FDA Releases New Guidance to Streamline Cell and Gene Therapy Development

WASHINGTON –September 24, 2025– The U.S. Food and Drug Administration (FDA) is taking steps to accelerate the development of novel cell and gene therapies, particularly for patients with rare diseases and limited treatment options. The agency’s Center for Biologics Evaluation and Research (CBER) has issued a trio of draft guidance documents outlining its recommendations for expedited programs, innovative clinical trial designs, and post-approval data collection.

These new guidances, which follow a recent public meeting, provide deeper insight into CBER’s strategy to fast-track approvals and reduce the burden on developers. This push is part of a broader initiative led by CBER Director Vinay Prasad to support children and other patients who have few, if any, treatment options. The agency had previously signaled its intent with the recent announcement of a new approval pathway for novel therapies intended for as few as a single patient.

Innovative Trial Designs for Small Patient Populations

The FDA’s eight-page draft guidance on clinical trial design for cell and gene therapies outlines a range of flexible approaches tailored for small patient populations. These designs are intended to generate the necessary evidence for approval while simultaneously expediting the development process. The guidance highlights six key types of trial designs:

• Single-arm trials: Suitable for conditions that are consistently degenerative, where efficacy can be measured using objective endpoints.
• Disease progression modeling: Leverages the natural course of a disease to evaluate a new therapy’s effectiveness.
• Externally controlled studies: Compares a new therapy against historical or real-world data from patients who did not receive the treatment.
• Adaptive trial designs: Allows for pre-planned modifications to a trial while it is ongoing.
• Bayesian trial designs: Uses existing data to reduce the required sample size of a new trial.
• Trials with master protocols: Enables the simultaneous testing of multiple therapies against a single, common control group.

While not suitable for every therapy, these designs provide developers with flexible options to accelerate the development of potentially life-saving treatments.

Expediting Regenerative Medicine Therapies

A separate 19-page draft guidance provides more detailed recommendations on how to qualify for expedited programs for regenerative therapies. It clarifies that to receive a special designation like Regenerative Medicine Advanced Therapy (RMAT), the manufacturing process for an early-stage product must closely match that of the final product submitted for approval.

The FDA warns that if there are significant differences between the early-phase and final manufacturing processes, the preliminary evidence may not be considered sufficient to support an RMAT designation. The guidance offers new examples of what constitutes “sufficient” preliminary clinical evidence, including positive results from a single-dose CRISPR-based therapy or an autologous T-cell immunotherapy that shows a high objective response rate compared to standard chemotherapy.

Guidance on Post-Approval Data Collection

Finally, a new seven-page draft guidance focuses on the importance of collecting long-term safety and effectiveness data for cell and gene therapies after they receive approval. Given that these products are often a one-time treatment and are tested in a limited number of patients, post-approval studies are crucial. The guidance recommends using various data sources, including electronic health records, claims data, and patient registries, to ensure the long-term safety and efficacy of these therapies.