Scaling Up Allogeneic Cell Therapies: A Biomanufacturing Success Story | Corning

Experts predict that allogeneic cell therapies will grow in 2022 and beyond thanks to a market that's more than ready for them.

Not only do these products stand to help more people, but they also represent a supply chain that's potentially less complex. While you can expand an allogeneic product from healthy donors to patients with relative ease, autologous therapies have the central challenge of having to work with cells taken from very sick people. These and other complexities have pushed researchers to explore allogeneic approaches for procedures such as CAR-T immunotherapy.

But at the same time, allogeneic cell therapies require a much more comprehensive scale-up strategy. You need to consider not only your desired yield (which may be a lot for a one-to-many therapy) but also how labor, cost-of-goods sold (COGS), space, and timeline pressures may impact plans to reproducibly expand cells for master cell banks, working cell banks, and ultimately the product itself.

In addition, if you're working with attachment-dependent cultures for those therapies, cell processing can be even more challenging. While bioreactor technologies like microcarriers exist for adherent cells, they're not considered a perfect match because the microcarriers need to be taken out of the therapy before it goes to patients.

Waisman Biomanufacturing, like so many others in the industry, experienced these pain points as it looked to expand capacity for a portfolio of human embryonic stem cell banks, mesenchymal stromal cells, and other cell lines. Not wanting to undergo significant renovations or a hiring spree, the organization reached for a low-maintenance stacked system that exponentially grew its cubic footprint.

Did it work? With a 250% jump in production power and only a modest 20-25% bump in costs, it's safe to say it did.

Scaling Up Allogeneic Cell Therapies: A Biomanufacturer's Success Story

From CellSTACK to HYPERStack

Waisman's move started with a transition from the facility's Corning® CellSTACK® platform to the high-capacity Corning® HYPERStack®, which expanded their existing stack system from 10 layers to 36 per vessel. Doing so provided more than three times the growth area of their legacy process but with similar space requirements. And because the new setup featured an easy closed-system gas and fluid exchange, the company didn't require more staff to manage the higher yield.

Those advantages carried through when Waisman connected 15 HYPERStacks together with tubing manifolds. Having all vessels operate as part of a single closed system created an aseptic process through and through for changing spent media and harvesting cells, even when the system wasn't under a biosafety cabinet.

Of course, one persistent challenge with these systems is the lack of process control. Whereas bioreactors have sensors that assess pH and oxygenation, you don't get that real-time monitoring with a stacked system, so you might not know how well the cells are doing. But Waisman addressed that too by using Corning® HYPERFlask® vessels alongside the large manifold setup as a sort of surveillance system. By looking at how cultures grew in the single vessel, Waisman's lab technicians could better predict the performance of the HYPERStacks in response to timelines for media changes or harvesting.

A Modular Approach for Multiple Applications

The approach Waisman Biomanufacturing used for this transition could be replicated by any other lab looking to expand capacity for allogeneic cell therapies without significantly increasing the costs or resources required. This is because the approach is modular.

Waisman used a manifold set of 15 HYPERStacks. Others might need less or more depending on t heir process and they can achieve their specific objectives with the same benefits of a compact footprint, moderate cost and labor.

Automation can also support a modular process when it's compatible, as the Corning® Automated Manipulator Platform is with HYPERStack and CellSTACK vessels. The manipulator platform generates the precise movements needed to apply disassociation reagents when it's time to harvest. But then again, you don't need those automations if you don't want them, or at least not right away.

After all, the benefit of being modular is that you can add capabilities as workflow demands evolve, without the need to invest in an entirely new system. As allogeneic therapies become more popular — and production needs change with market conditions — the ability to enhance an existing process to quickly increase scale offers a definite benefit to time-crunched biomanufacturers.

Making Medicine for the Masses

The demand for allogeneic cell and gene therapies is on the rise, so manufacturers will need to assess their current and projected production capacity to ensure they can take advantage of the many opportunities these one-to-many programs can bring. If adherent scale-up is a concern, consider how compact solutions like HYPERStack could help generate a more efficient yield in a relatively small footprint.

In Waisman's case, the biomanufacturer saw capacity gains equating to roughly 10 times the investment cost in their increased operating budget. This enhanced the company's ability to deliver the required cells for master and working cell banks, as well as the actual product. In a time when biotech competition is crowded but resources are slim, the impact of that ROI can make all of the difference.