Going with the Flow: Performance Drivers for Pharmaceutical Development and How Flow Chemistry Fits into the Mix

Flow processes offer differentiated advantages in their ability to carry out challenging chemical reactions safer and often faster, with smaller footprint, and with more consistent quality. However, much of pharmaceutical development is still performed in batch processing due to constraints of existing infrastructure, convention, perceived regulatory restrictions, and availability of adequate Engineering resources to support the scale-up challenges. In this talk, two case studies will be provided to discuss advantages and opportunities for pharmaceutical processes executed in flow vs. batch.

In the first case study, the emerging use of visible light as a “reagent” for photochemically-driven organic reactions will be discussed. Photochemical methodologies enable complex organic molecules to be synthesized with catalysts that can facilitate single-electron transfer from the catalyst’s excited state. Such reactions are often difficult to selectively enable through more conventional two-electron processes. However, to develop and scale-up such syntheses, appropriate chemical reactors must be designed and validated to enable demonstration and commercial production at manufacturing sites. For this purpose, flow reactors can provide an attractive advantage to improve reactor productivity, photon flux, heat transport, and mass transport. For this reason, a laser-driven continuously-stirred tank reactor (CSTR) has been successfully implemented for developing and scaling photocatalytic chemistries.

In the second case study, the role of reactor design on selective hydrogenation chemistry will be discussed. Reactor design and operating parameters (e.g. – pressure, temperature, gas-to-liquid ratio, catalyst loading, and residence time) may have a profound impact on substrate enantioselectivity and reactor robustness. While hydrogenations in flow are ubiquitous in the petroleum industry, their adoption in the pharmaceutical industry has not been nearly as widespread. For this reason, we will describe how fit-for-purpose modeling may be used to rapidly identify optimal conditions and configurations for flow hydrogenation development and why they can be advantaged over batch operation.

Finally, a brief perspective will be provided on barriers and scale-up challenges for processes in the pharmaceutical industry. This review will cover the constraints and areas of growth for future processing capabilities in batch and flow within the sector.