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Affordable Decentralized Cell Therapies? Next-Gen Technologies Make It Possible

Representation of human stem cells.
Credit: Doodlart / Pixabay
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In the 18th century, the Industrial Revolution introduced centralized manufacturing as a compelling production model. With the advancement in machinery, centralized manufacturing was able to leverage economies of scale to lower per-unit costs and increase margins. The model also allowed manufacturers to deliver consistent product quality while aligning both supply chains and distribution infrastructure. Centralized manufacturing remains the main product model for most technologies, including within biopharmaceuticals. However, with emerging therapeutics and personalized medicine, biopharma companies are taking a critical look at this approach, especially within the area of cell and gene therapy.

The genesis of cell therapy, and later gene therapy, emerged in academic centers, combining scientific discoveries of the immune system and implementing these discoveries in clinical trials to address unmet medical needs, particularly in cancer and infectious diseases. Cell and gene therapies use the body’s own biological elements to fight diseases. In effect, a patient’s own cells or genes are used as the treatment. Traditional pharmaceuticals that use chemistry to combine individual components to create a synthetic drug can be mass-produced and distributed across the globe. What’s unique about cell and gene therapies is that they are inherently personalized, and uniform mass production is not currently feasible.

For cell therapy, a centralized manufacturing approach would require cells from a patient to be preserved and sent to a centralized manufacturing facility. Once there, a therapy would be developed, undergo rigorous quality control protocols, be preserved, sent back to the point of care and then, finally, administered. This is a long, laborious and expensive process that creates a large gap in access to care. In fact, when looking at autologous CAR T-cell therapies, which use T cells from a patient’s blood and enable them to attack the cancer cells in a patient’s body, there are already significant unmet patient needs. In 2019, it was estimated that 450,000 cancer patients were eligible for this therapeutic, but in 2021, only 4,000 commercial doses of CAR T-cell therapy were manufactured. Unfortunately, it’s estimated that 20% of patients eligible for an FDA-approved cell therapy pass away before receiving their treatment, according to the MD Anderson Cancer Center.

In essence, decentralization is part of a potential solution to the challenges of globalized healthcare to help make cell and gene therapies more affordable for more patients and significantly reduce the waiting time for each patient.

The case for decentralization

There are two major strategies in the cell and gene therapy industry to address how to improve availability of these therapies globally. The first approach is to develop off-the-shelf cell and gene therapies (also called allogeneic therapies) that are ready to use. The second is to offer decentralized manufacturing closer to the patients (i.e., at the hospital).

Decentralized manufacturing is being evaluated as an approach to cell and gene therapy that can not only combat the high manufacturing cost of such therapies, but can also reduce logistical complexity, risk and time that ultimately will give patients and their families better healthcare. Centralized manufacturing necessitates layers of regulation to validate safety and efficacy throughout the transportation and logistics process. Through decentralized manufacturing a scenario could be created where the cost and time associated with transportation and therapy preservation is all but eliminated.

In addition to reduced manufacturing cost, this also supports the delivery of cell and gene therapy drugs of higher quality. With fewer steps “vein-to-vein”, that is the time from a cell or gene extraction from the patient to when the fully engineered therapy is reinserted into the patient, there’s fewer opportunities for error or failure. For cell and gene therapies where the initial cell comes from the patient itself rather than a donor, the time required to manufacture the personalized drug ranges between three and four weeks. Decentralization could reduce the vein-to-vein time by 50% or more. For patients awaiting treatment, this not only creates a better experience but improves the possibility of success because the decline in a patient’s health due to a rapidly progressing disease could mean that their body is unable to respond adequately to the treatment. The vision is that decentralization will make cell and gene therapies more attainable for more patients.

Technological considerations

In essence, decentralized and centralized manufacturing of cell and gene therapies can leverage the same technologies and systems. A major push within cell and gene therapy manufacturing is related to closing and automating the manufacturing workflow. The majority of cell and gene therapies are discovered and developed in academic settings characterized by complex and highly manual processes. With highly skilled scientists physically implementing each step, these processes aren’t scalable at a commercial level. Furthermore, these manual connection points are susceptible to failure due to contamination or inconsistent practices.

Closing the workflow to eliminate manual interventions decreases the likelihood of human error or contamination. Once the workflow is closed, automation can be introduced to further drive efficiency and help reduce costs.

Cell processing, cell isolation and genetic manipulation are labor-intensive steps in the workflow that, thanks to recent innovations, can be completed in a closed fashion. Historically, cell isolation has been time-consuming due to the collection and centrifugation steps which were conducted manually and required significant repetition to produce a single therapy. However, technologies now exist that need no manual intervention and have minimal operational oversight for the cell isolation and activation steps. This closed, automated workflow delivers great isolation efficiency and purity without impacting cell viability. It also significantly reduces the time needed for these steps, from up to four hours to as little as 70 minutes.

With increased efficiency and therapy manufacturing success rates, automation improves the speed of manufacturing, which is critical for both therapy developers and patients. In recent studies, new instrumentation that automates the bead removal process delivered significant time improvement. In one case, the automated system accelerated the debeading process from two hours to 29 minutes, representing a 76% reduction, without impacting cell recovery.

These technologies can be used in a decentralized model for cell therapy manufacturing at a suitable scale to be a part of each of the major oncology institutions across the world. However, the smarter technologies and methods for quality control of the cell and gene therapy drugs are still lagging, which is hindering the buildout of decentralized cell therapy infrastructure.

An evolving market

Even though progress has been made, cell and gene therapies as an approved treatment option are still relatively new. In fact, Kymriah, the first CAR T-cell therapy to receive FDA approval, came to market around six years ago. Today, only a handful of cell therapies have received FDA approval but there are more than 1,200 cell and gene therapies active in clinical trials, according to Statista. With its promise and potential, the cell and gene therapy market is projected to grow more than 22% annually between 2022 and 2030.

Decentralized manufacturing of these therapies would represent a strong departure from the models the industry is most accustomed to. The inherent challenges of these types of therapies might well justify it, though. As academia, non-governmental organizations and industry continue to explore ways to make these promising therapies more accessible to patients in need, more data will be available to inform the development of the most sustainable model for the manufacturing and delivery of treatments to patients.

The pace of innovation within the cell therapy space has been impressive and there are many reasons to remain optimistic about its potential in the future.

About the author

Evan Zynda is a senior staff scientist at Thermo Fisher Scientific.