A Review of Clinical Trials Involving Genetically Modified Bacteria, Bacteriophages and Their Associated Risk...

Area of Science:

• Biotechnology
• Microbiology
• Biosafety

Background:

• Gene-modified investigational products (IPs) in clinical trials traditionally focus on nucleic acid-based vectors, viral vectors, and mammalian cells.
• The use of bacteria and bacteriophages as IPs is experiencing a resurgence.
• This shift necessitates a focus on the biosafety risks associated with genetically modifying these microorganisms.

Purpose of the Study:

• To review the U.S. Food and Drug Administration (FDA) classification for bacterial and bacteriophage-based IPs.
• To provide an overview of clinical trials involving genetically modified bacteria.
• To discuss the specific risk assessment considerations for these novel biological agents.

Main Methods:

• Literature review of FDA classifications for bacterial and bacteriophage IPs.
• Survey of completed clinical trials utilizing genetically modified bacteria.
• Analysis of risk assessment methodologies for bacterial and bacteriophage-based IPs.

Main Results:

• Bacterial and bacteriophage-based IPs fall under specific FDA classifications.
• A growing number of clinical trials are investigating genetically modified bacteria.
• Risk assessment for these agents differs significantly from traditional gene therapy vectors.

Conclusions:

• The risk assessment for bacterial or bacteriophage-based IPs requires distinct considerations compared to gene expression vectors and mammalian cells.
• Factors such as virulence attenuation, replication competency, antibiotic susceptibility, and environmental persistence are critical.
• Biosafety professionals and Institutional Biosafety Committees must familiarize themselves with these unique risk assessment requirements due to the increase in clinical trials involving genetically modified bacteria.