Su Qinglin, Ganesh Sudarshan, Le Vo Dan Bao, Nukala Anushaa, Bommireddy Yasasvi, Gonzalez Marcial, Reklaitis Gintaras V, Nagy Zoltan K
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, United States.
School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, United States.
ESCAPE. 2019;46:1327-1332. doi: 10.1016/b978-0-12-818634-3.50222-8.
The pharmaceutical industry has been undergoing a paradigm shift towards continuous manufacturing, under which novel approaches to real-time product quality assurance have been investigated. A new perspective, entitled Quality-by-Control (QbC), has recently been proposed as an important extension and complementary approach to enable comprehensive Quality-by-Design (QbD) implementation. In this study, a QbC approach was demonstrated for a commercial scale tablet press in a continuous direct compaction process. First, the necessary understanding of the compressibility of a model formulation was obtained under QbD guidance using a pilot scale tablet press, Natoli BLP-16. Second, a data reconciliation strategy was used to reconcile the tablet weight measurement based on this understanding on a commercial scale tablet press, Natoli NP-400. Parameter estimation to monitor and update the material property variance was also considered. Third, a hierarchical three-level control strategy, which addressed the fast process dynamics of the commercial scale tablet press was designed. The strategy consisted of the Level 0 built-in machine control, Level 1 decoupled Proportional Integral Derivative (PID) control loops for tablet weight, pre-compression force, main compression force, and production rate control, and Level 2 data reconciliation of sensor measurements. The effective and reliable performance, which could be demonstrated on the rotary tablet press, confirmed that a QbC approach, based on product and process knowledge and advanced model-based techniques, can ensure robustness and efficiency in pharmaceutical continuous manufacturing.
制药行业正在经历向连续制造的范式转变，在此背景下，人们对实时产品质量保证的新方法进行了研究。最近，一种名为“控制即质量”（QbC）的新观点被提出，作为实现全面的“设计即质量”（QbD）的重要扩展和补充方法。在本研究中，在连续直接压片过程中，对一台商业规模的压片机展示了一种QbC方法。首先，在QbD指导下，使用中试规模的压片机Natoli BLP - 16，对一种模型配方的可压缩性有了必要的了解。其次，基于这种了解，在商业规模的压片机Natoli NP - 400上，使用数据协调策略对片剂重量测量进行协调。还考虑了用于监测和更新材料特性方差的参数估计。第三，设计了一种分层三级控制策略，以应对商业规模压片机的快速过程动态。该策略包括0级内置机器控制、1级用于片剂重量、预压力、主压力和生产率控制的解耦比例积分微分（PID）控制回路，以及2级传感器测量的数据协调。在旋转压片机上可以证明的有效且可靠的性能，证实了基于产品和过程知识以及先进的基于模型的技术的QbC方法能够确保制药连续制造中的稳健性和效率。
