Gene therapies and gene-based therapeutics are giving way to a new era of interventional genetics. Integrated ethics review and biosafety review have developed into an operational advantage to facilitate this research.
Headline-grabbing gene therapies and gene-based therapeutics have become the norm. In ophthalmology, various gene therapies have prevented blindness or delayed loss of vision. Chimeric antigen receptor (CAR) T cells, a type of gene-modified cellular therapy, have obtained multiple Food and Drug Administration (FDA) approvals for treating resistant or refractory B-cell malignancies and, in clinical trials, are also showing efficacy against various autoimmune diseases. Gene editing is now paving the way for personalized therapeutics that can correct mutations responsible for rare diseases, as demonstrated by the life-saving treatment for Baby KJ.
Recently, the Advanced Research Projects Agency for Health (ARPA-H) awarded up to $160 million to advance personalized curative medicines for rare genetic diseases. A more inclusive term has arisen to encompass the diverse approaches utilized in gene-based medicines: interventional genetic therapies. In this blog, we’ll provide an overview of the various techniques for interventional genetics and discuss the benefits of utilizing an integrated institutional review board (IRB) and institutional biosafety committee (IBC) to facilitate clinical trials for this exciting area of research.
Depending on the condition and therapeutic goal, interventional genetic medicine generally follows six primary strategies (Figure 1):
- Genetic vaccines: Delivery of genetic material encoding a piece of a microbe to stimulate an immune response against it (e.g., lipid nanoparticles containing messenger ribonucleic acid [mRNA] for mRNA-based vaccines).
- Gene delivery: Introducing a functional copy of a gene when the cell’s original is entirely missing or not working properly (e.g., conventional viral-vector-based gene therapy).
- Gene silencing: Reducing or blocking expression of a rogue, mutated gene to stop toxic or disease-causing instructions to the cell.
- Gene editing: Making targeted changes to deoxyribonucleic acid (DNA) to correct a disease-related genetic sequence (e.g., the use of clustered regularly interspaced short palindromic repeats [CRISPR] technology to save Baby KJ).
- Gene-modified cellular therapies: Modification of cells to provide cellular products, such as CAR T cells or cells modified to possess regenerative properties.
- Genetically modified organisms (GMOs): Examples include gene-modified bacteria to treat cancer or metabolic disorders. Gene-modified bacteriophages, viruses that infect bacteria, are studied as a means of combating antibiotic-resistant bacterial infections.
Beyond the investigational new drug (IND): Ethics and biosafety oversight of clinical trials for interventional genetics
For decades, IRBs and IBCs have occupied distinct roles in the clinical research oversight landscape.
IRBs emerged from a framework centered on the protection of research participants. IRB work focuses on informed consent, participant safety and welfare, equitable subject selection, and the ethical conduct of research involving human participants.
IBCs evolved from a different regulatory lineage, one focused on evaluating the safe handling of recombinant DNA, synthetic nucleic acids, and other biologics that may pose biosafety risks to research personnel, healthcare workers, patients, or the surrounding community.
The responsibilities of these committees remain fundamentally different. One protects participants’ rights, safety, and welfare in research. The other helps ensure research involving potentially hazardous biological materials is handled safely and responsibly.
Historically, that distinction has shaped how sponsors approach oversight. IRB review and IBC review have often been viewed as separate regulatory requirements, managed through separate operational pathways and frequently administered by different organizations.
Yet as advanced therapies become more common, oversight functions demand more communication and coordination.
An important shift is occurring across the clinical research enterprise. Ethics review and biosafety review are no longer simply parallel processes moving independently. Increasingly, they are becoming interconnected components of a broader risk management and study startup strategy.
Organizations that recognize this convergence are finding that the way IRB and IBC reviews are coordinated can affect startup timelines, site activation performance, and overall study execution.
The convergence of ethics and biosafety oversight
The growing importance of integrated oversight reflects the changing nature of the therapies entering clinical development. Human trials involving gene therapies, engineered microorganisms, viral vectors, or other engineered genetic material require a broader assessment of risk, and the responsibilities of the IRB and IBC can intersect during study startup.
An IBC may evaluate issues such as product-handling procedures, accidental exposure response plans, waste disposal practices, environmental containment measures, laboratory controls, and site personnel training requirements. These considerations are central to biosafety oversight, and they also can provide important context to the IRB regarding the overall conduct of the study and reasonably foreseeable risks that may need to be disclosed in the informed consent form.
Similarly, information reviewed by the IRB—including participant monitoring plans, informed consent language, protocol-specific risk mitigation strategies, and study procedures—may inform broader discussions regarding operational readiness and safety oversight during IBC review.
Neither committee assumes the role of the other, nor should it. Independent review remains an essential feature of effective research oversight. However, as therapies become more complex, the interactions between these oversight domains become more frequent and increasingly consequential.
The challenge for sponsors is that regulatory independence does not eliminate operational interdependence.
In many advanced therapy studies, the most important questions are no longer neatly confined to a single committee’s area of expertise.
Consider a study involving a replication-competent viral vector delivery platform. During its review, the IBC raised concerns about whether the informed consent document adequately described certain reasonably foreseeable risks associated with the investigational product. While informed consent is traditionally viewed as an IRB responsibility, the underlying concern stemmed from the IBC’s scientific assessment of the vector’s biological characteristics and potential safety implications.
Because both committees were administered within Advarra’s integrated review framework, committee staff were able to facilitate direct communication between the IRB and IBC review teams. Questions were discussed concurrently, scientific context was shared between the committees, and the issue was resolved without adding avoidable delay to the study startup timeline.
Had the reviews been administered through separate organizations, the process could have been more complex. Questions may have required multiple rounds of communication among the sponsor, site, IRB administrator, and IBC administrator before reaching the appropriate reviewers. Even when every stakeholder is acting promptly, these handoffs can introduce delays. In complex studies, significant time can be lost simply by moving information between otherwise independent review processes.
This example illustrates a central theme of advanced therapy oversight: Regulatory independence does not eliminate operational interdependence.
Where startup delays often occur
When discussions about study startup timelines arise, attention frequently focuses on review turnaround times. Sponsors naturally want approvals to occur quickly and predictably. In practice, some of the most significant startup delays in gene therapy research can occur not within individual review processes, but between them.
When IRB and IBC reviews are administered by separate organizations, sponsors often become responsible for coordinating communication among multiple review teams, operational groups, and research sites. Questions raised by one committee may need to be relayed through several stakeholders before they can be resolved. Requests for information may overlap. Timelines may drift apart. Site-level activities dependent on both approvals can become difficult to synchronize.
These challenges are not necessarily the result of poor performance by either committee. Rather, they are a natural consequence of managing interconnected activities through separate operational structures.
For studies involving a handful of sites, these inefficiencies may be manageable. For large multicenter programs involving dozens or even hundreds of research locations, they can become increasingly visible. This is particularly true for sponsors pursuing aggressive development timelines, where site activation speed can influence enrollment performance, development milestones, and overall program costs.
In these situations, the question is no longer simply how quickly an IRB or IBC can complete a review individually. The more important question becomes how effectively all review activities can be coordinated to support study startup.
From oversight function to startup strategy
As sponsors gain experience with advanced therapies, many are beginning to rethink how they approach regulatory review. Rather than viewing IRB and IBC oversight as isolated compliance requirements, organizations are increasingly viewing them as interconnected elements of a broader startup strategy.
The goal is not merely obtaining approvals. The goal is obtaining approvals through a coordinated process that aligns with site activation plans, training requirements, drug shipment schedules, and first-patient-in (FPI) milestones.
This shift has important implications.
When IRB and IBC administration operate within the same organizational framework, opportunities emerge to improve communication, reduce administrative burden, and create greater visibility across the startup process. Review schedules can be coordinated. Operational questions can be addressed more efficiently. Sponsors can work through a single point of contact who understands the status of both review pathways and can help identify potential bottlenecks before they affect activation timelines.
Importantly, integrated administration does not compromise committee independence. The IRB continues to evaluate participant protections. The IBC continues to evaluate biosafety risks. What changes is the infrastructure supporting those activities.
The distinction may appear subtle, but for sponsors operating under tight timelines, it can have meaningful operational consequences.
A growing need for coordination
The trend toward increasingly sophisticated therapies shows no signs of slowing. Gene therapies, cell therapies, ribonucleic acid (RNA)-based therapeutics, and other genetically engineered products continue to represent active areas of clinical development.
As these technologies advance, the need for specialized oversight will continue to grow. At the same time, sponsors will remain under pressure to improve development timelines and bring promising therapies to patients more efficiently.
Success in this environment will depend not only on scientific innovation but also on operational execution. Organizations best positioned to navigate this complexity will be those that recognize the growing convergence between ethics oversight and biosafety oversight and develop strategies that allow these functions to operate in a coordinated manner.
Compliance remains essential. But increasingly, coordination is becoming a strategic advantage.
Bringing ethics and biosafety together
At Advarra, we’ve seen how effective coordination between IRB and IBC review can help sponsors support study startup while maintaining rigorous participant protection and biosafety oversight.
Advarra supports sponsors, contract research organizations (CROs), academic medical centers, and research institutions conducting complex clinical research involving interventional genetic therapies.
Our integrated review model allows independent committees to operate within a coordinated administrative framework, helping organizations streamline communication, reduce operational complexity, and align review activities with critical startup milestones.
For sponsors conducting advanced therapy research, these efficiencies can support greater startup predictability and stronger coordination across site activation activities.
To learn more about how integrated IRB and IBC administration can support study startup, download our case study, “Leading CRO Accelerates Startup with Integrated, Centralized IRB/IBC Reviews.” It highlights how a leading global CRO used coordinated IRB and IBC review to support activation timelines for multicenter studies involving genetically engineered products and describes direct coordination between review teams, integrated planning with site activation groups, and startup strategies that helped support timelines for complex research programs.
To discuss how integrated ethics and biosafety oversight can support your next study, contact Advarra.
