In the Depths of the Fecal Microbiota: Unveiling the Secrets of Its Production

Introduction
The preparation of fecal microbiota transplants (FMT) in French hospital pharmacies has been described since 2014 (1). While several surveys have investigated the transplantation process, none have focused on the production of the transplants. This study aims to collect information on the production practices of FMT in hospital pharmacies.

Material and method
A French-language Google Forms questionnaire was emailed on March 27, 2024, to hospital pharmacists who are members of the GFTF (French Group for Fecal Transplantation) and the 2.0 committee of GERPAC. Available for 5 weeks, it included 57 questions covering the conditions for reception of the fecal matter (FM) donation, the production environment of the FMT, as well as the specifics of the preparation and the preservation methods of FM capsules and suspensions.

Results and discussion
Eight hospital pharmacies responded and have been preparing FMT in the form of suspensions; four also prepare capsules. The majority (n=6) operate in a non-classified area dedicated to FMT production. The production of suspensions exceeds 6 liters per year (n=5), and the production of capsules exceeds 1,000 units per year (n=2). FM donations are made on-site (n=6) and are never mixed intra- or inter-donors (n=8). FM donation is accepted by all if the stool quality, according to the Bristol scale, is type 3 or 4, and it is rejected if urine or blood is present (n=8). FM is stored frozen as FMT to be reconditioned just before administration (n=6), as ready-to-use FMT (n=3), or frozen to prepare FMT on demand (n=1). The minimum FM weight for production is 50 g (capsule or suspension). Homogenization of FM is done manually (n=1) or using equipment (pharmaceutical (n=1, e.g., Gako Ungator™), laboratory (n=3, Bag-Mixer®), or non-pharmaceutical (i.e., kitchen blender (n=3)). The diluent and cryoprotectant of choice are 0.9% NaCl and glycerol with varying concentrations (capsule 5-90% w/v and suspension 5-20% w/v). FM capsules are double-encapsulated (size 0 within size 00), and the packaging of FM suspensions varies according to administration and storage (syringe, bag, or bottle). After production, controls are performed (n=5), such as visual and parametric data examination, mass uniformity tests according to PhEur 2.9.5, or others. FMTs are stored at -80°C for 12-24 months (n=8).

Conclusion
FMT are most commonly prepared in non-classified areas; they consist of 50 g of FM, 0.9% NaCl, and glycerol, and are stored frozen. Our survey has outlined local production specifics for FMT.
Guidelines on FMT production processes would help standardize production despite the challenges of standardizing the raw material.

1. ANSM. La transplantation de microbiote fécal et son encadrement dans les essais cliniques, 03.2014

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