Courtney Jones, BS; Matt Adams MS; Rebiotix Inc, Roseville, MN
- Microbiota Restoration Therapy is the Rebiotix platform for delivering human-derived microbes into a sick patient’s intestinal tract to treat disease.
- RBX2660, a microbiota-based drug, is currently under investigation for recurrent Clostridium difficile infection (CDI).
- RBX2660 is sourced from human-derived microbes and manufactured using standardized, quality controlled processes.
- A donor program was implemented to provide a reliable source of raw material for Phase 2 studies.
Donor Recruiting and Screening
- Potential donors were recruited by word-of-mouth.
- Nearby universities were targeted as a source of young, healthy donors.
- A one-time recruitment bonus and nominal payments for accepted donations were offered.
- Potential donors underwent an initial screening process (Figure 1) for an extensive list of blood and stool pathogens prior to enrollment.
- Failures were permanently excluded.
- If accepted into the program, donors agreed to make a minimum of 3 donations per week. A maximum of 10 donations per week was allowed (2 times daily, Monday through Friday). Each donation was tested for stool pathogens. Each batch ofRBX2660 was manufactured from stool donated by a single donor. Donations from multiple donors were not pooled.
- Daily health and diet questionnaires were completed with each donation to ensure there were no major changes in travel, medication, diet and health status (Figure 2).
- All donations were made on site and stored under controlled conditions.
- Donations were not pooled; aliquots from every donated stool were tested for pathogens using an extensive screen.
- At the end of each approximately 45-day donation cycle (Figure 3), donors underwent blood testing and donated aliquots underwent testing for pathogens.
- A positive result on any of the screens triggered destruction of all drug product associated with the donor during a cycle and exclusion of the donor from the program.
- A total of 75 potential donors were screened from July 15, 2013 through December 31, 2015.
- Of these, 11 (14.7%) failed the initial screening protocols. An additional 8 potential donors (12.9%) were lost to follow-up prior to making a donation.
- A total of 56 (74.6%) passed the screening protocols and made at least one donation.
- On subsequent retesting, a further 36 donors (64.3%) of the remaining donor pool were excluded: 23 failed one or more of the blood and pathogen screens; 13 discontinued participation.
- A substantial number of outwardly healthy donors used to source intestinal microbes for a drug under study for recurrent Clostridium difficile infection were found unsuitable due to underlying conditions.
- Reasons for rejection included asymptomatic carriage of an E. coli strain associated with hemorrhagic diarrhea and asymptomatic norovirus and rotavirus, which typically cause symptoms.
- Stringent screening of donors is required when sourcing live human-microbes used for treatment of disease.