TY - JOUR
T1 - Design and manufacture of a lyophilised faecal microbiota capsule formulation to GMP standards
AU - Zain, Nur Masirah M.
AU - ter Linden, Daniëlle
AU - Lilley, Andrew K.
AU - Royall, Paul G.
AU - Tsoka, Sophia
AU - Bruce, Kenneth D.
AU - Mason, A. James
AU - Hatton, Grace B.
AU - Allen, Elizabeth
AU - Goldenberg, Simon D.
AU - Forbes, Ben
N1 - Funding Information:
SDG reports a relationship with Shionogi (consultation), Tillotts (consultation and honoraria), Enterobiotix (consultation) and Pfizer (consultation). KDB and NMZ receive funding grants from NIHR Nottingham Biomedical Research Centre. GBH receives honoraria from Symprove and part of Advisory Board, and Sensyne Health stocks.
Funding Information:
This work was funded by King's College London through King's Together Fund .
Publisher Copyright:
© 2022 The Authors
PY - 2022/10
Y1 - 2022/10
N2 - Faecal microbiota transplant (FMT) is an established and effective treatment for recurrent Clostridioides difficile infection (CDI) and has many other potential clinical applications. However, preparation and quality of FMT is poorly standardised and clinical studies are hampered by a lack of well-defined FMT formulations that meet regulatory standards for medicines. As an alternative to FMT suspensions for administration by nasojejunal tube or colonoscopy, which is invasive and disliked by many patients, this study aimed to develop a well-controlled, standardised method for manufacture of lyophilised FMT capsules and to provide stability data allowing storage for extended time periods. Faecal donations were collected from healthy, pre-screened individuals, homogenised, filtered and centrifuged to remove dietary matter. The suspension was centrifuged to pellet bacteria, which were resuspended with trehalose and lyophilised to produce a powder which was filled into 5 enteric-coated capsules (size 0). Live-dead bacterial cell quantitative PCR assay showed <10 fold viable bacterial load reduction through the manufacturing process. No significant loss of viable bacterial load was observed after storage at -80 °C for 36 weeks (p = 0.24, n = 5). Initial clinical experience demonstrated that the capsules produced clinical cure in patients with CDI with no adverse events reported (n = 7). We provide the first report of a detailed manufacturing protocol and specification for an encapsulated lyophilised formulation of FMT. As clinical trials into intestinal microbiota interventions proceed, it is important to use a well-controlled investigational medicinal product in the studies so that any beneficial results can be replicated in clinical practice.
AB - Faecal microbiota transplant (FMT) is an established and effective treatment for recurrent Clostridioides difficile infection (CDI) and has many other potential clinical applications. However, preparation and quality of FMT is poorly standardised and clinical studies are hampered by a lack of well-defined FMT formulations that meet regulatory standards for medicines. As an alternative to FMT suspensions for administration by nasojejunal tube or colonoscopy, which is invasive and disliked by many patients, this study aimed to develop a well-controlled, standardised method for manufacture of lyophilised FMT capsules and to provide stability data allowing storage for extended time periods. Faecal donations were collected from healthy, pre-screened individuals, homogenised, filtered and centrifuged to remove dietary matter. The suspension was centrifuged to pellet bacteria, which were resuspended with trehalose and lyophilised to produce a powder which was filled into 5 enteric-coated capsules (size 0). Live-dead bacterial cell quantitative PCR assay showed <10 fold viable bacterial load reduction through the manufacturing process. No significant loss of viable bacterial load was observed after storage at -80 °C for 36 weeks (p = 0.24, n = 5). Initial clinical experience demonstrated that the capsules produced clinical cure in patients with CDI with no adverse events reported (n = 7). We provide the first report of a detailed manufacturing protocol and specification for an encapsulated lyophilised formulation of FMT. As clinical trials into intestinal microbiota interventions proceed, it is important to use a well-controlled investigational medicinal product in the studies so that any beneficial results can be replicated in clinical practice.
KW - Capsule
KW - Faecal microbiota transplant
KW - FMT
KW - Lyophilisation
KW - Manufacturing
KW - Microbiome
KW - Quality control
KW - Stability
UR - http://www.scopus.com/inward/record.url?scp=85136599491&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2022.08.012
DO - 10.1016/j.jconrel.2022.08.012
M3 - Article
C2 - 35963468
AN - SCOPUS:85136599491
SN - 0168-3659
VL - 350
SP - 324
EP - 331
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -
