CHEM21 Project has published the following deliverables which were classified as publically available
As part of the University of Manchester’s Research Beacons Initiative, a Massive Open Online Course (MOOC) was designed to disseminate research and teaching excellence of the university in the area of Industrial Biotechnology. The aim was to provide high quality distance learning with global reach in an area relevant to the grand challenges facing the world today. The course was co-designed and coordinated by University of Manchester researcher Dr. Nicholas Weise, a Senior Fellow of the Higher Education Academy (SFHEA), in consultation with members of the CHEM21 consortium, particularly those in WP5. This allowed the sustainability principles emphasized by CHEM21 to be integrated into the teaching of Industrial Biotechnology throughout the course.
The course followed a standard eLearning format common to other initiatives from the university. Each module was designed to be a collection of recorded presentations, talking heads, references and extra reading material along with multiple choice tests. The first three modules introduce the learner to core principles of industrial biotechnology – namely Biocatalysis, Systems & Synthetic Biology, and Biochemical and Bioprocess Engineering. Of these, Module 1 was contributed to by CHEM21 associates Prof. Nicholas Turner and Dr. Nicholas Weise, featuring research examples from EU consortia (KYROBIO, P4FIFTY and CHEM21). These initial modules then lead into the application modules which introduce more specific areas with principles exemplified through case studies. For example, Module 4 – which is entirely on the pharmaceutical and industrial context of biocatalytic manufacture – was designed and delivered by Dr. Andy Wells from the CHEM21 consortium. The bite-sized, modular nature of the course allows learners to be flexible or dip in and out when choosing topics according to their background or time constraints they may have. As such, the course has been made to be a useful supplement for undergraduates (chemists, biologists, engineers), a welcome addition to postgraduate and postdoctoral training or part of the continuing professional development (CPD) of scientists, educators and others in industry.
Press release: CHEM21 method could dramatically cut production costs of essential anti-fungal medicine
Brussels, Belgium, 1 February 2017 – Scientists from the Innovative Medicines Initiative (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. The CHEM21 team is now working to scale up the method to the industrial scale.
People with HIV / AIDS have weakened immune systems and so are particularly susceptible to fungal infections such as cryptococcal meningitis (CM), which is caused by the fungus Cryptococcus neoformans. There are 950 000 cases of CM worldwide every year, and 625 000 deaths, making CM the leading fungal cause of death for people with HIV / AIDS. The majority of cases are in sub-Saharan Africa.
The recommended treatment for CM is a combination of flucytosine and another drug called amphotericin B, both of which feature in the World Health Organization (WHO) List of Essential Medicines. However, flucytosine is not registered for use in any African country and so cannot be prescribed as a treatment there. Flucytosine is also very expensive, as its patented manufacture involves carrying out a sequence of four chemical reactions.
That could now change thanks to the work of the CHEM21 team, who have cut the number of reactions needed from four to one. The story starts at the University of Durham in the UK, where Professor Graham Sandford and PhD student Antal Harsanyi devised a way of making flucytosine via a one-step ‘continuous flow’ method that uses the readily-available natural product cytosine as its starting point. In this technique, fluorine gas is passed through a steel tube together with a solution of cytosine in acid and, in the tube, fluorine atoms react with the cytosine molecules to make flucytosine. 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, saw the potential of the technique and 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 paper published in the American Chemical Society’s Organic Process Research and Development journal: ‘This operationally simple procedure from inexpensive starting materials offers the only alternative manufacturing procedure for flucytosine to the currently operated expensive four-step process,’ they write. ‘We envisage that this one-step low cost synthesis of flucytosine will help to raise awareness of the neglected CM health epidemic and ultimately contribute to meeting the urgent requirement for large quantities of flucytosine for low income nations.’
‘This is an excellent example of how through IMI, universities and pharmaceutical companies can work together to deliver a promising discovery that addresses an unmet medical need, and then rapidly progress it to a larger scale,’ said IMI Executive Director Pierre Meulien.
The new technique could also have wider implications as flucytosine is used in the synthesis of two other important medicines: the cancer drug capecitabine and the HIV treatment emtricitabine.
CHEM21 is funded by the Innovative Medicines Initiative, a €5 billion public-private partnership between the European Union (through the European Commission’s research framework programmes) and the European pharmaceutical industry (through EFPIA, the European Federation of Pharmaceutical Industries and Associations).
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The CHEM21 project launched its new online training platform http://learning.chem21.eu at the Royal Society of Chemistry on 13th June 2016. 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.
The launch event formed part of a 2 day workshop and symposium on ‘Practical Aspects of Green Chemistry in the Pharmaceutical Industry’ 13th-15th June, showcasing the research of the CHEM21 consortium in a series of presentations and exploring some of the key themes of the project in interactive small group exercises. The workshop was attended by 40 delegates and the feedback was overwhelmingly positive.
The RSC have published a book ‘
How are chemical reactions which are discovered and researched in a laboratory setting translated into industrial-scale manufacturing processes?The 33rd SCI Process Development Symposium will explore this highly interdisciplinary field by bringing together a broad range of experts from various backgrounds.
An important area to address when developing new and more sustainable methodolgies for API manufacturing are non-technical barriers to the uptake of the emerging technology.A number of CHEM 21 members have collaborated with a range of other multi-national pharmaceutical companies and biotechnology suppliers to produce a white paper to support the uptake of biocatalysis in the manufacture of API’s. The paper details some case studies on medicines both in development and approved for patients, and provides some practical guidance around quality issues to promote the uptake of biocatalysis .
The 2016 Organic Process Research and Development paper has just been just accepted and can be viewed at:http://pubs.acs.org/doi/abs/10.1021/acs.oprd.5b00369
The CHEM21 consortium is running a themed workshop and symposium on ‘Practical Aspects of Green Chemistry in the Pharmaceutical Industry’ on the 13th -15th June 2016 at RSC Burlington House, London, UK.
This highly interactive workshop will be delivered by a blend of CHEM21 academics and industry experts in the field, involving group work and problem solving exercises alongside seminars to explore a broad range of cutting-edge case studies and industrial examples on greening the synthesis of Active Pharmaceutical Ingredients (APIs). More information on the event can be found in the CHEM21 workshop flyer.
The workshop is free of charge and is open to students, academics and industrialists. Places are limited and will be allocated on case by case basis. If you are interested in attending please please complete the registration form including a brief supporting statement explaining your reasons for applying.
On 4th and 5th November, WP 5 members contributed to a successful workshop and symposium on sustainable chemistry in industry organised by Durham Chemistry post graduate researchers. The event was very well attended by Durham scientists alongside researchers from York, Newcastle and Huddersfield Universities and some industry-based attendees from local chemistry using companies like Thomas Swan, High Force Research and Johnson Matthey. The event was a mixture of interactive workshop activities and presentations with the underlying theme of sustainable chemistry.Joining WP5 members in delivering the event were speakers from AstraZeneca, Syngenta, and Johnston Matthey.