Institutional Biosafety Committee Review for Genetically Modified Vaccines and Gene Transfer Products

Key Takeaways: 

• IBC review focuses on biosafety. Unlike IRBs, which protect research participants, IBCs are primarily responsible for protecting staff, visitors, public health, and the environment from risks associated with genetically modified agents. 

• Many gene transfer studies require site-specific IBC review before initiation. Human gene transfer (HGT) trials involving recombinant or synthetic nucleic acids often fall under the NIH Guidelines, and each clinical trial site must obtain approval from its own IBC of record before the study begins. 

• The 2019 NIH changes streamlined oversight but increased local IBC responsibility. NIH no longer registers or tracks individual HGT protocols centrally, and Appendix M/RAC-related federal pre-review was removed. This reduced paperwork, but it also means local IBCs now carry greater responsibility for getting the review right. 

• IBC review is highly operational and risk-based. Committees evaluate issues such as product handling, storage, labeling, administration, waste disposal, exposure risks, shedding, spill response, SOPs, training, and biosafety level assignments to ensure the site can safely manage the investigational product. 

• Sites can use either local or centrally administered IBCs. Institutions may maintain their own IBC, use a central/commercially administered IBC, or both. The decision about which IBC reviews a study is up to the institution. 

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Transcript

Kylie Gullett: 

Hello, and welcome to this month’s WCG Global Research Network exclusive webinar on Institutional Biosafety Committee review for genetically modified vaccine and gene transfer products. My name is Kylie Gullett. I’m the marketing associate for WCG site services division. We’re very excited to have you all here today. Before we get started, I’d like to review how today’s webinar will work. The presentation will run for approximately 45 minutes, and then we’ll have around 15 minutes available for attendees’ questions at the end. You may submit questions to the speaker at any time during the presentation by typing a question into the ask questions box in the lower left portion of your player. If at any time during the presentation you require technical assistance, please click on the question mark button in the upper right corner of your player. There you will find a list of frequently asked questions or be able to contact technical support as needed.  

I’m excited to introduce today’s speaker, Dr. Daniel Kavanagh. Dr. Kavanagh is a senior scientific advisor of gene therapy at WCG. Prior to joining WCG, Dr. Kavanagh was an assistant professor of medicine and institutional biosafety committee vice chair at Harvard Medical School and an assistant immunologist at Massachusetts General Hospital. He was also co-chair of a phase one clinical trial of an autologous mRNA-transfected dendritic cell vaccine in HIV positive subjects. Dr. Kavanagh holds a PhD in molecular microbiology and immunology from the Oregon Health and Science University and is certified in regulatory affairs by the Regulatory Affairs Professional Society. He completed his postdoctoral training at Harvard Medical School, Boston, MA, and the Rockefeller University in New York. Now that I’ve introduced our speaker, I will now turn it over to Dr. Kavanagh to begin the presentation. 
 
Dr. Daniel Kavanagh: 

Okay, great, thanks, Kylie. And thank you, everyone, for attending. Please let the organizers know if there’s any problem with the sound, or if anyone can’t hear me. We’re more used to giving presentations in person. But during these COVID times, we’re becoming more and more used to the remote presentations, so for today’s topics, I’m going to review NIH guidelines and the role of institutional biosafety committees, answer the question of what research requires IBC approval, or at least discuss how that question will be answered for each protocol. Briefly look at some of the up-and-coming human gene transfer research technologies that are being applied and discuss how IBCs can be registered with the NIH locally or centrally and quickly run through what is involved in IBC review and approval. Next slide. 

So, to start out with, what is biosafety? The goal of biosafety is to manage risks associated with lease of or exposure to potentially hazardous biological materials, so at a large research institution, there’s going to be a biosafety program that has to address risks associated with infectious agents or toxins, synthetic manufactured toxins that may be used for research, genetically modified microbes or animals, and next slide.  

Importantly, for today’s conversation, biosafety committees have to review human gene transfer clinical trials, and so what we’re going to focus on today is this last topic, keeping in mind that an IBC at a major university may be spending 90% of their time on other stuff, whereas an IBC registered for a research hospital may spend 99% of their time specifically on human gene transfer research.  

Next slide. So, the rules for IBCs, why IBCs exist, and why we need to approach this discussion according to this framework come from the NIH guidelines for research involving recombinant or synthetic nucleic acid molecules. These guidelines have been in place for over 40 years. They were created by the NIH in consultation with the scientific community. When recombinant DNA research was first being discovered, the original idea was that the major universities doing recombinant DNA research would form committees to allow science to regulate itself. Each committee would include scientists from the university, and each committee must also include local community members not associated with the institution to provide community input, and that was probably historically very important for acceptance with municipal governments accepting this kind of research within their jurisdictions, and all those expectations remain in place today for the committees that we administer now. A companion document, which is jointly issued by CDC and NIH, is the BMBL handbook on the right side of your screen. Here, the fifth edition is out now. The sixth edition will be coming out soon, and this describes the best practices for handling of infectious agents and microbes, and other biohazards. So, together these documents provide the backbone for what biosafety professionals use in the United States to guide safe conduct of research. There are other journals in the field, and conferences, and meetings for biosafety professionals to discuss best practices and matters arising.  

Next slide, please. So, IBCs are defined by the NIH guidelines, and as such are required at any institution or clinical trial site that receives NIH funding for relevant molecular biology research or clinical trial sites that are conducting gene transfer trials that are subject to the guidelines. The purpose of EIBC is to ensure compliance with the guidelines, as well as safe conduct of research, and it does so by approving protocols, facilities, and biocontainment levels at the site. It advises sites on policies and must deliberate and vote on each proposal at a convened meeting, which are recommended to be held publicly. The IBC has to include experts on relevant topics, biosafety and scientific issues, and as mentioned, local members of the public are not affiliated with the institution as voting members.  

Next slide. So, a lot of researchers are more familiar with IRB than with IBC, and in many ways, they seem similar, but there are some important differences. The IRB oversight that we are all familiar with is mandated by federal law, mandated by international grievance, and it is focused on protecting research participants by assessing risk and benefit to the participant, informed consent, privacy, confidentiality, etc. IBCs are not mandated to focus on protecting the participants under the NIH guidelines: the purpose of the IBC is to protect laboratory staff, visitors, public health, and the environment. So, the focus of the IBC is environmental health and safety protection of the staff, as opposed to the protection of clinical trial participants. So, these are complementary reviews. Notably, IRBs can issue study-level approvals and multicenter trials. IBC approvals must issue each one from the respective IBC registered on behalf of each clinical trial site.  

Next slide. Another way to look at this is that previously it was expected that some IRBs would not understand gene therapy and molecular biology adequately, and previously IBCs were required to review informed consent, human subject protection, and adverse events. Last year, the FDA and NIH, after extensive consultation, decided to draw a brighter line between the minimally mandated reviews. Now, IBCs are focused on, as we just discussed, shedding by containment, things like needle stick prevention and biohazardous waste disposal. The IRBs are allowed to review the informed consent and human subject protection issues on their own. This is not to say that IBCs are forbidden from addressing the other issues. It’s up to the institution to decide what they want the IBC to review, but the minimal requirements of the guidelines have been separated.  

Next slide. So, when it comes to clinical trials, the type of clinical trial that requires IBC review is known as a human gene transfer trial, HGT. So, need to take a little bit of time to consider what that means on a technical level. HGT products are those that incorporate recombinant or synthetic DNA or RNA or nucleic acids derived therefrom, with certain exceptions for short or genetically inert categories.  

Next slide, and these definitions are laid out in quite a helpful manner in the guidelines section 3c one, where we have a clear technical definition of what is a human gene transfer trial. It’s the delivered transfer into a human research participant, either recombinant nucleic acid molecules, DNA, RNA derived therefrom, or synthetic nucleic acid molecules, DNA derived or RNA derived therefrom, with exceptions for molecules that have less than 100 nucleotides, if they are short, if they don’t integrate into the chromosome, if they don’t replicate and cannot produce other nucleic acids or proteins, then they may be exempt from the guidelines from this definition of a gene transfer trial, because they’re considered minimal risk. So, when it comes down to figuring out whether a particular protocol meets this definition. If you find a biosafety professional who does this every day, it’s almost always quite easy to make that determination from an investigator’s brochure product description. And we’re here to help.  

Next slide. One thing that trips people up when approaching human gene transfer trials is that there are other than the NIH: there are governing authorities who have different categories that they use to review and approve products at the FDA, they have cellular and gene therapy products as a category, and also vaccines in Europe and the UK. We see categories such as ATMs and GMOs. For each one of those shown on the screen, some of them qualify as HGT under the NIH guidelines, and stunt don’t, so it’s just best not to make any assumptions based on these other categories that have been applied by other authorities. You need to go back to the basic definition, which depends on the actual DNA and RNA content of the product, and as noted, find somebody who is an expert in the field if you need any help interpreting the investigator’s brochure to see how this definition applies.  

Next slide. So, this research has been going on for decades, and in the last five years, the FDA has actually approved, given marketing approval to products that meet the NIH definition of gene transfer products, and these include oncology products. Three of these here are our CAR-T chimeric antigen receptor T cell products, genetically modified lymphocytes that target cancer cells. One of them is an oncolytic virus, a genetically modified virus intended to destroy tumors. Two of these products are gene therapies for inherited rare diseases, and three of them right now are prophylactic vaccines for infectious diseases. In the coming months, we are all hoping to see approvals for Covid 19 vaccines, and many of those products under development are also human gene transfer products.  

Next slide. So, we just looked at how to define a human gene transfer product. The next question is, is IBC review required for these products? It depends partly on the definition we just discussed. It depends partly on funding history. When the NIH guidelines are mandatory, if the institution or site receives NIH funding for non-exempt recombinant synthetic nucleic acid research, basically molecular biology research funded by the NIH, anywhere at that institution. Then all such research at the institution is subject to the guidelines, and therefore, the clinical trial will be conducted if the sponsor receives such funding, the research falls under the guidelines if the study, or the trial is funded by the NIH or certain other federal agencies that mandate NIH compliance. It falls under the guidelines, and if the product was developed with NIH funding, it also falls under the guidelines for the entire clinical trial. Also, the NIH recommends what they call voluntary compliance. So, overall, you can see, you can guess that a very large percentage of products that are brought to clinical trials in the United States, all under the NIH guidelines, if they are imaging transfer, in which case IBC approval at each clinical trial site is required before initiation.  

Next slide, please. So, I did mention before that guidelines were amended last year. In fact, over the decades, they’ve been amended many times, which is good because technology keeps changing, and the commercial landscape keeps changing too. Those of you who may have filed for IBC approvals in the past may have had to deal with a document known as the Append Exam, which points to consider. It was Appendix M to the NRH guidelines, quite an extensive series of questions to be addressed by investigators prior to submission and filed with the NIH, so that was taken out, and the body that used to prove Appendix M to review Appendix M was known as the RAC, the Recombinant DNA Advisory Committee, and that committee in Bethesda has been renamed and repurposed, so as a result the NIH is no longer registering or tracking individual protocols, so good deal of effort you that used to be required by sponsors and by investigators was eliminated in 2019 so that is good news for everyone who has to have had to handle that paperwork as a result, because the federal level pre review by the Common DNA Advisory Committee was eliminated. It’s actually more responsibility on each IBC to get it right, because they’re doing it on their own. On the other hand, as a result of these changes, I\BCs, as we mentioned, have fewer responsibilities for addressing protection of human subjects, and they’re meant to focus on mitigating the risk to the staff, public, and the environment. Another change that was tagged onto this section when the guidelines were amended is an exemption for expanded access to IDs and protocols if they are single-subject studies. This comes up occasionally at some sites, and you know we’re happy to talk to any investigators who are involved in that kind of research to help figure out whether that research is exempt or not.  

Next slide. So, to look at what kinds of studies are being brought to the clinic that fall under this category and need these kinds of reviews. The actual diversity of technologies in preclinical and phase one is simply too broad to address today. It includes stem cells and probiotics, all different kinds of novel ideas that are being tested or being prepared for testing, but some of the major categories are vaccines, immuno-oncology products, gene therapy, and gene editing. So just going to view those briefly, so that people can get a taste of what kinds of technology may be coming to your clinic. We’re starting with the vaccines.  

Next slide. Vaccine for infectious disease are obviously of a major concern to people around the world in 2020 and historically the vaccines that those of us who are older received as children were all developed without recombinant DNA technology, and the live attenuated vaccines that were used through the decades were developed empirically by serial passage of viruses and different cell types until a hopefully safe vaccine was derived, and it turns out, you know, after extensive testing, those were very safe and effective technologies. The new generation of vaccines can be developed with new technology by proactive consideration of how we want the vaccines to work, and that means there’s a pretty large percentage of vaccines under development that are gene transfer products because they incorporate DNA or RNA. This includes naked DNA vaccines that may be just a plasmid, a circle of naked DNA that can be transferred into human cells by several different techniques and can induce an immune response. It includes synthetic mRNA, which is, in principle, quite similar, but it’s easier to trick cells into producing a lot of the protein you desire using mRNA in delivery. There are vectors derived from live viruses, for example, that are genetically engineered to be non-pathogenic, so they can be used rather than relying on random mutation. These are targeted genetic lesions introduced into a viral genome in order to create a virus that doesn’t cause disease, and that’s a way to produce live attenuated vaccines, and you can also take a viral vector, such as an adenovirus or a pox virus, and introduce antigens from the pathogen that you want to create a vaccine for, and use that as a vector, so broad array of technologies can be used to induce immune responses using gene transfer, and of the COVID 19 vaccines under development, several of them, several most prominent ones meet these definitions. Important to note that not all of the next-generation vaccines are gene transfer. Some of them do not contain genetically modified DNA or RNA. They may be based on synthetic peptides, recombinant proteins, or virus-like particles. So, you need to check before you gear up for an IBC review.  

Next slide, please. Another major area, and I can say for this year, before the pandemic, the majority, certainly not all, but you know, 60% of the protocols coming across my desk were oncology, and examples in this area include CAR T cells, DNA and RNA vaccines, therapeutic viral vectors on colydic viruses.  

Next slide. So, for those who don’t know, a very exciting development in immuno-oncology are chimeric antigen receptor modified lymphocytes, especially CAR-T. The way that CAR-T cells work is the white blood cells are isolated from the blood of a subject with cancer. If it’s an autologous therapy, there is some form of gene transfer to modify those T cells, and in the simplest version, the T cells will then express a T cell receptor targeting a known tumor antigen. Those cells can be reinfused into the patient and will hopefully attack the tumor sometimes with extremely dramatic results, and some amazing stories of recovery, as we noted before, of the four oncology products that have FDA approval, three of them are CAR-T products, as far in the HGT category, and it’s a very exciting area, and there’s a lot of new technologies that are applied to next generations of genetically modified lymphocytes.  

Next slide. And another approach in the oncology field are oncolytic viruses. One of the FDA-approved products that we saw is a genetically modified oncolytic virus. These are viruses that are programmed to preferentially reproduce in tumor cells. The result is hopefully one, killing the tumor cell, and two, frequently targeting intended to induce an immune response against the tumor, and sometimes they are also designed to do something like potentiate chemotherapy to make the chemotherapy more effective, specifically in the tumor. So, in combination, this is a powerful set of technologies that are also quite promising, and we’re seeing a lot of them in oncology trials.  

Next slide, please. Another area is gene therapy for inherited rare diseases. So, there are over, depending on how you come and whose definition you use, over 6000 or 8000 different rare diseases identified, the majority of these are inherited, and a very large percentage of those are homozygous recessive, which means that the affected individual has inherited a copy from a mother, copy from the father of two defective genes, so that they can produce a functional protein leading to the disease state. That type of genetic disease where there is a lack of a functional protein is a very promising target for gene therapy because we can build a vector that will introduce functional DNA and co-locating a functional protein into some target tissue, and hopefully restore function and modify or reverse the disease. So it it’s a very promising area, and you’ve seen the list of FDA approved products. There are two gene therapies approved for inherited rare diseases. The first one was Lux Turner for inherited retinal disease, and just the results have been spectacular in terms of seeing how children who previously couldn’t see in low light have their vision restored, and also adults, so it’s on its way to becoming one of the great success stories of modern medicine, in my opinion, and it’s very exciting to see each of these new therapies develop. There are challenges for manufacturing, for commercialization, etc., but those are going to be dealt with.  

Next slide. So, I just briefly touched on gene editing, especially relevant this week, because the Nobel Prize for chemistry this year was awarded to Jennifer Doudna and Emmanuel Chapindieg, who jointly made some of the major discoveries in CRISPR technology.  

Next slide. Gene editing, genome editing are actually a family of technologies that allow scientists to rewrite the genetic code in the human chromosome, so the kind of gene therapy we were talking about a minute ago is a vector that is introduced into the cells, but in general does not rewrite the content of the chromosome. Gene editing is able to go in and not unlike what we do when we use Microsoft Word to edit our documents, the content of the chromosome can be edited, and the most prominent, certainly not the only, but the most prominent current application in here are CRISPR technologies, and there are several clinical trials in the US using CRISPR to either develop T cells for treating tumors or to treat rare diseases, such as inherited blood disorders and other diseases, so it’s a promising area, and in most cases these clinical trials will fall under the definition of human gene transfer, according to the NIH guidelines.  

Next slide. Whenever we’ve mentioned CRISPR, we need to throw in a caveat, which is one application of gene editing is to attempt to create heritable or germline mutations that would be passed on to future generations, and this kind of technology is not permitted by controlling authorities in the US or most jurisdictions. Globally, all leading authorities in the area have said we should wait if we are ever going to implement this kind of approach, it’s now is not the time, and I’m sure people are familiar in the news that it did occur once in China. The scientists involved were charged with criminal offenses. Obviously, it’s nothing we’re going to deal with, but it’s kind of important when we talk about CRISPR to recognize the top part of this slide, which is normal therapeutic approaches for medicine that have nothing to do with these controversial approaches shown in red on the bottom.  

Next slide. So, we talked about the definition of what types of research need IBC review, and some examples of clinical trials that will require such review. Now, if you want to register an IBC, what do you have to do to comply with the guidelines? Each IBC must be registered with the NIH, so you could create a homegrown committee at your institution for safety. There’s nothing wrong with that, but if it’s not registered with the NIH, then it cannot issue approvals in compliance with the NIH guidelines. The process to get registered electronically goes through the IBC RMS records management system at the NIH. There are currently over 1500 IBCs registered in over 30 countries around the world, and the vast majority are in the United States, but this number is proliferated very much in the last few years because of phase two and phase three clinical trials, leaving the academic medical centers and going out to community hospitals and clinics, and each of those clinics needs their own registration as they get started. The registration package includes a roster of members when you submit to the NIH, which roster needs to include a chair, scientific experts on biosafety, and topics that are expected to be reviewed by the IBC. If the institution has a biological safety officer or equivalent, that person should be on the committee, and depending on research involvement, is required to be on the committee. As we mentioned, community members are very important. They have to live or work near the site and be recruited to be voting members on the committee and not have any affiliation with the institution, so in order to be official, the registration has to be authorized by an institutional official who speaks on behalf of the institution, and all of that work to do this registration can be carried out by the institution, or there are commercial providers who provide externally administered IBCs, and then they can do the work on behalf of the institution, although obviously the institutional official still needs to sign off.  

Next slide. So, at an academic medical center or other places that locally administer their own IBCs, you will see a committee comprised of a chair, maybe a co-chair or vice chair, faculty members, and other employees who are voting members on the committee. The institution will have a biological safety officer or EHS person sitting on the committee, and then we have the community representatives. Committees like this will probably meet every month or some other interval defined by the institution, and it’s going to spend time reviewing clinical and non-clinical projects, and there are a lot of work to run properly administratively either even administrators, you need a compliance team, and you need reviewers who are willing to set aside time from their grants and their own research to do those reviews. If this site shown here is part of a multicenter trial. The reviewers on this committee are going to be doing duplicative reviews compared to reviewers on other committees at other sites, as far as the risk assessment of the protocol goes, so that can result in combination with a certain amount of frustration when institutional committees are doing the reviews.  

Next slide. Another approach, something that’s been around for a couple of decades, is the centrally administered IBC model, where a commercial provider will register and manage an IBC on behalf of the site. The IBC still belongs to the site, still registered in the name of the site, but the management and operations are handled by central administrative team and chairs and scientific experts may be shared among many committees, which helps you circumvent the duplicative reviews when, because the same committee members are conducting risks, risk assessments for many sites, each committee separately registered for each institution must convene on its own and issue an approval specific to the site for which it’s registered. The committee follows this model and probably won’t be meeting on a regular schedule. We’ll probably be meeting on demand, and the reviewers involved are kind of dedicated to doing those reviews.  

Next slide. What this means for many sites is they like to do both, if they have a locally administered IBC to review their mouse and their animal work, or investigator-initiated studies. If that kind of research is going on, they may want to have the locally administered IBC, and then they can have an auxiliary IBC, which is centrally administered, and which reviews multicentric trials on behalf of the that are sponsored, usually then no cost to the institution, because the sponsor pays for it, and the important message here is that many institutions now have more than one IBC, and that hasn’t been a problem for the NIH, or really for oversight and safety. The division of labor is up to the institution.  

Next slide. So when it comes to actual approval of research, as we mentioned previously, clinical trials were actually registered, approved by the IBC, and registered with the NIH at a federal level since last year, that’s not happening at all. Now you registered your IBC with the NIH, but each protocol is tracked and approved by the IBC at an institutional level, not at a federal level. The site and the investigator are responsible for obtaining and documenting the approvals and initiation of research. Without the approval, it would be reportable to the NIH. So, want to make sure that all required approvals are in place for clinical trials before initiation.  

Next slide. When an IBC is doing a review, they’re going to ask, is the institution in compliance with the guidelines? Is the investigator qualified? Is there appropriate biocontainment? Are the facilities and equipment properly certified and operated? Are there adequate standard operating procedures? Do the personnel have appropriate training and compliance? And under the guidelines, the IBC must approve the assignment of a biosafety level to each protocol. Next slide, biosafety levels range from one through four in the United States. Each PI, after the guidelines, may propose the biosafety level for their protocol, and the IBC must approve or disapprove that proposal. Obviously, it’s best to collaborate ahead of time. Or researchers working with European-based sponsors, it’s important to keep in mind that BSL one or two in Europe doesn’t always map to the same definition in the US, so we need to track the NIH and CDC definitions when we make the BSL one, BSL two determinations in the US, notably gene transfer agents in the US now and for the foreseeable future will all be approvable at level one or level two, biosafe to level three and four for eye containment and higher, more hazardous research with infectious agents other than gene transfer. Basically, if your clinical trial is going to be one or two.  

Next slide. The IBC is required to minimally review things we’ve discussed. Institutions may request IBC review of other items beyond those required by the guidelines. Frequently, it’s a good idea because the committee members are experts in those closely related fields. So, there are cell therapies with lymphocytes or different kinds of adoptive transfer and stem cells that are not genetically modified, but they still have blood-borne pathogens associated with them. Makes sense to have a biosafety committee review it, depending on the institution. There may be nucleic acid products that don’t meet the definition of being transferred, but still look like they need a once-over, so institutions will frequently ask the IBC to review those. Some institutions like to have their IBC review informed consent; that’s what they used to do, and many institutions have carried that forward. In non-clinical research, if you’re doing research with tuberculosis or HIV, whatever infectious agents, it might be smart to have your biosafety committee review that. Some biosafety professionals absolutely should review that research, of course, and the committee’s there, even though it’s not genetically modified, it doesn’t fall under the guidelines.  

Next slide. So when a protocol comes up to review, a clinical trial protocol comes up to review by the IBC, they are going to be looking at the life cycle of the product in the in the institution, which is shipping and receiving, storage, labeling, handling, dosing, and administration preparation and dosing, and then disposal, the question of whether the patient who has been dosed may shed that product into the environment has to be addressed. SOP documentation, training, and compliance at the site all need to be demonstrated adequately, and that includes a plan for spills, exposures, and accidents. Beetle stick exposures being a very prominent risk, so all in all, they obviously want to know how the product is going to be handled, stored, labeled, and cleaned up during its life cycle at the institution.  

Next slide. So, six successful programs can be based on understanding and having a plan for the risks. What do they think about it? What are the routes of exposure to biohazards and how will it be contained? There’s a big emphasis on biosafety on cultures of safety, and that should be applied, of course, in every work environment. If there is an infection control department involved at the clinic, there should be good coordination. Clear lines of communication, or training and reporting are very important, and every institution that has an IBC should use them as an advisory body, because that’s what they’re there for. You don’t need to just talk to them once a year.  

Next slide. So, in summary, the purpose of the IBC is to protect the staff, visitors, and public from risks associated with genetically modified agents. Each IBC must be registered with the NIH on behalf of its respective site. Individual protocols are no longer registered with the NIH, but they have to be approved by the IBC of record at the site. IBCs are sometimes administered locally by the institution, sometimes administered externally or centrally by another provider. And institutions and investigators should plan ahead when they see a clinical trial coming and consult with safety professionals at the IBC to make sure things get started smoothly.  

Next slide questions and answers. Okay. 
 
Kylie Gullett: 

All right. Thank you so much, Dr. Kavanagh. We will take the remaining time we have now to answer some questions that we received from our attendees. The first question is, “When does a site need to have a biological safety cabinet?” 
 
Dr. Daniel Kavanagh: 

Right, so that is a matter of concern for a lot of sites that are just getting started on this kind of research, for a lot of clinical trials, it is not required, so there’s no reason to decline a clinical trial because you don’t have a biological safety cabinet, in most cases, people who are working with his materials on a daily basis like to use biological safety cabinets, because they’re handy, and of course, what that is, it’s a cabinet that you sit in front of, it’s a glass panel in front, you reach under the panel to handle the product, and there’s negative pressure inside, and the HEPA filter for the exiting air, and that creates a very safe way to handle infectious agents. They’re often recommended as best practice, but a lot of the gene transfer agents that are being used for clinical trials may be handled outside a cabinet with appropriate PE, so it’s good to get a consultation in advance about what project you plan to do and decide whether or not you need to get a cabinet installed, but it’s certainly not always required. 
 
Kylie Gullett: 

Great, thanks so much. Our second question is “If an institution has a local IBC and a central IBC, who decides which IBC is responsible for reviewing a particular study.” 
 
Dr. Daniel Kavanagh: 

It’s entirely up to the institution, so there may be two or more IBCs registered for the institution, and based on business considerations, expediency, expertise, and any other local considerations, the institution may refer the protocol to whichever IBC is registered on behalf of their site at their own discretion. One thing we discourage is duplicate reviews. We don’t think that serves anybody’s interest. So, pick one, and for each protocol, have one committee review that protocol. If necessary, transfer jurisdiction to a new committee, but make sure that there’s only one committee reviewing one protocol at a time. 
 
Kylie Gullett: 

Great. And our last question that we’ve gotten today is, what is the best way for a site to decide whether or not a study requires IBC review? 
 
Dr. Daniel Kavanagh: 

So basically, if you have a molecular biologist around who can read the investigator’s brochure or the product description and compare it to that list of criteria in section 3c of the guidelines, you can get an answer that way, but hopefully you will have a biological safety professional consultant that you can ask someone on your IBC, someone else who’s working with you, who can figure that out. And in 99% of the cases, we, you know, the biosafety people can answer that question. In a small percentage of cases, we’ll go to the NIH, or investigators to go to the NIH if they wish. The email address for that is on their website, and they will give you a definitive answer for each of those questions. So, in most cases, experienced people can figure it out pretty quickly, but they do need to read the product description, because it’s frequently not obvious from looking at the protocol in there. 
 
Kylie Gullett: 

Great, and we actually did receive one more question, and the question is, how long does it typically take to set up the IBC centrally? 
 
Dr. Daniel Kavanagh: 

Yep, good question. So, there are several steps involved. One is getting your institutional official to sign off, and that may take an hour, or may take weeks. It depends on how available that person is, and how much review they require ahead of time. But so after that sign-off, the submission on behalf of the site can be submitted to the NIH, and that’s taking six to eight weeks for a lot of clinical trials during that time period, the IBC cannot issue a final approval because it’s not authorized by the NIH. I can say that if we can flag the first study as a COVID 19 study in the NIH has been very cooperative about expediting those registrations, so they’re much, much quicker for COVID 19 research, but for other categories there is that lag, that time delay only applies to the first study, of course, because that’s the time it takes to get that IBC set up for subsequent studies. If you’ve elected to maintain a permanent standing committee, which we recommend, then you won’t have that delay during the review time, you’ll just be able to submit and get your approval on the calendar on demand as soon as you have your operational review in order, so short answer is six to eight weeks for non-COVID, and just a couple weeks or less for COVID 19 research. 

 
Kylie Gullett: 

Great, thanks so much. So that was our last question of the day, and I just wanted to take the last few minutes to thank our speaker today, as well as everyone who was able to attend. We hope that you enjoyed this webinar and that you found it relevant and informative. We will be making a recording of this webinar available to everyone, so you can watch it on demand or share it with your colleagues. Please keep an eye out for that recording via email in the next 24 hours. As always, we appreciate you as a member of the WCG Global Research Network and stay tuned over the next few weeks for information about our November webinar. Thank you and have a great day. 
 
Dr. Daniel Kavanagh: 

Thank you. Bye.