A Global Challenges Research Fund (GCRF) project aims to boost South Africa’s self-sufficiency in essential medication manufacture.
We’re trying to bridge [the] gap between academia and industry – to take these chemicals through to a much more advanced stage in the academic lab. Dr Ben Deadman Facility Manager, Centre for Rapid Online Analysis of Reactions (ROAR)
The GCRF-funded project facilitates a skills- and equipment-sharing collaboration between Imperial College London, the University of Pretoria and the Council for Scientific and Industrial Research (CSIR). It aims to support the establishment of pharmaceutical infrastructure in South Africa, which will enable the manufacture of vital components of drugs known as Active Pharmaceutical Ingredients (APIs) for essential medications.
South Africa currently produces less than five percent of its APIs locally, which leaves it susceptible to drugs shortages when global supplies are insufficient; management and logistical issues also exacerbate the problem. The growth of a local API manufacturing industry will not only reduce reliance on imports, but also mean that much-needed medication will be more affordable to the local population.
Valerie Maswanganyi, from the CSIR and the University of Pretoria, is currently visiting Imperial’s Department of Chemistry, exchanging expertise with researchers based at the Centre for Rapid Online Analysis of Reactions (ROAR). In this Q&A Valerie and project team members Dr Ben Deadman and Roddy Stark tell us a bit more about the project.
What are your goals for the project?
Ben: ‘The goal is to develop process routes to enable the translation of drug molecules that are in demand in South Africa – ultimately, so that they can be manufactured there. Another goal is to generate bi-lateral exchange of researchers to share expertise. That’s where ROAR comes in – we have technology which is very unique, so we’re trying to build international collaborations and provide access to these tools to many more researchers. If you think about a traditional chemical process, in an academic lab we tend to do things on a very small scale. We discover interesting chemistry, but these chemical reactions very rarely get translated through to an industrial process. We’re trying to bridge that gap between academia and industry – to take these chemicals through to a much more advanced stage in the academic lab, so that they’re ready to go into pilot plants, which is where CSIR comes in.’
Valerie: ‘Ideally, the main goal is to make drugs faster and cheaper, regardless of which process we use – all of us working together to see which is the best method to follow.’
Why is a multidisciplinary approach important?
Roddy: ‘Everyone brings different strengths to the table. We’ve got people who do the synthetic, hands-on chemistry who are in constant discussion with people in the Department of Chemical Engineering with regards to how those processes can be applied on a larger scale. It can work for us [in the chemistry lab] on a one-, five- and ten gram scale, but for the quantities of drugs that are required in real-world, practical contexts, those processes may not be amenable to larger scales. Valerie’s got expertise in the flow chemistry field, which is much more amenable to large scale, and I’ve got more of a batch background, so we’re able to complement each other because the goal is ultimately the same.’
Ben: ‘There’s a techno-economic element too. In addition to improving the chemistry, the chemical engineers are also looking at it from an infrastructure perspective – what infrastructure needs to be in place to make it a viable industry for South Africa. You don’t want it to be a massive money sink – if you don’t do it well, that’s the danger.’
Roddy ‘An example is a candidate drug that got to about stage two clinical trials and then failed, and that was the representation of about $50m worth of investment that went caput. We aren't trying to reinvent the wheel with this project – we’ve picked candidate drugs that are high-priority for obvious reasons. We’re trying to find the best way to manufacture them both for economic benefits and efficiency.’
What drugs are you focusing on?
Valerie: ‘Well, there are obviously drugs closer to home – there's no point in manufacturing drugs that are of no benefit to the region, so right now we are mostly focused on infectious diseases, such as TB, and also on oncology drugs.’
Say something happens in London where we buy an API, the ripple effect on us is quite great – we’re trying to [ensure] that no matter what happens elsewhere, we’ll still have our own supply. Valerie Maswanganyi Visiting researcher, University of Pretoria
Ben: ‘The project is currently focused on drugs that already exist. Drug discovery research is happening in South Africa, but at the moment it’s kind of siloed. Supporting a high-tech industry will bring wealth and create jobs on a local scale, and then there’ll hopefully be additional opportunities on an international front, to support a bigger drug discovery industry down the line.’
Valerie: ‘The expanded programme will enable South Africa to make our own APIs and push drug discovery, rather than relying on importing everything. Say something happens here in London, where we buy an API, then the ripple effect on us is quite great – we’re trying to bridge that gap, so that no matter what happens somewhere else, we’ll still have our own supply.’
What are the challenges of upscaling drug manufacture from academic lab to industrial production?
Ben: ‘There are difficulties in collaborating between different facilities – developing something in one place and it being reproducible in another. Big pharma companies have the same issue, as they outsource a lot of their manufacturing. This is where I think we’d like ROAR to provide some real benefits. The idea is if we collect more data about the reactions we run and more reliable information about how the instruments are set up, then you should be able to translate from one place to another much more easily.’
There’s no sense in getting ninety percent there and then finding out that the last step can’t be done on a different scale, or by a different person. So it’s also about minimising user error... Roddy Stark Research Assistant, Department of Chemistry
Roddy: ‘There’s no sense in getting ninety percent there and then finding out that the last step can’t be done on a different scale, or by a different person. So it’s also about minimising user error by having a more robust screening method for reactions, or by data analysis and interpretation. That’s a definite strength of ROAR and where we can see a lot of these sorts of collaborations going.’
Ben: ‘If you read a standard chemical synthesis procedure in a paper it’s quite old-school language. If you’re a trained chemist you can read it and understand what they’re doing, but there’s a lot of room for interpretation about how that’s done and so we’re trying to be much more descriptive, much more specific about the way these things are done.’
Valerie: ‘We’ve approached some industry partners with our work on the oncology drug and they are impressed with the progress the team have made to date – we’re at the point now where we need to demonstrate that we can produce at least a kilogram of material at the CSIR site. Then we can sit down with them to see how they can modify their existing infrastructure to take up the process. If you can find industry partners who are interested in collaboration, with infrastructure already in place it’s better than starting from scratch – i.e. finding the land and constructing totally new infrastructure – it’s cheaper to work with what already exists.’
Why is the project exciting?
Valerie: ‘It’s a passion – to help my people. My drive in this project is to get South Africa to the same level [of API self-sufficiency] as other countries. People are dying unnecessarily, even though there’s medication available – they can’t always get to it. So it’s a passion that I have to make sure people [in my country] don’t suffer. It’s also great to have the opportunity to travel with my research interest to other parts of the world to see what other people are getting up to, how they’re doing their chemistry. The way we’re taught [in South Africa] is different to the way it’s taught here [in the UK] – from the chemistry to the engineering – it’s exciting.’
Ben: ‘Usually when you’re doing synthetic chemistry the reality is you’re quite far-removed from having any real-world impact. We do reactions in the lab, and we like to think that if we make some amazing discoveries it’s going to mean all this wonderful stuff for humankind! This is actually a project where, as it comes together, we can see that in the work that Valerie, Roddy and others are doing there’s potential for it to have a real benefit to lives of people in South Africa. It’s really cool to think that we can make a difference with synthetic chemistry. By being able to make molecules well, cheaply and efficiently, that is actually going to have a real-world impact.’
Roddy: ‘Valerie’s come over here for three weeks to see how we’re set up and to find out more about the facilities we’re currently using. There will be an opportunity for us to go over to South Africa and learn from them – it’s going to be a constant dialogue and exchange of ideas going forward. It’s exciting to be involved in a project that has real-world implications and a tangible benefit to people.’
What’s so special about the facilities at ROAR?
Ben: ‘ROAR has 80 square metres of high tech lab space worth £4.5 million pounds – probably the only place in the world which combines all these tools and technologies, and the staff to help users, in one place. We’re one of the first of our kind to be targeting the technologies in the synthetic chemistry space, trying to do what universities have already done with NMR and mass spectrometry, which are now ubiquitous and you couldn’t imagine doing synthetic chemistry without. We’re thinking about the next step, where does the field need to go in terms of the equipment that gives you productivity gains, gives you additional information and gives you the data needed for the science to start really advancing.’
Valerie: ‘I think the set-up of the university provides an opportunity for us to come and learn, whereas in industry the tools might be closed to us or harder to access. When we get our own infrastructure in South Africa there will be a continued collaboration – we can keep working together to troubleshoot problems and share ideas. In academia – and this kind of in-house university set-up – ideas and the working environment is geared towards sharing openly and collaborating.’
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