FDA Develops Guidelines to Handle Expected Influx of Gene and Cell Therapy Approvals

Noting that the U.S. Food and Drug Administration (FDA) expects more than 200 investigational new drug applications (INDs) by 2020 per year, many of them cell and gene therapies, the agency issued an outline of new procedures it plans to implement this year.

Commissioner Scott Gottlieb and Peter Marks, director of the Center for Biologics Evaluation and Research, stated, “And by 2025, we predict that the FDA will be approving 10 to 20 cell and gene therapy products a year based on an assessment of the current pipeline and the clinical success rates of these products.”

The first proposal is that the agency will work with sponsor organizations to maximize the use of expedited programs. Those include regenerative medicine advanced therapy (RMAT) designation and accelerated approval. In particular, the agency believes the accelerated approval program may be the fastest route to approval for new treatments, especially when there is an unmet medical need, or the therapy cures the disease.

Gottlieb and Marks note, however, that if a gene or cell therapy treats symptoms, rather than actually cures the disease, a traditional approval pathway may be more appropriate.

Secondly, the FDA is planning several clinical guidance documents associated with different areas of active product development. “Among the clinical guidance documents that we intend to advance,” Gottlieb and Marks write, “include guidance documents for the development of gene therapy products for inherited blood disorders such as hemophilia, among others.”

The agency will also develop a guidance document that provides recommendations on product development issues for gene therapy products for specific neurodegenerative diseases. “Here,” they note, “the accelerated approval pathway may only be applicable in certain circumstances.”

Some of these guidance documents will focus on how the accelerated approval pathway could be used when a gene therapy treats a single genetic change, compared to more complex genetic diseases. Others will address the development of cell-based gene therapies like CAR-T, “including the complexities associated with manufacturing these products in a safe, reliable and cost-effective way, and in a manner that allows for the efficient use of these products in the clinic.”

The new guidance will offer parameters for introducing advances in manufacturing that lead to efficient development and application of CAR-T without expensive new clinical studies. The agency will also propose ways to guarantee the safety and effectiveness of the CAR-T products via technology and examinations.

The agency will also develop new guidance for efficient development of safe and effective cell-based regenerative medicine products. “Though we are very encouraged by the advances in science and clinical development in this field,” Gottlieb and Marks write, “we remain concerned at the FDA that a number of individuals working in this space are developing products that are subject to premarket approval, but these individuals are operating outside of regulatory compliance and, in some cases, these products are creating potential significant safety concerns to patients based on how we believe the cell therapies are being manufactured and delivered to patients.”

As a result, the agency plans to bolster is enforcement actions this year to address potentially harmful cell-based medicines.

The agency also expects to work to help small sponsors, including academic researchers, who “may not be of sufficient scale to conduct a clinical trial on their own, to band together with others similarly situated. These sponsors can then pool clinical data to demonstrate the safety and effectiveness of a product that is manufactured with a common manufacturing protocol and product quality specifications, and used for a common clinical purpose, but where the therapies are being delivered locally by different investigators and institutions.”