FDA Commissioner Scott Gottlieb, M.D. and Director of the Center for Biologics Evaluation and Research (CBER) Peter Marks, M.D., Ph.D., released a joint statement on January 15, 2019 previewing new FDA policies to advance the development of safe and effective cell and gene therapies.
This statement comes amid expectations for record numbers of Investigational New Drug (IND) applications and marketing approvals for these innovative products, including 200 IND filings per year by 2020 and 10-20 marketing approvals per year by 2025.
Product innovation was touted as the driver in cell and gene therapy development, and many of the new policies are meant to encourage innovation and efficient product development. The policies focus on four key initiatives:
- Ensuring sufficient review capacity at the FDA
- Promoting expedited programs
- Issuing new guidances
- Ensuring regulatory compliance
Ensuring Sufficient Review Capacity at the FDA
Given the anticipated avalanche of regulatory filings, one of the biggest challenges will be ensuring an adequate number of FDA staff to handle it. There are currently more than 800 active cell and gene therapy INDs at the FDA. To help alleviate potential bottlenecks, the FDA aims to add around 50 additional clinical reviewers to its ranks. These reviewers will be critical for ensuring timely review and adequate oversight for these products.
Promoting Expedited Programs
Many cell and gene therapy products target diseases for which there are currently no good therapeutic options, but may also carry with them potentially significant product class risks (e.g., lack of durability, rare off-target effects). Because these risks often take large sample sizes and extended study durations to adequately characterize, traditional safety requirements for marketing approval could add substantial time to the drug development timeline.
For therapies that are intended to address serious or life-threatening conditions and offer a meaningful treatment benefit over existing options, certain expedited development and accelerated approval programs could help speed up the time to market. These programs, including regenerative medicine advanced therapy (RMAT) designation and accelerated approval, provide development and review benefits to Sponsors but also provide additional regulatory authorities to the FDA regarding the collection of postmarketing safety data. As a result, potentially curative therapies can be made available more quickly to the patients who need them without having to sacrifice an adequate assessment of risk.
Issuing New Guidances
Novel products like cell and gene therapies often come with unique challenges for both product development and clinical use. In such cases, existing regulatory guidelines may prove inadequate or inappropriate. To address these deficiencies, Dr. Gottlieb and Dr. Marks specifically called out the following areas of focus for upcoming guidance documents:
- Gene therapy products for inherited blood disorders
- Gene therapy products for neurodegenerative diseases
- Challenges/approaches for cell-based therapies like CAR-T, including manufacturing requirements, clinical bridging studies, and real-world data
- Cell-based regenerative medicines
- The use of pooled safety/efficacy data from multiple research centers
CBER recently released a Guidance Agenda outlining CBER’s planned guidances for 2019, including nine for tissues and advanced therapies. At the time of this post, two of these had already been issued:
- Expedited Programs for Regenerative Medicine Therapies for Serious Conditions (Feb 2019)
- Evaluation of Devices Used with Regenerative Medicine Advanced Therapies (Feb 2019)
Ensuring Regulatory Compliance
While not highlighted as a standalone initiative in the policy preview statement, Dr. Gottlieb and Dr. Marks did raise concerns about certain cell and gene therapy product developers operating outside of regulatory compliance. Particularly alarming is that many of these products may actually be harmful to patients based upon the FDA’s current understanding of how they are manufactured and delivered. To combat this, the FDA is planning additional near-term enforcement actions against the offenders. The goal of these actions will be to bring these entities into compliance or at a minimum prevent them, and others like them, from providing potentially harmful products to patients.
Cell and gene therapies offer the promise of treating and even curing some of the most dreaded and intractable diseases. Given this, and the speed with which these therapies are making their way into the clinic, the FDA has offered a preview of policy initiatives aimed at spurring innovation, ensuring patient safety, and getting these products to market sooner. These initiatives include hiring new clinical reviewers at the FDA, promoting expedited development and approval programs, issuing new guidance documents, and ensuring regulatory compliance for all cellular and gene therapy product developers.
The cell and gene therapy fields are quickly evolving. This includes not only new insights and best practices for product development but also changes to the regulatory landscape. It is therefore more critical than ever to keep up with these developments and to understand the challenges and opportunities that they present to your program.
Contact Nuventra today to learn how our consultants can help you develop timely and effective nonclinical, clinical, regulatory, and overall drug development strategies to get your cellular or gene therapy product to market faster.