Allogeneic Cell Therapy: Options To Scale Up

Allogeneic Cell Therapy: What Options Do Sponsors Have To Scale Their Product?

At the Bench

As the allogeneic cell therapy industry moves beyond proof of principle experimentation and toward more human clinical trials, sponsors have a mighty challenge ahead of them: Growing more cells.

For example, a single patient dose of mesenchymal stem cell therapy could require hundreds of millions of cells or more. Because the cells themselves are the product, and that product, following downstream processing, goes to entire populations of patients, finding a way to scale up cell cultures while preserving underlying biology is essential.

That has historically been hard to do, according to Angel Garcia Martin, Ph.D., MBA, Business Development Manager at Corning Life Sciences. Culturing technologies that were available for early-phase cell therapy studies served lab-scale production just fine, but in the clinic, not so much. That's especially true for adherent cells.

"The kind of scale you need for allogeneic cell therapies can become unmanageable pretty quickly," says Garcia Martin. "Developers need a platform that can produce a ton of cells. While some cell lines have been adapted to support suspension cell cultures, most cells need to grow attached to a substrate. Up until recently, there has been no good technology out there that provides that kind of throughput these programs demand."

Scale Up Challenge Accepted

The recent development Garcia Martin alludes to is the advent of the Corning^® Ascent^® Fixed Bed Bioreactor (FBR) System, which enables efficient production and harvest of large quantities of cells in a cost-effective manner. Whereas previous FBRs supported the culture of adherent cells, researchers couldn't harvest the cells directly out of the reactor. That works for some cell-based products, but not for an autologous or allogeneic cell therapy. After all, if you can't effectively collect the cells, you don't have a product.

"The Ascent FBR system preserves the biology of the cells attached to the substrate," he said. "You can actually harvest the cells from the system and use them, which is a significant advantage."

Another advantage is the customizability, he adds. The Ascent FBR platform is flexible enough to adapt to different biologies, which is key in the fast and evolving world of stem cell therapies. For example, Corning has conducted experiments to determine the suitability of coating the surface of the FBR's mesh substrate with certain biologics. Garcia Martin says doing so can support especially difficult-to-grow cells that require specific conditions to better interact with the environment.

"Sometimes the cells just need extra help to attach to the substrate," he says. "It can be laminin or fibronectin, or some kind of collagen. But in our experiments, we've shown that it can be done, which emphasizes Ascent's customizability."

Operational Benefits of Automated Scale-Up

Garcia Martin has seen strong interest in the Ascent FBR system among scientists who develop therapies based on stem cells, such as MSCs, which are marginally easier to grow and maintain than other cell types. As these products approach first-in-human trials, many sponsors are realizing manufacturing bottlenecks that can delay market entry. That said, the Ascent FBR system can have utility in other areas as well, like gene therapy.

Bioreactors inherently enable automated processing, which offers technical benefits (such as the ability to monitor for pH or oxygen) and can also unlock operational benefits. The opportunity to lower the cost of materials as well as labor requirements can make a very big difference for these applications.

"You reduce the number of people who need to be in the lab, which is a significant advantage," says Garcia Martin.

Creating a Sustainable Seed Chain

Researchers should think ahead in designing and executing their allogeneic cell therapy seed chain from Phase 1 onward. While most labs can likely get by without a bioreactor for early work, Garcia Martin suggests that teams start thinking about their transition from stacked solutions, such as the Corning^® CellSTACK^® vessels, to the Ascent FBR system when dosage needs stand to multiply exponentially.

"It's best to think backward from the number of cells you will need per dose, and the number of doses you'll need for clinical trials," Garcia Martin notes. "Typically, you don't have that many patients in Phase 1 and can manage without high-volume solutions. This is what we're currently seeing in the market. But in Phase 2 and Phase 3, companies just can't produce enough cells without a bioreactor."

As such, Garcia Martin suggests that researchers consider an Ascent FBR platform when they are designing a Phase 1 and considering scale requirements for subsequent phases. Because of the regulatory hurdles involved in new drug approval, it's advisable to shore up processes at the time of IND submission. That means planning for scale well in advance. After all, manufacturing is a complex challenge in the world of stem cell therapies. Planning ahead may enable you to avoid potential issues and delays.

Explore What’s Possible With Stem Cell Therapies

In this playbook, we’ve asked our experts to explore the changing landscape of stem cell research and cell therapy production and how emerging solutions have facilitated a new era of more effective and efficient workflows.

This ebook reviews:

Stem cell applications and therapies
Factors that can influence cell quality
Breaking through expansion barriers with scale-up strategies
Making the most of stem cell innovations

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