FDA drafts Q&A guidance on cell and gene therapy development

The US Food and Drug Administration (FDA) on Monday issued draft guidance addressing key questions for drugmakers developing cell and gene therapies (CGTs). The guidance also addresses interactions with the agency, as well as considerations for conducting clinical and nonclinical studies.

FDA said the guidance was developed under its mandate to increase efficiency in the development of CGT products under the Prescription Drug User Fee Act (PDUFA VII) agreement. It includes a total of 36 questions and answers on issues such as regulatory review, chemistry, manufacturing, and controls, pharmacology/toxicology, clinical trials, and clinical pharmacology.

“This guidance is intended to support the development of CGT products by providing a repository of common questions posed to the Office of Therapeutic Products (OTP) in the Center for Biologics Evaluation and Research (CBER) by sponsors and other key stakeholders,” said FDA. “To develop this guidance, the agency compiled FAQs received from a variety of sources, including FDA interactions with sponsors in development programs, questions received following public presentations by FDA staff, questions received from public stakeholders via CBER’s [email protected] email address, and OTP’s virtual events series.”

The agency has held a series of virtual town hall meetings to gather information on the topics that stakeholders want clarity on to inform its guidance. It said the guidance will also be updated with additional FAQs over time.

The first and one of the most basic questions addressed by the guidance is, what sponsors should know about submitting an investigational new drug (IND) application. FDA noted that sponsors of commercial INDs should submit their applications through the Electronic Submission Gateway (ESG) in electronic common technical document (eCTD) format; eCTD is optional for sponsors of noncommercial INDs.

“A commercial IND is generally one for which the sponsor (usually a corporate entity) intends to commercialize the product by eventually submitting a marketing application,” FDA clarified. “In comparison, a noncommercial IND is an IND for a product that is not intended for commercial distribution and includes research and investigator-sponsored INDs.”

“The sponsor of a noncommercial IND may generally be an individual investigator, academic institution, or non-profit entity,” the agency added. “The studies proposed in these INDs are generally for research, and may result in publications in peer-reviewed journals.”

FDA also clarified that an INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT) meeting is an opportunity for sponsors to meet with regulators at a specific time early in the CGT product development. By comparison, a pre-IND meeting is an opportunity for sponsors to get feedback on their product development program before submitting an IND.

“The appropriate timing for an INTERACT meeting generally should be when a sponsor has identified the investigational product to be evaluated in a clinical study and conducted some preliminary preclinical proof-of-concept (POC) studies with the intended investigational product but has not yet designed and conducted definitive toxicology studies,” said FDA. “A pre-IND meeting is an opportunity to obtain feedback on the design of nonclinical studies, the design of the initial clinical study, and product manufacturing and quality controls needed to initiate human studies.”

“The meeting may also provide an opportunity to discuss the plans for studying the product in pediatric populations, strategize the target product profile, identify the design and results of any natural history studies, and discuss the best approach for presentation and formatting of data in the IND, among other possible relevant topics,” the agency added.

The guidance also delves into more complex considerations such as donor eligibility, product characterization, and analytical methods during product development. It also addresses questions that may arise when conducting nonclinical studies and human trials.

Stakeholders can comment on the draft guidance on www.regualtions.gov under docket no. FDA-2024-D-4311 until 18 February 2025.

Draft guidance

FDA drafts Q&A guidance on cell and gene therapy development

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