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Greener Pharma, Smarter Chemistry Angelini Pharma is leading the EU-funded LIFE-GREENAPI project to reduce the environmental footprint of active pharmaceutical ingredient (API) production. Anna Codazzi, William Herbert Gazzo, and Tommaso Iacoangeli explain how combining batch and flow chemistry, life cycle assessment, and collaboration with universities can help the pharmaceutical industry become more sustainable while staying globally competitive. The pharmaceutical industry plays a vital role in improving and saving lives. Yet behind every medicine lies an intensive manufacturing process, particularly in the production of APIs - the biologically active components of drugs. API production is resource-heavy, consuming large volumes of solvents, water, and energy, and generating substantial waste. For a company like Angelini Pharma, which operates a large fine chemicals plant in Aprilia, near Rome, the question became pressing: how could such processes be reimagined to reduce their environmental footprint while maintaining the highest quality standards? In 2022, Angelini Pharma began a structured reflection on how it could contribute to the European Green Deal, which calls for a 55% reduction in greenhouse gas emissions by 2030 and climate neutrality by 2050. The company identified the LIFE Programme as the natural partner - the EU’s only funding scheme dedicated entirely to environment and climate action, with an annual focus on greening the chemical sector. The answer took shape in LIFE-GREENAPI, a three-year, €2.5 million project co-funded

by the EU LIFE Programme. Launched in June 2023, the project set out to explore whether APIs could be produced with significantly lower environmental impacts. As Anna Codazzi, Global R&D Open Innovation Lead at Angelini Pharma, recalls: “The question we asked ourselves was simple: can we produce APIs with a smaller impact on the environment? That was the starting point for LIFE-GREENAPI.”

Smarter chemistry At the heart of LIFE-GREENAPI lies chemistry itself. For decades, pharmaceutical production has relied on batch chemistry, a well-established but resource-intensive method. In this approach, all reactants are loaded into a large vessel, the reaction is run to completion, and the finished product is discharged before the vessel is cleaned and prepared for the next cycle. It is a tried-andtested system, valued for its flexibility, but it also comes with drawbacks: large volumes of solvents, long reaction times, and high energy requirements, often leading to considerable waste generation. An increasingly attractive alternative is flow chemistry, where reactants are

continuously pumped through a narrow reactor, with the reaction occurring as they move along the system. This technique offers a number of advantages: greater control over reaction conditions, faster throughput, enhanced safety, and improved resource efficiency. Heat and mass transfer are far more effective in a flow reactor than in a large batch vessel, making it easier to run reactions under conditions that boost yield while cutting solvent and energy use. Long established in the petrochemical sector, flow chemistry has only recently begun to gain wider acceptance in pharmaceuticals - a shift supported by updated regulatory guidance and the industry’s growing sustainability commitments. Yet the project’s key insight was not to choose between batch and flow. Instead, it demonstrated that the most sustainable and competitive path often comes from combining the two. As Tommaso Iacoangeli, Fine Chemicals Business Project Manager at Angelini Pharma, explains: “It’s not enough to say you are more sustainable. You must also remain competitive. The innovation is learning when to use batch, when to use flow, or even when to adopt other methods

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like mechanochemistry. The best results come from choosing the right technology for each step.” The project is anchored in Angelini Pharma’s fine chemicals plant in Aprilia - a 70,000 square meter site with an annual capacity of 350–400 tons of output. Here, APIs, advanced intermediates, and original Angelini molecules are produced at scale, making it the ideal site to test greener processes with real-world impact. By “opening the box” on a historic API process, the team redesigned its multi-step synthesis, optimising traditional batch stages while introducing flow reactors where these offered advantages in energy use, solvent reduction, or yield.

Measurable impact In order to include additional outside experience, the project partnered with Leiden University in the Netherlands, which brought expertise in Life Cycle Assessment (LCA) - a rigorous method of quantifying environmental impacts across the entire production process. Key indicators included greenhouse gas emissions, electricity and methane consumption, water use, chemicals use, and waste generation. Preliminary results are striking: LIFEGREENAPI shows the potential to cut environmental impacts by up to 60% compared with baseline processes. While final numbers will be released at the project’s conclusion, improvements are already clear across solvents, water, waste, and energy. For example, solvent volumes - which can

account for up to 80% of material inputs in organic synthesis - were reduced through both optimisation and substitution with biobased, recyclable alternatives. Water usage was minimised not only by lowering volumes but also by treating and reusing process water. Energy efficiency was improved by exploiting flow chemistry’s ability to run under pressure, shifting reaction equilibria and cutting reaction times. “We discovered the best results came not from replacing batch with flow, but from combining the two approaches,” says Codazzi. “This hybrid process reduces emissions, saves resources, and creates cost advantages. It proves sustainability and competitiveness can go hand in hand.”

through green procurement, favouring partners with recognised sustainability certifications. “To tackle complex challenges like sustainability, you cannot act alone. Partnerships with academia, providers, and policymakers are essential,” notes Codazzi. As William Herbert Gazzo, R&D Funding Manager at Angelini Pharma, adds: “European projects like LIFE-GREENAPI are not only about technical results. They also build ecosystems where knowledge and resources can flow between companies, universities, and institutions. That is the real strength.” This collaborative ethos also extends to knowledge sharing. By demonstrating practical examples of sustainable chemistry, Angelini Pharma hopes LIFE-GREENAPI

“It’s not just about being greener. We need to prove that greener processes can also be efficient and cost-effective. That is what will convince companies to adopt them widely.” Collaboration matters No company can deliver a green transition alone. From its inception, LIFE-GREENAPI was designed as an open innovation project, engaging with universities, suppliers, and wider stakeholders. Collaboration with Leiden University was central, embedding environmental assessment into every stage of development. Industrial PhD programmes with Italian universities are exploring advanced fields such as mechanochemistry, which uses mechanical force rather than solvents to drive reactions. Suppliers are evaluated

can inspire others in the sector, helping to spread best practices across Europe’s pharmaceutical landscape.

Beyond sustainability While sustainability is a moral and regulatory imperative, competitiveness is the industry’s lifeblood. Developing and implementing new technologies is expensive: laboratory equipment may cost tens of thousands of euros, while scaling up to pilot plants or industrial lines requires millions. Public funding such as the LIFE Programme plays a crucial role in de-risking these investments. Angelini Pharma Fine Chemicals Business Unit, Aprilia.