On May 9, the Friends of Cancer Research and the Parker Institute for Cancer Immunotherapy hosted a public meeting focused on regulatory and manufacturing approaches to increase access to cell therapy products for small patient populations. Here, AgencyIQ provides a summary of the key points of discussion, including the FDA’s communication channels and postmarket surveillance.

Background: FDA’s oversight of cell and gene therapy products

• Applications for cell and gene therapy, or CGT, products are reviewed by the Center for Biologics Evaluation and Research’s Office of Therapeutic Products. Formerly known as the Office of Tissues and Advanced Therapies, OTP is responsible for the review of cellular therapies, gene therapies, therapeutic vaccines, and plasma-derived and coagulation products. Part of the reason for the office’s rebrand and reorganization in 2022 was to accommodate the surge in CGT products submitted to the FDA in the past five or so years and to “improve functional alignment, increase review capabilities, and enhance expertise on new cell and gene therapies.” [Read Agency IQ’s breakdown of the reorganization here.]
• Since the FDA approved its first gene therapy product in 2017, the agency has quickly racked up experience reviewing CGT products. By 2020, CBER had received more than 900 investigational new drug applications – a significant increase from previous years. OTP currently lists 44 licensed CGT products on its webpage.
• Over the years, the agency has leveraged its experience to build out its CGT guidance portfolio. Following a series of guidance documents in January 2020 focused on gene therapies, the suite now addresses a wide range of considerations, including manufacturing changes, potency assurance and disease-specific product development.
• In November 2024, the agency published a key draft guidance in line with capacity-building commitments under the most recent iteration of the FDA’s Prescription Drug User Fee program, PDUFA VII. The draft guidance features 36 questions and responses on four topics: interacting with the FDA; product development considerations, conducting nonclinical studies and conducting human trials. [Read full AgencyIQ analyses of the guidance content and subsequent stakeholder comments here.]

Regulatory context: Zooming in on emergent cell therapies

• Chimeric antigen receptor (CAR) T cell therapies are a form of adoptive cell therapy, where naturally occurring immune cells are genetically modified to enhance their capabilities. CAR T has demonstrated success treating several types of hematologic malignancies, with six products approved by the FDA, and work is underway to use the approach for other indications.
• The process to manufacture these products is complex and has important implications for the risks associated with them. In brief, the first half of this process relates to the development of a suitable vector to deliver the genetic material (called a CAR construct) into the T cells. Lentiviral and retroviral vectors have been predominantly used to date given their ability to efficiently infect cells, leading to long-term integration of their genetic “cargo” into the host cell’s genome. First, the vectors must themselves be genetically modified (often in several steps) before being exposed to the T cells. Next, the T cells are transfected with the genetic material (via the vector) so that they express the CAR construct. Finally, the now-modified CAR T cells are administered to patients intravenously. Although current methods entail the transfection of genetic material in the ex vivo setting (in which the cells are harvested and modified outside the patient’s body), the scientific community is seeking ways to direct the transfer of genetic material to T cells in vivo, without having to harvest cells from the patient at all.
• A few primary concerns regarding gene therapies with integrating vectors, including CAR T cell products, are the potential for vectors to generate a replication-competent retrovirus and the ability of the vector to integrate into the cell genome at sites responsible for regulating internal or external cellular processes, such as tumor suppressor genes. There are a few instances in which vector integration has triggered the activation of oncogenes or the deletion of tumor suppressor genes in patients administered CAR T cell therapies.
• The FDA issued draft guidance on developing CAR T cell therapies in March 2022 and finalized its guidance in February 2024. The introduction explains that information in the guidance can be generally, “applicable to other genetically modified lymphocyte products, such as CAR Natural Killer (NK) cells or T cell receptor (TCR)-modified T cells,” though those classes have some unique considerations. Half of the content presented in the final guidance relates exclusively to chemistry, manufacturing, and control, or CMC. The agency recommends rigorous testing of starting materials, product intermediates, and final drug products; the need for early development/qualification of suitable assays to characterize and assess the product; and the importance of stability studies, among others. Additional recommendations cover product design, nonclinical studies, clinical trial design and follow-up. [Read full AgencyIQ analysis here.]
• Between publication of the draft and final versions, the FDA released information on secondary cancers occurring in patients who had received CAR T treatment. In late 2023, the agency issued a safety alert saying that case reports indicate that the “risk of T-cell malignancies is applicable to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T cell immunotherapies.” The alert added, “Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies.” This was followed by early 2024 safety communications that directed manufacturers of all CAR T cell products to incorporate a Boxed Warning to their safety labeling, and an article in The New England Journal of Medicine by then-CBER Director PETER MARKS and OTP Director NICOLE VERDUN.
• The journal publication mentioned that FDA guidance recommends that “people who receive CAR T cells engineered with integrating vectors be monitored for extended periods for adverse events, including cancers.” That said, the final guidance does not require lifelong monitoring, instead maintaining that “subjects should be followed for 15 years after treatment with CAR T cells containing an integrated transgene,” with some flexibility depending on the features and indication. The final guidance adds that sponsors should develop a plan for “follow-up, including funding, in the event the sponsor ceases to operate or decides to inactivate, transfer, or withdraw the IND [investigational new drug application] before completion of the long term follow up.”

On May 9, 2025, stakeholders convened to discuss ideas to scale up availability of cell therapies

• Titled “Unlocking Next-Generation Therapies,” the meeting was jointly hosted by the Friends of Cancer Research and the Parker Institute for Cancer Immunotherapy. The meeting’s scope applied to genetically modified cell-based therapies, including both CAR T and T cell receptor-based approaches. The agenda featured remarks from stakeholders representing academia and industry, along with discussion panels that included the perspectives of some of the FDA’s top CGT regulators.
• Prior to the meeting, the organizations published a white paper that calls for “a structured approach … that balances regulatory oversight and development of evidence to demonstrate safety and effectiveness with operational feasibility and sustainable reimbursement and/or cost recovery.” From the regulatory angle, the paper recognizes existing flexibility in the development and approval of these products but argues that “the how and when” of regulatory flexibility for CMC requirements should be more clearly defined. Specifically, the whitepaper proposes, “FDA could consider issuing guidance to clarify fit-for-purpose, adaptable CMC requirements that may be acceptable for genetically modified cell-based therapies in rare or underserved populations.”
• In opening remarks, Stanford University professor CRYSTAL MACKALL said, “The problem of high costs of development are limiting innovation across the spectrum, and this problem is magnified for rare disease.” Mackall mentioned FDA Commissioner MARTIN MAKARY’s recently floated “conditional approval” pathway for certain rare disease drugs, and the particularly high unmet need in rare diseases was a key theme of the ensuing discussion.

The meeting participants discussed the role of OTP in providing feedback and how to streamline the flow of information to and from reviewers

• Verdun said she sees “some opportunities for earlier thought in terms of the CMC and manufacturing piece.” This can take the form of meetings with the agency earlier in the development and application cycle. According to Verdun, thorough early characterization of the product can aid future needs to switch aspects of manufacturing, especially because the move from academic to commercial settings can be a regulatory pain point. She emphasized the importance of aligning with the FDA’s advice, saying that there have been cases where a clinical program does not incorporate recommendations, “and then we have this wonderful clinical data at the end, and we still have all of these CMC pieces that are not there.” She later highlighted the CMC Development and Readiness Pilot program [Read AgencyIQ analysis here.], which currently has four participants, and the Regenerative Medicine Advanced Therapy and Breakthrough Therapy designations as important existing pathways to increased interactions.
• “We’re not the same FDA that we were 10 years ago,” Verdun pointed out, explaining that the agency’s approach to solving problems in the CGT space has evolved with experience. She encouraged developers, including those with stalled programs, to “set up meetings with us and come back and talk to us.”
• Other speakers on the panel agreed with the value of the FDA’s advice and sought ways to disseminate it beyond individual meetings and applications. Mackell expressed appreciation for the agency’s willingness to meet with developers, saying, “But I think there is also value in putting out some of these ideas in print that basically say we have flexibility around manufacturing, decentralized manufacturing, small batch.” She emphasized the importance of understanding regulatory risk for products for small populations that need investment to move development forward. KRISTEN HEGE, a member of several companies’ independent boards of directors, pointed out, “You comment the FDA evolves as the field evolves, but most sponsors aren’t aware of all the feedback you’ve given to the hundreds of other applicants.” She proposed sharing de-identified case studies that include information about interpretating regulations in different disease contexts, emphasizing that there can be convergent biology across products.
• Verdun encouraged collaboration and intentional data sharing among sponsors, particularly in the rare disease space. In the second panel, OTP Division Director KIM SCHULTZ echoed the sentiment, saying, “We can’t go out and tell everybody else’s trade secrets. That’s not where we live, but we do have mechanisms where we try to answer questions in a large format.” She pointed to the OTP town halls as a key opportunity for asking pointed questions and sharing information about guidance interpretation. The office held its ninth town hall on Dec. 12, 2024, focused on “best practices for regulatory interaction.” [Read full AgencyIQ analysis here.] While these meetings were held every few months beginning in 2022, the office has not hosted a meeting in 2025.
• “How can we get to a place where we’re using more platform-like approaches, where we are sharing information across those types of programs?” Verdun asked. From a review standpoint, she emphasized that the agency is “very comfortable in a space where we allow leverage across programs, if it makes sense.” She clarified that the agency’s formal Platform Technology designation program requires an existing FDA approval [Read AgencyIQ’s analysis of the May 2024 guidance document here], but her office aims to “move well beyond that.” For example, prior to having an approved therapy, the office sees “backbones that are being used across six, seven different indications” that leverage common nonclinical and CMC information.

Stakeholders addressed how to set appropriate roles and responsibilities for postmarket studies and registries

• From an industry perspective, requirements around these studies may have a chilling effect on development. Hege pointed out that these studies are completely funded by sponsors, saying that 15 years of follow-up may disincentivize development for rare diseases. “I mean, it’s incredibly important. Why not have the payers pay maybe?” she asked.
• LEE FLEISHER of Rubrum Advising (and formerly of the Centers for Medicare & Medicaid Services), painted a different picture of the resources required for these studies, which could potentially leverage existing data. “If you truly have interoperability, then most of the data will be in the [electronic health records],” he said. “You will be able to do this at low burden. So rather than industry pushing against this, we should all push towards interoperability and have the FDA be able to analyze it.”
• The University of Pennsylvania’s HOLLY FERNANDEZ LYNCH cautioned against overreliance on registries to answer certain questions. “What makes me worried is when we talk about things like the Promising Pathway Act, or this new kind of rare disease pathway that’s been floated, and the idea that maybe registries can substitute for other, more rigorous ways of knowing. And I think they all have a role to play. I get nervous when it comes to substitution.”

Analysis

• The meeting discussed additional methods to scale up cell therapy availability outside the FDA’s immediate purview, ranging from cost recovery to distributed manufacturing systems. From the economic side, a common refrain among stakeholders is that under the current paradigm, payers are not willing to cover cell therapies without an FDA approval.
• Will the agency act on calls for increased communications around CMC recommendations? Some traditional channels include holding meetings with sponsors and OTP Town Halls or issuing guidance documents. In light of a slowdown in meetings following the administration transition, and new deregulatory orders, the FDA may look to different approaches.
• The suggestion to release “case studies” has some recent precedent in the rare disease space. In March 2025, the FDA began to update the webpage of its Learning and Education to Advance and Empower Rare Disease Drug Developers, or LEADER 3D, program to new case study resources. These documents currently focus on six “success stories” and intend to showcase approaches for the design and conduct of rare disease drug development programs. While these resources mostly focus on the later stages of development (such as clinical trial design), a CMC-based approach could meet the needs of the cell therapy stakeholders.
• The discussion around the scope of cell therapy postmarket requirements comes as new FDA leadership looks to enhance the agency’s surveillance systems. As AgencyIQ recently discussed, FDA Commissioner Makary expressed his position in a recent media interview that real-world monitoring of authorized products should be a priority for the agency. “If we have massive electronic health record data, which we now have through something called the Health Information Exchange, we can have researchers go into there and look at real-world complication rates” as a tool for comprehensive post-market surveillance, Makary asserted. He also discussed how having better real world data-based postmarket surveillance may even support a reduced evidentiary burden in premarket settings. The FDA has also recently released two notices regarding data standards for regulatory use [See AgencyIQ analyses here and here.]

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