The following Insight is a featured article from WCG’s 2025 Trends & Insights Report. If you would like to read more insights from this report, please click here.

As we enter 2025, clinical research sites face an increasingly dynamic and complex environment. In the recently released WCG 2024 Clinical Research Site Challenges Report, we collected data from a variety of sites on the headwinds and obstacles they faced in 2024. Notably, the operational challenges sites face due to the increasing complexity of studies and the obstacles in the study start-up process, resulting in lengthy timelines, emerged among the top five trends. The operational and strategic choices sites make this year will define their ability to thrive in an era of adaptive trial designs, cutting-edge therapies, and heightened expectations for efficiency. 

Study Activation: Breaking the Barriers 

For many sites, the gold standard of study activation is the National Cancer Institute’s recommended 90-day “time to activation,” which is defined a bit differently by each institution. Even for sites not conducting a large volume of oncology studies, most sites target 90-120 days for their end-to-end start-up timeline. Often, looking at the median time to activation can be most helpful when understanding where a site currently stands but may lead to further investigation into outliers in the upper range, dragging down the overall average. So, how does a site prepare for a high degree of accountability in this ever-changing landscape?  

When it comes to complexity within the start-up process, few trials set the bar higher for sites than cell and gene therapy (CGT) studies. In the coming year, clinical trials involving CGT products are expected to play an important role in the development of new therapies in an expanding range of therapeutic areas.  For example, some CD19-directed therapeutic approaches developed for hematology/oncology indications are being repurposed for the treatment of autoimmune diseases, such as lupus, and many of these clinical trials will begin in 2025. 

Sites wishing to prepare for CGT research can take a variety of approaches. Any sites looking to become involved in CGT clinical trials should have an Institutional Biosafety Committee (IBC) registered with the NIH. Although approaches involving the manufacture of autologous cellular products can require a large investment in facilities, staffing, and training, many other CGT approaches can be undertaken with relatively small changes to equipment and procedures. For trials involving complex manufacturing and clinical management, new sites may wish to partner with larger, more experienced sites to enroll subjects in a “hub-and-spoke” model.   

Aside from the regulatory consequences, we have repeatedly seen the impact these challenging trial designs, like cell and gene therapies, can have on study start-up. A seemingly straightforward schedule of events can cascade into a web of extensive start-up tasks that impact the overall activation timeline.  

The operational complexity of CGT trials, for instance, often requires large, multi-disciplinary teams with expertise in areas like advanced storage solutions, patient-specific customization, and specialized clinical protocols. This complexity can lead to longer trial start-up times as every step builds on prior activities, impacting the activation timeline and trial readiness. And in advanced therapeutic trials, start-up challenges are compounded by regulatory hurdles and site selection requirements. CGT trials in particular are known for their lower throughput compared to traditional trials due to the bespoke nature of the therapies. 

For example, a single line item in the schedule of events, such as “patient assessment,” can expand into numerous detailed entries in a Medicare Coverage Analysis (MCA). When closely examined, this single procedure can encompass a wide array of specific tasks and requirements. For instance, a “patient assessment” could be parsed into distinct components like physical examinations, laboratory tests, imaging studies, and specialist consultations. Each of these components then needs to be analyzed in terms of cost, frequency, whether it qualifies as routine clinical care or a research-specific expense, specific billing codes, compliance with Medicare regulations, and which entity — sponsor or payer — bears the financial responsibility.  

Often, however, the sponsor-provided budget aligns differently from this detailed breakdown, as sponsors typically base budgets on overarching categories, overlooking the specifics uncovered during the MCA process. This budgetary misalignment can necessitate additional financial negotiations and adjustments, complicating the initial planning phase and extending activation timelines by weeks or even months. 

Integrating the MCA and final approved budget/Clinical Trial Agreement (CTA) into a Clinical Trial Management System (CTMS) presents another layer of complexity. Harmonizing the study calendar with the financials becomes a meticulous task, requiring an accurate reflection of every line item to ensure clinical and financial schedules match. Any discrepancies in the system can lead to budget inaccuracies, compliance risks, and logistical challenges. Consequently, this rigorous process underscores the necessity for meticulous coordination and continuous communication among all stakeholders to achieve a seamless start without significantly impacting study activation timelines.  

Budget Negotiations: The Hidden Bottleneck 

One specific piece of the process we’ve identified as typically having some of the greatest flexibility — for better or worse when it comes to the overall timeline — is budget negotiations. They are often the rate limiting step that extends start-up timelines beyond intended targets. Given the total dollar figures represented in many clinical trial budgets, this isn’t a surprising fact on its own.  

The “white space,” which we define as the unproductive time spent between active review, is a significant factor in extending the budget timelines. This is the time spent with any party waiting for approval, sitting in someone’s queue for review, or waiting to schedule a follow-up call.  

We see that negotiations take 5-10 hours of active effort for a site negotiator. Allowing for a similar amount on the sponsor’s side, that is 10-20 hours of total effort for a process that can often extend 9+ weeks. In that scenario, the budget is actively being worked on for less than 6% of the time over those 9 weeks.  

For organizations looking to reduce start-up timelines, the goal becomes clear: focus on reducing the white space. Each party can control a portion of this by limiting their own response timelines. Beyond that, you can influence white space on the other end by making it as easy as possible for the other party to review. Providing upfront justification, using standard editing practices like color coding, and employing a clean-as-you-go approach can all help eliminate confusion and prioritize your budget in what is often a large queue.  

Most importantly, know your limits and communicate that early. It’s common to see parties prolong negotiations but then agree to a budget on day 100 that isn’t materially different from the budget offer on day 50.  

The intricate network of activities involved in clinical trial start-up highlights the importance of meticulous planning, detailed analysis, and ongoing coordination among all stakeholders. Successfully navigating these complexities is essential for timely study activation and overall trial success. Through continued process reviews, stakeholder collaboration, and effective communication, the potential delays in study activation can be mitigated, paving the way for a seamless and efficient trial. 

The Human Side of Research: Supporting Teams 

Though we focus heavily on the metrics and data of what we do as an industry, we’d be remiss not to acknowledge the softer side of research. While serving participants and prioritizing their health is the north star of our work, so must be the wellness and health of our colleagues. While the impact of the Great Resignation has diminished, the risk of site staff burnout is real so supporting and equipping a high-performing team for success is critical to site excellence and individual motivation. 

Developing team camaraderie requires taking the time to develop an environment of trust where members feel valued and connected to each other and the goals of clinical research. This is the “secret sauce” that can propel a site from being adequate to high performing. All too often it is expected that as professionals we will naturally come together as a team and foster motivation in each other. Yes, sometimes that occurs organically and with a little extra work, but attention is generally required. This means having meetings with explicit discussions about building mutual trust – based on open and honest communication. The leaders at the site need to share challenges and mistakes and be willing to seek help and ideas from staff. This type of vulnerability demonstrates from the top down that team members are valuable. This type of safe environment will empower your team to act decisively and collaborate.  

Making sure there are some enjoyable “outside work” activities for team members to enjoy will also help to create a strong team. These activities do not have to be grand in nature. More casual outings can accomplish the goals of increased social interaction and recognition of team member accomplishments. The very nature of our work in helping to develop medicines, devices, and other treatments for diseases is compelling and should be reinforced as a part of your team’s development plan.  

High-functioning teams deliver better results and enhance a site’s reputation, making it more attractive to sponsors and top talent. Ultimately, this balance between operational excellence and human connection will define the most successful sites in the evolving clinical research landscape. 

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The following Insight is a featured article from WCG’s 2025 Trends & Insights Report. If you would like to read more insights from this report, please click here.

Precision medicine research relies on genetic and molecular data to identify eligible participants for a clinical trial, or to tailor the investigational treatment to the individual participant. This means that genetic and molecular markers may play a role both in subject recruitment/eligibility and in clinical endpoint determination, depending on protocol design.   

One expected trend in molecular biomarkers for oncology is the increasing use of a more diverse array of biological samples, such as blood, urine, or saliva, to gather more information about a person’s disease state. Tumors release biological information, in the form of free DNA, circulating tumor cells (CTCs), and as extracellular vesicles (EVs). CTCs are cancer cells that exit a tumor and enter circulation spontaneously or in response to therapeutic interventions. EVs are nanoscale particles that are naturally released by healthy cells and tumor cells and contain a broad range of bioactive compounds and genetic information. New forms of microfluidics technology are being deployed to efficiently capture these circulating tumor cells and EVs, and to distinguish and sort tumor-derived material for molecular analysis.  

Recent proof of concept studies show that information encoded by DNA and RNA found in EVs isolated from the blood of cancer patients can accurately reflect the genetic content of paired tumor biopsies from the same subjects. As modular and portable sample collection technologies are developed, we will see increasing opportunities for samples to be collected at home, allowing for less burdensome and less invasive procedures in recruitment and follow-up.  

These technologies will also enable gathering of more precise and more complete longitudinal information regarding subject response to investigational treatment over time. Robust longitudinal response data have the potential to greatly enhance the prognostic power of specific biomarkers and are likely to play a role in validation of biomarker endpoints in support of FDA approval via the accelerated pathway, for example. 

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CAR-T Cells Target Harmful B Cells in Lupus  

CAR-T cell technology, which uses genetic engineering to direct white blood cells to attack specific molecular targets, was originally proposed for treatment of HIV infection and hematological malignancies. Today there are six CAR-T products with FDA approval for the treatment of multiple myeloma and B cell malignancies, with many related and next-generation products under development. An expected and well-known side effect of these B cell-targeted therapies is “B cell aplasia”— i.e. partial or complete depletion of B cells from circulation and immune organs. In the context of anticancer treatment, B cell aplasia is considered an undesirable but manageable side effect of these therapies. Recently clinical investigators have found a way to turn what was an undesirable side effect in cancer patients into a clinical benefit for persons with certain autoimmune conditions. In these cases B cell depletion is a feature, not a bug. 

T cells and B cells —  both specialized white blood cells called “lymphocytes”– represent the two arms of the adaptive immune system responsible for immune memory and recall responses to vaccines and infections. Lymphocytes have an extraordinary capacity to proliferate in response to immune stimulation. This proliferative capacity allows a rapid response to an incoming threat, such as a viral infection. T cells and B cells also express specialized antigen receptors that impart specificity to the immune response, directing immune attack against foreign “non-self” targets while sparing “self” targets expressed by healthy tissue. When properly regulated these cellular features—proliferative capacity and receptor-directed specificity—largely account for the effectiveness of our adaptive immune system in protecting us from infectious disease. When dysregulated, these same features can have very serious and even deadly consequences. Lymphocytes undergoing uncontrolled proliferation can transform into lymphomas and related hematological malignancies. Lymphocytes that fail to distinguish self from non-self can drive autoimmune pathologies, such as lupus. This helps explain why two diseases categorized in distinct therapeutic areas are both potentially treatable by the same B-cell direct CAR approach.  

CAR-T products with FDA approval for treatment of B cell lymphomas express receptors engineered to recognize CD19. CD19 is a marker expressed on the surface of normal B cells and a wide range of B cell malignancies. The currently approved CD-19 CAR products are autologous, ex vivo cellular therapies. These therapies are manufactured by extracting T cells from the patient’s blood, genetically modifying them in the lab, and then reinfusing them back into the same donor patient. For a significant subset of patients with B cell malignancies, CD-19 CAR- T therapies are providing excellent clinical outcomes, and in some cases elimination of the malignancy, resulting in a cure.  

An expected side effect of CD-19-directed CAR-T treatment is destruction of healthy as well as malignant B cells (B cell aplasia).  B cells are needed in order to mount new antibody responses against vaccines and infections, so a lack of B cells can potentially result in immune deficiency and an increased risk of infection. If circulating antibody levels become too low, they may be supplemented with immunoglobulin therapy.  

In contrast to B cell malignancies, a hallmark of lupus is not uncontrolled cellular proliferation, but rather uncontrolled production of antibodies that bind to “self” targets — in particular to nucleic acids (DNA and RNA). The level of such antinuclear antibodies often correlates with the severity of disease. Therapies that target autoreactive B cells are seen as hopeful approaches to treat lupus and similar autoimmune diseases. Investigators hypothesized that B cell aplasia produced by CD-19 CAR-T treatment, far from being a detrimental side effect, might remove B cells producing the destructive autoantibodies.   

Recent publications, notably a case series published in the New England Journal of Medicine in February 2024,ⁱ cited significant clinical benefits, including alleviation of symptoms and elimination of autoantibodies. Although infections did occur, in general participants were able to stay healthy without supplemental immunoglobulin therapy. There is now increasing interest among industry and academic institutions to explore new ways to repurpose cellular therapeutic technologies from oncology indications into autoimmune disease and rheumatology.  

Notably, while current FDA approved CAR products use ex vivo manufactured T cells, there is a growing interest in other CAR technology using other types of white blood cells rather than T cells—these include Natural Killer (NK) and macrophage immune effectors. Another exciting concept is moving from ex vivo (manufactured in the lab) to in vivo (generated in the body) CAR production. Some in vivo CAR-T products under development resemble mRNA vaccines in terms of drug substance, and these approaches present the potential to make CAR technology more accessible and affordable to persons with cancer and persons with autoimmune diseases like lupus. 

WCG has many ways to support cell and gene therapy clinical trials for lupus. Independent Review Committees (IRBs) provide ethical oversight of all categories of clinical trials.  Institutional Biosafety Committees (IBCs) oversee safe handling, storage, and administration of genetically modified products such as CAR T cells. At WCG our IRB and IBC review teams work closely together to ensure proper consideration of risks to study participants and to staff and visitors at clinical trial sites.  

The Role of Scientific Review  

Patient safety is an ongoing concern in all clinical trials and can be particularly challenging with the use of CAR-T therapies. When used to treat cancers such as B cell lymphomas, patients may experience adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome in addition to secondary cancers. When using CAR-T therapies to treat autoimmune disorders, the risk-benefit assessment may be different and close monitoring of safety is critical. Data Monitoring Committees (DMCs) play a key role in guarding patient safety. DMCs review accumulating data from ongoing clinical trials to make independent recommendations to the Sponsor about the continuation, modification, or stopping of the trial. Their role is important and unique because they review cumulative and unblinded data. One of the fundamental responsibilities of a DMC is to assess the risk versus benefit of a therapy by evaluating the comparative safety in the context of efficacy. In patient populations with significant mortality, such as B-cell malignancies, a DMC may be more willing to accept an increased risk profile for a therapy when the severity of disease is high and prognosis of patients is poor. In therapeutic areas such as lupus where median expected survival is much longer than for multiple myeloma, a DMC may be less willing to tolerate an emerging safety risk for an investigational therapy.  

In all cases, it is crucial to ensure the DMC receives clear, accurate, and concise reporting so that the DMC can make an informed and timely decision. Design of a DMC report should reflect the data being collected, the disease under study, and the emerging pattern of risks present in the study or suspected for the class of agent. An experienced statistical reporting group recognizes the differences between interim data reporting and final analysis reports, providing the DMC with clearly written and well-structured reports that clinicians and statisticians can readily interpret. In the case of lupus trials investigating CAR-T therapies, clear and innovative techniques for summarizing and presenting data should be considered to help DMCs visualize emerging adverse event (AE) trends and ongoing safety monitoring. One example that WCG has used in reporting to DMCs is AE profile plots, plotting occurrence, duration, and severity of AEs of special interest in relationship to therapy administration and other patient disposition events. Figures such as these, see mockup below, afford the DMC the ability to review a substantial amount of data in a concise manner, where they can readily observe trends. Better detection of emerging safety signals by the DMC leads to increased vigilance in safety monitoring, and ultimately safer trials. 

References

i N Engl J Med 2024;390:687-700 

The post Spotlighting Lupus Awareness Month: CAR-T Technology Creates New Avenues for Treatment of a Devastating Disease appeared first on WCG.

I want to submit a study as a sponsor, with a site to submit their information separately. Is this possible with WCG IBC?

Answer:

Yes, WCG encourages sponsors and CROs to start working with our IBC experts as early as possible to get the most value out of central IBC services. Although NIH Guidelines require diligent evaluation of each site, resulting in issuance of site-level approvals, much of the review effort can be handled in advance if the sponsor or CRO begins to collaborate with WCG at an early stage. The IBC typically reviews documents such as Protocol, Investigator’s Brochure, and Pharmacy Manual (or other product-handling instructions). Often, these documents may be submitted in a draft form for early evaluation. To get started, complete the form below to request a short study-level submission form. This form involves no cost or commitment and sets the stage for WCG to provide the most efficient clinical trial initiation for sponsors and CROs.

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About this episode:

In this episode of WCG Talks Trials, our expert panel discusses various ethical, safety, and logistical challenges in accelerating clinical trials for gene and cell therapies in oncology. The conversation explores the role of Institutional Review Boards (IRBs), Institutional Biosafety Committees (IBCs), Endpoint Adjudication Committees (EACs), and Data Monitoring Committees (DMCs) in overseeing these trials, addressing issues such as patient safety, complex trial designs, and emerging biosafety concerns. Our panelists emphasize the importance of transparent communication and collaboration between IRBs and IBCs, highlighting the need to balance the urgency of advancing research with ethical considerations. Additionally, the podcast explores unrealized ethical and safety issues, such as the pace of technological advancements and potential risks associated with gene editing. The speakers also touch upon future opportunities in oncology research, including precision medicine, artificial intelligence, wearable devices, and accelerated regulatory pathways.

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The response to the COVID-19 pandemic included the rollout of a variety of innovative hybrid approaches to vaccine trials. As one example, participants were able to collect dried blood spots in the home setting for immune monitoring and to determine the development of vaccine-induced antiviral antibodies. The potential for remote monitoring for the efficacy of infection and safety events has been clearly demonstrated, and these approaches will play more prominent roles in the coming years.  

An emerging area under consideration is direct-to-participant investigational product delivery. With the ongoing development of oral, intranasal, and microneedle array patch vaccine delivery systems, at-home vaccine self-administration is becoming more plausible. The FDA is currently considering allowing at-home self-administration of an approved intranasal live attenuated influenza vaccine. However, for investigational products, significant concerns related to safety, shipment, stability, privacy, blinding, and compliance create barriers to the rapid adoption of comprehensive direct-to-participant vaccine testing approaches.  

Many of the most promising new vaccine technologies involve genetically modified products such as recombinant or synthetic mRNA or DNA, or viral and bacterial vectors. In the U.S., Institutional Biosafety Committees (IBCs) usually oversee the safe handling, administration, and disposal of genetically modified investigational vaccines. IBCs are traditionally based at research institutions and fixed clinical trial sites, and IBC approval requires assessment of facilities, equipment, and procedures at each site.

One solution to the limitations outlined above is the use of mobile research units. Mobile facilities housed in vans and trailers can bring research capabilities closer to the participants while allowing for careful management of product handling, safety, and privacy concerns. Importantly, with appropriate documentation and advanced planning, mobile research units can be reviewed and approved by an IBC, bringing cutting-edge research to neighborhoods and community settings.  

Regarding pandemic preparedness, flexible and adaptable clinical trial platforms will be critical for an agile and timely response to the next emergency. Increasing decentralization of vaccine trials in 2024 and beyond will play a key role in enabling that flexibility.   

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Per an existing FDA definition, an umbrella trial is “designed to evaluate multiple investigational drugs administered as single drugs or as drug combinations in a single disease population.”[2]  The present draft guidance is specifically intended for early stage umbrella trials where multiple versions of a cellular or gene therapy product are being studied in a single disease population, and the products are generally submitted in separate INDs that are cross-referenced among each other. Note that some umbrella trial designs, especially those involving late-stage products, may include a sorting step where participants are segregated into different study arms based on one or more biomarkers[3]; such segregation does not apply to the present draft guidance.

The draft guidance includes useful notes and an appendix with examples to clarify what types of products are “cellular or gene therapy products” and what kinds of changes to product design constitute “different versions” for purposes of this guidance. The draft guidance specifies that these early stage trials are not expected to be powered to demonstrate a statistically significant difference in efficacy between the study arms and are not intended to provide primary evidence to support a marketing application.

The focus of the draft guidance is to offer an orderly approach for sponsors to cross reference INDs to provide all necessary information to the FDA while minimizing submission of the same information to multiple INDs. The recommended approach is to designate a “Primary IND” that contains information about the master trial protocol, and to designate one or more “Secondary INDs” each containing specific information about the respective product version but not containing information about the umbrella trial. The draft guidance allows for various eventualities such as clinical holds, addition of new product versions, and discontinuation of clinical study for products referenced in the Primary or Secondary INDs. Safety reports regarding a specific product version must be submitted to both the Primary IND and to any Secondary IND referencing that product version (i.e. containing chemistry, manufacturing and control or pharmacology/toxicology information for that product).

Notable examples of products specifically mentioned as “cell and gene therapy products” in the Appendix include tumor infiltrating lymphocytes (TILs), chimeric antigen receptor (CAR)-T cells, dendritic cells, and gene therapy vectors. The Appendix also includes useful examples of changes to product design that constitute in new “versions” requiring a separate IND. In addition there are also examples of changes that do not result in a separate “version”—these examples are all changes at the level of the manufacturing process and the draft guidance does not suggest there is any situation where a change to the genetic sequence (of a vector, promoter/enhancer, or transgene) would not constitute a new “version.”

Overall it seems likely that this new draft guidance will be a valuable new piece in the puzzle of comprehensive gene therapy product development.

References

• [1] Studying Multiple Versions of a Cellular or Gene Therapy Product in an Early-Phase Clinical Trial. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/studying-multiple-versions-cellular-or-gene-therapy-product-early-phase-clinical-trial
• [2] Master Protocols: Efficient Clinical Trial Design Strategies To Expedite Development of Oncology Drugs and Biologics, Draft Guidance for Industry, OCTOBER 2018. https://www.fda.gov/media/120721/download
• [3] Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both. https://www.nejm.org/doi/full/10.1056/NEJMra1510062

The post Key Takeaways From FDA’s New Draft Guidance, “Studying Multiple Versions of a Cellular or Gene Therapy Product in an Early-Phase Clinical Trial” appeared first on WCG.

This growing market presents a multitude of challenges for sponsors, CROs, institutions, and sites that must be considered when running these trials. To meet these challenges, all stakeholders need to understand the important roles of not only the Institutional Review Board (IRB), but also the Institutional Biosafety Committee (IBC) in facilitating a safe and effective study. Below are key takeaways for research involving human gene transfer. 

Takeaway 1: Human Gene Transfer (HGT) Research Typically Requires IBC Oversight

The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) lay out requirements for IBC oversight clinical trials, which are based in part on the definition of Human Gene Transfer (HGT) research. In general, HGT research is the administration to a human research participant of a product containing genetically modified or synthesized DNA or RNA, or of a product capable of modifying cellular DNA via gene editing. Certain short nucleic acids, such as oligonucleotides may be excluded from the definition of HGT products. Products in this category range from classic gene therapy approaches to modalities involving gene editing, regenerative medicine, engineered stem cells, and vaccines, including DNA, RNA, and vectored vaccines. 

IBC approval is required when two criteria are met:

1. The research is HGT research as defined in the NIH Guidelines Section III-C, and;
2. The research is subject to NIH Guidelines due to relevant funding as defined in Section I-C.

Every clinical trial site engaged in research subject to NIH Guidelines must have an IBC of record registered with the NIH. As a provider of centralized IBC services, WCG works with clinical trial sponsors, CROs, sites, and investigators to ensure safety and compliance in HGT trials. When sponsors, CROs, institutions, and sites begin working with an IBC, they can expect the IBC to: 

• Provide review and approval of research protocols, facilities, and biocontainment levels according to the requirements and recommendations of the NIH Guidelines.  
• Advise the institution on policies.
• Assess the investigator/staff training and qualifications. 
• Be comprised of a committee that includes experts on relevant topics, representatives of the institution and members of the community unaffiliated with the institution. 
• Deliberate and vote on research proposals at convened meetings (in person or virtual). 

After the IBC approves the trial, they will continue to provide oversight for as long as dosing occurs. 

Takeaway 2: IRBs and IBCs Have Distinct Roles but Frequently Work Collaboratively

The requirement for IBC review is separate from — and in addition to — the requirement for IRB review. IBCs and IRBs are mandated by separate governing rules and have distinct roles and responsibilities. Here are three examples: 

• Areas of focus: IRBs consider the rights and welfare of research subjects. IBCs consider risks to the clinical and laboratory staff, the community, and the environment associated with genetically modified DNA and RNA and gene editing products.
• Jurisdiction: One IRB can oversee multiple sites. Each IBC registration applies to a specific research institution. That means a 20-site gene therapy trial (with relevant NIH funding) may require 20 unique IBC registrations. However, the administration of all those IBCs can be centralized. 
• Length of involvement. Once all products are administered or removed from the site, the sponsor can close IBC oversight of the respective trial. Obviously, such is not the case with IRBs, which are responsible for participant safety and follow-up. 

Ideally, the IRB and IBC will work together to coordinate risk assessments and safety recommendations. Especially when centrally administered, the combined expertise of IRB and IBC memberships can provide enhanced efficiency for simultaneous or parallel review and approval. 

Takeaway 3: No Matter Your Role in the Trial, Know What to Expect from Your Research Partners and the IBC

Keep in mind that the site team, investigators, and the CRO each have different responsibilities and various levels of knowledge. As a sponsor, you need to be able to educate them—and your colleagues—about IBC expectations in advance. This way, you avoid last-minute questions and pave the way for dealing with the complex issues involved in site activation and initiation. 

As already mentioned, the IBC is charged with evaluating the biosafety risks to the public and the environment. Among the things they’ll want to know: 

• The molecular content of the HGT product. 
• The plan for biocontainment: 
  • How is the investigational product transported, stored, prepared, administered, and disposed of? 
  • What is the risk of shedding, release, and loss of containment? 
• What spill response and emergency response plans are in place? 

While ultimately it is the institution’s responsibility to adhere to the NIH Guidelines, it is critical to keep an open line of communication among all stakeholders. This partnership between all parties will ensure you set your study up right from the outset. 

Takeaway 4: Seek Expert Guidance

As the gene therapy market expands, we see increased pressure to efficiently expedite trials to FDA approval while, at the same time, upholding safety and complying with NIH and FDA guidelines. HGT trials also face heightened regulatory scrutiny even as regulations are evolving. 

Planning for IBC oversight is crucial. Sponsors and CROs should seek expert advice at an early stage of clinical trial planning, particularly at the study kickoff meetings. You need biosafety expertise during the development of your Investigators Brochure, the Pharmacy Manual, as well as during the site selection and protocol preparation stages. 

Conclusion 

The rapid expansion of the gene therapy field necessitates careful consideration and expert oversight to navigate the complex landscape of human gene transfer (HGT) research. The roles of Institutional Biosafety Committees (IBCs) and Institutional Review Boards (IRBs) are distinct yet complementary, each playing a critical part in ensuring the safety of research participants, staff, and the broader community. Effective collaboration and communication among sponsors, CROs, institutions, and site teams are essential to address the multifaceted challenges involved. Early engagement with biosafety experts and adherence to guidelines set forth by entities like the NIH is imperative to streamline the trial process while maintaining compliance and safety. As the industry grows, a proactive approach to understanding and integrating IBC and IRB requirements will be paramount in setting up successful, safe, and compliant gene therapy trials. 

The post Four Key Elements You Need to Know About the Role of IBCs in Gene Therapy Trials appeared first on WCG.

I represent a clinical trial sponsor. Does my Human Gene Transfer (HGT) clinical trial require IBC approval at all sites?

Response:

Looking at this question from a sponsor perspective, points to consider include the following:

• Does the Sponsor currently receive any direct NIH funding for research involving recombinant or synthetic DNA or RNA (for this or for other projects)? If so, all Human Gene Transfer (HGT) research conducted by Sponsor company requires IBC approval at each domestic clinical trial site.
• Does the investigational product (IP) contain recombinant or synthetic DNA or RNA materials developed by the Sponsor using current or past NIH funding? If so, any clinical research using this IP requires IBC approval at each domestic clinical trial site.
• Does the investigational product (IP) contain recombinant or synthetic DNA or RNA materials developed using NIH funds by some other business or institution, such as an academic research institution, and does that business or institution currently have contractual arrangements with the Sponsor? If so, any clinical research involving those materials requires IBC approval at each domestic clinical trial site.

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I represent a clinical trial site. Does Human Gene Transfer (HGT) research at my site require IBC approval?

Response:

Looking at this question from a site perspective, points to consider include the following:

• Does my site belong to an institution or business that currently receives any direct NIH funding for research involving recombinant or synthetic DNA or RNA? If so, then all HGT clinical trials conducted at this site require IBC approval.
• Does a specific HGT clinical trial involve funding at the product or sponsor level as defined above? If so, then that specific clinical trial requires IBC approval.
• Our subject matter experts are happy to answer questions from Sponsors, CROs, and sites about specific applications of the NIH Guidelines and expectations for IBC review. Please address any questions to our online form. When we receive your question, a member of our team will personally follow up within the same business day.

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