CAPE-Lab - Computer-Aided Process Engineering Laboratory, Department of Industrial Engineering, University of Padova, via Marzolo 9, 35131 Padova PD, Italy.
Int J Pharm. 2013 Nov 30;457(1):283-97. doi: 10.1016/j.ijpharm.2013.08.074. Epub 2013 Sep 7.
The introduction of the Quality-by-Design (QbD) initiative and of the Process Analytical Technology (PAT) framework by the Food and Drug Administration has opened the route to the use of systematic and science-based approaches to support pharmaceutical development and manufacturing activities. In this review we discuss the role that latent variable models (LVMs) can play in the practical implementation of QbD paradigms in the pharmaceutical industry, and the potential they may have in assisting the development and manufacturing of new products. The ultimate scope is to provide practitioners with a perspective on the effectiveness of the use of LVMs in any phase of the development of a pharmaceutical product, from its design up to its commercial production. After an overview of the main regulatory paradigms the QbD initiative is founded on, we show how LVMs can be feasibly used to support pharmaceutical development and manufacturing activities while matching the regulatory Agencies' requirements. Three main areas are identified, wherein the use of LVMs can provide significant benefits: (i) process understanding, (ii) product and process design, and (iii) process monitoring and control. For each of them, the main contributions recently appeared in the literature are reviewed. Issues open for further research are also identified.
质量源于设计（QbD）倡议和过程分析技术（PAT）框架的引入，为采用系统的和基于科学的方法来支持药物开发和制造活动开辟了道路。在这篇综述中，我们讨论了潜在变量模型（LVMs）在药物工业中实际实施 QbD 范例中可以发挥的作用，以及它们在帮助开发和制造新产品方面可能具有的潜力。最终目的是为从业者提供一个视角，了解在药物产品开发的任何阶段（从设计到商业化生产）使用 LVM 的有效性。在概述了 QbD 倡议所依据的主要监管范例之后，我们展示了如何使用 LVM 来支持药物开发和制造活动，同时满足监管机构的要求。确定了三个主要领域，其中 LVM 的使用可以提供显著的好处：（i）工艺理解，（ii）产品和工艺设计，以及（iii）工艺监测和控制。对于每一个领域，我们都回顾了最近在文献中出现的主要贡献。还确定了需要进一步研究的问题。
