Cell and gene therapy manufacturing has been a pertinent topic for a while now, largely due to the fact it is such a complicated process, involving a number of moving parts and excessive costs. As such, figuring out how to make these types of therapies scalable, less time consuming and cost-effective is still an ongoing hurdle that is yet to be overcome. In this article, we take a look at the current state of cell and gene therapy manufacturing, including the main challenges companies face, and the progress that has been made.
Cell and gene therapies generally involve a long process that can take weeks to complete, as a patient’s cells are collected, multiplied, and modified in a laboratory. Even in vivo treatments – which are simpler – involve multiple steps, including engineered viruses and synthetic genetic materials.
All of this is very difficult to manufacture at scale. Even in a research setting, where small amounts of the aforementioned materials are required, it can be a tricky business.
But, it seems companies are not put off by the complexity of the manufacturing process, as cell and gene therapy research is currently booming, with more than 2,200 ongoing clinical trials evaluating these types of therapies as of last year, according to the Alliance for Regenerative Medicine.
With so much research going on, it makes sense that innovative technologies, tools and ideas are going to be needed in the very near future to make sure that cell and gene therapies can be mass-manufactured, so that larger patient populations can benefit from these novel treatments.
Scalability: a key challenge
Scalability is perhaps one of the key challenges currently facing cell and gene therapy manufacturing. One of the main problems in this area is the fact that the manufacturing process often involves manual labor, which is both time-consuming and expensive.
“Cell therapy developers with marketed or late-stage clinical therapies are hitting a ceiling in terms of capacity: they just cannot scale and this is due issues with lack of mass-manufacturing bioprocessing tools (i.e., truly automated, small footprint) and lack of automation in quality control (QC) as well (i.e., lots of samples and data being generated manually, having to be sent to different places, etc),” commented Antoine Espinet, chief executive officer (CEO) of MicrofluidX.
“…We need to develop therapies that have robust processes by exploring the design space and understanding the biology at a small scale, and then scale to manufacturing in low-footprint systems, combining automated bioprocessing, integrated analytics, and connected to data management systems.”
It’s also worth noting that autologous therapies – whereby a patient’s own cells are collected, processed ex vivo, and then returned to the patient – are seen by some as a major obstacle to mass-producing cell and gene therapies, as they are extremely personalized and time consuming.
For this reason, according to ‘Horizons: Life Sciences’ report, some companies are beginning to shift away from autologous therapy production towards more commercially viable allogeneic processes, which would reduce costs and allow a larger patient population to be addressed.
However, as Espinet pointed out, the issue at the moment is that allogeneic therapies have not quite had the same clinical efficacy as autologous treatments.
“The view in the industry is that we will get there for some indications, but that autologous will still remain the best way for some other indications,” he said.
Bringing down the cost
Cell and gene therapies are notoriously expensive to manufacture, which comes as no surprise, given the complexity of the process. These high prices play a key role in making these therapies less accessible to patients, and also less scalable. But, fortunately, there are ongoing efforts to try and drive down the costs.
“As with any new technology, we expect costs to come down over time with more innovation. Everyone is working to lower the costs involved in making these treatments more available. Not only for new geographies, but making them cost-effective to a larger group of patients who may benefit (especially in oncology),” said Cem Zorlular, CEO of Er-Kim Pharmaceuticals.
He explained that, although manufacturing autologous treatments remains a challenge, companies are setting up more facilities in order to decrease the costs associated with this. However, he also said that, as touched upon previously, the real innovation here will likely come from switching autologous treatments to off-the-shelf treatments.
Meanwhile, Espinet believes that automation is the biggest driver in reducing the cost of cell and gene therapy manufacturing.
“There are already ‘automated’ devices out there but they alarm a lot, or they don’t quite cover the full manufacturing process, or they require some manual step at some point in the middle of a run. This means that operators have to be in the cleanroom tending to those devices and the cost savings compared to a manual process are not that great,” he said.
Therefore, he believes there will be a true change in costs once automation can handle longer chunks of process sequences without there needing to be any intervention.
On the other hand, Mert Zorlular, chief financial officer (CFO) of Er-Kim Pharmaceuticals, said that something important to consider is that the price tags of cell and gene therapies are often misjudged.
“Gene therapies are often curative or disease modifying in nature and require only one or very few applications, providing a significantly better course of treatment than other available alternatives, which often require a life-time of support and medication for patients in dire need,” he said.
“If present value of costs associated with gene therapies are compared to existing alternatives, a potentially significant chunk of these gene therapies can indeed be priced at negative premium, let alone offer additional benefits such as safety and overall health to patients despite exorbitant price tags. This initial unfounded pushback against pricing can often be a significant challenge when manufacturers look to commercialize these products.”
A “tipping point” for cell and gene therapy manufacturing
It is clear that vast improvements need to be made to the cell and gene therapy manufacturing process in order to make it easier to produce cell and gene therapies at a much larger scale, so that ultimately they can become more accessible to patients and really help to save many lives.
As more and more cell and gene therapies become approved, the hope is that there will be enough of a push to develop technology that will also be able to improve manufacturing, and, with it, commercialization.
Cem Zorlular said he believes the future for cell and gene therapy manufacturing holds great potential, and that, as costs eventually go down and more innovative commercial models come into play, the treatments will be more globally available.
Espinet, on the other hand, believes that we are reaching a tipping point. “I think we are getting closer to a tipping point where we either solve the manufacturing issues for personalized therapies or we risk seeing autologous remaining in a very limited scope, and having to wait another 10 years for other cell and gene therapy modalities to emerge. I think that once the manufacturing is fixed, commercialization will follow because the business case for these therapies will become more obvious.”