Safer, scalable pharmaceutical manufacturing with flow chemistry
As pharmaceutical production methods continue to evolve, flow chemistry is emerging as a safer, more scalable and selective alternative to conventional batch manufacturing.
Katrin Schmidt, Business Development Manager EMEA, Evonik
The pharmaceutical and fine chemicals industries are facing rising pressure to adopt production methods that are faster, safer and more flexible. This shift is being driven by growing global demand, stricter quality requirements and the need for more reliable, modernized manufacturing operations. Increasingly, manufacturers are turning to continuous applications – often referred to as flow chemistry in the context of smaller, flexible set-ups typical for pharma and fine chemicals -, with industry surveys indicating that more than three quarters of pharmaceutical manufacturers are already using, or plan to implement, continuous technologies within the next five years.
The rising interest in flow applications comes from an increase in pressure placed on producers at all stages of production. From early-stage clinical trials to commercial-scale manufacturing, producers are simultaneously juggling speed capabilities, quality, and regulatory compliances - all while managing hazardous substances, highly exothermic reactions, and growing sustainability expectations.
Traditionally, many active pharmaceutical ingredients (APIs) have been produced using batch processes. Whilst this has historically been an effective method of production, modern pain points have shown that batch manufacturing comes with its limitations when scaling reactions, particularly those involving highly exothermic or hazardous substances. Long cycle times, inconsistent heat and mass transfer, and limited real-time process control can also introduce inefficiencies and operational risk, especially as molecules become more complex.
A major accelerator for the recent surge in interest is the finalization of ICH Q13 guidelines (2022/2023), in which the FDA and other regulatory bodies formally recognized continuous production for both drug substances and drug products.
As the industry shift towards more variable production models – especially in countries such as China and India – manufacturers are seeking processes that support rapid development and safer handling of challenging reactions. Improved safety, enhanced selectivity and better performance are often highlighted as key advantages, as these translate directly into commercial value. Producer in Europe and the U.S. also mention flexibility as driver for implementing new processes.
One technology increasingly addressing these challenges is flow chemistry, also known as continuous processing. Flow chemistry enables chemical reactions to take place continuously in controlled environments such as, for example, tubular and micro reactors, allowing for real-time quality control, shorter throughput times, and greater process reliability.
These characteristics make flow chemistry especially well suited to reactions that are difficult or risky to perform in batch. Improved heat dissipation and controlled reaction volumes enhance safety, while steady-state operation can reduce variability and shorten throughput times. For pharmaceutical manufacturers, this translates into improved process reliability and reproducibility, and more efficient use of raw materials and energy. This can lead to safer production, better selectivity and increased performance.
Flow chemistry also offers a scalable pathway across the production chain as processes can be scaled up to larger quantities by numbering up, this means using multiple of the small tube reactors in parallel, or sizing up, when increasing the size of the reactor.
As flow chemistry becomes more widely adopted, the supporting technologies must advance in parallel. Catalysts are especially critical because continuous processes rely on catalysts with well-defined particle sizes, consistent activity, and reliable performance. The majority of existing catalysts for batch processes as well as larger continuous processes are either too small or too big in particle size to be applied into the small fixed bed tubes often used for flow chemistry. To overcome this issue Evonik launched the flow-optimized NOBLYST F series of precious metal catalysts, developed specifically for microreactor systems. With particle sizes of 200 and 600 micrometers, the range ensures optimal flow and high reactivity, particularly useful for pharmaceutical manufacturers transitioning from batch to continuous processes.
Beyond pharmaceuticals, similar process requirements are driving interest in flow chemistry across agrochemical and fine chemical manufacturing, where safety, selectivity, and scalability are equally critical. As regulatory requirements become more demanding and supply chains become more globalized, flow chemistry offers a compelling route to more resilient and efficient manufacturing models. As the industry continues to evolve, flow applications are set to become the standard for next-generation pharmaceutical production.
