There can be no doubt that cell and gene therapy is showing astonishing results for otherwise untreatable diseases – with the main ones being blood-borne cancers such as leukaemia. The process by which cells are removed from a patient, modified and then reintroduced so that the body heals itself, sounds so simple and elegant. But with a price tag in the region of $500,000 per patient, it is clear that this revolutionary type of therapy is still a painstakingly slow and expensive business.
PureSentry: Can real-time contamination detection transform cell therapy manufacture?
One of the key stumbling blocks to producing cell therapies more easily is the considerable risk posed by contaminated batches. A recent study has found that two per cent of all cell therapy batches fail due to sterility issues. This means the whole procedure has to be started again, with new cells harvested from the patient, modified, cultured and then checked for contamination once more. It all takes time – up to 24 days from cell harvest before a batch can be approved for introduction to the patient. And often time is not on the patient’s side.
It all costs money, too. Cells have to be cultivated and tested by highly skilled technicians in Class A clean rooms. So, is there a way, we wondered, of making the whole procedure simpler, quicker and more automated? A team of us here at Cambridge Consultants set to work thinking about how this could be done.
Suited to machine learning and artificial intelligence
Our first lightbulb moment came with the news of a novel type of camera. Produced by Prophesee, the technology offers something very different, which the company calls metavision. The camera is neuromorphic, working like an eye to spot changes and filter out irrelevances in a split second. The similarity to our eyes also means the data is particularly well suited to machine learning and artificial intelligence, providing high density information for rapid and low-cost analysis. When we came across this camera in a physics publication, there was talk of using it in industrial applications such as driverless cars and logistics warehouses. But could it also detect microscopic cells and spot anomalies in cell therapy batches?
The team here was the first to try Prophesee’s technology for cell therapy applications – and I’m delighted to say it has worked very effectively. So effectively in fact that we have filed for a patent covering the use of this technology for contamination detection in biomanufacturing. This camera is now the heart (or perhaps, more accurately, the eyes) of our prototyped novel cell therapy manufacturing tool, PureSentry. It is a revolutionary piece of on-line testing hardware that can check cell batches for contamination in real time, improving the efficiency of creating personalised cell therapy treatments for patients.
PureSentry uses the Prophesee camera to continuously monitor a cell batch in real time using microfluidics, instantly flagging up any appearances of individual bacteria (and potentially other microbes) which would cause a batch to fail quality control. Crucially, we have been able to make PureSentry extremely affordable using low cost components, simple optics and scalable electronics. It is several orders of magnitude cheaper than the cost of a cell therapy batch, meaning it’s feasible to monitor every batch 24/7 during manufacturing.
So how does it work? PureSentry has a microfluidic chip which is connected to the cell therapy bioreactor and operates hands-free. The event-based camera monitors the cell batch continuously, allowing for any contaminants to be spotted immediately. This enables the contamination detection process to be much swifter than is currently possible. If a batch fails, new cells can be harvested from the patient and the production process restarted much sooner. In addition, the monitoring of the batch is non-destructive, unlike in current practice where some of the precious cells are destroyed in order to check their sterility. What is more, PureSentry is easy to use with gloves via a touch screen interface and so is suitable for use in hyperclean biomanufacturing environments.
Automation of sterility testing
A recent report from GlaxoSmithKline into the current state of play in the field of cell and gene therapy has found that 59% of its overall cost can be attributed to cell handling and analytics. With the price of treatment in the region of half a million dollars per patient, there is a huge incentive here to bring the price down and make it more accessible. PureSentry has the potential to do just that. Crucially it is eminently scalable, allowing for many samples to be monitored for safety at the same time, using far fewer skilled technicians. Automation of sterility testing in this way has the potential to radically reduce the cost of cell and gene therapy, enabling far more patients to receive its lifesaving benefits.
We started this project back in December 2019 with a team of around seven colleagues, all in-house. By January 2020 it was well underway, the team doubled in size and we approached the UK government’s Cell and Gene Therapy Catapult, a public technology initiative, to validate that our approach would meet the concerns of cell and gene therapy manufacturers. Along the way we have certainly overcome a fair few challenges, not least in translating the very specific user needs of cell therapy manufacturers into a device which can run autonomously for long periods of time with a high degree of sensitivity. Getting the optics right and working with novel event-based data was also far from straightforward because the raw output represents events in time rather than the familiar images we acquire from standard cameras.
The next step for the team is to forge a collaboration, perhaps with a cell therapy manufacturer, an equipment vendor or scientific instrument specialist whose customers need faster more rigorous contamination detection in order to grow their business and succeed. Our ambition is to help develop a commercial system for market launch, ultimately reducing cost and manufacturing time for the cell therapies of the future. It’s an exciting prospect – so please do drop me a line if you’d like to continue the conversation.