Su Qinglin, Ganesh Sudarshan, Moreno Mariana, Bommireddy Yasasvi, Gonzalez Marcial, Reklaitis Gintaras V, Nagy Zoltan K
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.
School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Comput Chem Eng. 2019 Jun 9;125:216-231. doi: 10.1016/j.compchemeng.2019.03.001.
The Quality-by-Design (QbD) guidance issued by the US Food and Drug Administration (FDA) has catalyzed the modernization of pharmaceutical manufacturing practices including the adoption of continuous manufacturing. Active process control was highlighted recently as a means to improve the QbD implementation. This advance has since been evolving into the concept of Quality-by-Control (QbC). In this study, the concept of QbC is discussed, including a definition of QbC, a review of the recent developments towards the QbC, and a perspective on the challenges of QbC implementation in continuous manufacturing. The QbC concept is demonstrated using a rotary tablet press, integrated into a pilot scale continuous direct compaction process. The results conclusively showed that active process control, based on product and process knowledge and advanced model-based techniques, including data reconciliation, model predictive control (MPC), and risk analysis, is indispensable to comprehensive QbC implementation, and ensures robustness and efficiency.
美国食品药品监督管理局（FDA）发布的质量源于设计（QbD）指南推动了制药生产实践的现代化，包括采用连续制造。主动过程控制最近被视为改善QbD实施的一种手段。此后，这一进展已演变为质量源于控制（QbC）的概念。在本研究中，讨论了QbC的概念，包括QbC的定义、QbC的最新进展回顾以及对在连续制造中实施QbC所面临挑战的展望。使用旋转压片机展示了QbC概念，并将其集成到中试规模的连续直接压片过程中。结果确凿地表明，基于产品和过程知识以及先进的基于模型的技术（包括数据调和、模型预测控制（MPC）和风险分析）的主动过程控制对于全面实施QbC是不可或缺的，并确保了稳健性和效率。
