When looking at the environmental impact, pharma is one of the most polluting industries, causing even more CO2 emissions than the automotive sector. IMPACTIVE, funded by the European Commission, focuses on developing greener pharmaceuticals. How? With a little help from mechanochemistry, a branch of chemistry that uses mechanical forces to drive chemical reactions. To achieve this, IMPACTIVE relies on experts from academia, industries, and SMEs across Europe. Let’s introduce the various partners involved in the project and explore the tasks they are engaged in.
University of Montpellier
This is our project leader. The University of Montpellier, in France, is making sure everyone works together smoothly. This means guaranteeing an effective communication flow between the project partners. The management team also ensures the project meets its goals and objectives, and prepares all the important documents and reports for the European Commission. Alongside this, the University of Montpellier is behind the development of mechanochemistry methods in both discontinuous (batch) and continuous processing, at a small lab scale. This means they’re handling techniques like Ball Milling, twin screw extrusion and Resonant Acoustic Mixing.
Coleading the batch and continuous processing with the University of Montpellier, Radboud Universiteit, in the Netherlands, will go further in this task. Some compounds are like both hands of the body: they are the same, but a bit different and you can’t overlap them. In chemistry we call this chirality. Separating a mixture of these ‘chemical hands’ into a sample that contains just one of them is a chemical process known as deracemization. And this is Radboud University duty.
Université Catholique de Louvain
The Université Catholique de Louvain, in Belgium, will also help with the separation of right-handed and left-handed compounds from mixtures. In other words, they will work on chirality control. Our partner’s field of work is multicomponent systems, especially co-crystals. So one of their tasks will be the co-crystal formation of enantiopure compounds — just left or right hands. They will also perform further tests on a larger scale.
RWTH Aachen University
Mechanochemistry involves a myriad of techniques to generate chemical reactions using the mechanical force. One of them is ball milling, which basically consists of grinding compounds against each other, using colliding balls within a rotating reactor. At the RWTH Aachen University, in Germany, our colleagues are conducting experiments using this technique. Thanks to their contacts with industry, they can do that from the very small scales to larger ones.
Trinity College Dublin
Trinity College Dublin, in Ireland, is leading the development of multicomponent systems, such as co-crystals and salts, using mechanochemical processes. Among all the techniques to do so, our partner has a vast expertise in one of them: spray drying. It involves atomizing a liquid solution into small droplets and then drying or cooling these droplets in contact with gas. Once particles are formed, they are separated from the gas and collected. These methods are just proofs of concept, which will allow us to test and study these new mechanochemical routes towards scale-up. We must ensure everything works before building big stuff! Trinity College Dublin’s background of collaboration with industry will be vital to choose the correct path.
Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento (IST-ID)
The other protagonist in multicomponent systems development is our partner from the Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento (IST-ID), in Portugal. IST-ID is working on the synthesis of these compounds by ball milling and solution crystallisation, and contributing to its characterisation by comparing them with benchmarks obtained by solution crystallisation. The latter is a method to prepare pure chemical compounds from mixtures, by triggering the formation of pure crystals from saturated solutions.ThisAlso, and as a previous step, our partner is relying on data mining and computational analysis to establish the most promising mechanochemical synthetic strategies of these new multicomponent systems.
Center for Colloid and Surface Science (CSGI)
What is going on between molecules when they are smashing with each other? Our colleagues at the Center for Colloid and Surface Science (CSGI), in Italy, look at reactions really, really closely. The aim is to understand how atoms and molecules behave in ball mills, extruders and other mechanochemical equipment, to analyse reaction rates and optimise reactions. This involves tasks like doing numerical simulations of reactions or developing unique experimental settings to measure local reaction conditions. In fact, our partner is developing a novel form of spectroscopy. It goes down to a temporal resolution of microseconds, allowing our team to extract valuable information about the chemical reaction.
Apart from helping with molecule characterisation, our partners at BAM Institut, in Germany, also play a very important role in the modelling of the reactions. To have a coherent methodology throughout the project, they have worked on a model system to develop an experimental protocol. This systematic guide forms the bedrock for all partners within IMPACTIVE. A unified approach ensures that insights from the molecular level resonate across the project, enhancing the collective ability to harness kinetics for groundbreaking results.
OK, things work in the lab. Now, our team will ensure things also work industrially, which usually means scaling up quantities and smoothing some aspects to ensure efficiency. It’s all about developing the production processes. The team in charge of this mission will be DES Solutio, in Portugal. We plan to combine experimental findings with modelling outcomes and test the most interesting case studies on increasingly larger scales. And, as green is our favourite colour, processes will be designed to comply with the 12 Principles of Green Engineering, without forgetting the 12 Green Chemistry Principles.
Max Planck Institute für Kohlenforschung
Thanks to the existing industry collaboration from Max Planck Institute, in Germany, we will upscale ball milling processes. So we are going from grams range up to kilograms range. But this is not all they do. Our colleagues at MPI also characterise products, determine the yield of the reactions and assess their greenness. Even the resulting impurities from the mechanochemical processes will pass through the scrutiny.
Haute Ecole Spécialisée de Suisse occidentale (HES·SO)
HES·SO, in Switzerland, also participates in scaling up the most promising systems to a small pilot scale. As we said before, chemistry works in discontinuous (batch) and continuous processes. The second one will be our partner’s field in this mission. HES·SO, helped by other partners from the consortium, will be monitoring the process and characterising the compounds.
To make green pharmaceuticals we have to take a look into the whole manufacturing cycle. Technion, in Israel, will be in charge of closely monitoring all the IMPACTIVE processes, to account for environmental, health and societal impacts. This is our guiding beacon, applying life cycle assessment, techno-economic analysis, and green chemistry tools to assess the environmental impact of IMPACTIVE’s mechanochemical processes. Our partner champions the delicate balance between innovation and environmental responsibility, to achieve the perfect combination of both.
Pollution hazard control is in Taltech’s hands, in Estonia. Our partner makes sure that the LCA process conforms to pharmaceutical industry standards. This means looking at toxicity standards and making sure that the processes leave no toxic residues. Taltech has two main goals: to develop analytical methods to identify pollutants and harmful impurities, and to come up with ways to eliminate them.
Novartis, in Switzerland, helps us source materials and bring processes up to pharmaceutical industry standards. This team will assess process greenness using quantitative green metrics. This task aims to reduce the environmental impact of the production cycle by identifying potential hotspots. If we discover any problematic areas, we’ll change how we do things to stop or lower the chance of releasing harmful stuff into the environment.
MERCK, in Switzerland, is also part of the green team. That is why they have developed DOZN 2.0: Green Chemistry Evaluator, a key tool in safety and risk assessment. Actually, one of the main achievements for the last year involved applying the DOZN 2.0 Green Chemistry Evaluator to benchmark the batch process of pharmaceutical cocrystals against the Twelve Principles of Green Chemistry. This systematic evaluation ensures that the most promising processes align with principles of sustainability and minimal ecological footprint.
Agata Comunicación Científica
While cool things happen in the lab, Agata Comunicación Científica, in Spain, ensures everybody knows. Our primary objective is to make IMPACTIVE science accessible to all. This means translating the scientific language to a more general-daily-use register. To do so, the communication team uses different channels like our website or social media. And we also like to play with formats and create amazing animations or images. We can use anything to explain our science!
The IMPACTIVE project is not just about doing science but to put that science at the service of people. This means the exploitation of the results. Behind this goal is SATT Axlr, in France, who will talk to investors and industry in the field of API production. Our partner’s tasks include protecting the results with patents, developing collaborative projects with SMEs or the creation of start-ups, among others — all about technology transfer.
So now you know who we are! If you want to know more details about our work (or get in touch with any of our partners!), send us an e-mail! We’ll be delighted to talk with you.