The completion of the human genome project and advances in genetic engineering have paved the way for clinical trials involving human gene transfer, colloquially known as gene therapy research, to enter the mainstream. Gene therapy research involves the deliberate transfer of engineered genetic material to humans, with the goal of compensating for genetic mutations, conferring the capability to produce potentially therapeutic substances, or eliciting immune responses to fight disease.
While genetic engineering brings hope for new medical breakthroughs, the technology is not without risks. Scientists have looked to nature to find an efficient way of delivering genetic material to target cells and found viruses to serve as unlikely allies in the fight against disease. Viral infection involves the transfer of the virus’ genetic material to host cells, making viruses ideal tools for gene transfer once the viral genes responsible for viral replication and disease are removed. While genetically modified viruses have a greater safety profile than the naturally occurring unmodified variety, they remain infectious and capable of posing risks.
NIH Guidelines require a thorough risk assessment be performed prior to conducting research with genetic engineering to ensure the risks are identified and adequately mitigated. Clinical trials involving human gene transfer that have been funded by the NIH or take place at sites that have received NIH funding must comply with the requirements outlined in NIH Guidelines. To assess and monitor the risks surrounding human gene transfer research, NIH Guidelines require institutional biosafety committee (IBC) review—in addition to review by an institutional review board (IRB).
What Is an IBC?
Both the IRB and IBC focus on risk, but the committees have contrasting responsibilities. While IRBs are tasked with protecting the rights and welfare of research participants; IBCs seek to protect study personnel, the community and the environment from exposure to engineered genetic material and other biohazardous agents. An IBC may also advise the IRB to aid in the assessment of risks to the study subjects. IBCs are locally based at the research site and comprised of membership possessing expertise in genetic engineering, biological safety, infectious diseases and environmental protection. Each IBC is required to possess at least two community members who are unaffiliated with the institution or research site and represent the interests of the community and the local environment.
In reviewing a study, IBC members assess the facilities, procedures, safety practices, training and expertise of personnel involved in the research. The committee also assesses the research itself, including the characteristics of the proposed genetic modifications, microorganisms that may be utilized and the target cells, tissues or organs which will ultimately be affected. Facility inspections are required as part of the approval process as well as periodic reviews to ensure appropriate safety measures remain in place.
NIH Guidelines were revised effective April 2016 to bestow greater authority on the reviewing IBC (or IRB) clinical trials taking place at the initial study site. These local oversight bodies perform the initial determination of whether the research poses novel risks which merit review by the NIH Recombinant DNA Advisory Committee (RAC), a national panel of experts in genetic engineering, infectious diseases as well as occupational safety and environmental protection. RAC review is necessary in cases where:
- A new vector, genetic modification or delivery methodology is being used that represents a first in human experience and poses unknown risks or
- The pre-clinical safety data was produced with a new model of unconfirmed value or
- The proposed genetic modifications or delivery methods are associated with possible toxicities that are not widely known.
My Study Needs IBC Review—What Do I Do?
Be proactive in checking with your institution. Some sites such as universities and academic medical centers may already have IBCs in place to monitor basic science or pre-clinical studies; however, these IBCs may or may not be prepared to review clinical research. The latter may result in unnecessary frustration and costly delays.
If your institution does not have an IBC or requires additional expertise, there are a few commercial IBC services available. Keep in mind, however, that an IBC must include a local component. NIH Guidelines do not permit IBC review to be centralized in the same manner as IRB review. Commercial IBC services may create and externally administer an IBC for the site and provide efficiencies over purely local oversight.
IBC review is a new concept to many clinical researchers, but it shouldn’t be an obstacle to research. Include IBC review in your study planning to ensure your research is conducted safely, responsibly and without start up delays.