Manufacturing Processes of a Purified Microbiome Therapeutic Reduce Risk of Transmission of Potential Bacterial Pathogens in Donor Stool

BACKGROUND: Although fecal microbiota transplant has been used to prevent recurrent Clostridioides difficile infection (rCDI), documented pathogen transmissions highlight inherent safety risks of minimally processed stool. We describe manufacturing processes for fecal microbiota spores, live (VOWST; VOS, formerly SER-109), a microbiota-based oral therapeutic of Firmicutes spores. METHODS: Bacterial inactivation kill curves were obtained after ethanol exposure for 4 model organisms spiked into process intermediates. RESULTS: Bacterial log reduction factors ranged from 6.5 log(10) to 7.4 log(10) and lysis of spiked organisms occurred rapidly within 30 seconds. CONCLUSIONS: These experiments demonstrate substantial and rapid inactivation of representative organisms, supporting the potential benefit of VOS manufacturing processes to mitigate risk.