Manufacturing
and lymphoma in some patients, and is now a standard treatment for aggressive lymphomas in the USA and other countries. While much of the CAR-T cell therapy innovation has come out of Philadelphia and Boston, there are currently more CAR-T clinical trials in China than anywhere else in the world.
The UK, too, punches well above its weight in the field of CGT. In particular, University College London (UCL) has been at the forefront of developing cell and gene therapies for a wide range of human genetic disorders, with several spin-out biotechnology companies attracting millions of public and private finance over the last few years. These include Autolus, Orchard Therapeutics and more recently, AGORA (Access to Gene Therapies fOr RAre Disease). AGORA is working with London’s Great Ormond Street Hospital for Children to create a sustainable way to provide children with rare and ultra-rare diseases access to gene therapies shown to be effective in clinical trials, but that never reach the market because they are prohibitively expensive. This focus on cost is perhaps the greatest barrier to getting CGT therapies to patients. For cancer, where CGT has the limelight right now due to the breakthrough results seen in CAR-T cell treatment, costs often run into the hundreds of thousands. Other CGT products, especially those for rare diseases with low survival rates, can be well over $1m.
Scaling automation
One reason for this exponential pricing, is that turning cells into a living medicine is a highly- skilled process that takes places on a small scale. Not only do you need a platform to support cell growth, but you need to maintain and measure the phenotype, genomic stability and health of cells throughout the process, as well as tightly controlling the risk of contamination through the use of cleanroom facilities. Dr Qasim Rafiq is an associate professor at University College London in Cell and Gene Therapy Bioprocess Engineering. He’s tackling the challenges of translating these advanced therapies from the laboratory to industrial and clinical use with the grand ambition of lowering manufacturing costs. “At the moment, the cost is unaffordable for health services,” he says. “But we are entering a period where the curative effect of a single personalised treatment may be more cost effective than a patient using outpatient services and taking drugs for the rest of their lives to deal with a chronic illness.” On the manufacturing side, in order to reach a scale that would make this ambition economically viable, experts like Rafiq see process automation as paramount. “There is a huge impetus with lots of technology being developed around automation,” he
World Pharmaceutical Frontiers /
www.worldpharmaceuticals.net
says. “Innovations could be around decision making, liquid handling or how to transfer one therapy to the next. We are at Automation 1.0 currently, so we have some way to go.”
In terms of what is currently possible, Rafiq says we are at the level where technology can sense and measure things like temperature and pH online in real time, and yet there is even a next level to reach before it can make informed decisions. “There are already some technologies that can measure temperature, but we are now talking about the next level, such as the cell quality, the number of cells, whether cells are consuming (glucose) and producing (lactose) in a closed system. Building a response system is where we are heading at the moment.”
A 3D illustration of a double helix DNA molecule with modified genes, correcting mutation through genetic engineering.
“Innovations could be around decision making, liquid handling or how to transfer one therapy to the next. We are at Automation 1.0 currently, so we have some way to go.”
There is no shortage of funding to innovate around scaling up automation to make production faster and more reliable and bring down manufacturing costs. The UK Government has invested heavily in the field with its Catapult programme putting in £100m of public money so far, and even this figure is surpassed by private investment. “There’s a large push in Europe, including at UCL, to integrate AI and machine learning to improve manufacturing processes,” says Rafiq. “These [processes] are patient specific and that is where the challenge is, because every patient is different. How do we manage that variability? One area is using AI and machine
41
nobeastsofierce/
Shutterstock.com
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53
