Improving Study Activation Time for Gene Therapy Research

Research in gene therapies and genetically engineered drugs and vaccines are growing exponentially, and will only continue to become more popular. Per a report from the American Society of Cell and Gene Therapy (ASGCT), gene therapy research is an increasingly important part of an institution’s research portfolio, with over 3,500 therapies in preclinical or clinical.

The accelerating gene therapy market is expected to grow globally by 16.6% between 2020-2027. As human gene therapies enter the research pipeline at a growing pace, research sites need to consider how prepared they are to take on the additional review requirements of these studies in their activation programs.

This was just one of many questions we explore in our comprehensive survey of research sites and their internal activation practices. Diving deeper, this blog explores how research sites are focusing on their institutional biosafety committee (IBC) programs as part of overall study activation time.

Understanding When IBCs are Needed

First, let’s define what an IBC is and when institutions need their approval.

When treatments involve recombinant or synthetic nucleic acids, including messenger RNA (mRNA) or viral vector vaccines, additional IBC oversight is necessary. Some of these treatments potentially make permanent changes to the humans they are introduced into. Additionally, in some cases, gene therapy treatments make permanent changes to a human’s genetic profile, which is different than typical drug treatments.

Further precautions and IBC oversight are necessary when handling and administering these novel research compounds. The U.S. National Institutes of Health Office of Science Policy (NIH OSP) sets the guidelines for research involving recombinant or synthetic nucleic acid molecules.

Activation Insights

Survey results indicated many larger research sites reported they have an IBC in place to review research subject to the NIH OSP guidelines. Not surprisingly, these organizations were primarily large academic medical centers with sizable research portfolios.

However, simply having an IBC is much different than actively managing the IBC review process as part of an overall strategy to streamline trial activation.

Of the respondents who have an IBC at their organization, 54% indicated the review process for human trials exceeds 30 days. Additionally, more than a third of the institutions with an IBC indicated their institutional review board (IRB) and IBC review process for human trials are not integrated, nor run in parallel. For these institutions, human gene therapy trials are likely taking significantly longer to activate than their more traditional drug study counterparts.

Improving Activation for Gene Therapy Trials

Know the Process

First and foremost, researchers and clinical teams need to clearly understand the overall study activation processes at their organization, including IBC and other oversight committee reviews. An IRB tends to get the most attention since all human trials need IRB approval. However, if an organization does not focus on the efficiency and expertise of the additional committees, like the IBC, it does not matter how quickly the IRB moves.

The overall activation time is only as fast as the slowest committee, and that’s assuming the process allows for parallel review.

In the survey, many institutions indicated they don’t have a specific measure for IBC performance. In total, 88% of respondents who have an IBC reported they have no turnaround time goal or key performance metrics for their IBC program. The result is not knowing if a gene therapy-related clinical trial can even be activated within the activation timeline typically given to a sponsor during site initiation.

Build Expertise on the IBC

For many institutional IBCs, the majority of research oversight is preclinical. As more therapies are moving out of the lab and into human clinical trials, this paradigm is changing.

If an IBC does not have the requisite expertise to apply the NIH OSP guidelines to human clinical trials, it is generally advised to not try to do the review in-house. At best, an inexperienced in-house IBC review may result in a delay while the committee seeks additional expertise or due to unnecessary questions from the committee back to the investigators. At worst, an inexperienced IBC review may not apply the guidelines appropriately and introduce regulatory risk for the institution.

In either case, if the IBC does not have experience with human clinical trials, study activation time will likely be delayed.

Defer IBC Review, Keep the Local Biosafety Infrastructure

As human gene transfer trials are increasingly reaching Phases II and III, industry sponsors are routinely selecting a single central IBC and IRB provider to review all sites in a multicenter clinical trial. NIH, and soon Food and Drug Administration (FDA), mandate institutions rely on the single IRB (sIRB) designated by the sponsor. However, according to our survey, most institutions are not also deferring their IBC reviews off to a single IBC in the same way they defer oversight to the designated single/central IRB.

Very similar to how IRB deferrals work, biosafety programs can defer the formal IBC committee review component (e.g., five members convening an IBC meeting, minutes, etc.) to an independent IBC provider. Often, the sponsor will establish the protocol and scientific review at the central IBC and handle billing, both of which reduce burden on the research site staff.

Sites should consider using sponsor-selected, independent IBC services. Not only are commercial IBC services typically faster, but they also allow the biosafety officer to focus their attention on staff training, physical lab tracking, and other local issues. These are keenly important, but can be separated from the formal process of conducting IBC review per the NIH OSP guidelines.

Innovative treatments using gene therapy are growing, and public perception of genetically engineered drug therapeutics is changing due to the mRNA COVID-19 vaccines. An organization should ensure it has an efficient activation process through an IBC, so participants can take advantage of these new, cutting-edge investigational products.

Note: This article was originally published May 17, 2021, and has been updated to include new and clarifying information.

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