(686b) Slow Is Smooth and Smooth Is Fast: Implementation of Workflows for the Development of Processes and Equipment for the Manufacture of Critical Care Medicines

Most generic pharmaceuticals sold in the United States of America are synthesized or formulated overseas, which leaves them vulnerable to supply chain disruptions. Many of these generic pharmaceuticals are considered to be essential for modern medicine. However, due to aging infrastructure and consolidated batch manufacturing processes, there is on average 200 active shortages every year, of which, IV drugs over 50 % of the drugs on the shortage list.

The COVID-19 pandemic exacerbated the shortages experienced by hospitals and other care facilities for critical care medicines required to successfully sedate ventilated patients. As part of our effort to develop manufacturing processes for these critical care meds, ODP has developed and scaled up continuous flow syntheses for several IV-drugs on the shortage list. Kinetic modeling was employed in the design of the reactor and determination of operating conditions, with a full reaction network describing the formation of products, intermediates, and impurities being developed. Several continuous, automated processing skids were designed, built, and implemented based on process understanding gathered from small-scale experimentation. Automated control of the system and sub-system unit operations system were achieved through LabVIEW. Temperatures, pressures, flow rates, and masses were taken as inputs to control algorithms that adjusted heaters, pump speeds, and valves to allow the system to operate autonomously at steady state. This talk will focus on the workflows and strategies developed to rapidly gather, assess, and iterate on experimental and equipment design.