Feb 18, 2025

Understanding the FDA’s Role in Cell and Gene Therapy

Effective regulation of emerging highly personalized cell and gene therapies is crucial in ensuring the safety and efficacy of these groundbreaking treatments. FDA regulatory frameworks are designed to prioritize patient’s access to safe therapies by standardizing protocols, streamlining approval processes, and providing clear guidelines for developers. In the rapidly evolving field of cell and gene therapy, the FDA endeavors to address regulatory hurdles to foster an environment where innovative therapies can reach the market more efficiently, ensuring that patients benefit from the latest medical advancements without compromising safety.

Why Regulation Matters for Cell & Gene Therapy

Cell and gene therapies are predominantly developed to target rare diseases or highly specific genetic profiles and, therefore, are often tailored to individual patients, involving the modification of their own cells (e.g., autologous cell therapy) or genetic material. This high level of personalization poses unique challenges in terms of manufacturing, consistency across therapy developers, and logistics for timely patient treatment, among others. Moreover, the evaluation of personalized cell and gene therapies commonly involves small clinical trials with few patients, which complicates the review process and the demonstration of efficacy and safety.

Regulatory frameworks, like those established by the FDA, provide essential guidelines that help standardize these processes, ensuring that each therapy meets rigorous safety and quality standards. Clear and efficient regulatory pathways can expedite the approval process, allowing groundbreaking treatments to be delivered to patients more rapidly.

Key FDA Regulatory Pathways

In the cell and gene therapy space, various FDA regulatory pathways are designed to streamline the development and approval of these advanced treatments while ensuring their safety and efficacy. One notable pathway is the Breakthrough Therapy designation, which is designed to accelerate the development and review of therapies that show substantial improvement over existing treatments for serious conditions.¹ Another critical pathway is the Regenerative Medicine Advanced Therapy (RMAT) designation, specifically tailored for regenerative therapies, including cell therapies, therapeutic tissue engineering products, human cell and tissue products, or any combination of such therapies that demonstrate the potential to address unmet medical needs.² Additionally, the Fast Track designation facilitates the expedited review of drugs that treat serious conditions and fill an unmet medical need by providing more frequent interactions with the FDA and rolling review of the marketing application.³ These pathways, among others, are instrumental in reducing the time it takes for innovative cell and gene therapies to reach patients, ensuring that life-saving treatments are accessible more quickly while maintaining stringent safety standards.

Major FDA Updates Impacting Cell & Gene Therapy

From the first approvals of CAR-T cell and gene therapies in 2017, corresponding to Kymriah, an anti-CD19 autologous CAR-T cell for B Cell Acute Lymphoblastic Leukemia (ALL), and Luxturna for restoration of RPE65 gene expression in Hereditary retinal dystrophies, 22 therapies for cancer and rare disease indications are currently available to patients in the United States. The progress in the field has been remarkable, especially in light of the novelty and complexity of personalized cell and gene therapies.

Despite the breakthroughs and demonstrated high efficacy of these therapies, such as the long-term remission achieved by CD19 targeting CAR T cells in blood cancers and the resolution of severe vaso-occlusive crises in patients with Sickle cell disease by CRISPR/Cas9 engineered stem cells (i.e., Casgevy), experts agree that the newness of these approaches often presents many regulatory challenges, ultimately impacting innovation in the field and the accessibility of therapies to patients in need of one-shot cures.

Over twenty leaders and experts in cell and gene therapy from research, manufacturing, regulatory, and investment organizations gathered at the 2025 GenScript Biotech Global Forum (GenScript BGF) to share deep insight into the advancements and challenges that lie ahead for this highly innovative field. A central theme of the forum was the complexities of the regulatory landscape faced by developers of cell and gene therapies and how the FDA is taking steps to improve patient’s access to these innovative personalized therapies while prioritizing safety. Next, we highlight several significant regulatory developments that promise to help expedite safe personalized cell and gene therapies for patients in the United States.

CAR-T Cell Therapy Boxed Warning Update

In November 2023, adverse events in CAR-T cell therapy recipients were reported through the FDA Adverse Event Reporting System (FAERS). This database contains adverse event reports, medication error reports, and reports on product quality complaints resulting in adverse events. Briefly, the report indicated an increased risk of developing CAR T cell-related tumors in CD19 or BCMA CAR-T cell recipients. This report prompted the FDA to include a Boxed Warning to highlight the serious risk of secondary malignancies, implemented in January 2024.⁴

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In an effort to balance addressing safety concerns and promoting innovation in cell and gene therapy, the FDA is diligently communicating with leaders in the field and following up on data collected from the thousands of patients who have received CAR-T cell therapies to date. Ongoing studies from Dr. Carl June’s group at the University of Pennsylvania are shedding light on the safety of CAR-T cell therapies, indicating that the risk of secondary cancers in these patients is low and appears unrelated to CAR-T cell activity.

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Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research at the US Food and Drug Administration, emphasized that the agency has a greater understanding of the true low risk of secondary malignancies in CAR-T cell patients. Therefore, refinement of the Boxed Warning for CAR T-cells is expected in the near future, encouraging continued development of these therapies, especially for autoimmune diseases.

Decentralized Manufacturing: What It Means for the Industry

In the United States, production of the predominant autologous cell therapies, such as all approved CAR-T cells, has followed centralized manufacturing logistics to date.⁵ Briefly, the current centralized workflows rely on the handoff of the patient’s cells to commercial entities for process development and manufacturing, creating logistical challenges for the timely delivery of therapies to patients.⁵ Therefore, to facilitate patient’s access to innovative cell and gene therapies closer to home, in academic and ultimately community hospital settings, the field is eager to move towards decentralized manufacturing.

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To ensure high-quality and consistent cell therapy products across different sites, the field is increasingly looking towards facing out manual processes and implementing semi-automated to fully automated closed systems in manufacturing and quality control checkpoints. With decentralization, there are also concerns about data storage and sharing. Therefore, a robust digital infrastructure is critical, as emphasized by Dr. Jason Bock, CEO at CTMC, “one of the things that I think is critical, and we're moving that way, is digital quality systems, electronic quality systems. We need the infrastructure to be completely digital and interconnected.”

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The FDA is aware of the increasing dialogue and is exploring decentralized manufacturing models for CAR T-cells, particularly for smaller indications and solid tumors. About shifting to decentralized manufacturing of cell therapies, Dr. Peter Marks said, "We don't really care either way, as long as the products all end up being made with high quality."

Platform Technology Designation for CRISPR-Based Therapies

The first FDA gene-editing therapy approval in 2023 of a CRISPR/Cas9-based cell therapy marked a significant breakthrough. With hundreds of CRISPR/Cas-based cell and gene therapies at different stages of development, a priority is to streamline and facilitate the delivery of life-changing therapies to patients. With this goal in mind, in 2024, the FDA released a draft guidance for the industry about the provision: “Platform Technology Designation Program for Drug Development,” which aims to streamline drug development by recognizing and facilitating the use of well-characterized technologies that can be applied across multiple products.⁶

For CRISPR/Cas-based therapies, this program can significantly accelerate the approval process by:

• Improving Regulatory Efficiency – when a CRISPR/Cas-based platform technology (e.g., a gene-editing delivery system) is designated under this program, future drugs using the same technology may require less redundant testing, reducing regulatory burden.
• Standardizing Development Pathways – Once a CRISPR/Cas technology is reviewed and designated, sponsors can leverage established data to support new drug applications, expediting preclinical and clinical development.
• Facilitating Engagement with FDA – Companies using a designated platform technology gain enhanced interactions with FDA reviewers, leading to clearer guidance and faster resolution of regulatory questions.
• Reducing Preclinical Work – Since certain safety and efficacy aspects of the platform technology may already be evaluated, new therapies using the same platform may require less additional preclinical testing.
• Expediting IND and BLA Approvals – By relying on previously validated platform data, Investigational New Drug (IND) and Biologics License Application (BLA) submissions may be processed more quickly.

Overall, the FDA Platform Technology Designation helps CRISPR/Cas-based therapies by creating a regulatory framework that reduces redundancy, enhances consistency, and accelerates gene-editing therapy approvals, ultimately bringing treatments to patients faster.

Future Implications of FDA’s Regulatory Strategy

How These Changes Affect Research and Development

New FDA regulatory guidelines are significantly influencing cell and gene therapy research by streamlining the approval process and enhancing communication and collaboration between regulatory bodies and developers. The introduction of accelerated approval pathways allows for faster access to therapies by enabling the use of intermediate clinical endpoints and biomarkers, which can predict clinical benefits more rapidly than traditional methods.

Additionally, the FDA is working to harmonize review processes with international regulatory agencies, reducing the burden of reworking applications for different markets. This collaborative approach fosters innovation and encourages the development of therapies for rare diseases, ultimately aiming to bring effective treatments to patients more efficiently. Furthermore, the application of platform technology provisions, particularly in gene therapies utilizing similar vectors, allows for shared manufacturing information across products, potentially expediting the development of multiple therapies targeting various diseases.

What’s Next for the Cell & Gene Therapy Industry?

The future of the cell and gene therapy industry is poised for significant advancements driven by innovations in manufacturing and regulatory frameworks. With the increasing adoption of decentralized manufacturing models and automation technologies, the production of CAR T-cells and other therapies is expected to become more efficient and cost-effective. The integration of genome editing tools like CRISPR is opening new avenues for developing allogeneic CAR T-cells, which could enhance treatment options for solid tumors and rare diseases.

Regulatory bodies are also working to streamline approval processes, allowing for accelerated pathways that can bring therapies to market more rapidly. Additionally, the application of platform technologies will enable the development of multiple therapies from a single manufacturing process, potentially addressing a broader range of diseases. Overall, the industry is on the brink of a transformative phase that could lead to a substantial increase in the number of available cell and gene therapies and improved patient outcomes.

Reference

• FDA (2018). Breakthrough Therapy Designation. www.fda.gov. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy
• FDA (2023). Regenerative Medicine Advanced Therapy Designation. www.fda.gov. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/regenerative-medicine-advanced-therapy-designation
• FDA (2024). Fast Track Designation. www.fda.gov. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track
• FDA (2024). FDA Requires Boxed Warning for T cell Malignancies Following Treatment with BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies. Https://www.fda.gov/. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed
• Kassim, S., & Dropulić, B. (2021). Centralized vs Decentralized Manufacturing of Personalized Cell Therapies: Overview and Logistics. https://caringcross.org/wp-content/uploads/2021/11/Part-1-Overview-and-Logistics-1.pdf
• FDA (2024). Platform Technology Designation Program for Drug Development.Https://www.fda.gov/. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/platform-technology-designation-program-drug-development