If a site needs to submit to create an IBC with WCG, how long does the NIH registration process typically take? 

• Submitter: Regulatory Coordinator, CRO 

Answer:

Under Section IV-Bⁱ of the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), institutions must establish an IBC that includes, at a minimum: 

• At least five members who collectively have the experience, expertise, and capability to assess the safety of research covered by the NIH Guidelines; 

• At least two members who work or reside in the surrounding community and are not affiliated with the institution (apart from their membership on the IBC); 

• Plant, animal, and/or gene transfer experts as applicable for the research being reviewed. 

Once the IBC has been established in accordance with the NIH Guidelines, institutions are responsible for filing annual reports with the NIH that include a current IBC roster and biosketches for all members. The NIH encourages institutions to use their IBC Roster Management System (IBC-RMS) database to file these reports and to track the ongoing status and composition of the IBCⁱⁱ. 

At WCG, we partner with institutions to create IBCs staffed with experts from our extensive network of clinicians, scientists, and biosafety professionals around the country, enabling us to establish new IBCs in just a matter of days. Once an IBC has been established, the NIH’s IBC-RMS database is used to track its status and provide required annual updates to the NIH on behalf of the institution. Our approach includes parallel processes for IBC establishment and study review, meaning many IBCs can review and approve research as soon as the committee is established. Institutions wishing to partner with WCG and establish a new IBC are encouraged to complete and submit Submission Form – Part A or contact WCG IBC Services at ibcservices@wcgclinical.com with any questions. 

References

1. Section IV-B. Responsibilities of the Institution. https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.pdf 
2. FAQs on Institutional Biosafety Committee (IBC) Administration – April 2024 https://osp.od.nih.gov/policies/biosafety-and-biosecurity-policy/faqs-on-institutional-biosafety-committee-ibc-administration-april-2024/ 

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For investigational drugs needing IBC review, what is the difference between a Risk Group and a Biosafety Level?  Are they always equivalent?

• Regulatory Coordinator, Oncology Clinic

Answer:

Institutional Biosafety Committees (IBCs) exist to protect research staff, the public, and the environment from risks posed by research with biological agents containing recombinant or synthetic nucleic acids (i.e. DNA/RNA).  As part of these responsibilities, the National Institutes of Health (NIH) requires IBCs to comprehensively assess biosafety-related risks associated with the research, and outlines a number of items IBCs should consider when conducting these risk assessments.  As a starting point, investigational agents are assigned to a Risk Group (RG) based on several criteria related to the agent itself, or for genetically modified agents, the parental organism from which the agent was derived:

• Ability to cause disease in healthy adult humans;
• Anticipated disease severity;
• Availability of preventative or therapeutic interventions.  

Risk Groups range from 1-4, with level 1 for the lowest-risk agents and level 4 for the highest-risk agents (Table 1).  

Biosafety Levels (BSL) are similar to RGs in that they are used to classify research based on risk.  Biosafety Levels also range from levels 1-4, with 1 for low-risk research and 4 for the highest-risk research.  In contrast to RGs, however, which generally do not dictate behaviors or work practices, BSLs are used to identify and characterize specific work practices, facilities, and safety equipment required for the research in question.  In general, BSLs and RGs are aligned, meaning RG2 agents are usually approved by IBCs for handling at BSL-2.  The NIH also requires certain BSLs for several categories of research, including BSL-4 for all work with RG4 agents (Table 2). 

However, there are also times that the IBC-determined BSL and the RG of the agent being worked with do not align.  This can happen because risk assessments and BSL determinations are not based solely on an agent’s assigned RG.  In addition to RG, IBCs also consider the agent’s “virulence, pathogenicity, infectious dose, environmental stability, route of spread, communicability, operations, quantity, availability of vaccine or treatment, and gene product effects such as toxicity, physiological activity, and allergenicity”, and as a result, BSLs “may be raised or lowered as a result of [these] considerations”¹.  This is a common occurrence for certain agents; for example, many IBCs approve research with lentivirus-modified chimeric antigen receptor (CAR) T cells at BSL-2 despite lentiviruses being RG3 agents.  Similarly, IBCs often approve research at a BSL higher than the RG of the agent being handled, particularly if it harbors genetic modifications or transgenes that increase biosafety risks. 

It should be noted that nearly all clinical trial research can be safely conducted at BSL-1 or BSL-2.  At many institutions, the pharmacies, laboratories, and patient rooms used for clinical research are set up such that they meet the requirements of both BSL-1 and BSL-2; in these cases the distinction between BSL-1 and BSL-2 may be largely administrative.  Whatever the case, communication between investigators and their staff with the IBC is one of the most effective ways of ensuring biosafety.  Lastly, as certain genetic engineering technologies advance to the point where they can be used without infectious microbial vectors (and therefore have no assigned RG), it will be critical that IBCs and research staff fully understand the nature of each agent so that risk assessments and the research can be conducted appropriately.

References

1. Comprehensive Risk Assessment. NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines). April 2019. National Institutes of Health. Available at https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.pdf. Accessed 12 November 2023.

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I was told my upcoming gene therapy study needs IRB and IBC approval.  Does one need to come before the other?

-Trial Specialist, Clinical Research Center

Response:

Both IRB and IBC approval are required for most human gene transfer research subject to the NIH Guidelines¹.  While many institutions require IBC approval before full IRB approval can be granted (or vice versa), there is no regulatory requirement as to which must be obtained first. 

That said, there are times when it can be helpful to go through the IBC review process first, as IBCs often identify problems that IRBs may not even consider due to differences in their scope and composition.  For example, most IBCs are better positioned to evaluate biosafety risks associated with genetically modified products – many of which are often derived from viral pathogens that are inherently hazardous.  Similarly, most IBCs can easily assess the likelihood that a genetically modified product will be transmitted from study participants to others (children, coworkers, etc.), and evaluate the risks posed to those individuals if transmission were to occur.  These and similar issues identified by the IBC during its review would be helpful for IRBs to consider as they conduct their reviews and request changes to consent documents or study procedures. 

Whatever your choice – IRB approval or IBC approval first – communication between both entities is one of the most effective ways to accelerate study startup while ensuring the safety of research subjects and the public at large. 

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We are thinking about starting a study that may need IBC review before we can begin.  Do we need to buy any special safety equipment for studies needing IBC approval?

– Clinical Trial Coordinator, Research Institution

Response:

When reviewing a study that requires IBC approval before initiation, most IBCs expect basic safety precautions and equipment to be in place.  Handwashing sinks, eyewashes, spill cleanup kits, and appropriate biohazardous waste containers are good examples of such equipment. 

The need for any additional “non-standard” safety equipment – like respirators, biosafety cabinets (BSC), or other containment devices – is driven by a combination of factors that have to do with the investigational product and how it is handled.  For example, a replication-capable viral vector derived from an airborne pathogen like Adenovirus will often require a BSC for mixing, dilution, or other activities with the potential to generate infectious aerosols.  Lower-risk products, like mRNA vaccines or other non-infectious agents, can usually be handled without special safety equipment.  Sites should rely on their IBC or a similar safety committee as a resource that can be utilized to make safety-related determinations.

Lastly, investigators and their staff should be aware that product handling instructions provided by clinical trial sponsors are not always written with IBCs and best biosafety practices in mind, oftentimes calling for unnecessary or inappropriate equipment.  To ensure staff safety and avoid study startup delays, trial sites and their IBCs should always review sponsor-provided handling instructions and address any concerns as early as possible.   

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Meet the Speaker

Christopher Doyle, PhD

Director, WCG IRB Services

Chris currently serves as an Institutional Biosafety Committee (IBC) Chair and Director of IBC Services working with research sites, sponsors, and CROs to ensure human gene transfer clinical trials are conducted safely. Prior to joining WCG IRB in early 2018, Chris was a research fellow at the Albert Einstein College of Medicine (Bronx, NY), where he explored mechanisms of antibody activity against Streptococcus pneumoniae.

Chris received his BA in Biology from Assumption College (Worcester, MA) in 2008 and his PhD in Molecular Genetics and Microbiology from Stony Brook University (Stony Brook, NY) in 2014, where he studied the pathogenesis of Francisella tularensis in a high containment Biosafety Level 3 laboratory. Chris has authored a number of peer-reviewed publications describing his past research, has served as an ad-hoc reviewer for Infection and Immunity, and is a member of the American Society for Microbiology (ASM) and the American Biological Safety Association (ABSA).

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