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Gene therapy research is beginning to boom in the clinical setting. In this blog, I’ll summarize the growth, risks, and regulatory requirements for gene therapy research. I’ll also discuss how a centralized biosafety review process can be beneficial for this type of research.

Introduction

The gene therapy field is experiencing explosive growth in today’s competitive research environment. Gene therapy entails the transfer of engineered genetic materials to human research subjects. These studies were previously considered to be highly experimental and limited to early phase trials at a handful of highly specialized academic medical centers. However, well-established safety profiles, promising research results, and the FDA issuing the first gene therapy approvals in recent years have led to dramatic growth.

Searching clinicaltrials.gov for gene therapy studies results in 4070 hits with 1067 studies currently recruiting or enrolling research subjects. As of September 2019, 295 phase III studies are listed, representing a growing pipeline of gene therapy products are preparing to undergo consideration for FDA approval.

Risks and Regulatory Requirements

Most clinical researchers are familiar with the regulatory requirements pertaining to the FDA phases of review as well as with IRB review. However, gene therapy studies require additional review to assess the risks associated with the engineered genetic material, especially as the technology frequently utilizes genetically engineered viruses to deliver genetic information into target cells. Viral infection involves the transfer of the virus’ genetic material to host cells, making viruses ideal tools for gene transfer—once the 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 causing harm.

NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) provide the standard for oversight of research involving genetic engineering and gene therapy. NIH Guidelines are promulgated by the NIH Office of Science Policy (OSP) and call for local oversight at the research site by institutional biosafety committees (IBCs) that report to the NIH OSP. IBCs are charged with protecting study personnel, the community, and the environment from exposure to engineered genetic material. An IBC may also advise the IRB to aid in assessing risks to the study subjects.

IBCs are comprised of at least 5 members, including at least 2 unaffiliated community members, that collectively possess the expertise to assess the risks associated with the proposed research which may include preclinical, clinical or non-clinical research. IBC membership is required to include additional expertise for research involving animal models, human subjects, high containment infectious disease laboratories, industrial scale greater than 10 liters, and plants or plant pathogens.

IBC review involves assessing the risks associated with the genetically modified investigational product as well as the adequacy of a facility’s safety practices and training intended for use of the investigational product at the site.

  • The IBC ensures the site has adequate incident reporting and response plans in place to address potential occupational exposures, spills, or environmental releases of the investigational product.
  • The IBC may review informed consent forms (ICFs) and other research subject materials to mitigate possible risks to casual or close contacts in the community.
  • Reviewing the site’s plans for disposal of the investigational product and associated biomedical waste allows the IBC to ensure environmental protection.

Efficiencies from a Centralized Review

While NIH Guidelines call for local oversight provided by IBCs at the site level, the process can be externally administered by a central body to provide similar benefits as centralized IRB review. Organizations providing centralized review can provide greater speed and efficiencies. Many offer a web-based submission portal, which allows sponsors and CROs to create a single submission for multiple sites. Additionally, centralized IBC organizations can administer IBCs for sites lacking their own committees or can serve as a second committee specifically for clinical trials when the existing IBC lacks the expertise for such reviews (many local IBCs focus only on preclinical or non-clinical research).

The greatest benefit is faster turnaround times from submission to approval. Academic medical centers are typically limited to monthly IBC meetings and routinely take 2-3 months to issue an approval for a gene therapy study. Centralized IBC organizations have more frequent committee meetings: for example, Advarra’s IBC is able to provide 2-week turnaround times for registered sites and has been providing approvals to NCI-designated cancer centers in under 8 business days.

As a result of these centralized efficiencies, sponsors experience faster study startups, achieve experimental endpoints earlier, and cut costs. Sites that work with a centralized IBC are more competitive for being selected for studies and are more likely to meet recruitment goals. Most importantly of all, a centralized review process lets patients experience accelerated access to the latest biomedical science has to offer.

Wondering whether you’ll need an IBC for your upcoming study? Read our blog Does This Study Require IBC Review?

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