Why CMC Is Becoming a Strategic Priority in Cell Therapy Development
As cell therapy development matures, manufacturing readiness is becoming a key determiner of success.
Cell therapy has shown remarkable success in the treatment of hematological cancers and is now expanding into broader disease areas, including treating solid tumors and autoimmune diseases. As cell therapy innovation matures, success increasingly depends on how well therapies are developed, characterized, and manufactured.
In an IBTV x Technology Networks Expert Perspectives episode, John Tomtishen, global head of cell therapy field application scientists and strategic alliances at Catalent, explained why chemistry, manufacturing, and controls (CMC) considerations are shifting from a late-stage requirement to a central pillar of successful cell therapy development.
The importance of CMC in cell therapy development
CMC encompasses the processes, testing, and documentation required in pharmaceutical production and quality control. It is typically more complex for cell therapy development compared to small molecule drug development due to the biological nature of the starting and end products.
Strict CMC regulatory expectations are reflected in the number of cell and gene therapy programs that become stalled—not by safety or efficacy concerns—but by shortcomings in manufacturing readiness.
In 2025, the US Food and Drug Administration (FDA) released over 200 Complete Response Letters (CRLs), which are issued in response to either a new or amended drug application or a biologics license application, informing the submitter that the application will not be approved in its current form. Analysis of the published CRLs revealed that 74% of those issued between 2020 and 2024 were in response to quality and manufacturing deficiencies.
The FDA has since announced information on its new approach to overseeing CMC requirements for cell and gene therapies, highlighting a shift towards more flexible, risk-based frameworks.
Ever-changing regulatory expectations have placed greater pressure on early-stage development decisions. “I think one of the key things for cell therapy and therapeutic developers within the space is really to think about CMC at the beginning,” said Tomtishen.
A key part of this is defining critical quality attributes (CQAs), potency, and measurable product characteristics early in the development process.
“Whether you're using a lentiviral vector or nonviral delivery for your gene of interest, I think it's really critical to think about the overall holistic approach of ultimately how you characterize your drug product and then ultimately understand your CQAs as you advance your product from pre-clinical development to commercial licensure,” Tomtishen explained.
Historically, many cell therapy developers have focused on proof-of-concept and early clinical milestones, deferring CMC to later stages. It is at these later stages when manufacturing and regulatory challenges often emerge, by which time process changes are more difficult and expensive.
Many developers are now investing earlier in manufacturing infrastructure, building internal teams with deep technical expertise, or forging strategic partnerships with contract development and manufacturing organizations (CDMOs) to ensure CMC planning is in place. This can help reduce the risk of redesigning manufacturing processes during late-stage development and ultimately allows you to streamline comparability studies.
AI-driven technologies and partnerships are becoming competitive advantages
Another key challenge in cell therapy development is managing inherent variability. In autologous cell therapy, where cells are collected from a patient, patient histories, disease states, and prior treatments can all introduce substantial variability. Downstream, this can make it difficult to achieve the specific CQAs and release specifications for that drug product.
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Tomtishen believes that leveraging AI and predictive modeling could help simplify some of the inherent complexity of cell therapy manufacturing.
“If you have well-characterized starting material, then you can understand how that product is going to interact or interface throughout that manufacturing process,” he said. Combining this with process analytical technology enables a greater view of real-time processes. “So you really have that overall overarching understanding of the drug product as you manufacture that for a specific patient.”
Partnerships and integration that harmonize individual expertise can also give a cell therapy developer the edge. “I think that's one of the benefits of working with the CDMO. So, leveraging your scientific understanding, the therapeutic that you developed, and then ultimately leveraging CDMOs' CMC expertise to take your drug product from pre-clinical development to commercial licensure,” Tomtishen explained.
CDMOs that colocalize manufacturing, quality, and technical development teams can leverage their expertise early in the decision-making process to help developers determine their quality target product profile and address issues or challenges as they arise.
As cell therapy development matures and the industry broadens into new disease areas, product characterization and manufacturability are becoming critical success factors. Success will rely on leveraging strategic partnerships that can help developers navigate technical and regulatory complexity. “I think there's going to be a lot of focus on building strategic collaborations with partners that really complement your skill sets and complement your science to get your therapy into the hands of patients faster,” concluded Tomtishen.
About the interviewee:
John Tomtishen is the global head of field application scientists and strategic alliances at Catalent. He is a cell therapy industry veteran and a recognized CMC leader within biopharmaceutical manufacturing, having served in diverse business and technical roles throughout his career. Tomtishen played pivotal roles in the filing and approval of the first CAR T-cell therapy, Kymriah™ (tisagenlecleucel), while at Novartis, and the clinical development and commercial filing of Carvykti™ (ciltacabtagene autoleucel) at Legend Biotech.
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