CHEM21

Chemical manufacturing methods for the 21st century pharmaceutical industries
Chemical manufacturing methods for the 21st century pharmaceutical industries

FACTS & FIGURES

Start Date
End Date
Call
IMI1 - Call 4
Grant agreement number
115360

Contributions
IMI Funding
9 829 638
EFPIA in kind
13 871 772
Other
3 009 396
Total Cost26 710 806

Summary

The CHEM21 project plans to generate a range of methods to make the drug development process more environmentally friendly. What’s more, as well as being good for the planet, the methods developed by CHEM21 will also help the pharmaceutical industry to cut costs, resulting in cheaper medicines for patients.

Towards more sustainability in drug manufacture

Today, drug manufacture often requires 100 kg of materials to produce just 1 kg of active ingredient. This inefficiency means that many products require long lead times and large facilities for their production and to deal with any waste materials. This is not just bad for the environment; medicines produced in this way are expensive to develop and produce.

Meanwhile, another emerging issue for the pharmaceutical sector is the scarcity of precious metals, like platinum, that are essential in the synthesis of many drugs but are being depleted at alarming rates.

Solving these problems will require a major revision in the way drugs are synthesised.

Smarter synthesis

CHEM21 will link leading academics in the field of green chemistry with scientists working in drug synthesis in industry to tackle the challenges found in the commercial manufacture of drugs.

Specifically, the CHEM21 project aims to generate a range of technologies for medicines manufacture that are demonstrably more sustainable that existing methods. Part of the project will be devoted to designing catalysts based on common metals (such as copper, iron and nickel) instead of the rarer and more expensive precious metals used now. The team also aims to reduce the amount of solvent used and develop methods that favour starting materials that result in less harmful waste. An additional aim of the team is to provide new tools for medicinal chemists which are greener and are robust for scaling up.

Elsewhere, the project plans to boost the use of enzymes as catalysts and to investigate what steps are needed to implement synthetic biology for the sustainable production of more complex molecules.

In addition to promoting green and sustainable methodologies among current medicinal and process chemists, CHEM21 wants to make ‘green’ drug production second nature for the next generation of scientists in this area. To this end, the project will develop and disseminate educational material, case studies, and reviews and trial them in selected universities and EFPIA companies.

Cheaper medicines for patients

Inefficient production processes and the use of rare precious metals raise the costs of drug production. By making drug production more efficient and swapping expensive materials for cheaper alternatives, CHEM 21 will help to lower the cost of medicines.

Achievements & News

CHEM21 contributes to Manchester MOOC
September 2017

IMI’s CHEM21 project has contributed strongly to a massive open online course (‘MOOC’) on industrial biotechnology run by the University of Manchester. The course has six modules – three on the core principles of industrial biotechnology, and three on specific applications. All modules comprise a mixture of recorded presentations, videos, reading material and multiple choice tests. CHEM21 is devising new, more environmentally friendly ways of synthesising medicines, and scientists from the project were heavily involved in the design of the course. As a result, the sustainability principles underpinning CHEM21’s work are integrated into the entire course, particularly in the module on pharmaceuticals. The course was launched in July and the organisers hope that the bite-sized, modular nature of the course will make it attractive to both undergraduates and existing professionals who are using it as part of their continuing professional development.

CHEM21 method could cut production costs of essential anti-fungal medicine
Scientists from the IMI project CHEM21 have developed a new, more efficient way of producing flucytosine, a medicine used to treat a common and often deadly fungal form of meningitis in people with HIV / AIDS. The new method, which is described in a paper in Organic Process Research & Development (OPR&D), is expected to decrease drastically costs of production, and so make the medicine more affordable for the many people with HIV/AIDS who live in low income countries. ###Flucytosine is very expensive, as its patented manufacture involves carrying out a sequence of four chemical reactions. That could now change thanks CHEM21 scientists from the University of Durham in the UK, who have cut the number of reactions needed from four to one. Because it involves just one selective reaction instead of four, the new method uses significantly less energy and raw materials and produces less waste than conventional techniques to manufacture flucytosine. It is also less expensive. Pharmaceutical company Sanofi, which is also part of CHEM21, contracted MEPI, a French non-profit association, to investigate ways to scale up the process. With input from scientists from Durham and Sanofi, MEPI succeeded in setting up a small reactor capable of producing 1 kg per day of raw material. The next challenge will be for the team at Sanofi to transform the raw material into an active medicine that meets international standards. The University of Durham and Sanofi will also work on a technical and economic evaluation of the process. Meanwhile, the University of Durham has applied for a patent for the technique. The hopes of the team are summed up in the closing paragraph of the OPR&D paper: ‘We envisage that this one-step low cost synthesis of flucytosine will help to raise awareness of the neglected [cryptococcal meningitis] health epidemic and ultimately contribute to meeting the urgent requirement for large quantities of flucytosine for low income nations.’ (February 2017)

CHEM21 launches a new online training platform
Interested in the greening of the drug development process? Don’t miss the new online training platform which was launched by IMI’s CHEM21 project as part of their recent workshop ‘Practical Aspects of Green Chemistry in the Pharmaceutical Industry’. ###The platform comprises a range of free, shareable, and interactive educational and training materials created to promote the uptake of green and sustainable methodologies, with a particular focus on the synthesis of pharmaceuticals. This online resource is supplemented by a book, Green and Sustainable Medicinal Chemistry, edited and authored by CHEM21 consortium members and collaborating external experts. Available in both hardcopy and electronic format, the book addresses current challenges in modern green chemical technologies and sustainability thinking. It covers a broad range of CHEM21 topics, providing an overview of the key green chemistry tools, guidance and considerations aimed at developing greener processes, as well as cutting-edge synthetic methodologies. IMI’s CHEM 21 project is Europe’s largest public-private partnership dedicated to the development of manufacturing sustainable pharmaceuticals. One of the primary aims of this project is to promote the uptake of green and sustainable methodologies and to embed them in everyday practice. (July 2016)

CHEM21 workshop on green chemistry in the pharmaceutical industry
IMI’s CHEM21 project will hold a workshop entitled ‘Practical aspects of green chemistry in the pharmaceutical industry’ in London, UK on 13-15 June 2016. This highly interactive workshop will be delivered by CHEM21 academics and industry experts in the field. ### It will involve group work, problem solving exercises and seminars to explore a broad range of cutting-edge case studies and industrial examples on greening the synthesis of active pharmaceutical ingredients (APIs). The workshop is free and is open to students, academics and industrialists. Places are limited and will be allocated on case by case basis – details of how to apply to take part can be found on the CHEM21 website. The goal of the CHEM21 project is to generate methods to make the drug development process more environmentally friendly.

CHEM21 scientists go green to create chemicals
July 2015 - Austrian scientists working on IMI’s CHEM21 project have successfully used yeast and bacteria to generate complex molecules such as carotene and violacein. They achieved this by inserting up to nine genes into yeast, which allowed the yeast to carry out the series of reactions needed to synthesise these molecules in parallel. ###Scientists have inserted foreign genes into yeast before. However, to insert so many genes successfully is a real achievement, and the scientists, who work at the Austrian Centre of Industrial Biotechnology, have filed a patent for the method used. The researchers’ findings are published in a paper in Chemical Communications. The team is now looking at ways of increasing the number of genes inserted to constitute biosynthesis pathways for valuable products. CHEM21’s goal is to develop new, more sustainable ways of synthesising medicines, as current methods can be energy and resource intensive and require the use of rare substances such as precious metals.

How green are your reactions? CHEM21 delivers toolkit to find out
April 2015 - The CHEM21 project has developed a unified metrics toolkit to comprehensively evaluate the sustainability of chemical and bio-chemical reactions. Details of the toolkit are published in the journal Green Chemistry. The toolkit uses a blend of both qualitative and quantitative criteria to assess how green a reaction is, as well as considering factors both upstream and downstream of the reaction itself. ###This ensures a truly holistic approach. The toolkit allows the user to assess/demonstrate the ‘green credentials’ of their research; benchmark against current state of the art for a particular reaction or pathway and evaluate new methodologies to ensure that solving one problem does not give rise to others elsewhere in the process. The toolkit is specifically structured with a series of ‘passes’ to cover everything from bench top research right through to industrial scale with increasing levels of complexity. The acceptability of a particular process or reaction step is shown by a system of flags: green denotes ‘preferred’, amber is ‘acceptable – some issues’ and red is ‘undesirable’. The purpose of the toolkit is to ensure a holistic approach is taken so that no parameter is looked at in isolation. CHEM21’s aim is that this toolkit will encourage continuous improvement whilst training researchers to think critically about sustainability and environmental acceptability, making analysis of their synthetic routes and the use of greener and more sustainable techniques part of everyday practice.

CHEM21 – the University of York on screen during Chemistry Week
November 2013 - To celebrate Chemistry Week, researchers at the University of York released a series of short films about how PhD students participating in IMI’s CHEM21 project are working towards a greener pharmaceutical industry. CHEM21 (full name ‘Chemical manufacturing methods for the 21st century pharmaceutical industries’) aims to ###generate a range of methods to make the drug development process more environmentally friendly. The methods developed by CHEM21 will also help the pharmaceutical industry to cut costs, resulting in cheaper medicines for patients. CHEM21 started in October 2012 and will last for 4 years. Chemistry Week was a themed week of events promoted by the UK’s Royal Society of Chemistry (RSC), running from 16 to 23 November. The event is held every two years to promote a positive image of chemistry and increase public understanding of the importance of chemical science in our everyday lives. This year’s theme for Chemistry Week was health.
   - Watch the videos on the Green Chemistry at York YouTube channel.

Participants Show participants on map

EFPIA companies
  • Bayer AG, Berlin, Germany
  • Glaxosmithkline Research And Development LTD, Brentford, Middlesex, United Kingdom
  • Janssen Pharmaceutica NV, Beerse, Belgium
  • Orion Corporation, Espoo, Finland
  • Pfizer Limited, Sandwich, Kent , United Kingdom
  • Sanofi Chimie, Gentilly, France
Universities, research organisations, public bodies, non-profit groups
  • Leibniz - Institut Fur Katalyse Ev An Der Universitat Rostock, Rostock, Germany
  • Stichting VU, Amsterdam, Netherlands
  • The University of Manchester, Manchester, United Kingdom
  • Universitaet Stuttgart, Stuttgart, Germany
  • Universiteit Antwerpen, Antwerp, Belgium
  • University of Durham, Durham, United Kingdom
  • University of Leeds, Leeds, United Kingdom
  • University of York, York, United Kingdom
Small and medium-sized enterprises (SMEs)
  • ACIB GmbH, Graz, Austria
  • CatScI Ltd, Wentloog, Cardiff, United Kingdom
  • Evolva SA, Reinach, Switzerland
  • Reaxa Limited, Leeds, United Kingdom
  • charnwood technical consulting ltd, quorn, United Kingdom
Third parties
  • Technische Universitaet Graz, Graz, Austria
  • Universitaet Graz, Graz, Austria

CONTACT

Project coordinator
Murray Brown
GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LTD
+44 7920 568896
Murray.J.Brown[at]gsk.com
Managing entity
Nicholas Turner
The University of Manchester
nicholas.turner[at]manchester.ac.uk