Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection

Abstract

Background: Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product. Methods: Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days. Findings: Clinical response was 83¢9% (95% CI 76¢0%À90¢0%) after one treatment. Clinical cure was 78¢2% (95% CI 67¢4%À89¢0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups. Interpretation: The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.

Structuring a Fecal Microbiota Transplantation Center in a University Hospital in Brazil

“…British cohort with 124 patients showed a resolution rate of 91.0% for recurrent CDI and 73.0% for refractory CDI on the seventh day (P=0.007). However, at the end of the third month of follow-up, the rates became equivalent (75.0% vs 82.0%, P=0.4) (116) . In addition, serious and complicated CDI can manifest as refractory infection, with persistence of symptoms despite antimicrobial treatment.…”

Stool banking for fecal microbiota transplantation: methods and operations at a large stool bank

“…2,19 There are two main models supplying stool for FMT: patient-selected donors and stool banking. [20][21][22][23][24][25] Under the patient-selected donor model, the patient or their guardian identifies their own stool donor candidate. The treating physician screens the candidate and processes the donor's stool into an FMT preparation.…”

“…30 Centralized processing is more cost-efficient and controlled: qualified donors provide material that can be used to treat many patients, and a purpose-built facility allows for stringent manufacturing quality standards. 23,25,31 Centralized distribution minimizes the delay in treating the patient, as physicians can access a well-screened, quality-assured FMT preparation delivered overnight.…”

“…Although there are differences between stool banks, in part due to variation in FMT regulation between countries, 32 stool banks generally adhere to a common-six part methodology, shown below. 5,21,[23][24][25]31,33,34 In some banks, these six elements are joined together by rigorous quality systems. 23,25 1.…”

“…Patient Safety: Evaluate FMT safety and quality, and respond to emerging safety and quality issues Despite the field's coalescence around this overall methodology, stool banking continues to evolve, delivering material that is more rigorously screened and more carefully prepared, with greater efficiency and reliability. Because consensus guidelines for stool bank operations have been strongly informed by the practice of existing stool banks, 20,31,34,35 improved sharing of different banks' methodologies, 36 exemplified by recent reports from English and Danish stool banks that emphasized the importance of quality management systems, 23,25 should help advance consensus standards and, in turn, to improve patient care. Improved sharing will also support the development of other stool banks and invite broader participation in the improvement of stool banking methods.…”