One of the fastest growing areas in clinical research is clinical trials involving recombinant DNA, or gene therapy research. It’s an exciting space that is full of promise, but because of the risks involved, it’s also a highly regulated space. As many clinical research professionals are new to gene therapy research, confusion is common regarding the regulatory requirements.
While clinical research professionals are familiar with the role of the IRB to protect research subjects, most are unfamiliar with the added need for an Institutional Biosafety Committee (IBC) to review the risks associated with engineered genetic material in clinical trials. NIH Guidelines require IBC review for any genetic engineering research, including gene therapy research, that receives NIH funding or takes place at sites receiving NIH funding. This means any funding—even $1 of NIH funds for the site or the study means the study must be reviewed by an IBC.
Studies and sites completely independent of NIH funding may still require IBC review if the R&D that led to the investigational product was funded by the NIH. Even if there are truly zero NIH funds involved, IBC review is a best practice: NIH Guidelines state that “individuals, corporations, and institutions not otherwise covered by the NIH Guidelines are encouraged to adhere to the standards and procedures set forth” in the Guidelines (Section IV-D-1).
The rationale behind IBC review is to ensure a thorough risk assessment is performed regarding the risks associated with the genetically modified materials and a comprehensive risk mitigation plan is in place prior to conducting the research. Gene therapy research requires safety measures to ensure that research participants and study staff as well as the community and the environment surrounding the research site are not harmed by the modified genetic material or the infectious agents that may be utilized to deliver them. An IBC can help researchers utilize the appropriate safety measures to ensure research is conducted safely and responsibly.
Certain key words can aid in determining if IBC review is likely required. The following is a list of common terms found in research protocols requiring IBC review:
|Likely Needs IBC Review|
|Viral vector / Virus based gene delivery vector
Common viruses include:
• Adenovirus (Ad)
• Adeno-Associated Virus (AAV)
• Lentivirus (e.g. HIV based vector)
• Herpes virus (HSV)
• Pox virus (e.g. vaccinia, canary pox or fowl pox)
|Genetically modified or reprogrammed immune cells/white blood cells (e.g. CAR T cells)|
|Recombinant DNA (rDNA)|
|Synthetic Nucleic Acids|
|Gene editing: CRISPR-Cas9, TALEN, Zinc Finger Nuclease (ZFN)|
Micro RNA (miRNA), RNA interference (RNAi), short hairpin RNA (shRNA), silencing RNA (siRNA)
|Institutional Biosafety Committee (IBC)|
The following list includes terms associated with types of clinical trials that increasingly utilize genetically modified materials and, in such cases, may require IBC review. The latter list includes terms that generally do not point to requiring IBC review.
|Maybe Needs IBC Review (need more info about the design of the investigational product)|
|Vaccines, especially for cancer and infectious agents (Ebola, SARS, MERS, Zika, etc.)|
|Not Likely to Need IBC Review|
|Genetic screening or testing
(e.g. 23 and me)
|Monoclonal antibody based therapy
(Anything with a name ending in “Mab”)
|Tests that do not involve extraction and manipulation of genetic material (e.g. routine blood or urine tests)|
If you’re still unsure about whether your study requires IBC review, contact your IBC office for assistance. A quick call or email can likely resolve the question. If your site or institution lacks an IBC, or your IBC lacks the expertise to review a particular study, feel free to contact Advarra’s commercial IBC service. Our panel of experts is comfortable with the diverse challenges associated with genetic engineering research regardless of whether it is clinical, pre-clinical, non-clinical.
IBC review shouldn’t be an obstacle to conducting innovative research. Rather, consider the IBC your guide to understanding proper safety measures with gene therapy research. Gene therapy is inherently risky, and IBC review helps make sure those risks are minimized and properly managed.