Research into manufacture of life-saving drug wins industry-sponsored award
(10 April 2018)
Durham University chemists have won a national award for research that could increase the availability of an effective treatment for a strain of meningitis in less developed countries.
Professor Graham Sandford has received the 2018 AstraZeneca, GlaxoSmithKline (GSK), Pfizer and Syngenta Prize for Process Chemistry Research on behalf of the Durham Fluorine Group.
This is the 13th time the annual prize has been awarded to a UK based academic who has developed chemistry that has the potential to be of relevance to large scale manufacturing.
The Durham group’s work could see drugs for the treatment of Cryptococcal Meningitis (CM) become more readily available.
Reducing cost of vital medicine
CM is the leading cause of meningitis in sub-Saharan Africa and also accounts for 20 per cent of HIV/AIDs related deaths worldwide.
In developed nations around nine per cent of those diagnosed with CM die, but this figure rises to 70 per cent in sub-Saharan Africa where the availability of suitable drug treatment is limited, due in part to cost.
Research by Professor Sandford, in Durham University’s Department of Chemistry, and former PhD student Antal Harsanyi, resulted in an innovative, simplified method of producing the drug flucytosine, which could significantly reduce the cost of this vital medicine.
The research is part of a long-term project by the Durham Fluorine Group to harness the use of the chemical element fluorine gas for practical application via the techniques of continuous flow fluorination and selective direct fluorination.
The prize was presented to Professor Sandford at the SCI Process Development Symposium, in Cambridge.
A panel of eight process chemists from AstraZeneca, GSK, Pfizer and Syngenta selected the winner.
Partnerships with industry
Professor Sandford said: “The technology and techniques we are developing at Durham can be used by industry and could have significant benefits in enhancing the use and application of fluorine gas.
“This award is for everyone who has worked on our fluorination research, including students, analytical support staff and for our successful knowledge transfer partnerships with industry.”
The Durham Fluorine Group developed a method of making flucytosine from a starting material of cytosine which is a readily available, naturally occurring product.
The new technique - called continuous flow fluorination - continuously passes fluorine gas through a reactor tube, together with a solution of cytosine in acid. In the tube the fluorine gas reacts with the cytosine molecules to make flucytosine in a very controlled process.
This method uses less energy, fewer raw materials and produces less waste than existing production processes and is also less expensive.
Tackling global infectious disease
Research into new methods for manufacturing anti-fungal drugs is part of the commitment to health research overseen by Durham University’s Centre for Global Infectious Disease, which brings together specific, multidisciplinary expertise between the biological, chemical and physical sciences to tackle challenges in global infectious disease
Another process developed earlier by the Durham Fluorine Group – direct selective fluorination – is used by industry to produce chemical intermediates that are used in making the world’s top-selling anti-fungal drug, V-Fend® (Pfizer).
V-Fend® is used to treat invasive pulmonary aspergillosis, a fungal infection of the lung, which is potentially fatal and develops mainly in people whose immune systems have been compromised by disease or cancer treatment.
The Durham Fluorine Group has collaborated in research programmes with a number of national and international industrial partners including Asahi Glass (Japan), F2 Chemicals, Pfizer, Murata Manufacturing Co. (Japan), Syngenta, AstraZeneca, Afton Chemical, SONY (Germany), GSK, Sanofi (France) and Mepi (France).
New, efficient, and responsible medicine
Laurent Pichon, President of Mepi, in Toulouse, France, said: “We are really proud to have been given the opportunity to work with Professor Graham Sandford and his team, throughout the flucytosine project.
“We were able to combine challenging process innovation available at MEPI, together with fluorine chemistry expertise developed by Durham University, to achieve fantastic results.
“Beside technical excellence, we shared an unrivalled human experience that will remain for long, and open the door to a new, efficient, and responsible medicine.”
Alain Rabion, expert in chemistry at Sanofi, France, said: “It has been a great opportunity for Sanofi to develop a very efficient and fruitful partnership with Professor Graham Sandford and his team in the framework of the European Community Innovative Medicines Initiative (IMI) project CHEM21 consortium.
“Based on excellence with fluorine chemistry expertise developed by Durham University and thanks to knowledge transfer proposed by Graham and his team, it has been possible for Sanofi to study a new fluorination methodology based on the use of elemental Fluorine gas as electrophilic reagent and continuous process using flow conditions as technology (milli-reactor).
“This successful collaboration involving Durham University, Sanofi and MEPI ended up with a new, readily scalable method for the direct synthesis of Flucytosine from cytosine using fluorine gas, which is unquestionably a technical success.”
Dr Alan Steven, Associate Principal Scientist, AstraZeneca, said: “Graham’s progress and achievements in taming fluorine gas, particularly from a technology point of view, are starting to change the way process chemists go about incorporating a fluorine atom into a target molecule.”