By Roushan Afroze and Suzanne M. Sensabaugh, MS, MBA
Near the end of 2016, the United States Congress enacted the 21st Century Cures Act to expedite the development and review of biologics that address unmet medical needs. This is to be accomplished by introducing a new designation process for regenerative advanced therapies, called Regenerative Medicine Advanced Therapies (RMATs). FDA’s Draft Guidance for Industry Expedited Programs for Regenerative Medicine Therapies for Serious Conditions (November 2017) describes the Agency’s recommendations for the development and review of these therapies.
To obtain RMAT designation the product must meet the following criteria:
The biologic must fall under the regenerative medicine therapy definition;
The biologic must be intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
The preliminary clinical evidence of the biologic must indicate that the biologic has the potential to address unmet medical needs for such disease or condition.
RMAT designation applies to cell therapies, therapeutic tissue engineering products, human cell and tissue products, or any combination product using any such therapies or products. Products regulated solely through the Public Health Service (PHS) Act §361 and 21 CFR Part 1271 do not qualify for RMAT designation. Products with the RMAT designation are also eligible for FDA’s other expedited programs, which include fast track designation, breakthrough therapy designation, accelerated approval, and priority review designation, if they meet the criteria for such programs.
A request for RMAT designation must be made with or after the Investigational New Drug (IND) application is submitted to the FDA. In most cases, the RMAT designation request is submitted as an amendment to an existing IND. As opposed to breakthrough designations, the RMAT designation does not require evidence to indicate that the biologic may offer a substantial improvement over available therapies – it must only have preliminary clinical evidence that the biologic has the potential to address an unmet medical need.
The designation request should include:
• A rationale that the biologic meets the definition of a regenerative medicine therapy;
• A discussion to support that the disease or condition, or the aspect of the disease or condition, that the product is intended to treat is serious;
• A summary of the risks and benefits associated with the therapies, if any, currently available for this condition;
• A description of the unmet medical need that the product has the potential to address; and
• The preliminary clinical evidence that the product has the potential to address the specified unmet medical need for this serious condition.
Upon receipt of the request, the FDA Center for Biologics Evaluation and Research (CBER) Office of Tissues and Advanced Therapies (OTAT) has 60 calendar days to determine if a RMAT designation can be granted. If the RMAT designation request does not meet the criteria for designation, the FDA sends a written explanation for its decision to the sponsor.
The draft guidance document Expedited Programs for Regenerative Medicine Therapies for Serious Conditions (November 2017) is for comment purposes only. The document contrasts key features of the Breakthrough Therapy Designation and the RMAT Designation (see table below)
Source: FDA Draft Guidance document for Industry: Expedited Programs for Regenerative Medicine Therapies for Serious Conditions available at
For those therapies which receive RMAT designation and accelerated approval, post-approval requirements may be fulfilled through the submission of the following:
Clinical evidence, clinical studies, patient registries, or other sources of real world evidence such as electronic health records;
Collection of larger confirmatory clinical trials as agreed upon during product development; or
Post-approval monitoring of all patients treated with the therapy prior to approval of the therapy
CBER will determine what type of post-approval requirements will be necessary to confirm the clinical benefits of a RMAT that receives accelerated approval upon review of the BLA.
Finally, CBER encourages interested sponsors seeking accelerated approval for their RMAT to consult with the agency early in development. More information about RMATs and the application process can be found on the FDA website. https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm537670.htm
Suzanne M. Sensabaugh has advanced the development of over 130 biologics, biosimilars, and biologic/device combination products since 2009. She has successfully requested and received RMAT designation from the FDA. She can be reached at smsensabaugh@hw-fda,com.
Suzanne M. Sensabaugh has advanced the development of over 130 biologics, biosimilars, and combination products since 2009. She can be reached at firstname.lastname@example.org.