This is also the first continuous process to be run in our new clinical manufacturing facility, which will also be used for commercial production. The process consists of three reaction steps telescoped together, all utilizing plug flow reactors. The total residence time of the three steps is 5 minutes. Two of the steps were continuously monitored via in-line IR and the final outlet was also monitored by on-line UPLC, providing a robust data-rich process. All process parameters were controlled and monitored using DeltaV automation software, through which any deviations could be diverted manually, via PAT, or based on process parameters (parametric control). Additionally, PI vision and Seeq were used for process monitoring and post-campaign data analysis across sites.
Modular equipment was fit to the chemistry, enabling extremely short residence times and efficient processing, while meeting required output quality. After collecting material out of the continuous process, the product solution was processed in batch mode, yielding isolated solid intermediate. Additional modules are still being designed and constructed to expand both the depth and breadth of unit operations that can be utilized to produce small molecule intermediates and APIs using continuous processing.