Technology Offer

Three-step solvent-free processing of API intermediate for mid-scale productivity, using flow chemistry

1. Innovation

The EU-funded project PICASCO has, for the first time*, developed a continuous 3-step solvent-free flow manufacturing of a pharmaceutically relevant API compound at industrial scale. Besides common strategies like increasing tubing diameters and flow–rates.
* to our best knowledge and reported in open literature

2. Industrial showcase & opportunity

The pharmaceutical industry has decided to undergo an industrial transformation from batch to continuous processing (until the year 2026). All major pharmaceutical companies test the implementation of continuous-flow technology, and several have brought it to pilot- and production-scale. While there is becoming routine in scaling-up single chemical processes, the operation of multi-step chemical processes in continuous-flow at larger scale is still a challenge. It is so essential to pharmaceutical industry which need in average about 8 steps to their final product, the drug or active pharmaceutical ingredient. Problems start with simple issues such starting-up the plant, which needs much more than just feeding the solutions into the system.

3. Benefits, achieved

• Process time reduction to 90 min for the whole process.
• Solvent free operation increases the productivity at maximum capacity.
• Compact fully continuous cascade multistep solvent-free mini-plant with a production capacity of 613 Tones/year of 2,6-difluorobenzyl azide and 411 tons/year of rufinamide precursor.
• Solvent free purification.
• 50% process water savings.
• The plant combines three industrially demanding process operations: Taylor flow with HCl, segmented flow with azides and high-p,T with deactivated dipolarophile.
• Business plan and market study at hand
• Cost study underway (by partner Microinnova)
The outcome comprises as well cutting-edge advantages reported before for single-reaction processes in continuous-flow:
• Faster time-to-market operation
• The novel concept of end-to-end flow manufacturing in industrial scale.
• The corresponding compact flow mini plant for the synthesis of APIs
• Productivity on-demand, reducing storage inventory and overcapacity
• Reduced costs related to reagents, quality assurance and time-savings

4. Steps to commercial success and/or benefit to society

The project includes a complete market and business case proposal carried out with the advice of ttopstart with an evaluation of commercialization strategies. Such approach makes easy to transfer the know-how from academia to industry. That is because already 7 world-relevant Companies are permanent members of the users committee: Corning, Chemtrix, Microinnova, GSK, Kobe Steel, HNP-mikrosysteme and Patheon. PICASCO overcomes the traditional batch manufacturing techniques, achieving comparable quality, but with a simultaneous improvement in efficiency, cost-effectiveness and environmental friendliness, using the last technologies e.g. a Kobelco Stacked Micro Channel Reactor (SMCR®). With continuous manufacturing, the manufacturing costs for pharmaceutically relevant compounds could be reduced by an estimated 15% to 50%, including automated production and quality assurance control, which would lead to an increased productivity, since the multistep organic synthesis will be reduced from weeks to hours.

5. Wanna know more about that?

The project is funded by the highly competitive ERC-Proof of Concept grant awarded to Prof. Volker Hessel at Eindhoven University of Technology-TUe (Netherlands), at which the larger part of the work was conducted. The piloting studies were finally done at MicroInnova’s pilot site in Austria. Nowadays Prof. Hessel works at the University of Adelaide (Australia) and contributed from here to the innovation inventory of the project. The execution was performed in both at the TUe and at Microinnova Engineering GmbH (Austria), and was led by Dr. Marc Escribà Gelonch, nowadays at the National Scientific Research Center (CNRS) in Lyon (France).