The field of cell and gene therapy continues to expand. According to the Alliance for Regenerative Medicine, as of July 2024, the global sector encompasses 2,919 drug developers globally, conducting 1,851 clinical trials.1
This growing market presents a multitude of challenges for sponsors, CROs, institutions, and sites that must be considered when running these trials. To meet these challenges, all stakeholders need to understand the important roles of not only the Institutional Review Board (IRB), but also the Institutional Biosafety Committee (IBC) in facilitating a safe and effective study. Below are key takeaways for research involving human gene transfer.
Takeaway 1: Human Gene Transfer (HGT) Research Typically Requires IBC Oversight
The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) lay out requirements for IBC oversight clinical trials, which are based in part on the definition of Human Gene Transfer (HGT) research. In general, HGT research is the administration to a human research participant of a product containing genetically modified or synthesized DNA or RNA, or of a product capable of modifying cellular DNA via gene editing. Certain short nucleic acids, such as oligonucleotides may be excluded from the definition of HGT products. Products in this category range from classic gene therapy approaches to modalities involving gene editing, regenerative medicine, engineered stem cells, and vaccines, including DNA, RNA, and vectored vaccines.
IBC approval is required when two criteria are met:
- The research is HGT research as defined in the NIH Guidelines Section III-C, and;
- The research is subject to NIH Guidelines due to relevant funding as defined in Section I-C.
Every clinical trial site engaged in research subject to NIH Guidelines must have an IBC of record registered with the NIH. As a provider of centralized IBC services, WCG works with clinical trial sponsors, CROs, sites, and investigators to ensure safety and compliance in HGT trials. When sponsors, CROs, institutions, and sites begin working with an IBC, they can expect the IBC to:
- Provide review and approval of research protocols, facilities, and biocontainment levels according to the requirements and recommendations of the NIH Guidelines.
- Advise the institution on policies.
- Assess the investigator/staff training and qualifications.
- Be comprised of a committee that includes experts on relevant topics, representatives of the institution and members of the community unaffiliated with the institution.
- Deliberate and vote on research proposals at convened meetings (in person or virtual).
After the IBC approves the trial, they will continue to provide oversight for as long as dosing occurs.
Takeaway 2: IRBs and IBCs Have Distinct Roles but Frequently Work Collaboratively
The requirement for IBC review is separate from — and in addition to — the requirement for IRB review. IBCs and IRBs are mandated by separate governing rules and have distinct roles and responsibilities. Here are three examples:
- Areas of focus: IRBs consider the rights and welfare of research subjects. IBCs consider risks to the clinical and laboratory staff, the community, and the environment associated with genetically modified DNA and RNA and gene editing products.
- Jurisdiction: One IRB can oversee multiple sites. Each IBC registration applies to a specific research institution. That means a 20-site gene therapy trial (with relevant NIH funding) may require 20 unique IBC registrations. However, the administration of all those IBCs can be centralized.
- Length of involvement. Once all products are administered or removed from the site, the sponsor can close IBC oversight of the respective trial. Obviously, such is not the case with IRBs, which are responsible for participant safety and follow-up.
Ideally, the IRB and IBC will work together to coordinate risk assessments and safety recommendations. Especially when centrally administered, the combined expertise of IRB and IBC memberships can provide enhanced efficiency for simultaneous or parallel review and approval.
Takeaway 3: No Matter Your Role in the Trial, Know What to Expect from Your Research Partners and the IBC
Keep in mind that the site team, investigators, and the CRO each have different responsibilities and various levels of knowledge. As a sponsor, you need to be able to educate them—and your colleagues—about IBC expectations in advance. This way, you avoid last-minute questions and pave the way for dealing with the complex issues involved in site activation and initiation.
As already mentioned, the IBC is charged with evaluating the biosafety risks to the public and the environment. Among the things they’ll want to know:
- The molecular content of the HGT product.
- The plan for biocontainment:
- How is the investigational product transported, stored, prepared, administered, and disposed of?
- What is the risk of shedding, release, and loss of containment?
- What spill response and emergency response plans are in place?
While ultimately it is the institution’s responsibility to adhere to the NIH Guidelines, it is critical to keep an open line of communication among all stakeholders. This partnership between all parties will ensure you set your study up right from the outset.
Takeaway 4: Seek Expert Guidance
As the gene therapy market expands, we see increased pressure to efficiently expedite trials to FDA approval while, at the same time, upholding safety and complying with NIH and FDA guidelines. HGT trials also face heightened regulatory scrutiny even as regulations are evolving.
Planning for IBC oversight is crucial. Sponsors and CROs should seek expert advice at an early stage of clinical trial planning, particularly at the study kickoff meetings. You need biosafety expertise during the development of your Investigators Brochure, the Pharmacy Manual, as well as during the site selection and protocol preparation stages.
Conclusion
The rapid expansion of the gene therapy field necessitates careful consideration and expert oversight to navigate the complex landscape of human gene transfer (HGT) research. The roles of Institutional Biosafety Committees (IBCs) and Institutional Review Boards (IRBs) are distinct yet complementary, each playing a critical part in ensuring the safety of research participants, staff, and the broader community. Effective collaboration and communication among sponsors, CROs, institutions, and site teams are essential to address the multifaceted challenges involved. Early engagement with biosafety experts and adherence to guidelines set forth by entities like the NIH is imperative to streamline the trial process while maintaining compliance and safety. As the industry grows, a proactive approach to understanding and integrating IBC and IRB requirements will be paramount in setting up successful, safe, and compliant gene therapy trials.