Ethical, Regulatory, and Operational Considerations for Cell and Gene Therapy Research in Children

30 November 2023


Cell and Gene Therapy (CGT) has the potential to transform the life trajectory of children with genetic conditions amendable to gene modification with advances in treatment and possible cures. Many of these conditions are rare, debilitating, serious or life-threatening, and do not exist in adults, and consequently, first-in-human trials may need to be initiated in children. Nonclinical in vitro data and nonclinical in vivo studies in relevant animal models are often the only information available to support trials in children.1 Because of the small number of children with some of these conditions, it may not be possible to conduct multiple trials. Clinical trials in children should be carefully designed to support a marketing application, if necessary.

Institutional Review Boards (IRBs) have a responsibility to carefully review information to support benefit and evaluate risk when CGT trials are submitted for IRB approval. Pediatric expertise and knowledge of the human subject protections for children is paramount.2 The informed consent should include the unique and potentially nonreversible risks that may pertain to certain CGT modalities, as well as discuss the possibility of off-target effects or risks with procedures used to administer the therapy. Additionally, depending on the type of genetic intervention involved, once an individual has received a gene therapy, they may be ineligible for future CGT trials with similar products. For children, the decision regarding whether to participate in a current trial vs. a future one will be dependent not only on the risk and benefits of the current research, but also on the promise of future modalities for treatment and the expected lifespan of the individual.3 Given the potential long-term effects of CGT, 15 years follow-up is often recommended. IRBs must determine appropriate requirements for assent for a child to participate, with consideration for age and maturity. Children who become adults during the trial should be reconsented to ensure their willingness to continue to participate in the research.4

In addition to IRB review, gene therapy trials in the USA generally require review by an Institutional Biosafety Committee (IBC) registered with the National Institutes of Health (NIH).5 Requirements for IBC review are found in the NIH Guidelines for Research Involving Recombinant and Synthetic Nucleic Acid Molecules (NIH Guidelines).6 In contrast to IRB review, which is focused on protection of study participants, IBC review is intended to mitigate risks-- to clinic staff, close contacts, and the general public-- associated with genetically modified products. For example, an IBC can oversee safe storage, preparation, injection, and disposal of genetically modified viral vectors used in many gene therapies. IBCs review facilities, procedures and training at each site and IBC approvals are issued on a site-by-site basis.

There are many challenges with CGT trials, including lack of access to all individuals who may benefit from the therapy. For children with very rare conditions, there may only be a few specialized sites with the appropriate pediatric expertise able to administer the treatment. There may be additional burdens on families, since participating in the trial may require extensive travel and missed work. Providing broader access to CGT trials will require establishing additional sites with adequate training, infrastructure, and medical expertise to successfully administer the therapy and monitor for adverse events post-administration.7

In summary, CGT has the potential to cure diseases and prolong lifespans in ways drugs and other biologics do not. CGT trials may be conducted in children early in product development because there may be few or no adults with the condition to evaluate. Families should understand the added risks of CGT and weigh those risks with the potential benefit of the therapy, if successful. Careful ethical and IBC review is critical to ensure individuals in trials and caretakers are adequately protected. Better access to gene therapies will enhance trial diversity and product availability, but in many cases, operational challenges currently exist that make it difficult to access CGT beyond specialized sites equipped to provide this therapy.  

Authors’ Biographies:

Daniel Kavanagh is Senior Scientific Advisor, Gene Therapy, Vaccines, and Biologics at WCG. Previously he was a Clinical Trial Co-Chair and Institutional Biosafety Committee Vice Chair at Harvard Medical School. He serves on technical and scientific committees for ABSA International and the American Society for Gene and Cell Therapy. He holds a PhD in Molecular Microbiology and Immunology and a RAC-US Regulatory Affairs Certificate.

Donna Snyder, MD, MBE, is the Executive Physician of WCG providing guidance on medicine, research, and regulations. Before WCG, Dr. Snyder served as Senior Pediatric Ethicist, in the Office of Pediatric Therapeutics, at the U.S. FDA. She is a board-certified pediatrician with experience in pediatric practice and research ethics.

1 Preclinical Assessment of Investigational Cellular and Gene Therapy Products, FDA Guidance for Industry, November 2013.

2 Ethical Considerations for Clinical Investigations of Medical Products Involving Children, FDA Draft Guidance September 2022.

3 Bateman-House, A., Shah, L.D., Escandon, R. et al. Somatic Gene Therapy Research in Pediatric Populations: Ethical Issues and Guidance for Operationalizing Early Phase Trials. Pharm Med 37, 17–24 (2023).

4 Donna Snyder, MD, MBE, What you should know about the FDA Final Informed Consent Guidance. Accessed October 31, 2023.

5 Kavanagh DG. Highlighting the Growing Importance of Institutional Biosafety Committees in Clinical Research. Clinical Researcher, Volume 36, Issue 4. (2022).


7 Sanjay Srivastava, Rahul Mirchandani and Joe De Pinto, Part 2: Getting The System Ready: Enabling Investment In Community Hospitals To Improve Patient Access To Cell And Gene Therapies, Cell&Gene, Accessed October 31, 2023.



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