How To Overcome Process Scale-Up Challenges Using Process Analytical Technology (PAT)

Process Analytical Technology for Scale-up

Process Analytical Technology

During Part I of his two part The Role of Process Analytical Technology (PAT) in Green Chemistry and Green Engineering online seminar series, Dominique Hebrault discussed scale-up challenges faced today by chemists and engineers.  Too often, offline sampling methods – mostly chromatographic methods such as High Performance Liquid Chromatography (HPLC) or Gas Chromatography (GC) – are used to monitor processes which fail to resolve common issues like reaction monitoring, poor mass balance, delayed initiation/reaction stalled, and loss of yield/by-products.  From a reaction engineering standpoint, obtaining heat mass balance information and preliminary kinetic data can be difficult using traditional offline methods during process scale-up.  Forming the final solid can be challenging using traditional offline methods, including filtration/drying a bottleneck, excessive washing, polymorph inconsistency, and batch to batch variability can be difficult.

Dominique presents several case studies on how process chemists and engineers have overcome challenges in process scale-up using Process Analytical Technology.  In the first case study, Dominique discusses how reaction calorimetry analysis was used in specialty chemical manufacturing to acquire process safety parameters to make the chemical process safer, greener, and more economical.  In the example Dominique presented, reaction calorimetry was used to overcome thermal accumulation which is a process safety hazard, shortened the process reaction time, and decreased the amount of solvent wasted.

The next case study discussed by Dominique was regarding inline analysis of the impurity effects on crystallization at AstraZeneca PR&D in Macclesfield, United Kingdom.  AstraZeneca PR&D used FBRM inline particle characterization technology to make studying the impact of impurities on crystallization kinetics a greener process.

The final example presented involved the use of real time chemical reaction monitoring for grignard reaction formation at Pfizer PR&D in Groton, CT.  Dominique discusses how Pfizer used real-time composition monitoring of reaction initiation, accumulation, and kinetics in order to optimize process performance and process safety.

If you would like to learn more about the use of Process Analytical Technology (PAT) for green chemistry and green engineering, I invite you to view Dom’s presentation, The Role of Process Analytical Technology (PAT) in Green Chemistry and Green Engineering, which is now available on-demand.