Senior Principal Scientist, Medicinal Chemistry, Early Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca

Director, Global High-Throughput Experimentation, AstraZeneca

Embedding sustainable practices into our R&D drug discovery programmes demands innovative thinking with a real sense of urgency, so we can act now to minimise resource use and waste generation. 

We recognise the strong connection between a healthy planet and healthy people. Using a science-led approach, we have set clear and ambitious targets to reduce our environmental impact across all areas of our business.

Through our Ambition Zero Carbon programme, we are on track to reduce greenhouse gas emissions from our global operations (Scope 1 and 2) by 98% by 2026 and halve our entire value chain footprint (from 2015 baseline) by 2030 on the way to a 90% reduction by 2045 (from 2019 baseline). 

Green Chemistry is a framework based on 12 principles, which encourages chemists to use greener chemicals, processes or products to maximise the efficiency of experiments, and to find new ways to reduce waste, conserve energy and eliminate the use of hazardous substances.1

Having carried out Lifecycle Assessments on the environmental impacts of many of our products, we are aware that the production of an Active Pharmaceutical Intermediate (API) – the active components of a pharmaceutical drug – often carries the largest environmental impact, especially in terms of carbon footprint. Therefore, we are always on the lookout for ways to decrease the impact of our API syntheses. One way we do this, is through the application of the principles of ‘Green Chemistry’.

Our chemists play a pivotal role in improving our sustainability as a business. We ask everyone in our laboratories to adopt a ‘greener’ mindset – to ensure that new medicines are designed and developed in the most sustainable way.

Our work, and through the collaborations we have formed with a number of leading research institutes and universities, has resulted in several new tools and techniques that can make drug design and discovery more sustainable, without sacrificing safety or effectiveness. 

Choosing the right catalyst is crucial to designing greener chemical reactions. Catalysts can enable reactions to proceed more quickly, enable chemistries that are otherwise impossible, and crucially, reduce the number of steps required to make the active component in our medicines. The right catalyst can also limit the use of environmentally harmful reagents and our reliance on precious metals.

Together with the Leonori Group at the University of Manchester, we explored the use of light as a clean, environmentally friendly reagent to develop two, novel ‘photocatalytic reactions’ to make anilines – a common synthetic building block that is widely used in drug design.

The exploration of light as a promoter is now one of the fastest growing fields in organic chemistry. It has huge potential to become an important enabling technology in drug discovery and is attracting widespread attention from across the pharmaceutical industry4. We are actively incorporating light into our R&D and have a late-stage compound in our pipeline that utilises light chemistry during the manufacturing process. Once approved, we estimate that it will save approximately 500,000kg of carbon dioxide each year versus traditional processes.5

By successfully incorporating light into more of our drug development processes we will help our labs, and our production, become more efficient and greener in the future.

In addition to finding alternative methods to accelerate chemical processes, our scientists are exploring new ways to create the ‘building blocks’ of chemical reactions that are so crucial in drug development. For example, carboxylation reactions are important in the design of new medicines (where a carboxyl group may need to be added into a drug molecule), but they typically need highly reactive, and often relatively complex, reagents. This not only increases the danger posed to our scientists and production teams, but is also not ideal for long term sustainability. In partnership with a number of leading research institutes, our chemists have successfully identified safer and more environmentally-benign building blocks that can be used within a number of our chemical processes.

Finding alternative and more sustainable building blocks for chemical reactions is hoped to transform the future of drug discovery and development. If our chemists are able to use readily available and greener materials, this will reduce the environmental footprint of the industry and protect resources for future generations to come.

Developing new ways to modify molecules late in their development can help chemists find ‘shortcuts’ to discovering the next wave of innovative medicines – by reducing time and resource-intensive reaction steps or allowing chemists to generate molecular diversity more readily. This technique has already been used to make over 50 different drug candidate molecules, and we are now applying ‘late-stage functionalisation’ as one of our Green Chemistry approaches to create a broader range of potential medicines of the future.

Although late-stage functionalisation is still somewhat in its infancy, our knowledge of how this novel technique might make drug discovery more efficient and less wasteful is growing rapidly. The use of late-stage functionalisation is hoped to revolutionise chemical synthesis across a broad range of industries, and its potential to fast-track drug discovery will become ever more evident as more powerful and reliable methods are developed.10

Not only have we demonstrated multiple examples of the application of visible light to chemical synthesis on a ‘discovery scale’, we have recently published a 'proof-of-concept’ study that uses visible light photocatalysis to produce one of our late stage development compounds, with potential for application of this technology to produce large quantities of this compound, should it be approved. This work demonstrates the improved efficiency that can be achieved through the application of this chemistry, with the approach leading to a significantly shorter and more efficient synthesis of this API.5

If you’re interested to find out how novel, green reactions are being applied beyond traditional synthetic chemistry then take a look at our article, published in Nature Reviews Chemistry, which explores their use in drug development. We have also recently published a Nature Reviews Primer on C-H activation in collaboration with world leading scientists in this field.

To achieve our goal of becoming net zero it is essential that we approach our R&D with a new and more sustainable mindset. Green Chemistry is key to this, helping chemists to design reactions and processes with improved efficiency, reduced waste and lower environmental impact. Innovation in this area is also supporting the development of new drug candidates, using novel, more sustainable methods, that are providing alternative routes for drug discovery.

We are driving chemical innovation both internally as well as in partnership with leading academic laboratories globally to develop new sustainable processes. We are also working with other industries and academics in a precompetitive collaboration called SAFECHEM to advance Green Chemistry and sustainability within chemical industries.

Green Chemistry is not only contributing to our reduced carbon footprint and sustainability goals but is proving that strategies that support a healthier planet can also lead to improved human health and the advancement of science.

How R&D is helping drive a greener future

Embracing the ethics of data and AI

Digitally transforming R&D to help improve patient outcomes

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Veeva ID: Z4-45001 Date of preparation: May 2022

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