Continuous Manufacturing (CM) — also called Flow Chemistry or Micro Reaction Technology (MRT) — is a technique that has been gaining global importance over the past decade as a result of improved process control and reduced operating costs, leading to increased manufacturing profits and a competitive edge. Recent years have shown that the reason for a company to change from “batch” to “flow” have been varied, often depending on the sector, process type of interest and scale of operation. Supply chain security and improvements in process sustainability are strong emerging drivers for the adoption of CM.

With the product key, the infrastructure needed varies greatly and depends on the available chemistry, cost of goods, volumes required and the hazard profile of a transformation. The modularity and flexibility of continuous flow set-ups enables the development of small, agile production plants that can be used for the manufacture of multiple products — with easy re-configuration allowing for rapid product changeover.

Following on from this, the ease of replicating these small footprint systems represents an opportunity for manufacturers to develop a process and subsequently deliver production units across multiple countries to serve the local product demands. This is in stark contrast to the current approach of a single large-scale plant, with warehousing used to manage supply chain disruptions.
With all of these benefits, a logical question follows: Why the slow adoption of MRT?

CHEManager asked executives and industry experts to share their views on drivers as well as barriers for the use of flow chemistry and the prospect for this technology in their industry sector. We proposed to discuss the following aspects:

• In your opinion, what are the strongest drivers (success factors) of the implementation of flow chemistry processes?
• Which barriers are slowing down or impede the implementation of flow chemistry processes?
• What does it need for flow chemistry to be implemented more widely?

Flow chemistry has become increasingly important in API manufacturing over the last two decades, and even more recently, with the difficulties encountered in the supply chain during the Covid-19 crisis, and the necessity to accelerate time to market to answer patients’ needs.
Flow chemistry is particularly suitable for reactions with fast kinetics due to the increased heat and mass transfer characteristics of flow reactors. It is a very powerful technology for reactions requiring conditions difficult to meet with traditional batch reactors (e.g.: high temperature, high pressure) and opens the way to new chemical transformations with technologies that were previously complicated to scale-up (photochemistry or electrochemistry). It is also a great tool to better control the formation of unstable intermediates, increase selectivities, or produce highly energetic intermediates under safer conditions.

“Flow chemistry has become increasingly important in API manufacturing over the last two decades.”

Thanks to increased performance of these reactors, continuous processing is often performed under higher concentration and milder temperature conditions, allowing a decreased energy consumption and decreased process mass intensity (PMI). Sustainability is a key metric to be taken into consideration from early development up to commercial manufacturing, therefore technologies allowing us to reduce the carbon footprint of chemical processes are extremely attractive.
Even if the pharmaceutical industry has been slow in implementing this technology, compared with other industries, continuous processing has been used for many years in this sector (e.g.: continuous chromatography —SMB), demonstrating its robustness at manufacturing scale. Given the widespread use of batch reactors, barriers for a wider adoption of this technology remain, but recent investments in this field will result in growing applications.
Axplora, created from the merger of Farmabios, Novasep and PharmaZell, is a reliable and agile partner, with 30 years of experience in continuous processing, able to evaluate and propose the most efficient solutions for the manufacturing of APIs.