The FDA announced a comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies.
The framework—outlined in a suite of four guidance documents—builds upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products. Further, two of the guidance documents propose an efficient, science-based process for helping to ensure the safety and effectiveness of these therapies, while supporting development in this area. The suite of guidance documents also defines a risk-based framework for how the FDA intends to focus its enforcement actions against those products that raise potential significant safety concerns. This modern framework is intended to balance the agency’s commitment to safety with mechanisms to drive further advances in regenerative medicine so innovators can bring new, effective therapies to patients as quickly and safely as possible. The policy also delivers on important provisions of the 21st Century Cures Act.
“We’re at the beginning of a paradigm change in medicine with the promise of being able to facilitate regeneration of parts of the human body, where cells and tissues can be engineered to grow healthy, functional organs to replace diseased ones; new genes can be introduced into the body to combat disease; and adult stem cells can generate replacements for cells that are lost to injury or disease. This is no longer the stuff of science fiction. This is the practical promise of modern applications of regenerative medicine,” said FDA Commissioner Scott Gottlieb, M.D. “But this field is dynamic and complex. As such, it has presented unique challenges to researchers, health care providers, and the FDA as we seek to provide a clear pathway for those developing new therapies in this promising field, while making sure that the FDA meets its obligation to ensure the safety and efficacy of the medical products that patients rely upon. Alongside all the promise, we’ve also seen products marketed that are dangerous and have harmed people. With the policy framework the FDA is announcing today, we’re adopting a risk-based and science-based approach that builds upon existing regulations to support innovative product development while clarifying the FDA’s authorities and enforcement priorities. This will protect patients from products that pose potential significant risks, while accelerating access to safe and effective new therapies.”
The framework includes two final guidance documents and two draft guidance documents.
The two final guidance documents clarify the FDA’s interpretation of the risk-based criteria manufacturers use to determine whether a product is subject to the FDA’s premarket review.
The first guidance provides greater clarity around when cell and tissue-based products would be excepted from the established regulations if they are removed from and implanted into the same individual within the same surgical procedure and remain in their original form. The second final guidance helps stakeholders better understand how existing regulatory criteria apply to their products by clarifying how the agency interprets the existing regulatory definitions “minimal manipulation” and “homologous use.” As this field advances, the FDA has noted that there are a growing number of regenerative medicine products subject to FDA premarket authorization. These guidance documents will help explain how the FDA will provide a risk-based framework for its oversight. The policy framework defines how we intend to take action against unsafe products while facilitating continued innovation of promising technologies.
To accomplish this goal, the guidance document has clarified the FDA’s view of “minimal manipulation” and “homologous use.” These are two concepts that are defined in current regulation to establish the legal threshold for when a product is subject to the FDA’s premarket approval requirements. By further clarifying these terms in the final guidance, the FDA is applying a modern framework for its oversight. Under the new policy, in order to allow manufacturers of products time to comply with the requirements, for the first 36 months following issuance of the final guidance document the FDA intends to exercise enforcement discretion for certain products that are subject to the FDA’s premarket review under the existing regulations, but are not currently meeting these requirements. The FDA does not intend to exercise such enforcement discretion for those products that pose a potential significant safety concern. Going forward, the FDA will apply a risk-based approach to enforcement, taking into account how products are being administered as well as the diseases and conditions for which they are being used. This risk-based approach allows product manufacturers time to engage with the FDA, as to determine if they need to submit a marketing authorization application and, if so, submit their application to the FDA for approval.
The two draft guidances provide important information to help spur development and access to innovative regenerative therapies. The first draft guidance, which builds off the regenerative medicine provisions in the 21st Century Cures Act, addresses how the FDA intends to simplify and streamline its application of the regulatory requirements for devices used in the recovery, isolation, and delivery of regenerative medicine advanced therapies (RMATs), including combination products. The guidance specifies that devices intended for use with a specific RMAT may, together with the RMAT, be considered to comprise a combination product.
The second draft guidance describes the expedited programs that may be available to sponsors of regenerative medicine therapies, including the new Regenerative Medicine Advanced Therapy (RMAT) designation created by the 21st Century Cures Act, Priority Review, and Accelerated Approval. In addition, the guidance describes the regenerative medicine therapies that may be eligible for RMAT designation—including cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, as well as gene therapies that lead to a durable modification of cells or tissues (including genetically modified cells).
“As a molecular and cell biologist and physician, it has been exciting to witness the approval of the first two gene therapies in the U.S. this year. Given the great opportunities that the field of regenerative medicine presents, we have undertaken a rigorous process to clarify our regulations that included solicitation of public input, and I believe today marks a significant step forward for all stakeholders,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “In addition to clarifying some of the more complex areas of the regulations, we have taken meaningful new steps to encourage and expedite the development of innovative therapies. We welcome public comment on our draft guidance documents as we work toward finalizing this framework.”
Both draft guidance documents will have 90-day comment periods.