A Quality-by-Control Approach in Pharmaceutical Continuous Manufacturing of Oral Solid Dosage via Direct Compaction

Area of Science:

• Pharmaceutical Manufacturing
• Chemical Engineering
• Process Control

Background:

• The pharmaceutical industry is shifting towards continuous manufacturing for improved efficiency.
• Quality-by-Design (QbD) principles are essential for comprehensive quality assurance.
• Quality-by-Control (QbD) is proposed as a complementary approach to QbD for real-time quality assurance.

Purpose of the Study:

• To demonstrate a Quality-by-Control (QbD) approach for a commercial-scale tablet press in continuous direct compaction.
• To integrate process understanding with real-time control strategies.
• To validate the effectiveness of QbC in ensuring robustness and efficiency.

Main Methods:

• Characterization of model formulation compressibility using a pilot scale tablet press.
• Implementation of a data reconciliation strategy for tablet weight on a commercial scale tablet press.
• Design of a hierarchical three-level control strategy (machine control, PID loops, data reconciliation).

Main Results:

• Successful demonstration of QbC on a commercial scale tablet press (Natoli NP-400).
• Effective reconciliation of tablet weight measurements using process knowledge.
• Validated hierarchical control strategy addressing fast process dynamics.

Conclusions:

• The demonstrated QbC approach ensures robustness and efficiency in pharmaceutical continuous manufacturing.
• Model-based techniques combined with product and process knowledge are key to successful QbC implementation.
• QbD provides a framework for developing advanced control strategies in continuous manufacturing.