Why Institutions Should Consider an Externally Administered IBC
Clinical trials for gene therapy are booming, especially in the fields of oncology, infectious diseases, rare diseases, and regenerative medicine. In January of 2019, then-Food and Drug Administration (FDA) Commissioner Scott Gottlieb and Peter Marks, Director of the FDA Center for Biologics Evaluation and Research (CBER), announced new policies to advance gene therapy research and described the current state of gene therapy as “…similar to the period marking an acceleration in the development of antibody drugs in the late 1990s, and the mainstreaming of monoclonal antibodies as the backbone of modern treatment regimens.”
That prediction is already becoming reality. Consider: the FDA set records in subsequent years for Investigational New Drug (IND) applications for products containing engineered genetic material. Also, the three COVID-19 vaccines with FDA emergency use authorization (Pfizer, Moderna, and Janssen) all contain engineered genetic material.
Data adapted with permission from Peter Marks, Director, FDA Center for Biologics Evaluation and Research (CBER). Originally published in Applied Biosafety, 2019.
Current State of Gene Therapy Oversight at Institutions
Institutions receiving National Institutes of Health (NIH) support are required to have an institutional biosafety committee (IBC) review of research involving engineered genetic material (recombinant or synthetic nucleic acid molecules). Traditionally, IBCs at academic institutions meet monthly or sometimes quarterly, predominantly focusing on basic science research performed in laboratories and animal facilities rather than clinical trials. Given their charge, many IBCs may lack the expertise or experience to review clinical trials. To efficiently review gene therapy studies, the IBC should have expertise in human gene transfer as well as policies and procedures for the review of clinical trials.
Waiting until a gene therapy clinical trial is submitted to recruit an ad hoc reviewer or develop procedures for performing the review can introduce unnecessary and lengthy delays. Furthermore, some institutions’ institutional review boards (IRBs) will not accept a submission for a gene therapy study unless it is accompanied by the IBC review. Additionally, multisite studies can experience startup challenges on a greater scale, as sites with individual and locally administered IBCs involve different submission deadlines, meetings schedules, policies, and procedures and increased variability in review outcomes.
What Can Institutions Do to Prepare for a Surge in Gene Therapy Research?
The NIH allows institutions to utilize multiple IBCs, creating a situation where an institution can rely on an externally administered IBC with reviewer expertise in the clinical environment and human gene transfer research, while retaining their locally administered IBC for basic science research involving laboratories and animal models.
This approach provides similar benefits as central IRB review for clinical trials, such as increased review efficiency and consistent protections and oversight for multisite studies. The central IRB review concept was considered so beneficial that the NIH instituted a single IRB policy for NIH funded studies (effective January 25, 2018). The federal government followed suit with revisions to the Common Rule (45 CFR 46), the rule of ethics in the United States regarding biomedical and behavioral research involving human subjects, to require a single IRB (sIRB) of record for all federally funded research (effective January 20, 2020).
Institutions with externally administered central IBCs may position themselves as “gene therapy ready” to reflect the benefits of such a partnership and make them more attractive to sponsors and contract research organizations (CROs) during the site selection process.
In a 2021 interview with Advarra, Dr. Fred Locke, Director of the Moffitt Cancer Center’s Immune Cell Therapy program, stated, “If you can have a centralized IRB and IBC review, it simplifies the process.” Minimizing startup delays is of paramount importance, particularly in resistant or refractory disease cases.
As an example, the externally administered IBC review performed by Advarra has significantly streamlined study activation timelines. Advarra’s IBC averaged turnaround times of 3.3 business days (N = 118 reviews) from submission to review for National Cancer Institute (NCI) designated cancer centers. These centers previously experienced turnaround times of up to three to four months when working with their locally administered IBCs.
When the COVID-19 pandemic hit North America, Advarra’s IBC was able to prioritize review of COVID-19 research. Because Advarra has full-time resources dedicated to conducting and managing IBC review activities, Advarra’s IBC averaged 1.7 business day (N = 152 reviews) turnaround times on reviews for COVID-19 vaccine research. Advarra has also accelerated startup for the Meridian Clinical Research Network and IQVIA, the world’s largest CRO.
Where Should Institutions Start?
The best way an institution can prepare to participate in any gene therapy studies is to register an IBC with the NIH and become familiar with the basic requirements for IBC review. As the NIH Office of Science Policy (OSP) review of an institution’s IBC registration may take four to six weeks, institutions can compress timelines by registering their IBCs well in advance of having a new study ready for IBC review. This way institutions are ready to start the IBC review process immediately. There is no cost associated with registering an IBC with the NIH, and institutions may be registered with several IBCs.