Control Strategies in Continuous Direct Compression

Abstract

Continuous manufacturing (CM) offers the opportunity to advance the manufacturing technology used in the pharmaceutical industry wherein higher quality is assured through better process design and the ability to monitor and control quality in real-time. In CM, all the unit operations are integrated with each other which leads to differences in the methods used for process design and control. In this chapter, continuous direct compression (CDC) is used as an example to illustrate key concepts involved in the process design of continuous unit operations in an integrated CM line. For pharmaceutical products, quality is assured using a control strategy that details controls on raw material attributes, process parameters and in-process material attributes. Control strategies typically used in batch manufacturing are not sufficient for integrated continuous processes. CM requires methods to monitor relevant quality attributes in real-time, execute closed-loop control and divert non-conforming materials if needed, and a high level of automation to execute the associated control strategies. In this chapter, key considerations behind the development of in-process control (IPC) methods and associated unit operation control strategies are presented. Given that quality attributes are monitored continuously, real-time release (RTR) strategies can be implemented for products manufactured using CM. Considerations in implementing RTR strategies for drug product critical quality attributes are also presented in this chapter.