Inside Scaling Next-Gen MSCs Without Scaling Risk
By Erin Harris, Editor-In-Chief, Cell & Gene
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Scaling a cell therapy is never as simple as making more cells was one of the clearest takeaways from our recent Cell & Gene Live, “Scaling Next-Gen MSCs Without Scaling Risk.” For this one, I was joined by three luminaries with firsthand experience developing and manufacturing MSC therapies. Miguel Forte, M.D., Ph.D., CEO and Co-Founder of Kiji Therapeutics and immediate past president of ISCT; Michael Schuster, Co-Founder and Head of Business Development at Mesoblast; and Ed Ahn, Ph.D., CEO and Director of MEDIPOST, brought perspectives spanning adult donor-derived, umbilical cord-derived, and iPSC-derived MSC approaches.
One of the most important themes of our discussion was the challenge of maintaining product consistency as manufacturing evolves. Early clinical success can create momentum, but changes made during scale-up can introduce new questions around potency, comparability, and ultimately clinical performance.
“The product is the process,” said Schuster. “The product must stay the same as the process scales.”
Dr. Forte emphasized that scale-up needs to preserve the connection between what the cells do and the therapeutic benefit they are expected to deliver. “It is the consistency; it's the comparability; it is the characterization to make sure that throughout the scale up, you maintain your product as it is linked to the benefit that you’ve documented,” he said.
That becomes particularly important as companies consider changes to manufacturing platforms, automation, formulation, or other elements of the process. As our panelists discussed, what appears to be a relatively small change can have implications that are not immediately apparent.
Cell Source is Only the Beginning
Our panelists also explored how different approaches to sourcing MSCs can shape manufacturing strategy. Donor-derived bone marrow and umbilical cord-derived MSCs bring their own considerations around donor variability and expansion, while iPSC-derived approaches offer a different path toward consistency in starting material.
Dr. Forte discussed how Kiji Therapeutics is approaching iPSC-derived, gene-engineered MSCs and the potential advantages of establishing a consistent cell source. “Once we establish the master cell bank, then we have a consistency throughout the process because there’s no variability from the point we establish the master cell bank,” he said.
Regardless of the starting material, our panelists agreed that developers need a clear understanding of what defines their product and which characteristics are tied to function and potency. Schuster pointed to the complexity of MSC biology and the importance of understanding the many factors that contribute to therapeutic activity.
“It’s every step along the way, screening, testing, showing assays that ensure you have identified the right cells, that they haven't been changed,” said Schuster.
Comparability Cannot be an Afterthought
Our conversation also highlighted a difficult reality for emerging MSC companies. The process used in early clinical development may not be the process ultimately needed for commercial manufacturing. Companies therefore must make decisions about when to optimize, when to make changes, and how much risk those changes are introduced.
Dr. Ahn noted that the key is understanding the relationship between manufacturing conditions, product biology and clinical function as early as possible. “The question will be unique for every development team in terms of what they’re trying to optimize for,” he said. “It may be time; it may be money; it may be some critical process parameter or product performance.”
That tension becomes especially important as companies approach pivotal development and begin thinking about commercial readiness. The panel discussed why making a manufacturing change simply because it improves efficiency or economics may not be as straightforward as it appears.
A Practical Take on AI for Manufacturing
AI also came up as an emerging opportunity, but our discussion was notably practical. Rather than treating AI as a solution to every manufacturing challenge, we discussed where it could potentially help with automation, data analysis, process development, and identifying relationships across large datasets. Indeed, the bigger opportunity may be the data infrastructure companies build today. “The AI model is cheap,” said Ahn. “It’s the training data that’s expensive.”
Dr. Forte added that biotechs will need to think carefully about the investment required to build AI tools that are tailored to their processes and datasets. “It needs to have specific AI programs written on the base of existing, but needs specification, which requires quite a bit of investment,” he said.
We wrapped up our discussion by asking each expert what they would prioritize before a company enters pivotal development. The answers reinforced our major discussion topics, including manufacturing strategy, and that product characterization and comparability need to be considered well before a company is under pressure to produce a commercial-scale product.
For MSC developers, the challenge is not simply increasing manufacturing capacity. It is increasing capacity while maintaining the biological characteristics, potency, and consistency that support clinical data.
There was much more ground covered during our discussion that you’ll want to check out, including cell sourcing, donor variability, passage number, cryopreservation, regulatory considerations, and more. Be sure to tune in to our full conversation that offers a deeper look at the decisions that can shape a program well before commercialization.