Sustainable medicines development and use: Challenges and opportunities in the sustainable production of active pharmaceutical ingredients

Unofficial AI-generated summary based on the public title and abstract. Not an official translation.

🔬研究者:Provides a concise overview of LCA and PMI applications in API production, useful for understanding environmental hotspots in pharmaceutical supply chains.

🏢実務担当者:Offers actionable insights on solvent recycling and process design to reduce carbon footprint, relevant for corporate sustainability teams in pharma.

🏛政策担当者:Highlights the need for regulatory support to promote circular economy practices in pharmaceutical manufacturing, aligning with green deal policies.

The development of medicines has had a positive impact on the quality and longevity of our lives, and it is of central importance to society that we maintain and enhance our ability to treat disease. However, to continue to deliver life-changing medicines for patients, we must minimize the impact of these activities on the planet. A shared blueprint for peace and prosperity for people and the planet, now and into the future, has been outlined by the UN in a collection of 17 sustainable development goals (SDGs).1 It is self-evident that the production and development of medicines, like every other commercial enterprise, will have to play its part in ensuring that these goals are met. The sustainable production of medicines is a very broad topic, encompassing equitable access to healthcare, ethical research and production practices and product environmental stewardship, to name just a few. This commentary centres on the key environmental impacts of active pharmaceutical ingredient (API) production—which can account for a significant percentage of the overall environmental footprint of a medicine (vide infra)—and highlights activities and practices that help to minimize this footprint. In the production of medicines, synthetic chemists and process engineers have always been conscious of developing the most efficient processes, in terms of use of resources and cost. However, since the advent of ‘Green Chemistry’, these considerations have become ever more central.2 To this end, we employ multiple tools and metrics to help us understand and quantify our environmental footprint.3, 4 However, arguably, the most important of these is lifecycle assessment (LCA). We employ this standardized, science-based methodology to assess the magnitude and significance of key environmental impacts, for example, global warming potential, ozone depletion, resource intensity and freshwater ecotoxicity. This approach can be applied right across the pharmaceutical value chain, from raw material extraction to use by the patient. Employing a holistic tool such as LCA ensures that we take a ‘systems level’ viewpoint, thus avoiding burden-shifting, where one impact is reduced but another impact is increased or created in its stead. The LCA approach also allows us to identify ‘hotspots’ of environmental impact, empowering us to make targeted improvements, allocating the greatest resource to the areas of most concern. According to a WHO report in 2019, global health spent as a percentage of GDP is increasing year-on-year worldwide, while the number of new drugs gaining approval each year is also following an upward trajectory.5 Due to an increasing number of regulatory requirements around sustainable production, it is ever more important that environmental impacts are decoupled from the manufacturing processes of medicines. Climate change, impacted biodiversity and pollution threaten the long-term survival of many species on this planet, including our own. In absolute terms, the pharmaceutical industry is considered a ‘medium-impact’ sector.6 However, in order to address climate change, pollution and loss of biodiversity, every industry needs to take responsibility for the environmental impacts of their business activities. There is increased momentum from governments to implement policy proposals under the banner of a ‘Green New Deal’ to facilitate the transition to low carbon, low waste, zero-pollution societies. For example, the EU has included the European Green Deal as one of six priorities7 and has recently recognized the challenges of the Environment Action Programme and the ambition for zero pollution.8 The United States has also introduced legislation known as the Inflation Reduction Act, pledging over $350 billion dollars of investment over the next 10 years to reduce emissions.9 The recent publication of the pharmaceutical strategy for Europe makes clear reference to the ambitions articulated in the EU Green Deal and outlines specific initiatives to embed environmental sustainability in legislative instruments relevant to the Pharma Industry.10 But where are the challenges and opportunities in small molecule APIs? APIs are manufactured through multi-stage, often complex synthetic processes. These processes involve a wide variety of chemical reactions that are necessary to ‘build’ the API. Chemical reactions are energetic processes bound by the physical laws of thermodynamics. To put it plainly, the reactants must be reactive, otherwise they may not react in a beneficial manner. Substances that are highly reactive or have the potential to be highly reactive under specific conditions will invariably be classed as highly hazardous due to their inherent physical and chemical properties. Hazardous chemicals may be toxic, bioaccumulative, persistent and mobile in the environment and are controlled under legislation to protect people and the environment. However, synthetic organic chemistry, the scientific discipline employed to build ‘small molecule drugs’, often requires the use of hazardous chemicals and solvents. The distinction here between Hazard and Risk is particularly relevant, because when appropriate controls, safety measures and fail-safes are ‘designed-in’ to a process, even the most Hazardous materials can pose minimal Risk to the environment or to the people operating the process. In process development, we follow what has become known as the ‘waste hierarchy’ approach: prevention, reduction, recycling, recovery and as a last resort, disposal. The preference is for prevention, or avoidance of the use of a particular material. But sometimes, this is not possible. Currently, we depend on oil-derived compounds to produce many of our solvents and starting materials. This is likely to be the case for the foreseeable future, so we must endeavour to reduce and recycle these precious materials where possible, while we invest in research to develop alternatives. Resource efficiency is a cornerstone of chemical process development, and we make sure that our processes are as ‘mass efficient’ as possible. To measure this, we use a metric known as process mass intensity (PMI). This number is the sum of the masses (kilogram) of all the materials required in a chemical process to produce 1 kg of desired API; by applying this metric, we strive to minimize the amount of waste that we generate per kilogram of API produced. Despite its simplicity, there is a welcome correlation between reduction in PMI and carbon footprint reduction. As process chemists, we can realize reductions in waste in several ways. By simplifying the synthesis of the API through reducing the number of chemical steps/transformations, we can minimize the amount of solvent and reagents (and therefore raw materials) we use to run our chemical reactions. This can increase the chemical yields and throughput of our processes to develop more efficient work-up and isolation, reducing the number of unit operations required as well as the volumes of solvent used. LCA data for the production of oral solid dose drugs have shown us many times that API production is the largest contributor to the carbon footprint. The large footprint for API production is largely down to the ‘single use’ and incineration of solvents. Therefore, one way to reduce waste and environmental impact significantly is to use the same solvent multiple times, that is, solvent recycling. Solvent recycling and reuse is an area of much untapped potential in API production. It has been an industry-standard approach in pharmaceuticals, to incinerate the bulk of the waste produced in chemical processes, although there are many exceptions where solvent recycling is carried out for certain stages of API processes. Accepting concerns for the potential toxicity of the waste streams, part of the reason for this practice was that, historically, as well as there being much less focus on the circularity of chemical processes, the technology required to separate complex waste streams was also underdeveloped. However, with more sophisticated separation science, together with the application of computational modelling, the isolation of high purity solvent suitable for reuse is now a possibility for relatively complex mixtures, providing safe, economic and environmentally viable access to more circular chemical processes. To this end, it is enabling us to ‘bake-in’ simplified recovery of materials by ‘beginning with the waste in mind’. For example, where possible, reactions should use a single organic solvent, with post-reaction operations (e.g., work-up and isolation) also using only this solvent plus another immiscible solvent—water being the most common—thus enabling more straightforward recycling and reuse. With appropriate testing and controls in place, widespread solvent recycling in API production processes has the potential to dramatically reduce the carbon footprint of API production. As an industry, we need a collective change of mindset to a point where we no longer refer to waste solvent but speak instead of used solvent, highlighting the inherent societal value of the material and its potential for reuse. Even in cases where the quality of solvent recovered is not appropriate for the production of medicines, the solvent could find use beyond the pharmaceutical industry. The use of certain bio-renewable solvents, generated from agricultural waste products, could also lead to low carbon, or even carbon-negative API production processes. Apart from solvent recycling, what else could be recycled? It may not be apparent to the reader, but the pharmaceutical industry often employs significant quantities of precious metals, for example, palladium, rhodium and ruthenium as catalysts to carry out our chemical reactions. One way to consider these catalysts is that they facilitate reactions; they are ‘breakers’ of weaker chemical bonds in the starting materials and ‘formers’ of materials with stronger bonds in the products. T

• openalex https://doi.org/10.1111/bcp.16279first seen 2026-08-02 18:25:09