Best step to freeze faecal microbiota transplants: native faeces, faecal suspension or pharmaceutical forms ?

Introduction
Procedures for preparing and preserving fecal microbiota transplants (FMT) have considerably evolved since the establishment of first preparation units ten years ago. Nowadays, after donations are processed, transplants obtained can be stored for up to 2 years at -80°C. However, as freezing can be introduced at different step of the process, it seems interesting to compare the methods in order to optimize our activity.

Method
Transplants batch records of Saint-Antoine Hospital FMT center were used to create 3 groups differing in freezing stage position in the circuit : frozen native stool (FNS), frozen stool suspensions (FSS) and frozen pharmaceutical form (FPF). To compare the convenience of the three methods, preparation times and pharmaceutical costs were calculated. The time under investigation is only for preparation phase, as other phases are common to each type of procedure. They were compared statistically using a Mann-Whitney test (α = 5%). Beforehand, a study of syringes resistance to freezing/thawing and an effectiveness study of FNS transplants in the treatment of recurrent Clostridoides difficile infection were proceed.

Results
67 preparations were compared, 34 in FNS group, 17 in FSS group and 16 in FPF group. Average preparation times are 45.3 min for FNS, 39.4 min for FSS and 36.1 min for FPF. Only times taken by FNSs and FPFs to prepare transplants were significantly different. When donor is not biologically validated, the time lost is 5 and 9 folds less for FNSs than for FSSs and FPFs, respectively (4.6 minutes vs. 24 minutes and 36.1 minutes). In terms of pharmaceutical costs, preparation of ready-to-use syringes offers maximum savings of 54.4%, but only if the donor is biologically validated. If not, 69.4% of the cost of preparation is wasted, compared with 40% for conventional preparation (FNS and FSS). However, if we consider the cost of materials alone, freezing fresh faeces costs up to 3 times less than other procedures and is therefore more cost effective if not bioconfirmed.

Conclusions
This study traces the evolution of practices in a fecal microbiota transplant preparation unit. It shows that preparation using FNS avoids wasting time and materials (while achieving equivalent efficacy). This procedure also has the advantage of avoiding handling without stool biosafety validation. Furthermore, if the donation is compliant, production of a ready-to-use pharmaceutical form may prove practical, as it enables transplants to be dispensed over a wider area at no extra cost.

Key words : FMT – cryopreservation – pharmacotechnic

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