(423d) Digital Real-Time Release Testing in Continuous Tablet Manufacturing

In traditional pharmaceutical manufacturing, the quality is assured via in-process controls and end-product testing. After approval of samples in the quality control laboratory, the batch is released to the next process step or at the end of the line for the patient. No real-time information is required for this quality by testing (QbT) approach. The implementation of quality by design (QbD) and the application of process analytical technology (PAT) have led to a paradigm change. PAT is an enabler for the evaluation of the material quality and for control actions in real-time, which are essential for continuous manufacturing. Data acquisition during the process is also required for real-time release testing (RTRT). RTRT strategies have been developed for a few unit operations and combinations thereof. However, in continuous manufacturing lines, a huge amount of data is available in addition to PAT sensors, which comes from univariate measurements and from the equipment. Residence time distribution (RTD) models can be used to match the information with the material.

In this study, for the first time comprehensive data from a fully integrated continuous manufacturing line is matched with specific amounts of product. The data are acquired from PAT tools, process equipment, and soft sensors and collected in a process control and data management platform. An RTD model of the plant and a material tracking algorithm are used to match the data with the material. At the end of the manufacturing cycle, the complete history of process conditions is digitally available for each specific amount of product. The approach was implemented and demonstrated at a Consigma 25 tableting line.