Control strategy definition for a drug product continuous wet granulation process: Industrial case study

Area of Science:

• Pharmaceutical Manufacturing
• Chemical Engineering
• Process Control

Background:

• Continuous manufacturing offers advantages over traditional batch processes for pharmaceutical production.
• Implementing robust control strategies is crucial for ensuring consistent product quality in continuous manufacturing.
• Quality by Design (QbD) principles guide the development of effective control strategies.

Purpose of the Study:

• To describe the control strategy for a commercial continuous manufacturing process of immediate release tablets.
• To detail the application of Quality by Design (QbD) principles in defining this control strategy.
• To present an industrial case study of control strategy implementation for continuous manufacturing.

Main Methods:

• Multivariate experimental designs were used to identify critical material attributes (CMAs) and critical process parameters (CPPs).
• Process Analytical Technology (PAT) was implemented for enhanced process understanding and monitoring.
• Soft sensor models and in-process controls were developed to monitor critical quality attributes (CQAs) like residual moisture, assay, and dissolution.

Main Results:

• Identification of key CMAs and CPPs influencing product quality.
• Development of a specific control strategy integrating batch and continuous operations.
• Successful implementation of in-process controls and soft sensor models for real-time monitoring of granule and tablet attributes.

Conclusions:

• The defined control strategy effectively ensures intermediate and end-product quality in a commercial continuous manufacturing process.
• The study demonstrates a practical industrial application of QbD and PAT in continuous pharmaceutical manufacturing.
• This approach provides a robust framework for controlling complex, hybrid (batch/continuous) manufacturing processes.