Strategies To Support Commercially Ready iPSC Therapeutics

Induced pluripotent stem cells (iPSCs) were first discovered in 2006, but two decades passed before the first therapeutics based on this technology were approved. Even then, only two iPSC-based therapies were approved—in one country—on a time-limited, conditional basis.

Like a diamond in the rough, iPSCs hold significant therapeutic potential, but this can only be realized following extensive cutting, polishing, and refining.

In a recent IBTV x Technology Networks Expert Perspectives Episode, Dr. Delara Motlagh, chief operating officer at Fujifilm Cellular Dynamics, shared her perspectives on the challenges in iPSC-based therapy development and how to anticipate and overcome them.

iPSCs hold potential, but scalable therapies are not promised yet

After decades of research, the value of iPSC-based therapeutics is finally reaching clinical practice. For example, of the two aforementioned approvals, one followed the results of a Phase 1/2 trial that demonstrated improved motor scores following dopamine-producing iPSC cell transplantation into the brains of patients with Parkinson’s disease.

However, therapeutic potential does not always translate into promise. And this holds across other applications of iPSCs: disease-in-a-dish modeling, drug discovery, and toxicology screening.

“If you look at the different stages of development from discovery through manufacturing and scalability, there are a few key challenges that must be tackled earlier on,” commented Motlagh. She highlighted two points that can be overlooked early on, leading to barriers in therapeutic production later down the line:

1. iPSCs are a cell source, not the final therapeutic material.
2. Scalability depends on a reproducible process.

She expanded on the first point: “One of the early things that must happen is determining what the cell type that you’re differentiating into is, and establishing the process that can efficiently generate this.” This presents a scientific challenge and a manufacturing challenge, as the process needs to be scalable from the start.

“You need to have something scalable from the beginning.” — Dr. Delara Motlagh.

Scalability led Motlagh to her second point: “Once you move into the manufacturing environment, you have a reproducible process that you have defined. Now it needs to be put into a standardized, repeatable process that works across various hands. This is where the translation of the science hits the engineering.”

Designing scalability into the process for commercially ready iPSCs

Motlagh separated scalability into two camps: “There's the scaling of the actual iPSC banks in order to have source material for your cell therapy, and then there's the scaling of the final cell type.”

“Your scaling strategy may be to make a large number of iPSC banks, and then do the differentiation, so you minimize the scale of the final cell. Or you may take the opposite approach, where you will scale the banks to a smaller extent, but those banks can be differentiated, and then that cell product can be scaled,” Motlagh explained. She highlighted that the cell type being produced, its characteristics, and its amenability to multiple rounds of replication will guide prioritization of scalability.

In discussing strategies, Motlagh circled back to one of those key determinants of scalability success: “Ultimately, as you scale your process, it's not just about the final number; it's about the reproducibility at each step of that process.”

And in process development, she highlighted “quality by design” as critical for teams to work proactively rather than reactively. “At the beginning of the process, when you know what it is you're trying to make, defining what that product end state looks like early is really important,” Motlagh commented. She highlighted several process development considerations:

• Phenotypic features of the product cell (size, shape, structure)
• Behavioral characteristics of the product cell (movement, signaling, cycle phase)
• Cell viability

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“Defining these early gives you a roadmap to be able to do the process development thoughtfully,” Motlagh added. When both the end and the beginning are known, along with the route from one to the other, process parameters for reliable manufacturing are built in rather than considered as an afterthought.

The process should come before the platform in iPSC workflows

Platform-based approaches are increasingly recognized as essential for achieving reproducibility and scalability in iPSC-based therapeutic production.

In a 2025 study, Shimizu et al. developed an automated, closed-system workflow for autologous iPSC production. Within this, they developed a single-device process that conducted key workflow steps that would typically be isolated. Through optimization, they enhanced the development of therapeutic cells and improved workflow reproducibility. “The approach offers a practical pathway toward standardized, cost-effective manufacturing to support future clinical applications in cell therapy and regenerative medicine,” said the authors.

“Platform development is key for cell therapy overall,” noted Motlagh, though she cautioned that platforms are not a stand-alone solution. “The platforms themselves will not solve the problem… You must first have a process that’s ready for that automation in those platforms, and then it works hand in hand.” She referenced bioreactors as an example of why developers need a process in place before going straight to a platform. Although bioreactors support large-scale production, they are less amenable to adherent cells, so standard bioreactor platforms will not suit every workflow.

“Understanding the dynamics of your cell type will be very important in choosing that platform,” commented Motlagh. “Then, incorporating that in your development early allows you to save a lot of time—not only in development, but once you hit clinical—to minimize the changes you need to make later.”

Ensuring regulatory readiness and accessibility of iPSC-based therapeutics

Once developers have bridged biology and engineering to develop a scalable, reproducible iPSC-based therapy, they face another challenge: ensuring that the entire process meets regulatory standards.

Motlagh outlined two key factors, inherent to iPSC-based therapies, which can create challenges when it comes to regulatory approval:

1. Many iPSC-based therapeutics begin in academic settings. Despite “fantastic science at the bench,” these are open systems that are not designed for scale or regulation.
2. iPSC-based therapeutics are “living therapies.” Compared with traditional pharmaceuticals, this raises a different set of questions about when a therapy is ready to enter human trials. As a result, there is an inconsistency in regulatory standards worldwide.

Both regulatory and manufacturing readiness are continuing to evolve as the industry matures. Motlagh advised developers to consider the whole process from both perspectives, early on. From selecting source material to selecting product vials, each step should be suited to Good Manufacturing Practice standards and supply chain capabilities.

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“These are important considerations that, for iPSCs in particular, have become more accelerated. As these programs enter the clinic, they are enjoying more accelerated regulatory approval periods,” added Motlagh. “[Therapies] may go from an early human phase straight into a pivotal trial. After your pivotal trial, you don’t want to be making a lot of changes.”

The manufacturing process, alongside other factors, is critical beyond regulatory requirements; it will determine whether the therapy reaches patients following approval. “Access comes in different ways,” said Motlagh. “There is physical access… a lot of education is needed for physicians as well as for patients themselves. Then there is access in where these [therapies] can be made. Are they off the shelf? Do they require an intricate network? iPSCs serve that [accessibility] purpose well as an off-the-shelf solution.”

The other side of accessibility is affordability, and Motlagh explained that a balance must be met. Processes need to be streamlined to the point that the cost of goods—and therefore the therapeutic price tag—is reduced, but not so much that developers lose their incentive.

The future of iPSC-based therapeutics: scale, compliance, and access

The potential of iPSC-based therapies is clear, and the clinical need is evident, particularly in regenerative medicine. But whether iPSC-based therapeutics actually deliver hinges on three critical questions: Can they be produced on a scale? Is the process that produces a given therapy at scale compliant with regulatory standards? And, with both of those factors met, can the therapy reach patients?

According to Motlagh, next-generation engineering techniques and novel differentiation tools have already “bolstered” the use of iPSCs as a source for cell therapies. For example, gene editing can be used to produce hypoimmune cell lines, enabling them to evade immune detection and destruction.

“Innovation continues, and it becomes very important when you think about making [therapies] more accessible in various indications where you want to deliver them without [adverse] reactions,” she noted.

“I’m quite optimistic about what [these tools] will do for their scalability,” Motlagh concluded.

About the interviewee:

Dr. Delara Motlagh is chief operating officer at Fujifilm Cellular Dynamics. She has more than two decades of experience in the biomedical and healthcare field, with insights spanning research and development, operations, manufacturing, and market access.

Motlagh has expertise in commercial strategy and product development across pharmaceutical drugs, biologics, and medical devices, particularly in the cell and gene therapy market.