Application Note: Raman-based endpoint detection of a heterogeneous etherification reaction

Regulatory guidelines, from the 2004 U.S. FDA PAT framework to ICH Q8, Q9, Q10 and Q11 documents, have brought a shift to pharmaceutical processes and manufacturing…

The PAT and QbD approach described in these and other regulatory documents provides strategic guidance for a more thorough understanding of risks in pharmaceutical manufacturing and how those risks affect a product’s critical quality attributes. PAT and QbD have created opportunities for integration of real-time analyses, enabling a shift from tested-in quality to real-time quality and process measurements. In addition to the strong regulatory support, the benefits to using PAT and QbD strategies include the ability to consistently make a quality product efficiently and safely, optimized plant occupancy, and reduced costs.

From primary API production to continuous tablet coating, Raman spectroscopy has been successfully integrated in laboratory, pilot, process development and GMP manufacturing environments.

This application note describes in-line Raman spectroscopy at the pilot scale to detect the endpoint of a heterogeneous etherification reaction. Fast, real-time Raman measurements enabled automated closed-loop feed-forward/feedback control and remote process monitoring by process chemists 200 miles away.