Why Biosafety Infrastructure Is Struggling to Keep Pace with CGT Growth

The numbers tell a clear story about where the cell and gene therapy field is heading. According to the Alliance for Regenerative Medicine, as of July 2024, the global sector encompasses 2,919 drug developers conducting 1,851 active clinical trials, a figure that had already grown to more than 2,000 clinical investigations by Q4 2025¹. What those numbers don’t capture is the operational complexity sitting behind each one of those trials.

Cell and gene therapy (CGT) programs are not simply more intensive versions of conventional drug trials. They involve genetically modified biological agents, viral vectors, engineered cells, recombinant nucleic acid molecules, that require a fundamentally different approach to safety oversight, site qualification, and compliance planning. The regulatory requirements that govern how these agents are handled, stored, administered, and disposed of are layered, specific, and often discovered later in development than they should be.

The result is a pattern that many clinical operations teams have experienced firsthand: biosafety requirements that surface at the wrong moment, after protocols are drafted, after sites are selected, after timelines are committed to stakeholders. By that point, the cost of addressing them is far higher than it needed to be.

Most clinical sponsors are well-versed in IRB requirements. Fewer are equally prepared for what IBC review actually entails in a CGT context, or how early it needs to start.

An Institutional Biosafety Committee (IBC) is a separately mandated regulatory body that operates independently from the IRB. While an IRB focuses on protecting the rights and welfare of research subjects, an IBC is responsible for assessing risks to clinical and laboratory staff, local communities, and the surrounding environment from exposure to genetically modified biological agents. Both are required for CGT trials. Neither substitutes for the other.

IBC oversight is triggered by a two-part test under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules: the research must qualify as Human Gene Transfer (HGT) under Section III-C, and it must be subject to NIH Guidelines due to relevant funding under Section I-C². Sponsors sometimes assume IBC requirements apply only to publicly funded academic research. That assumption tends not to survive contact with a CRO or site activation team.

The scope of what qualifies as HGT is also broader than many sponsors initially recognize. Classic gene therapy approaches are the obvious case, but the definition extends to gene editing, engineered stem cells, regenerative medicine approaches, and certain nucleic acid vaccines. If your program involves these modalities, the question is not whether IBC oversight applies, it is how early you have engaged with it and how prepared your sites are to meet its requirements.

Once triggered, IBC oversight is not a one-time review. It continues for the full duration of dosing, and any changes to the protocol, the investigational agent, or the handling procedures require re-review. That makes the IBC a continuous compliance function throughout the study, not a startup checkbox.

The April 2024 update to the NIH Guidelines expanded institutional responsibilities further, adding explicit requirements around gene drive modified organisms, IBC membership qualifications for certain types of research, and the Biosafety Officer’s role³. Sponsors running programs that touch on these areas should be reviewing those updates with biosafety expertise, not discovering them during an inspection.

The pattern of late-stage biosafety surprises in CGT programs is consistent enough that it is worth naming the specific failure modes driving it. Three in particular account for a significant share of the delays Sitero’s biosafety team encounters when engaging with sponsors whose programs are already in motion.

Many teams approach IBC review as a procedural formality rather than a substantive technical review. The IBC will want to understand the molecular content of the investigational product, how it will be transported, stored, prepared, administered, and disposed of at the site, what containment risks exist, and what incident response plans are in place. When the biosafety documentation does not clearly answer these questions, or when it is built on assumptions borrowed from chemical safety frameworks rather than biological risk frameworks, the result is IBC stipulations that require protocol restructuring, delayed site activation, and credibility problems with internal stakeholders and sites. The fix is an early, vector-specific NIH and IBC scope review, planned IBC timelines built into the project plan, and a biosafety narrative embedded in the protocol from the start.

Biosafety Level (BSL) and ABSL determinations for cell and gene therapy products involve a risk-based analysis that is specific to the vector type and route of administration. Applying standard containment criteria without vector-specific risk assessment, or inconsistently across sites, creates downstream problems. Facility workflows and SOPs may need reworking late in development. Capital changes may be required to bring sites into compliance. Inspection findings tied to containment decisions can undermine confidence in the entire biosafety program. The foundation here is a risk-based containment assessment conducted across R&D, GMP scale-up, and clinical settings, with consistent criteria applied across sites and SOPs aligned to the agreed BSL decisions.

Biosafety training for CGT programs needs to be role-specific and vector-specific. Generic laboratory safety training does not adequately prepare manufacturing staff for lentiviral vector handling, or clinical staff for the occupational exposure considerations associated with viral shedding. When training records are not mapped to actual vector and workflow risks, or when refresher training has not kept pace with protocol changes, inspection findings and near-misses follow. The solution is role-based training content tied to the specific vectors and workflows in the program, maintained and refreshed as the study evolves.

What these three pitfalls share is that they are all significantly easier to address at the start of a program than in the middle of one. That is not a novel observation, it is the reason biosafety expertise should be engaged at study kickoff meetings, during Investigator’s Brochure development, during Pharmacy Manual preparation, and during site selection⁴. By the time the protocol is finalized and sites are being activated, many of the decisions that determine biosafety readiness have already been made.

Site activation for a multi-site CGT trial involves a regulatory burden that is frequently underestimated in sponsor timelines: every institution participating in a trial involving r/sNA research subject to NIH Guidelines must have its own IBC of record registered with the NIH.(2) That means a 20-site gene therapy trial requires 20 separate IBC registrations, one for each institution. A 40-site trial requires 40. The administration of those registrations can be centralized, but the per-site requirement does not go away.

For sponsors working with academic medical centers, internal IBCs present an additional scheduling constraint. Most academic IBCs convene monthly and review studies in batches. A site that misses one meeting cycle may not receive approval for another four to six weeks. For programs with ambitious startup timelines, that cadence can quietly absorb the buffer that was built into the schedule for other reasons.

NIH registration itself is a process with complexity. Incomplete submissions, errors in documentation, and gaps in the materials provided to the IBC, including required information about BSC certifications, spill response procedures, waste disposal protocols, and staff training, are among the most common causes of additional review cycles and delayed approval.
External IBC services help address this directly. Sitero’s IBC team works with sites to prepare all required documentation, guides institutions through the NIH registration process, and can conduct reviews on an as-needed basis rather than being constrained to a fixed monthly schedule. For gene therapy trials, Sitero’s support, including complimentary NIH registration assistance, can reduce site activation timelines by four to six weeks⁵. For multi-site programs, Sitero’s Site Network Central IBC model streamlines IBC requirements across multiple locations, avoiding the duplication and coordination overhead that comes with managing 10, 20, or more separate institution-level processes simultaneously.

The IBC does not operate in isolation from IRB review. Ideally, the two reviews run concurrently, with the combined expertise of IRB and IBC memberships informing both subject safety and community safety considerations simultaneously. When those review processes are fragmented across different vendors or handled sequentially, the time cost compounds. Sitero’s integrated IRB and IBC capabilities support concurrent review, which matters when startup timelines are tight.

One of the clearest ways to understand where biosafety planning should begin is to map it across the CGT development lifecycle. Biosafety decisions do not start at clinical trial initiation, they start in R&D, when vectors are being selected and preclinical work is underway, long before an IBC review or IRB submission is on the horizon.

Vector selection has biosafety implications that propagate forward through every subsequent stage of development. BSL determinations made in preclinical settings establish the baseline that clinical sites will need to match or exceed. Shedding risk assessments inform what containment measures are appropriate for administration and follow-up. NIH Guideline applicability decisions made early will determine whether IBC review is required and, if so, what the committee will need to evaluate.
The problem is that many CGT programs treat biosafety as a clinical-phase concern. By the time the program reaches GMP scale-up or clinical start, biosafety decisions that should have been made in R&D are being revisited under time pressure. The result is rework, facility changes, SOP revisions, protocol amendments, that could have been avoided if biosafety expertise had been part of the program team from the beginning.

Sitero supports CGT biosafety planning across the full development continuum: R&D and preclinical work, GMP scale-up, and clinical trial operations. The services include vector-specific risk assessments (AAV, lentivirus, retrovirus, adenovirus, and related modalities), NIH Guideline applicability and IBC scope reviews, BSL and ABSL determinations, environmental and viral shedding risk evaluations, IBC protocol development and submission support, response to IBC stipulations and committee questions, and readiness assessments prior to site activation, inspections, or other key milestones⁵.

Sitero provides advisory and consulting support to help clients prepare for biosafety reviews and inspections. Institutional IBCs, IRBs, and regulators retain full authority over timelines and decisions. The role of Sitero’s biosafety team is to help clients develop positions that are technically sound, defensible under scrutiny, and practical to implement, not to guarantee specific committee or regulatory outcomes.

The CGT pipeline is not slowing down. The number of programs moving into clinical development, the increasing complexity of the modalities involved, and the growing expectations from regulatory agencies and inspection bodies all point toward a future where biosafety infrastructure will matter more, not less.

For sponsors, the question is not whether to engage with CGT biosafety requirements, it is whether that engagement happens early enough and with enough depth to prevent it from becoming a source of delay and rework. Programs that treat biosafety as an afterthought to protocol development consistently encounter the same problems: late IBC questions that require protocol restructuring, containment decisions that need revision under time pressure, training gaps that surface during inspections.

The programs that move more efficiently are the ones where biosafety planning began when vector decisions were being made, where IBC timelines were built into the project schedule from the start, where containment criteria were established with vector-specific risk data, and where training was role-based and documented before the first site was activated.

Sitero’s biosafety team works with CGT sponsors and sites at each of these stages, combining technical biosafety expertise with practical knowledge of what IBC committees and regulatory reviewers expect to see. To discuss your program’s biosafety requirements or upcoming milestones, speak with a Sitero CGT expert or visit our cell and gene therapy biosafety services page.

1. Alliance for Regenerative Medicine. Sector Snapshot: August 2024. https://alliancerm.org/sector-snapshot-august-2024/
2. NIH Office of Science Policy. NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules. https://osp.od.nih.gov/biotechnology/nih-guidelines/
3. Sitero. Sitero Summarizes Important Updates to NIH Guidelines, April 2024. https://sitero.com/blog-sitero-summarizes-important-updates-to-nih-guidelines-april-2024/
4. Kavanagh, D. Four Key Elements You Need to Know About the Role of IBCs in Gene Therapy Trials. WCG Clinical, 2021 (updated 2026). https://www.wcgclinical.com/insights/four-key-elements-you-need-to-know-about-the-role-of-ibcs-in-gene-therapy-trials/
5. Bartlett, Ryan, Senior Biosafety Officer, Sitero. Expert interview conducted for this article. July 2026.