FDA finalizes Q&A guidance on developing cell and gene therapies
The US Food and Drug Administration (FDA) on Wednesday finalized guidance addressing frequently asked questions related to the development of cellular and gene therapy (CGT) products.
The guidance is little changed from the draft version issued on 19 November 2024. (RELATED: FDA drafts Q&A guidance on cell and gene therapy development, Regulatory Focus 19 November 2024)
The issuance of the guidance fulfills a commitment made under the Prescription Drug User Fee Act (PDUFA VII) to enhance efficiency and support the development of CGT products. The guidance notes that "CGT-related research and development in the United States continues to grow rapidly, with several products already approved and many more progressing through clinical development."
The document includes 36 questions and addresses FDA reviews, product development considerations, conducting nonclinical studies, and conducting human trials.
One of the changes involves the inclusion of new terminology related to approach methodologies (NAMs) for nonclinical studies, which was not addressed in the draft guidance. In Question 21, there is a query regarding FDA’s recommendations for selecting appropriate animal species for certain nonclinical studies of cell and gene therapy products.
In its response, FDA states, “FDA supports the use of New Approach Methodologies (NAMs) and the principles of the 3Rs (i.e., reduce, refine, and replace animal use) to encourage the judicious use of animals in nonclinical development programs.” The draft guidance did not mention NAMs, focusing solely on the principles of the 3Rs.
One question addressed in the guidance is the difference between INTERACT meetings and pre-investigational new drug (IND) meetings. FDA states that INTERACT meetings are held at a specific time early in the product development process and are intended for novel products and development programs that face unique challenges during early development.
In contrast, the primary purpose of a pre-IND meeting is for sponsors to receive feedback on their product development programs before submitting an IND application. Pre-IND meetings allow sponsors to gather input on the design of nonclinical studies, the initial clinical study, and the manufacturing and quality control processes required to commence human studies.
The guidance also discusses whether FDA recommends a pre-biologics license application (BLA) meeting and outlines what should be included in the briefing package if sponsors decide to request one. FDA notes that it "strongly recommends" these meetings to expedite reviews and eliminate delays.
Another question relates to what chemistry, manufacturing and controls (CMC) issues sponsors should consider as they prepare to submit a BLA. The guidance states that “specific CMC concerns are guided by the stage of product development. Nonclinical and CMC safety testing data must be provided prior to initiation of Phase 1 studies, along with basic product and process characterization data. Product development activities may be implemented incrementally but should progress along with clinical development.”
FDA also provides guidance regarding what sponsors should consider for short- and long-term safety monitoring in trials of investigational CGT products.
According to the guidance, many CGT products are administered once. Therefore, close monitoring of subjects immediately following product administration is essential to identify early safety signals. This requires intensive safety monitoring during and immediately after the administration of the product, including frequent checks of vital signs, physical examinations, laboratory tests, and radiologic assessments.
