Process analytical technology (PAT): applications to flow processes for active pharmaceutical ingredient (API) development

As flow processes are being increasingly utilized for development of active pharmaceutical ingredients (APIs), the importance of process analytical technology (PAT) in the pharmaceutical industry is growing. Here, we describe a variety of PAT tools (FTIR, on-line UPLC-MS, flow NMR) used in support of flow chemistry platforms at Pfizer as part of the Flexible API Supply Technology (FAST) initiative. A blend of qualitative and quantitative PAT approaches are described, with each method tailored to the specific aims of each individual platform. PAT is demonstrated to be beneficial for real-time process understanding and for rapid optimization of chemical reactions in the flow-chemistry space, reducing the need for off-line analytics and helping to accelerate development timelines.