The U.S. Food and Drug Administration (FDA) has published draft guidance to clarify the development and application process for cell and gene therapies (CGTs). This 44-page document addresses frequently asked questions (FAQs) regarding investigational new drug (IND) quality and submission, aiming to streamline the path for these innovative therapies.
Expanding on Existing Guidelines
This new guidance builds upon the recommendations issued in January 2020 concerning chemistry, manufacturing, and control information for human gene therapy IND applications. The FDA aims to provide comprehensive support for sponsors navigating the complexities of CGT development.
Key Recommendations for Sponsors
The guidance addresses a range of topics, including FDA recommendations for pre-biologics license application (BLA) meetings and safety considerations for short- and long-term monitoring in CGT trials. The FDA "strongly recommends sponsors schedule a pre-BLA meeting with their review team" to preemptively address potential information gaps and ensure a smooth review process. This proactive exchange of information can significantly reduce delays typically associated with the initial review of a marketing application.
Safety Monitoring
On the critical aspect of safety, the FDA emphasizes close monitoring of subjects during and immediately following product administration. This includes frequent monitoring of vital signs, physical examinations, laboratory studies, radiologic evaluations, and other relevant assessments as warranted. Furthermore, the agency advises sponsors to observe subjects for delayed adverse events for as long as 15 years following exposure to the investigational product.
Trial Design and Endpoints
The guidance also provides recommendations regarding trial design and the selection of endpoints, including the use of surrogate endpoints and biomarkers. Sponsors are encouraged to carefully consider the suitability of surrogate endpoints and the appropriate use of biomarkers in their CGT development programs.
Commitment to CGT Development
This FAQ draft is part of the FDA’s response to the Prescription Drug User Fee Act (PDUFA VII), which provides resources to the FDA. The FDA has restated its "commitment to increase efficiency in the development of CGT products," acknowledging the rapid growth of this field in the U.S. Recent data indicates a significant increase in CGT approvals, with over 70% of the 14 approved CGTs being approved within the last five years. Currently, there are 694 CGTs in development across various therapy areas in the U.S., highlighting the continued potential for growth and innovation in this field.
