Gene therapy research has moved from the realm of science fiction to mainstream clinical research. The maturation of this field in the US has resulted in multiple FDA-approved gene therapies as well as the creation of the FDA’s Regenerative Medicine and Advanced Therapies (RMAT) designation to allow for fast-track review of advanced therapies, including gene therapies. Last June, FDA commissioner Scott Gottlieb mentioned he expects the FDA to issue 40 gene therapy approvals by 2022.
Given the growth in gene therapy research, sponsors, CROs and sites have become increasingly curious about the requirements to be able to conduct such studies. While clinical researchers are typically familiar with IRB review, they may not be as familiar regarding requirements for review by an institutional biosafety committee (IBC). IBC review is required for any research involving engineered genetic material where there is any NIH funding for the research and development of the investigational product, the clinical trial or if the site has received any NIH funding in the past or present.
Why Is Biosafety Review Required?
The regulatory requirement for IBC review stems from NIH Guidelines which date back to public concerns about the nascent field of genetic engineering in the 1970s and the possibility for misuses of this technology to engineer more dangerous microorganisms or create designer human beings. The NIH Guidelines have been revised multiple times to keep up with advancements in the field of genetic engineering. In fact, NIH Guidelines are currently being revised to streamline the review process for clinical trials involving human gene transfer/gene therapy.
NIH Guidelines call for IBC review to protect study personnel, the community and the environment from exposure to engineered genetic material and other biohazardous agents. An important part of IBC review involves evaluating the way potentially infectious materials are handled at the research site.
Investigational gene therapies typically involve the use of viral vectors, which are comprised of viruses that have been refashioned to deliver engineered genetical material. Viruses are natural tools for delivering genetic material, as the process of viral infection involves delivery of the virus’ genome into the host organism’s cells. During the manufacturing process for gene transfer products, the genes involved in viral replication and causing disease are removed. This allows the virus to serve as a “genetic syringe,” with its functions limited to delivering genetic information in a single round of infection.
While investigational products for gene therapies are designed with safety features, they must be handled with appropriate precautions. Most gene therapy research involves Risk Group 2 microorganisms, meaning they can cause mild to moderate disease in healthy adults. Individuals with compromised immune systems or other pre-existing conditions may be at increased risk from exposure.
Gene therapy research is an emerging field, and many clinical research sites are unfamiliar with the concept of IBC oversight and biosafety. With that in mind, let’s look at the basics of biosafety and infection control and the IBC’s role in helping ensure these considerations are properly addressed in research.
Biosafety and Infection Control
Infection control focuses on utilizing an established set of precautions intended to disrupt transmission of infectious diseases caused by well-characterized microorganisms. Infection control focuses on prevention and control of infection among patients and research participants.
Biosafety is a risk assessment-based process that looks to create project-specific risk mitigation plans based on each study’s unique risk profile. A biosafety risk assessment looks at the risk group (virulence), mode of transmission, genetic modifications and study procedures before determining the precautions required for a particular study. Biosafety strives to protect the occupational safety of the research staff as well as the community (including individuals with whom the research participant may come in contact) and the environment. Environmental protection may include reviewing the site’s waste management plans as well as assessing and mitigating risks of environmental release of biohazardous materials.
The IBC provides regulatory oversight of research involving genetic engineering or gene therapy to make sure the research can be done safely at the proposed research site. As part of IBC review, research sites require inspection to ensure compliance with the NIH and CDC biosafety guidelines, Biosafety in Microbiological and Biomedical Laboratories, ed. 5 (BMBL).
The BMBL is compatible with existing requirements in the clinical setting, such as the OSHA bloodborne pathogen standard and precautions utilized for infection prevention and control.
Since no 2 research facilities are exactly alike, the IBC reviews the information provided by the study sponsor, investigator and site inspector to evaluate the research site’s facilities and safety practices to make sure proper protections are in place.
I hope this has provided you with a helpful introduction to biosafety and infection control in gene therapy research. In future blogs, we’ll explore these topics in more detail and discuss why the IBC may require specific precautions with certain types of research.