FDA official tells CGT developers to leverage multiple meeting opportunities with agency
Regulatory News | 24 June 2024 |
Left to right: Stephanie Cherqui, Paulla Dennis, and Najat Bouchkouj address cell and gene therapy product development at DIA meeting. (Photo credit: Joanne S. Eglovitch)
San Diego – Cell and gene therapy (CGT) manufacturers should take advantage of the numerous pathways available and meet with the US Food and Drug Administration early to iron out any questions they have during product development, Najat Bouchkouj advised at the DIA Global Annual Meeting.
Bouchkouj, acting associate director for pediatrics in the Office of Clinical Evaluation for the Office of Therapeutic Product (OTP) in the Center for Biologics Evaluation and Research (CBER), and industry representatives also explored the regulatory and ethical considerations in developing CGT products for the neonatal and pediatric population.
Paulla Dennis, senior director, Rare Diseases, Advanced Therapies and Pediatrics at Fortrea, said that pediatric drug development “is a very interesting space. You can have a tremendous impact on someone’s life, but there are also a lot of responsibility whether you are on the [contract research organization] side, the site side or the regulator [side].”
Specific product development tactics utilized for common diseases may not be feasible for CGTs to treat rare diseases. For example, a single-arm study may be enough to support regulatory approval, and a well-designed natural history study may be acceptable for treating a rapidly progressing rare disease, Bouchkouj said.
FDA has devised different ways for sponsors to meet and engage with reviewers to ensure companies are on the right path in developing CGTs.
Such pathways include the INTERACT meetings before filing an investigational new drug application (IND) and a pre-IND meeting at the end of Phase 1 or Phase 2 clinical trials before filing a biologics license application (BLA).
Other opportunities for interactions with OTP during product development exist via the office’s Rare Disease Endpoint Advancement (RDEA) program. This program aims to help sponsors develop treatments for rare diseases by providing a mechanism to collaborate with FDA through the endpoint development process.
Companies can also meet with FDA through its platform designation for their product. Under this program, non-clinical data and manufacturing information from one product may be leveraged into another product to accelerate gene therapy product development for rare diseases. FDA released guidance detailing plans for implementing the platform designation program in May (RELATED: FDA issues platform technology designation draft guidance, Regulatory Focus 28 May 2024).
Sponsors can also interact with the agency through its Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot, which aims to further accelerate the development pace for products intended to address an unmet medical need. The program was launched in September 2023 (RELATED: Convergence: CBER chief discusses priorities, touts gene therapy approvals, Regulatory Focus 5 October 2023).
Bouchkouj said the number of gene and cell therapies available to patients is “moving rapidly from bench to bedside.” Gene therapy INDs steadily increased from eight applications in 2008 to 200 in 2023. She also reported that the number of applications for CAR-T cell therapies increased from two in 2007 to 95 in in 2023. Currently, there are 400 CAR-T cell research INDs, and out of these 60% are for hematologic malignancies while 34% are for solid tumors and 6% are for autoimmune diseases.
Bouchkouj also addressed some special considerations in developing CGTs for pediatric patients. FDA regulations under 21 CFR 56.111 state that children should not be enrolled in trials unless necessary to answer “important scientific or public health questions” and that vulnerable populations “should be protected” and patients capable of informed consent should be enrolled first.
Further, regulations under 45 CFR part 46, subpart D, and 21 CFR part 50, subpart D, collectively referred to as “subpart D,” govern all human subjects research overseen by HHS and FDA, respectively. These regulations ensure that research does not involve greater than minimal risk, or in cases where there is greater than minimal risk, there is the “prospect of direct benefit to the individual subjects” or for the research to “yield generalizable knowledge about the subjects’ disease or condition.”
Dennis advised sponsors and CROs to “reach out to advocacy groups and “not be afraid to talk to regulators for their advice. It is better to get this advice early rather than later and have to restart everything.”
DIA Global Annual Meeting
Bouchkouj, acting associate director for pediatrics in the Office of Clinical Evaluation for the Office of Therapeutic Product (OTP) in the Center for Biologics Evaluation and Research (CBER), and industry representatives also explored the regulatory and ethical considerations in developing CGT products for the neonatal and pediatric population.
Paulla Dennis, senior director, Rare Diseases, Advanced Therapies and Pediatrics at Fortrea, said that pediatric drug development “is a very interesting space. You can have a tremendous impact on someone’s life, but there are also a lot of responsibility whether you are on the [contract research organization] side, the site side or the regulator [side].”
Specific product development tactics utilized for common diseases may not be feasible for CGTs to treat rare diseases. For example, a single-arm study may be enough to support regulatory approval, and a well-designed natural history study may be acceptable for treating a rapidly progressing rare disease, Bouchkouj said.
FDA has devised different ways for sponsors to meet and engage with reviewers to ensure companies are on the right path in developing CGTs.
Such pathways include the INTERACT meetings before filing an investigational new drug application (IND) and a pre-IND meeting at the end of Phase 1 or Phase 2 clinical trials before filing a biologics license application (BLA).
Other opportunities for interactions with OTP during product development exist via the office’s Rare Disease Endpoint Advancement (RDEA) program. This program aims to help sponsors develop treatments for rare diseases by providing a mechanism to collaborate with FDA through the endpoint development process.
Companies can also meet with FDA through its platform designation for their product. Under this program, non-clinical data and manufacturing information from one product may be leveraged into another product to accelerate gene therapy product development for rare diseases. FDA released guidance detailing plans for implementing the platform designation program in May (RELATED: FDA issues platform technology designation draft guidance, Regulatory Focus 28 May 2024).
Sponsors can also interact with the agency through its Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot, which aims to further accelerate the development pace for products intended to address an unmet medical need. The program was launched in September 2023 (RELATED: Convergence: CBER chief discusses priorities, touts gene therapy approvals, Regulatory Focus 5 October 2023).
Bouchkouj said the number of gene and cell therapies available to patients is “moving rapidly from bench to bedside.” Gene therapy INDs steadily increased from eight applications in 2008 to 200 in 2023. She also reported that the number of applications for CAR-T cell therapies increased from two in 2007 to 95 in in 2023. Currently, there are 400 CAR-T cell research INDs, and out of these 60% are for hematologic malignancies while 34% are for solid tumors and 6% are for autoimmune diseases.
Bouchkouj also addressed some special considerations in developing CGTs for pediatric patients. FDA regulations under 21 CFR 56.111 state that children should not be enrolled in trials unless necessary to answer “important scientific or public health questions” and that vulnerable populations “should be protected” and patients capable of informed consent should be enrolled first.
Further, regulations under 45 CFR part 46, subpart D, and 21 CFR part 50, subpart D, collectively referred to as “subpart D,” govern all human subjects research overseen by HHS and FDA, respectively. These regulations ensure that research does not involve greater than minimal risk, or in cases where there is greater than minimal risk, there is the “prospect of direct benefit to the individual subjects” or for the research to “yield generalizable knowledge about the subjects’ disease or condition.”
Dennis advised sponsors and CROs to “reach out to advocacy groups and “not be afraid to talk to regulators for their advice. It is better to get this advice early rather than later and have to restart everything.”
DIA Global Annual Meeting
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