The advancement of induced pluripotent stem cell (iPSC) technology has transformed regenerative medicine, enabling innovation in disease modeling, drug discovery, and cell replacement therapies. 

iPSC-based medicines use reprogrammed adult cells to treat diseases through regenerative therapies and disease modeling. Some examples include repairing heart tissue with iPSC-derived cardiomyocytes, replacing neurons in Parkinson’s disease patients, and developing retinal pigment epithelium for macular degeneration.

FUJIFILM Cellular Dynamics, a provider of iPSC technology for research and cell therapy, has worked to enable the development and manufacture of scalable, high-quality iPSC-derived cells for advanced therapies.

Nina Bauer, EVP Strategy & Commercial at FUJIFILM Cellular Dynamics shares insight on key challenges with scaling iPSC-based therapies, successful manufacturing, how the company helps support developers heading towards commercialization.

Contract Pharma: What are the key challenges associated with scaling iPSC-based therapies?

Nina Bauer: There is a set of interconnected challenges for iPSC therapeutic development that begin very early in development and extend through commercialization. Sometimes, early strategies that seem “good enough for preclinical work” can later constrain scale-up and the potential to reduce costs through optimization.

One of the most critical early hurdles is selecting and then validating a high-quality iPSC line that can support long-term expansion, maintain genomic stability, and demonstrate consistent differentiation performance over many years of manufacturing. Confirming genomic stability is both time-consuming and costly, particularly as whole-genome sequencing has become a regulatory expectation. Programs that start with well-characterized iPSC lines are better positioned to manage downstream risk and timelines.

With allogeneic therapies, another foundational challenge is establishing robust master and working cell banks. Allogeneic programs must ensure that their master cell bank is sufficiently large and reproducible to support multiple working banks across the full lifecycle of development and commercialization. Banking strategies must preserve high post-thaw viability, recovery, and retained differentiation capacity, as variability at this stage can become a root cause of inconsistency later in manufacturing.

People often expect expansion to be difficult at scale, but differentiation is where programs struggle most. Differentiation is one of the most sensitive and complex aspects of iPSC-derived therapy development. Achieving batch-to-batch reproducibility at commercial scale requires tight process control, in-process testing strategies that represent the full batch, and an understanding of how scale-up and scale-out affect product quality attributes.

Raw material sourcing introduces additional constraints. Many differentiation processes rely on specialized, fully defined GMP-grade reagents that are expensive and subject to lot-to-lot variability. GMP-grade materials are often not available, requiring the use of clinical- or RUO-grade materials that require extra steps to ensure their safe use and mitigate risks, such as strong testing strategies and robust raw material qualification programs. At the same time, there is increasing pressure to eliminate animal-derived components.

Finally, quality control, regulatory, and economic pressures converge as programs mature. iPSC-derived products require extensive genetic, phenotypic, and functional characterization, along with long-term safety validation. Developers must balance the need to reduce cost of goods and improve yields while making significant upfront investments in cell banking, analytical development, facilities, and talent capable of operating at the interface of R&D innovation and GMP commercialization. 

Contract Pharma: What capabilities are needed to produce iPSC-based therapies, and how can these challenges be addressed?

Nina Bauer: Successful manufacturing requires an integrated set of capabilities that span development, manufacturing, analytics, and regulatory strategy. 

A foundational capability when producing iPSC-based therapies is the ability to perform thoughtful risk assessments across all stages of a program – with an understanding that not all risks can be fully eliminated.

Manufacturing iPSC banks requires a combination of scientific expertise and operational understanding. Programs need well-defined SOPs and manufacturing procedures, as well as GMP-compliant infrastructure capable of supporting both master and working cell bank strategies. Closed culture systems that enable media exchange, cell harvest, wash, and concentration help improve reproducibility and scalability. Banking strategies must also remain adaptable to the stage-specific needs of individual programs.

Scalable differentiation and bioprocessing capabilities are equally critical. Robust process development and optimization – particularly for lineage-specific differentiation – must be paired with bioreactor and scale-out strategies that preserve product quality. These processes need to be designed with in-process monitoring and downstream testing in mind from the outset.

Analytical development underpins all these efforts. Comprehensive assays for identity, purity, potency, safety, sterility, genome stability, and residual iPSC detection are required across iPSCs, drug substance, and drug product. Technologies such as single-cell RNA sequencing and whole-genome sequencing provide deeper insight into batch-to-batch consistency and off-target populations, while clearly defined target product profiles help guide clinically relevant potency assays. Seamless tech transfer from analytical development into QC hinges on utilization of well-understood and managed equipment and robust training, which can reduce the need for late-stage comparability studies.

Finally, early regulatory alignment is critical. Risk-based CMC strategies that focus on the most clinically relevant critical quality attributes, combined with documentation readiness and familiarity with IND submission requirements, help minimize costly changes as programs approach commercialization. 

Contract Pharma: How does FUJIFILM Cellular Dynamics help support developers heading toward commercialization?

Nina Bauer: An experienced team like ours is well-positioned to address scaling challenges because we have taken cell therapies from preclinical development through commercialization.

With iPSCs, we provide highly characterized, high-quality cell lines that serve as reliable starting material, reducing variability and accelerating both early development and downstream manufacturing.

Our teams bring deep expertise in GMP manufacturing of iPSC-derived cell products, helping bridge the gap from research-grade processes to clinical and commercial-grade production. Our infrastructure is designed to support scale-up under controlled conditions, enabling developers to plan for commercialization while still in development.

In addition, developers can leverage our experience in custom iPSC engineering and differentiation. Our track record in genome engineering and lineage-specific differentiation, as evidenced by our off the shelf iCell(R) catalog products, allows knowledge generated in research settings to translate directly into cell therapy development programs. This includes proven approaches for achieving reproducibility and functional performance at scale.

With no approved iPSC-derived therapies in the market, most iPSC therapy developers have little experience meeting regulatory expectations, but we can support them. Regulators are familiar with our overall CMC processes and procedures, as well as our specific iPSC lines. FDA has Master Files on our lines that have been successfully cross-referenced in multiple IND submissions. We maintain robust documentation, traceability systems, and quality control assay development.

Early-stage start-ups are often challenged by financial constraints and internal capabilities. Larger CDMOs may suggest experience but can come with limited focus on smaller customers. We know what developers go through and work collaboratively to leverage our experience to help them navigate product development, scale-up, and commercialization.