IMPACTIVE: Innovative Mechanochemical Processes to synthesise green ACTIVE pharmaceutical ingredients.
Prof. Lidia Tajber, Trinity College Dublin and SSPC investigator is deputy coordinator on the €8M consortium project. The project aims to address the issue of creating new methods by using mechanochemistry, which is a a solvent-free, highly efficient, environmentally friendly, and affordable disruptive technology to produce APIs.

Website: https://mechanochemistry.eu/

Challenge
The environmental impact of the pharmaceutical industry is a huge problem. The production and use of pharmaceuticals cause high CO2 emissions (52 Mtons in 2015, which is more than the automotive industry), contamination of soils, biota, and water, and even dangers to human health through carcinogenic impurities. Although there have been efforts to reduce the environmental impact of active pharmaceutical ingredient (API) production, the use of organic solvents (responsible for 75% of energy used) is still a critical step in many processes. The strict regulations implemented by the European Green Deal have caused manufacturers to move outside of the EU due to the high costs associated with reducing environmental impact. This results in supply chain fragility, which has serious consequences for crisis preparedness in Europe. Clearly, new methods to produce pharmaceuticals in a green, efficient, and economically friendly way are required.

Solution
We aim to address this issue by using mechanochemistry: a solvent-free, highly efficient, environmentally friendly, and affordable disruptive technology to produce APIs. Mechanochemistry is a term for methods that use mechanical energy to perform chemical reactions, such as ball milling, twin-screw extrusion, resonant acoustic mixing etc. Mechanochemistry has been successfully adopted in other industries already, including aerospace, cosmetics, biomass transformation and agro-foods. Now is the time to validate the use of mechanochemistry for API manufacturing, which is the goal of the IMPACTIVE project.

Impact
A goal of the IMPACTIVE project aims to validate the use of mechanochemistry for API manufacturing. Mechanochemistry has already been successfully adopted in other industries already, including aerospace, cosmetics, biomass transformation and agro-foods. Ultimately Pharmaceutical industries will have a better understanding of the environmental impact of pharmaceuticals.

To achieve this goal, the IMPACTIVE consortium has the following objectives:

• To replace at least 1 solvent-based step in the synthesis of 6 APIs from 3 different families of compounds (C-aryl glycosides, Acrolein derivatives, and Ureas and UHP moieties) by a mechanochemical alternative at a laboratory scale.
• To synthesise and characterise at least 6 multi-component systems and 3 formulation prototypes through mechanochemical pathways (in batch and in continuous).
• To model the description of the relationship between mechanochemical transformation rates and processing parameters.
• To scale up the most promising systems to small pilot scale.
• To benchmark and quantitatively assess the optimised mechanochemical processes against conventional solvent-based methods in terms of their greenness, including Life-Cycle Assessment (LCA) and techno-economical metrics.

By achieving the above objectives of the IMPACTIVE project and showing that mechanochemistry is a green, efficient, and affordable alternative to current API manufacturing methods, we will reduce environmental pollution, as well as the EU economy and supply chain stability. Recent data published by the consortium members showed that switching to mechanochemistry for the production of a single API (among those listed World Health Organisation, WHO essential medicines) can reduce ecotoxicity and CO2 emissions by more than 85%, while also reducing the production costs by 12%.

Partnerships
(Coordinator), University of Montpellier, (UOM) France, Radboud Universiteit, (RADBOUD), Netherlands, Université Catholique de Louvain (UCL) Belgium, Taltech (TALTECH) Estonia, BAM Institut, (BAM), Germany,  RWTH Aachen University (UOA), Germany,  Max Planck Institute (MPI), Germany,  Trinity College Dublin, (TCD), Ireland, Technion (TECHNION), Israel, Center for Colloid and Surface Science (CSGI), Italy,  IST-ID, (IST-ID), Portugal, DES Solutio, (DES), Portugal, Haute école d’ingénierie et d’architecture de Fribourg (HES-SO/HEIA-FR), Switzerland, France, Agata agency, (AGATA), UK, SATT Axlr, (SATTA), France, Merck, (MERCK), Switzerland, Novartis Basel, Switzerland, Johnson Matthey, (JMATTHEY), UK.