Regenerative medicine—a field that includes stem cells, bioengineered tissues, and gene therapies—holds great potential. In November 2017, the Food and Drug Administration updated its regulatory framework for these products. Peter Marks, who leads the agency’s Center for Biologics Evaluation and Research (CBER), about the framework gave this interview.

Q: What led FDA to update its regulatory framework for regenerative medicine?

A: Cell therapies are the product of advances in science and medicine, and they hold the potential to treat or even cure a diverse array of diseases. The policy framework announced in 2017 that is outlined in four guidance documents builds upon FDA’s existing risk-based regulatory approach to cell therapies. The framework more clearly describes which products are regulated as drugs, devices, and/or biological products, and which are not. This modern framework is intended to balance the agency’s commitment to ensuring safety and efficacy with mechanisms to drive further advances in regenerative medicine so innovators can bring new, effective therapies to patients as quickly and safely as possible.

Q: How will FDA strike the right balance between ensuring patient safety and facilitating the development of new regenerative products?

A: We are aware that there are unprincipled providers who prey on the hope of patients, and the agency is continuing to step up taking action against them. We’ve adopted a science-based, risk-based approach that builds upon existing regulations to support innovative product development, allowing developers time to engage with the FDA to determine if they need to submit a marketing authorization application.

FDA also intends to focus enforcement actions on products that pose a higher risk to patients, such as those administered by intravenous injection or infusion, over those associated with a lower risk.

Q: Since the framework was announced, what have been some big successes for the agency and/or some major challenges?

A: One clear measure of success has been the implementation of the regenerative medicine advanced therapy designation program established in the 2016 21st Century Cures Act, which enables regenerative therapy developers to access FDA’s expedited programs and other benefits to help facilitate the development and approval of these novel technologies. As of April 1, 2019, we had received 97 requests and granted 33 designations. Many of these are for products that are targeted to the treatment of rare diseases.

Also, last year CBER launched the INTERACT (Initial Targeted Engagement for Regulatory Advice on CBER Products) Meetings program to help foster the development of CBER-regulated products by encouraging early discussions and feedback from the center. The program applies to all products evaluated by CBER and aims to address the many questions product sponsors have during the transition from preclinical to clinical development. However, it is particularly relevant for cell therapies. This early engagement can help sponsors meet FDA’s science-based requirements more effectively and avoid costly delays that can unnecessarily impede access to beneficial new products.

In terms of challenges, some cellular therapies may present manufacturing challenges that arise from their variability and inherent complexity. For these products, it can be difficult to ensure that they are being manufactured consistently over time, which is something that we as regulators are particularly focused on. Ensuring safe and efficient delivery of these products—particularly those that are individualized to patients—also presents challenges, both for developers and for us as regulators.

Q: What are the agency’s priorities with respect to implementing the framework?

A: Patient safety is always FDA’s main priority.

FDA will continue to take steps in this area to prevent the use of unproven and potentially dangerous products through whatever enforceable legal means are necessary to protect the public. At the same time, we will continue to engage with patients and industry to promote innovation and responsible and flexible regulation that leverages this field’s scientific potential to improve public health.

Our goal is to advance an efficient and “least-burdensome” regulatory framework as a way to help new products remain compliant with the law, implementing a development pathway that does not become a barrier to beneficial new innovation. As part of that process, FDA is committed to ensuring that responsible product developers understand the regulatory structure that is in place.

Going forward, FDA will continue to 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. Until November 2020, FDA intends to exercise enforcement discretion for certain products with respect to the FDA’s premarket review under the existing regulations. This policy will allow for a more orderly transition and limit the impact on available resources within the FDA.

However, FDA does not intend to exercise such enforcement discretion for tissues and cellular therapies that pose a potential significant safety concern. We expect anyone involved with recovering, processing, or otherwise manufacturing cell and tissue therapies, including stem cells, to familiarize themselves and comply with the regulations. FDA created the Tissue Reference Group to respond to questions from sponsors, investigators, and manufacturers about how the criteria apply to a specific regenerative medicine product.

Q: Where do you see the field going in the coming years?

A: Cell-based regenerative medicine is rapidly evolving and requires a nimble, flexible approach to help ensure that these products are available to patients with serious unmet medical needs. It is likely that we will see the development and approval of multiple cell-based gene therapies over the next several years. In addition, during that time, tissue engineering—the creation of combination products consisting of human cells growing on artificial scaffolds—may come into its own, making possible simple replacement tissues and organs like blood vessels and bladders for use in surgical reconstruction. This is an exciting time to be involved at the leading edge of science and medicine.

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