The UK cell and gene therapy manufacturing space showed positive signs last week, after a report was published showing a 60% expansion of the GMP licensed manufacturing space and increased investment from the government.
The latter announcement saw £4.3m ($5.5m) split between three companies to improve the efficiency of manufacturing processes for advanced therapeutics. In addition, funding worth £3m was provided to Advanced Therapy Treatment Centres across the UK to develop methods of delivering next-generation therapies.
While the former research emerged from the Cell and Gene Therapy Catapult (CGTC), which detailed how, in the past year, the UK has experienced a growth of 60% in manufacturing space and a 30% increase in employment. Total cleanroom space is also scheduled to be boosted to 8,000m2 by 2019 – with 1,500m2 of space projected to be added over the coming year.
With a number of developments on-going in the area, Biopharma-Report (BPR) spoke to Keith Thompson (KT), CEO of CGTC, about where this growth is emerging from and whether these positive signs will continue for the UK with Brexit on the horizon.
BPR: How has the cell and gene therapy space developed in the last few years?
KT: If you look back to 2012, the industry has grown from a handful of companies that collectively only raised about £20m, to about 70 companies in the UK that have raised £2.5bn over that period. If you look at the clinical trial pipeline, candidates are moving more and more to Phase III and are operated by companies. This frames the growth of the manufacturing sector and, specifically, that it is now in the commercial space. In 2012, nearly all of the space was in the NHS or in academia.
The industry, as in the rest of the world, has grown significantly off the back of all the research that has been in place for many years. The Catapult has been a major agent in driving that change, through the technical support we've been able to give or by working in the environment to improve the regulatory pathways. What we've got now is an ecosystem in the UK, which, frankly, is second to none.
BPR: How did the development of the Cell and Therapy Manufacturing Centre begin?
KT: In 2014, we identified that the absence of large-scale facilities was going to cause bottlenecks for the industry and that's why we requested investment from the UK government to build the manufacturing centre in Stevenage – this has just come online this year. You can now see firms that have entered the manufacturing centre in Stevenage actually producing products through the centre.
BPR: The sector is developing rapidly, how does this create challenges for the manufacturing process?
KT: Unlike regular pharmaceutical and biopharmaceutical products, where the development cycles are quite long, in cell and gene therapies they can be relatively short because the clinical signals are so strong. They move through the clinic much faster, they don't really go through the Phase I, II and III stage, but instead through an 'adaptive trial' – where you get a small trial of 10 or 20 patients, and 20 respond, then the next trial is a registration trial. That is fantastic news but it's also putting greater strain on the way companies can prepare for manufacturing these complex products. In addition, what you're trying to do is get the technologies that were not long ago being used for first-in-man studies in good enough shape for fully industrialised processes.
BPR: How does this speed impact processes?
KT: What we might see is what we called 'leapfrogging products'. Technology is developing at such a clip that improved products are going to be coming out, addressing the same issues, at a fast pace as well. That is going to drive the need for flexible manufacturing, it is going to drive more and more automation, and the need for flexible facilities. Here in the UK, we've got a great environment for facilitating that kind of growth.
BPR: How much support has the UK government provided?
KT: The UK government's support has been both deep and broad. There's been a long tradition of supporting the research sector, but there's been great support for clinical translation through the NIHR (National Institute for Health Research) and the Biomedical Research Centres throughout the UK. You can also look at the amount of support through Innovate UK, now part of UKRI (UK Research and Innovation), with things like collaborative R&D grants and the Industrial Strategy Challenge Fund. In addition, setting up the Cell and Gene Therapy Catapult specifically to bridge the gap between academia and industry, in order to accelerate industry progress.
We've also had many science and technology committees in the House of Lords and House of Commons that have looked at the detail and come out with recommendations, giving further support to the sector. This has seen things like the regulatory process speed up.
[The committees] have been absolutely terrific in providing the background for political support and desire from the government to work with the NHS to really be the first outside of the US to give fully authorised CAR-T treatment. If you think about the NHS as being a slow adopter, think again. This has been one of the fastest adoptions of a new technology you've ever seen.
BPR: How has regulation changed over the last few years?
KT: If we characterised regulation five years ago, it would be 'labyrinthine', but about four years the MHRA (Medicines and Healthcare products Regulatory Agency) took the decision to open the ‘one stop shop’ for innovation and streamline that process. I don't think you'll find anyone, anywhere that wouldn't support the statement that this is the most supportive regulatory environment for the development of these advanced products – they've been fantastic.
BPR: How could Brexit impact this regulatory landscape? Are there opportunities within it?
KT: You have to look at the opportunities, we fully understand and expect a pragmatic mutual equivalence agreement, which is not going to get in the way of the two-way trade of medicines in and out of the UK. Everyone has got a lot to lose if they mess that one up, that's for sure.
At the same time, without necessarily seeking an unfair advantage, one of the key things is that within the existing rules, the MHRA and NICE have shown that they are able to do things a lot faster than the old-fashioned way. I think first and foremost, the speed and decision making, without losing the rigour of scientific analysis, of our regulatory system still puts us at a competitive advantage.
Frankly, for some products, it's not going to make a huge difference – maybe some extra paperwork before you fly it in or out. For others, it means there are more technical considerations. Certainly with several of the companies that we've spoken to, once you get past the 'What about Brexit?' story, they recognise that the overwhelming benefit of the ecosystem in the UK actually still swings the pendulum towards a positive decision on developing and manufacturing advanced therapeutics in the UK.
BPR: Looking to the future, how do you expect the manufacture of advanced therapeutics to develop?
KT: What we expect is that factories will need to be built of the same size, or bigger, than our current facility in Stevenage, as the industry outgrows either our facility or their existing space. [The UK’s] rich and vibrant manufacturing cluster will help attract more and more companies because you need the talent and the supply chain to grow. We've helped to start up an apprenticeship programme, and we'll be expanding that over the next few years. Companies need talent, facilities and product, and we see all that growing in the UK.
In terms of the technology, we definitely do want to see technology drive automation to improve the cost and quality of the products in this space. This automation will decrease the cost of facilities but also enable the growth to keep going at a fantastic rate of knots. We may well see some step-changes come through, from CRISPR and gene editing that provide new ways of getting to the same molecular solutions. All of these developments will be based on what has already been established in the UK.
Keith Thompson is the CEO of the Cell and Gene Therapy Catapult. Thompson has built a team of more than 180 cell and gene therapy experts in London and a large-scale manufacturing centre in Stevenage.