(92e) Continuous Manufacturing at Commercial Scale: Three Step Reaction Telescope with PAT & Advanced Automation

Pfizer’s approach to continuous manufacturing, Flexible API Supply Technologies (FAST), has been developing technology and processes over the past 7 years, as well as bringing new facilities online to manufacture at scale, for our small molecule drug substance portfolio. A modular design approach was taken to de-risk scale-up and utilize the same modular equipment across our global manufacturing facilities. As of early 2024, our internal kilo lab manufacturing facility in Groton, CT was approved for GMP use and since then has been used for two campaigns. This work will describe the scale-up, implementation of custom modules, incorporation of on-line and in-line process analytical technologies (PAT), and fully integrated automation through DeltaV to produce a drug substance intermediate for our portfolio.

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.