Effect of extended -80°C storage on physical integrity of fecal microbiota capsules: a prospective study

6 October 2023

C. Stampfli 1, M. Kroemer 1, M. Audry 1, A. Mitouassiwou-Samba 2, F. Aparicio 2, A. Ballif 2, T. Galperine 2,3, B. Guery 2,3, L. Carrez 1, F. Sadeghipour 1,4,5
1 Service of Pharmacy, Lausanne University Hospital, 1011 Lausanne (Switzerland),
2 Service of Infectious Disease, Fecal Microbiota Transplantation Center, Lausanne University Hospital and University of Lausanne, 1011 Lausanne (Switzerland),
3 French Group of Fecal Microbiota Transplantation (GFTF), Paris (France),
4 Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne (Switzerland)
5 Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva and University of Lausanne (Switzerland)

Since 2021, the pharmacy department of Lausanne University Hospital has been compounding fecal microbiota (FM) capsules sourced from diverse eligible and selected donors for the oral treatment of patients with recurrent Clostridoides difficile infections. These treatments, enclosed in modified-release hypromellose capsules (DRCapsTM, Capsugel, Lonza, Basel, Switzerland), are designed to resist low pH levels, ensuring targeted release in the small intestine. The FM-containing capsules, along with 0.9% NaCl and 80% glycerol are stored at -80°C. The aim of this study is to assess the impact of extended storage at -80°C on the physical integrity of FM capsules.

Material and method
Conducted as a prospective, single-center, longitudinal study, two carefully selected stool donors participated between 16 and 23 August 2022. Donor 1 contributed three separate donations, while donor 2 provided a single donation. Control capsules (CC) containing only 80% glycerol were also prepared. Each capsule, whether FM or CC, was double encapsulated, with a size 0 capsule placed within a size 00 capsule. Capsules were promptly stored at -80°C, upon production completion, typically within six hours of receiving the donation. Seven time points were established: production day (M0), 1 month (M1), 3 months (M3), 6 months (M6), 12 months (M12), 18 months (M18) and 24 months (M24). At each time point, capsule underwent visual examination and a disintegration test. The disintegration test followed manufacturer specifications as per United States (<701>) and European (2.9.1) Pharmacopoeias. The testing apparatus and its component, complied to test specifications (DT50, Sotax, Aesch, Switzerland). Successful disintegration of DRcapsTM capsule was defined as capsules (n=6) remaining intact and not opened after 30 minutes exposure to a pH 1.2 / 37±2°C medium.

Results and discussion
A total of 240 capsules were prepared, including 48 CC, using a validated manufacturing process. Capsules from M0 to M6 (n=120) maintained their integrity, showing no defects or adhesion; none of the capsules subjected to the disintegration test showed signs of disintegration or opening following exposure to pH 1.2 / 37±2°C for 30 minutes. CC (n=30) also passed both tests.

DRCaps cTMpsules, stored at -80°C for six months and double-encapsulated with either MF or glycerol, retain their 15-25°C-defined specifications, as evidenced by visual inspections and disintegration tests. MF does not appear to alter capsule integrity based on our formulation. These findings on the physical integrity of the capsules serve to affirm our compounding practices with a clinical assessment up to 93% success rate after a single allogenic fecal microbiota transfer in 27 recipient patients. Ongoing analysis of data at M12, M18, and M24 is ongoing.

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