The Catapult believes the UK has the chance to become an international center for cell and gene therapies, thanks to its clinical and research strengths in the area – although notes that manufacturing continues to pose a challenge the growth of the sector.
“The UK is recognised as a world leader in ATMP research, although traditionally its manufacturing capacity has been low,” notes the report.
“In the case of CAR T and ex vivo products, once cells are harvested from a patient, they are often shipped to the USA or Europe to be modified before being shipped back for administration. This can lead to delays in access which can have implications for disease progression.
“To help secure its status as a global hub for researching, developing, manufacturing and adopting ATMPs, a national cell and gene therapy vision must outline how the UK will catch up on manufacturing.”
Increase in available cell and gene therapies
The number of cell and gene therapies coming to market is expected to rise significantly in the coming years. These products have the potential to significantly change the way certain patients are treated and, consequently, the way the UK’s National Health Service (NHS) manages certain diseases.
In Europe, as of 2021, 16 cell and gene therapies had been approved by the European Medicines Agency (EMA) – though four were withdrawn - and 12 have been granted marketing authorisation by the MHRA since the beginning of 2021.
There are nearly 300 cell and gene therapies that are currently in development encompassing more than 100 therapy areas that might be approved in the next few years.
Beyond the benefits that cell and gene therapies offer to individual patients, they could also benefit the health and social care system with reduced care costs and fewer rounds of invasive treatment.
Meanwhile, the sector offers the UK life science industry a runway to grow with increased research, clinical trials and manufacturing.
“The UK is already a world leader in the provision of cell and gene therapies," notes the report.
"In 2018, the NHS in England became the first national health system in Europe to make CAR T therapy available, an important step in the evolution of cancer treatment, having reached rapid commercial agreements with two manufacturers.
In September 2019, NICE recommended another ATMP on the NHS – a novel gene therapy for a rare inherited eye disorder. In January 2021, NICE then recommended a third CAR T therapy be made available on the NHS via the Cancer Drugs Fund (CDF), for people with a rare type of non-Hodgkin lymphoma, 10 as well as a further gene therapy for Spinal Muscular Atrophy. There are also a handful of other advanced therapies awaiting approval.”
Manufacturing restrictions
One of the main barriers for the sector, however, is the complexities in manufacture.
“Cell and gene therapies, both those that involve the extraction and manipulation of a patient’s cells as well as in vivo therapies, in which the therapy is directly delivered to cells inside the patient’s body, pose a unique set of manufacturing and transport challenges, with strict requirements on storage, handling and staff training,” notes the report.
“Unlike small molecule drugs, the individualised nature of cell and gene therapies means it is not currently possible to prepare, test and manufacture them at scale, with specialist manufacturing centres required. The timing of manufacturing of an ATMP is therefore dictated by a number of parameters associated with the patient's underlying condition and prior treatments, leading to a defined treatment window.
“The manufacturing process also requires specialist staff meaning that the recruitment and retention of operators will become increasingly challenging as more cell and gene therapies are made available.
“Whilst the UK has sought to address this challenge with the development of an apprenticeship scheme specific to ATMPs, further measures to build the manufacturing workforce will likely prove necessary.”
A cell and gene therapy plan for the UK, consequently, should set out plans to build up a domestic manufacturing sector to help secure supply and reduce delays in treatment initiation. And when manufacturing takes place outside of the UK, the plan will also need to set out how to ensure supply chains are uninterrupted.
“There remains uncertainty on how the UK’s departure from the EU will affect the manufacturing of ATMPs in relation to batch testing, concerning how products destined for the UK and originating from the EU will be certified as safe for the UK market once the unilateral grace period ends," says the report.
"It is important that the UK speeds up efforts to address uncertainty on batch testing to ensure the UK remains an attractive place for manufacturing in future.
“The MHRA has recognised the manufacturing challenges posed by ATMPs and has carried out work looking at the future regulatory framework of point of care (POC) products – those which tend to have very short shelf lives or which may be highly personalised, requiring them to be manufactured and supplied at POC – as is the case for some ATMPs.
"For POC products, the MHRA has published a framework that proposes the creation of a Control Site, a physical site that will be named on the clinical trial or MA application and responsible for overseeing all aspects of the POC manufacturing system, including the addition of new manufacturing sites and their activities. Plans to build a domestic manufacturing sector in the UK would be able to build on this work in addressing the wider manufacturing challenges posed by ATMPs – including those that do not have short shelf lives.”