CDER, FDA, Silver Spring, Maryland, USA.
Biotechnol Bioeng. 2010 Feb 1;105(2):285-95. doi: 10.1002/bit.22529.
Implementing real-time product quality control meets one or both of the key goals outlined in FDA's PAT guidance: "variability is managed by the process" and "product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions." The first part of the paper presented an overview of PAT concepts and applications in the areas of upstream and downstream processing. In this second part, we present principles and case studies to illustrate implementation of PAT for drug product manufacturing, rapid microbiology, and chemometrics. We further present our thoughts on how PAT will be applied to biotech processes going forward. The role of PAT as an enabling component of the Quality by Design framework is highlighted. Integration of PAT with the principles stated in the ICH Q8, Q9, and Q10 guidance documents is also discussed.
实施实时产品质量控制符合 FDA 的 PAT 指南中概述的一个或两个关键目标：“通过过程管理变异性”和“可以准确可靠地预测在为所用材料、工艺参数、制造、环境和其他条件建立的设计空间内的产品质量属性”。本文的第一部分介绍了 PAT 概念及其在上下游加工领域的应用概述。在第二部分中，我们介绍了用于药物产品制造、快速微生物学和化学计量学的 PAT 实施的原则和案例研究。我们进一步阐述了我们对 PAT 将如何应用于生物技术工艺的看法。强调了 PAT 作为质量源于设计框架的一个支持性组成部分的作用。还讨论了 PAT 与 ICH Q8、Q9 和 Q10 指导文件中规定的原则的集成。
