Continuous flow reactors (CFRs) are flow cells which are optimized for the continuous production of a target compound. Small volume CFRs avoid the reaction control problems associated with scale-up to large-batch chemistry, while still allowing for process intensification through modular scale-out. Compared to batch reactors, CFRs are much more energy efficient due to their superior mixing schemes and heat transfer properties. Reactions carried out in CFRs are typically much faster than in batch and require less excess solvent—significantly reducing waste. Currently, CFRs are limited by their validation methods, which require product stream sampling and off-line analytics.

We are working with the Food and Drug Administration (FDA) to demonstrate the ability to monitor a CFR with on-line analytics and to develop a predictive model of product quality without the need for off-line validation. We have engineered a custom sampling system able to interface with continuous low-flow reactors and software to monitor and control the temperature, pressure, and flow rates of each reactor stream. Knowledge of these critical process parameters (CPP) combined with appropriate on-line process analytical technologies, such as Raman or infrared spectroscopy, yields a full understanding of the physical and chemical system able to greatly reduce the time and effort required to develop and optimize a chemical reaction for large-scale continuous production.