Abstract
INTRODUCTION: Discussion of gene-modified investigational products (IPs) in clinical trials has largely focused on nucleic acid-based vectors, viral vectors, and gene-modified cellular products involving mammalian cells. Use of bacteria and bacteriophages as IPs is resurgent, and discussion of the risks associated with genetic modification of these organisms has become pertinent to the biosafety community. METHODS: This review article summarizes the United States Food and Drug Administration classification for IPs comprising bacteria or bacteriophages and provides an overview of clinical trials conducted to date involving genetically modified bacteria. The risk assessment for bacterial or bacteriophage-based IPs is discussed. CONCLUSION: The risk assessment process for bacterial or bacteriophage-based IPs is different from that of gene expression vectors and mammalian cells. Greater consideration must be given to the attenuating mutations affecting virulence, replication competency, antibiotic susceptibility, and persistence in the environment. With the recent growth in clinical trials involving genetically modified bacteria, biosafety professionals and Institutional Biosafety Committees with responsibilities including oversight of clinical trials must become familiar with the associated risk assessment.