1. A Quality-by-Control Approach in Pharmaceutical Continuous Manufacturing of Oral Solid Dosage via Direct Compaction
- Author
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Yasasvi Bommireddy, Sudarshan Ganesh, Qinglin Su, Marcial Gonzalez, Anushaa Nukala, Dan Bao Le Vo, Zoltan K. Nagy, and Gintaras V. Reklaitis
- Subjects
Computer science ,business.industry ,Estimation theory ,media_common.quotation_subject ,Process (computing) ,PID controller ,Control engineering ,Variance (accounting) ,Article ,Robustness (computer science) ,Quality (business) ,business ,Quality assurance ,Machine control ,media_common - Abstract
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.
- Published
- 2019