“Automation” means different things to different people. To me, this word primarily means “tasks completed with minimal human interaction” – less than 5%, to put a number. In automation, more than 95% of the tasks to be performed are performed by a non-human system, especially tasks that span several days, such as cell culture. An automated device must be able to perform an assigned protocol repeatedly without requiring human assistance.
It is not necessary to explain all the benefits that automation can offer modern industrialized economies, nor to discuss the basic benefits that automation can offer to cell and gene therapy – many iterations of these articles exist. already.
However, it is absolutely useful to take stock of some of the most important recent advances in the automation of cell and gene therapies.
First, I’m excited about my company’s new cellular expansion platform, Quantum Flex. But this year, a new release from Investech also caught my eye – a device for washing and concentrating cells. Both innovations have received considerable attention, but not as much as advances in cell and gene therapy science in general. Approvals of CAR T therapies, for example, always receive far louder fanfare than the release of any automated miracle tool.
Is it a problem? I do not think so. Technology and its suppliers are the enablers of science. Scientists and doctors working on therapies will always lead the way. I see no problem with this aspect of the status quo. Cell and gene therapy has shown high response rates in the clinic, and so as a technology provider, I’m quite satisfied to be one of the people who are paving the way for scientists and doctors to do advance their discoveries towards commercialization.
In the past, cell and gene therapy companies have borrowed technologies from the blood and transplantation fields and started implementing them in their own field to address new unmet medical needs. The goal was simply for the cellular and genetic field to work. Now, technologies are specifically designed for the cell and gene therapy market. As the field matures, the transition from borrowed automated technologies to “native” technologies is one aspect of the new era.
Approvals of CAR T therapies always receive far louder fanfare than the release of any automated miracle tool
However, the big hurdle to fully entering this era is cost. It is common knowledge that labor is a large part of the cost of cell and gene therapy, and it is true that automation has brought down costs by removing labor from equation since the 18th century. The less obvious point I would like to make is that automation is not the only way to reduce labor costs in cell and gene therapy. If we stay focused on the non-human entities of the domain – on the machines and the buildings that house them – then we can look at a one-time investment in an efficient manufacturing system as a way to reduce running costs. The initial build may not be cheap, but over time it will pay for itself.
If we also look at the humans who turn the wheels of cell and gene therapy, we must consider their career ambitions and the economic dynamics of the labor market in which they navigate. The supply of highly skilled and educated scientists and technicians is far below the demand, which has created a highly competitive market. Individual workers have plenty of opportunities to raise their wages as they jump ship, and companies have a strong incentive to catch them before they even hit the water, so to speak. Everyone takes from everyone, which increases operating costs. If better training and workforce development can attract more talent to the field and strengthen the incentives that connect employees and employers, these costs may be able to be reduced over time.
Using the right automated devices can also increase production and the scale of the production process, thereby reducing the cost burden without necessarily reducing or increasing labor. In the case of manufacturing CAR T-cell therapy, the possibilities are particularly exciting. If you want engineered CAR T cells to grow, you have to meet their special needs: the right cell culture environment and the right cytokines. You can meet these needs in bags, flasks and containers – but I would recommend growing them in a hollow fiber.
If we look at the humans who turn the wheels of cell and gene therapy, we must consider their career ambitions and the economic dynamics of the job market in which they operate.
Let’s say you need to grow 2 billion cells. If you choose to do this inside a bag, you will need to add a high volume of expensive cytokines and nutrients because there is no membrane-based separation inside this bag. Hollow fiber bioreactors create a dual-chamber system – in simple terms, think of it as a straw made up of a semi-permeable membrane that only allows a specified size of molecules to pass through its pores. Essentially, it allows you to keep the cells inside the straw and provide them with what they need. The membrane allows small molecules, such as glucose, lactate, oxygen and CO2 to pass freely, allowing control of the cell culture environment. Large molecules – such as expensive cytokines and media components – can be stored in the cellular compartment, intra-capillary (IC) side. A practical consequence of this is that the total volume of full supports you need for CAR T production may decrease, as well as the cost.
Another practical advantage of applying the hollow fiber approach relates to time. The hollow fiber system requires a much lower number of seed cells than a bag culture. This can save valuable time that would otherwise be spent jumping hurdles when extracting sufficient cell samples from patients.
I want to emphasize that hollow fiber devices are not a new technology. When first released around 2011, they offered a very futuristic approach. But now – in a sense – that future is here and normalized. Numerous studies have demonstrated the ability of hollow fiber technology in expanding a multitude of cell types. Looking ahead to the next ten years, we can get a sense of the new normals that the next wave of automated cellular and genetic technologies may usher in.
Currently, we are seeing a lot of work on biosensing tools to monitor and modify the cell culture environment. While biosensors are currently being adopted at many levels of cell manufacturing, we are only just beginning to understand the applications of machine learning and feedback circuits in cell and gene therapy. Right now we leave the cells in incubators and watch their environment, but we don’t try to change that environment. As practices around cell culture evolve, we should see ways to more closely analyze key markers – such as glucose, lactate, oxygen, CO2 and pH. Given enough data, machine learning models may be able to train the systems through feedback loops to optimize cell cultures. Right now we don’t have enough data – and even five years from now we may still be discussing the possibilities rather than implementing them. But I believe this is an area to keep a close eye on – an area where great things are sure to emerge. In that sense, it has a lot in common with the history of cell and gene therapy so far.
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