Expert Statement: Ulrich Mayerhoeffer, Arxada

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?

When discussing flow chemistry, we often hear buzzwords or phrases such as ‘faster and safer processes’, ‘ease of scalability’, and ‘improved quality’. Nevertheless, the CDMO space in pharmaceuticals and fine chemicals is still widely dominated by batch and semi-batch processes. At Arxada, we operate a variety of both semi-batch and flow processes within our multipurpose plants at our site in Visp.

“We are strong
believers in the benefits of flow chemistry.”

Our technology selection is mainly driven by process safety, quality, sustainability, and overall economic considerations, with safety as the strongest driver towards a flow process. For us, flow chemistry facilitates the safe handling of thermally labile compounds, such as azides and nitro compounds. By minimizing the reaction volume, flow processes offer excellent heat exchange performance to control highly exothermic reactions. Within a cascading reaction set-up, the accumulation of explosive or hazardous intermediates can be minimized as they are directly telescoped and converted in the next stage of the process.
These advantages in terms of process parameter control are often also beneficial quality-wise. The strengths of flow chemistry are clearly demonstrated in reactions where the control of side product formation or the control and preservation of stereo-information are vital. Other than in semi-batch mode, flow technologies allow processes to run in steady states at the ideal reaction conditions.
At Arxada, we are strong believers in the benefits of flow chemistry. That’s why we are constantly investing in our technological development capabilities to facilitate the use of flow processing as an integral part of our CDMO service offerings.