Pharmaceuticals: A Spoonful of Sugar
Above: Investigating the application of genome editing to revolutionise bio therapeutic production at the National Biologics Manufacturing Centre.
The bitter pill of the loss of the European Medicines Agency (EMA) from London may be sweetened by the news of both inward and domestic investments announced during 2017, and the possibility of closer scrutiny of formulation and production of post-Brexit UK therapies by the EU may be balanced by the LifeSciences sector deal in the Government’s Industrial Strategy. Sarah Houlton reports.
“For the mutual benefit of patients and the life sciences sector in the UK and the EU, we want the UK to seek to negotiate continued alignment and commonality with the EU for the regulation of medicines,” a spokesman for the Association of the British Pharmaceutical Industry (ABPI) said. “The vehicle for this could be a regulatory cooperation agreement for medicines between the UK and EU. This could involve continued alignment of current and future regulations – and the UK’s continued participation in EU regulatory processes and the supervision of medicines, including the sharing of data.”
It poses particular issues for the manufacturing sector. EMA has already stated that a non-EU UK will, like China and India, the USA and Japan, be considered a ‘third country’ for the manufacture of pharmaceutical ingredients and formulated medicines.
The uncertainty regarding Brexit has also been causing concerns about the future of investments in the UK, where the life sciences represents a significant sector for R&D spending, at more than £4bn annually. The UK was picked by foreign companies, such as Shionogi and Eisai, as their European home because of its proximity to EMA’s headquarters, and it remains to be seen whether they will now rethink their decisions.
Some positive signs
Merck is not alone. US biotech Alnylam is creating a development and commercial site in Maidenhead, and Danish diabetes specialist Novo Nordisk is investing £115m in a research unit in Oxford. German company Qiagen announced an expanded investment in clinical and diagnostic services in Manchester.
Changes are under way at the two British-headquartered big pharma companies. AstraZeneca’s plans to create a new headquarters and R&D hub in Cambridge continue. It also realigned its portfolio on cancer, respiratory, cardiovascular and metabolic diseases, and sold several now-sidelined products and development projects.
GSK – an extra £140bn
In July, GlaxoSmithKline announced plans to invest an additional £140m at its Ware, Hertfordshire; Barnard Castle, Co Durham; and Montrose, Scotland sites, by 2020. The investments will support expansion of manufacturing for its respiratory and HIV medicines. However, it also announced that it will no longer be building a planned biopharmaceuticals manufacturing plant in Ulverston, Cumbria. Like AZ, GSK is also refocusing its R&D portfolio. It will put a bigger emphasis on infection, respiratory, cancer and immuno-inflammation, and stopping 30 research projects.
‘We are continuing to invest in science and our core businesses in the UK and we continue to see the UK as an attractive place for the life sciences industry,’ said Phil Thomson, GSK’s president of global affairs. ‘We are working constructively with the government and others to develop an ambitious plan for the sector as part of the UK government’s new Industrial Strategy.’
Crucial R&D in life sciences
The Industrial Strategy, first announced in green paper form in January 2017 and then formally launched at the end of November, places a huge focus on the importance of R&D in the life sciences sector, traditionally one of the UK’s strongest areas of manufacturing expertise. The aim is to ensure the UK remains at the forefront of innovation: life sciences already generates £64bn of annual turnover, and employs nearly 250,000 people.
“[The Life Sciences sector deal] will help ensure new pioneering treatments and medical technologies are produced in the UK,’ said Sir John Bell, GBE FRS FMedSci FREng, who led the Life Sciences Industrial Strategy. “[It] involves substantial investment from private and charitable sectors and significant commitments in R&D from the government.” Industry is clear that the strategy needs to be long-term, not just a moment in time when a sector deal is agreed, he explained.
“To retain the UK’s competitive edge there is a requirement for sustained effort over a longer period of time, and the proposals are designed to be thought about in that longer-term context, with both industry and government having responsibilities and commitments over a longer time frame.”
“The industrial programme is moving ahead, with those eight companies driving key areas of activity,’ said Clive Badman, industrial chair at CMAC and head of precompetitive activities in GSK’s platform technology and science group.
“With CMAC, we realised early on that many companies were supportive of continuous manufacturing in R&D, yet getting it embedded in commercial manufacturing was a challenge,” Badman added. “We realised we had to treat continuous manufacturing as a platform technology, and are there other platforms across the pharmaceutical supply chain that might benefit?”
This led to an advanced manufacturing supply chain initiative and its ReMediES (Re-configuring Medicines end to End Supply) project, which is led by Badman and GSK, and includes 24 members across industry and academia.
The programme is looking at how efficiency can be improved and cycle times shortened, in both clinical and commercial activities. The programme, which will come to an end in June 2018, has had some successes already, Badman revealed, including new equipment being brought to the marketplace and a new opportunity in clinical packaging that could reduce lead times from four months to a week.
“It is creating and safeguarding jobs, reducing cycle times and improving efficiency,” he said. There are plans to create a Medicines Manufacturing Innovation Centre (MMIC) in Scotland by 2020. Funding bids, to Innovate UK and Scottish Enterprise, would provide half the £56m cost, with the rest raised from industrial partners. In the interim, the CMAC facility and CPI’s formulation centre will be used to get the project started.
“The purpose of MMIC is to accelerate and de-risk the adoption of technology by giving companies the opportunity to try new technologies in a proprietary environment,’ Badman explained. “We want it to be a GMP-capable facility, so it can produce clinical trials supply before companies go on and build a facility.”
The first two CAR-T cell therapies to treat cancer were approved in 2017: Kymriah from Novartis; and Yescarta from Kite Pharma (now part of Gilead). Many other advanced therapies are under development, with several UK companies working in the field, such as Autolus, Cobra Biologics, Oxford BioMedica and ReNeuron.
They are difficult to make and the UK has the opportunity to be a leader in this field – with the right investment. As GSK’s Ian McCubbin, outgoing chair of the Medicines Manufacturing Industry Partnership, told the ABPI annual conference in April, it is not low-cost labour that drives cost of goods in manufacturing; it is technology that will drive productivity. While much manufacture of small molecules and biologics has already left the UK, this is not the case for advanced therapies.
“The Life Sciences Industrial Strategy is a one-off opportunity to build on the capability of the industry and work with government to create the conditions that will cause existing manufacturers to expand in the UK where they have a choice, and others to come here,’ he said.
The focus on advanced therapy manufacture provides many opportunities for UK-based companies. Cells must be carefully tracked on their journey from patient, through all the steps of genetic modification and manufacture, and back to the patient. Pioneering technology from Cardiff-based Trakcel allows this to be done. It works with pharma companies, CROs (contract research organisations), logistics providers, testing labs and equipment manufacturers to collate data into a single system that manages the whole supply chain.
“If the patient gets the wrong cells, they could be dead in less than an hour,” said EVP Martin Lamb. ‘The materials have a very short shelf life, and the patients are often so sick there is no opportunity to collect more cells.”
Clients include UCL spin-out Autolus, which is also working on a chimeric antigen receptors (chimeric T cell receptors or CAR-T) product, and the government-backed Cell & Gene Therapy Catapult in Stevenage.
“As CAR-Ts become more specific they are expected to be the fourth pillar of cancer treatment,” Lamb says. “It is good that the UK government has invested heavily in this sector. The UK has a leading position, and it will be important to the future economy where we develop innovative medicines that we continue to take a leading role.”