Institutional Biosafety Committees: A Unique Requirement for Gene Transfer Research

Gene transfer research, also known as gene therapy, is a current media darling for good reason.

With applications ranging from correcting single gene diseases such as hemophilia, cystic fibrosis, and Huntington disease to treating multifactorial diseases like cancer, diabetes, and cardiovascular disease, gene transfer research offers the promise of a panacea for our most dreaded diseases.

Gene transfer is commonly defined as “the administration of genetic material to modify or manipulate the expression of a gene product or to alter the biological properties of living cells for therapeutic use.” By employing this transfer, the new genetic material can potentially “fix” a disease by replacing a defective gene or by giving a “normal” cell new-found capabilities.

However, as with any innovative treatment, this great curative potential comes with many unknowns, including the possibility of significant unexpected risks. To mitigate this uncertainty, gene transfer research operates under a complex regulatory framework that requires special review above and beyond those required for traditional research, including by an Institutional Biosafety Committee (IBC) and potentially a special Recombinant DNA Advisory Committee (RAC) based at NIH. Below is a look at these more unfamiliar aspects of conducting gene transfer research and, specifically, the unique role and responsibilities of IBCs.

 

Basis for Additional Oversight

A gene transfer protocol must not only meet the FDA’s Investigative New Drug (IND) and human subjects protections requirements (i.e., obtaining IRB review), but also usually those of the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acids (NIH guidelines). The NIH guidelines, which are a rather dense 129 pages of text, are distinct from other NIH requirements in that an institution only has to be in receipt of federal funds for recombinant DNA based research (e.g., basic science research) in order for them to apply. Put differently, a privately funded gene transfer protocol may still be subject to the NIH guidelines if conducted at an institution that receives any NIH support for other recombinant DNA based activities. This is distinct from many other NIH requirements, which are tied directly to the administration of a NIH award. The increased footprint of the NIH guidelines demonstrates the exceptional nature of gene transfer research and the NIH’s concern about ensuring the safety of such research.

 

IBCs Are the Cornerstone of the NIH Guidelines

An IBC has a distinct purpose from an IRB.

An IRB ensures that a clinical investigation meets certain requirements based on the ethical principles of respect for persons, beneficence, and justice. It focuses solely on the research participant. Alternatively, an IBC ensures a clinical investigation can be safely conducted at an institution. An IBC’s focus goes beyond the research participant and includes the PI, the research staff, the institution, and even the general public.

Accordingly, the NIH guidelines place IBCs front and center. The IBC must determine the adequacy of the institution’s facilities, procedures, practices, and training and expertise of personnel and ensure that all requirements (e.g., protocol registration with NIH and additional reporting requirements) of the NIH guidelines are met. The IBC must also determine the appropriate physical containment levels for each protocol and recommend whether additional public review and discussion (through the RAC) may be warranted before the first participant is enrolled.

Since an IBC’s responsibilities are vast and require specialized knowledge, the NIH Guidelines require that an IBC have, at minimum, the following characteristics:

  • Individuals with expertise in gene therapy technology, biological safety, and physical containment
  • 2 members unaffiliated with the institution
  • 1 member representing laboratory technical staff
  • A designated Biological Safety Officer, if it engages in large-scale research or production activities involving viable organisms containing recombinant or synthetic nucleic acid molecules1

The NIH guidelines also require that the IBC have access to consultants who are knowledgeable in institutional policies, applicable law, professional codes of conduct, and community attitudes. In fact, to ensure that community interests are represented, the NIH encourages IBCs to open their reviews to the public and requires IBCs to make meeting minutes available to the public upon request.

 

IBCs for All

Even for the most stout-hearted researcher, gene transfer research provides a dizzying array of requirements and possibilities. Ensuring that a proper IBC is in place, for example, can be quite challenging. Although IBCs are designed to operate with a local focus, the NIH Office of Science Policy (OSP) recognizes externally administered IBCs as an effective alternative and released an FAQ on such IBCs to assist institutions and researchers.

The same criteria used for a locally administered IBC applies to an externally administered one, with a few extra requirements added for good measure.

An externally administered IBC must provide the NIH with documentation showing that it has knowledge of local institutional characteristics, such as lab conditions, operating procedures, and training. The IBC must also demonstrate that an individual at the registering institution has the authority and responsibility to implement IBC directives.

Externally administered IBCs are especially useful when conducting multi-site clinical trials since the NIH OSP allows the same externally administered IBC to oversee the entire protocol. Note that each individual trial site must register the IBC with the NIH OSP and also must fulfill the necessary membership and expertise requirements, including the requirement that two unaffiliated members represent the local community interests at each site.2

Whether you are pursuing the local or external route, Kinetiq offers assistance in developing a compliant and effective IBC. From developing policies and procedures to managing interim staffing for IBCs, Kinetiq can provide solutions.

 

AAHRPP

Executive Insight

James Riddle, MCSE, CIP, CPIA, VP of Client Services

Organizations looking to participate in research involving gene transfer should thoughtfully consider the numerous regulatory requirements.  Make sure your compliance organization knows the ins and outs of the Office of Science Policy guidelines.