摘要
Mathematical modeling of pharmaceutical manufacturing processes can provide insights and understanding regarding the key factors impacting product quality. In this study, we describe the development of a dynamic model for a stage in an active pharmaceutical ingredient (API) manufacturing process, its calibration and validation versus industrial experimental data, and its use to address three objectives: (1) assessment of process operating parameter criticality on key performance indicators (KPIs); (2) confirming whether the considered process operating space safely respected limits of critical quality attribute (CQA) impurities; and (3) finding process setpoints that can potentially improve the KPIs. Objective 1 used global sensitivity analysis (GSA) to find that only operating parameters associated with the reactor were significant. Objectives 2 and 3 used nonlinear optimization, confirming that impurity limits are respected at any point in the considered process operating space and suggesting a shifted process setpoint that could allow enhanced yield (∼4% absolute increase) and reduced impurity content (∼0.5 mol % absolute reduction).
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