FDA Publishes New Draft Guidance On Regenerative Medicine Therapies

Highlights

• The U.S. Food and Drug Administration (FDA) issued new draft guidance on Sept. 20, 2025, surrounding expedited programs for regenerative medicine therapies for serious conditions.
• The draft guidance details FDA's expedited review pathways to facilitate development and streamlined review of cell and gene therapies and other regenerative medicine products.
• Once finalized, this draft guidance will supersede earlier FDA guidance on the topic.

The U.S. Food and Drug Administration (FDA) on Sept. 20, 2025, issued draft guidance, "Expedited Programs for Regenerative Medicine Therapies for Serious Conditions," outlining how sponsors can utilize FDA's expedited review pathways to facilitate development and streamlined review of cell and gene therapies and other regenerative medicine products. Once finalized, the draft guidance will supersede earlier FDA guidance on this topic from February 2019.

Previous Guidance Compared to Draft Guidance

The 21st Century Cures Act added the Regenerative Medicine Advanced Therapy (RMAT) designation to the Federal Food, Drug, and Cosmetic Act (FDCA) in 2016. The RMAT designation was designed to support development and approval of regenerative medicine products, including cell and gene therapies that target unmet medical needs in patients with serious conditions. As of September 2025, the FDA has received almost 370 designation requests and approved 184 (though not all approvals are publicly disclosed). As of June 2025, 13 of the RMAT designated products have been approved for marketing.

The new draft guidance reiterates FDA policies regarding RMAT eligibility, including how the agency determines whether a sponsor has provided sufficient evidence to support a designation request. It also provides details for sponsors about the application process. As in the earlier guidance, the FDA provides an in-depth discussion of clinical trial design considerations for trials for rare diseases. In such situations, FDA pledges to work with sponsors and will "encourage flexibility" in clinical trial design. Some specific examples detailed by FDA in the draft guidance include:

• innovative trial designs such as those that compare several different investigational agents to each other and a common control
• natural history data that may provide the basis of a historical control but only if the control and treatment populations are adequately matched in terms of demographics, concurrent treatment, disease state and other relevant factors

The draft guidance encourages trial designs where multiple clinical sites participate in a trial investigating a regenerative medicine therapy with the intent of sharing the combined clinical trial data to support Biologics License Applications (BLA) from each of the individual centers or institutions. The FDA further states that manufacturing may be performed at all clinical sites using a common manufacturing protocol and product quality testing specifications.

The FDA also encourages sponsors to obtain input from the affected patient communities regarding the clinical endpoints that would be clinically relevant to the patients suffering from the disease.

The draft guidance differs from previous guidance on safety issues. For example, the draft guidance notes that regenerative therapies "are likely to raise unique safety considerations that would benefit from long-term safety monitoring." Consequently, the FDA recommends that monitoring plans for clinical trials should include both short-term and long-term safety assessments. In a new development, sponsors also are encouraged to explore using digital health technologies to collect safety information.

In addition, the FDA specifies that an RMAT or other expedited review designation does not change the chemistry, manufacturing and controls (CMC) information required to assure product quality. The draft guidance notes regenerative medicine therapies with expedited clinical development activities may "face unique challenges in expediting product development activities to align with faster clinical timelines." To ensure CMC readiness for expedited development, sponsors of regenerative medicine therapies may need to pursue a more rapid CMC development program to accommodate the faster pace of the clinical program.

If product manufacturing changes are made after receiving the RMAT designation, the post-change product may no longer qualify for the designation if comparability cannot be established with the pre-change product. If manufacturing changes are planned or anticipated, FDA recommends that sponsors conduct a risk assessment to determine whether the changes impact product quality.

The draft also notes that sponsors can use real-world evidence (RWE) to support an accelerated approval application. For purposes of this guidance, FDA defines real-world evidence (RWE) as the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of real-world data.

Next Steps

FDA recommends that sponsors of regenerative medicine therapies engage with the Office of Therapeutic Products (OTP) staff early in product development. This will allow sponsors to get FDA input on their clinical trial design, safety monitoring and other components of their clinical plan.

FDA is accepting comments on the draft guidance through Nov. 24, 2025. Sponsors should view the draft guidance as a reflection of the agency's thinking and its recommendations for sponsors. Though the document reiterates many FDA views expressed in earlier guidance, it provides sponsors with specific recommendations on several new topics. Sponsors should consider submitting comments to ensure FDA takes into account any concerns before it finalizes the guidance.

Holland & Knight's attorneys continue to monitor developments at FDA and are available to assist sponsors and other stakeholders. If you have any questions, please contact the authors or another member of Holland & Knight's Healthcare Team.