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. Clearly, new methods to produce pharmaceuticals in a green, efficient, and economically friendly way are required. The IMPACTIVE project brings together the expertise and knowledge from two COST Actions and develops novel green methods to produce active pharmaceutical ingredients (APIs) using mechanochemistry as a disruptive technology. Mechanochemistry uses mechanical processes, such as ball milling, twin-screw extrusion, resonant acoustic mixing, and spray drying, to induce chemical reactions. Mechanochemistry is a solvent-free, highly efficient, environmentally friendly, and affordable disruptive technology to produce APIs. Mechanochemistry has been successfully adopted in other industries already, including aerospace, cosmetics, biomass transformation and agro-foods. IMPACTIVE is moving mechanochemistry from a promising green chemistry concept towards a credible route for more sustainable pharmaceutical manufacturing. The project has advanced the total synthesis of targeted APIs, explored multiple mechanochemical routes for producing them, and developed several new multicomponent crystal forms designed to improve key pharmaceutical properties such as solubility, stability and bioavailability. In parallel, the project has generated high-quality kinetic datasets, improved modelling tools to compare reactions across different mechanochemical setups, and strengthened the basis for scaling up from laboratory synthesis towards industrially relevant production. Progress has also been made on batch and continuous processing, on defining recovery and recirculation strategies for material and energy streams. To contribute to the green chemistry landscape, IMPACTIVE has also launched an Educational Platform. IMPACTIVE is also focused on protecting key results, and has filed 5 European patent demands, 3 of which are now published, and 2 have reached the PCT status.
