How FMT is regulated in other countries:
FMT in Europe:
The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey (2021)
https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(21)00158-7/fulltext - the UK has the highest rate of non-CDI use.
Regulation varied across countries and centres. Formal regulation was in place at 12/31 (39%) centres; of whom 7/31 (23%) were regulated by the national medicines’ authorities, 4/31 (13%) were regulated by the national tissue authorities, and 1/31 (3%) were regulated locally by the hospital administration. Informal regulation where the centres were in dialogue with the national health authorities were present at 9/31 (29%) centres, and 3/31 (10%) centres reported having ethics approval only. Seven (23%) centres reported having no regulation.
Regulation, risk and safety of Faecal Microbiota Transplant (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280140/ - by UK authors. Table 1 has a
list of countries and how they regulate FMT.
In the EU, a medicinal product can only be placed on the market if quality, efficacy and safety standards are met and a marketing authorisation has been issued. Currently there are no MHRA (UK agency) marketing authorisations for FMT products, thus material used for FMT is considered to be unlicensed in the UK.
Unlicensed medicinal products are often used in clinical practice; this is permitted by a derogation in the Medicines Directive (Article 5.1 of Directive 2001/83/EC relating to medicinal products for human use (Medicinal Products Directive). This allows member states to develop national provisions to allow supply of unlicensed products to meet the “special needs” of certain patients providing the supply is unsolicited.
One could argue that FMT has similarities with probiotics which are generally considered foods or dietary supplements rather than drugs and thus have minimal regulatory requirements. It is the lack of characterisation of microbial strains that precludes the classification of FMT as a probiotic according to expert consensus.
"The
European Commission recently proposed a regulation to classify FMT as a transplant"
https://european-union.europa.eu/institutions-law-budget/institutions-and-bodies/search-all-eu-institutions-and-bodies_en
European Medicines Agency https://www.ema.europa.eu/en/about-us/contacts-european-medicines-agency/send-question-european-medicines-agency
HMA (Heads of Medicines Agency)
https://www.hma.eu/contact.html
https://www.ema.europa.eu/en/documents/report/faecal-microbiota-transplantation-eu-horizon-scanning-report_en.pdf - June 2022 document indicating there was European Commission discussion about it, but it doesn't currently fall under any of the existing divisions, so it's being left up to Member States for now.
Page 7 has a
list of countries and how they've classified FMT.
28/05/2024
webinar https://ec.europa.eu/newsroom/ema/items/826606/ - the Borderline Classification Group of the EU Innovation Network (EU-IN BLCG) and by the
Substances of Human Origin (SoHO) team of DG Sante at the European Commission.
https://www.ecdc.europa.eu/en/substances-human-origin
The contact is for the
ECDC (European Centre for Disease Prevention and Control)
https://www.ecdc.europa.eu/en/about-us/contact-ecdc
European consensus conference on faecal microbiota transplantation in clinical practice
https://gut.bmj.com/content/66/4/569
FMT in the UK:
The growth of faecal microbiota transplantation in the UK: time for a registry? (2022)
https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00436-2/abstract - paywalled.
Regulation of faecal microbiota transplant (
Human Tissue Authority)
https://www.hta.gov.uk/guidance-professionals/regulated-sectors/human-application/regulation-faecal-microbiota-transplant
"FMT is outside the scope of the Human Tissue (Quality and Safety for Human Application) Regulations, 2007 (as amended) and is not regulated by the HTA. Establishments seeking to perform FMT should contact the
MHRA Medicines Borderline Section for further advice."
On behalf of the
UK Licensing Authority, the
Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicinal products for human use in accordance with the European Community’s medicinal products directive.
If a classifier does decide that a product is a medicinal product, then unless an exemption applies, it will be subject to the
Human Medicines Regulations 2012 [SI 2012/1916] (“the Regulations”).
The MHRA view is that
claims to “maintain” or “help to maintain” “dietary maintenance” or “support”
health or a healthy lifestyle,
can be approved under food law, and would not normally regard such claims to be medicinal.
(ii) Obtaining a
licence to supply a licensed medicine
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/872742/GN8_FINAL_10_03_2020__combined_.pdf -
FMT and marketing authorization are covered on the last two pages.
The MHRA is aware of the recent guidance issued by the
National Institute for Health and Care Excellence (NICE) in March 2014, regarding the use of FMT to treat for recurrent Clostridium difficile infection.
MHRA is of the view that
FMT falls within the definition of a medicinal product.
Products that are not
industrially prepared are not subject to the requirements of the Medicines Directive.
The Medicines Directive shall not apply to medicinal products
intended for research and development trials, but without prejudice to the provisions of Directive 2001/20/EC regarding clinical trials on medicinal products for human use (further to Article 3).
FMT in Australia:
Faecal microbiota transplantation in Australia: bogged down in regulatory uncertainty (Feb 2019):
https://onlinelibrary.wiley.com/doi/full/10.1111/imj.14212
FMT is not neatly classifiable under the current regulatory Therapeutic Goods Association (TGA) definitions of a drug, tissue or organ. At present, there is both under- and over-regulation of FMT in Australia. On one hand, FMT may be delivered in the local care setting without being subject to agreed standards for screening and manufacturing practice. Medical practitioners are able to compound and administer a therapeutic product to a patient under their care with appropriate consent. On the other hand, supply of FMT aliquots from stool banks that adhere to rigorous standards is not currently permissible. Current legislation prohibits the wider distribution of therapeutic products that are not certified according to Good Manufacturing Practice (GMP) protocols.
The need for GMP certification, as currently interpreted, represents a significant barrier to the establishment of a National Stool Bank. Beyond stringent screening for potentially transmissible conditions, a GMP requirement for standardisation of donor faecal product is not achievable. Moreover, the costs of setting up and maintaining a GMP-licensed stool bank facility are prohibitive.
Faecal microbiota transplant products
regulation (2023)
https://www.tga.gov.au/products/biologicals-blood-and-tissues-and-advanced-therapies/biologicals/faecal-microbiota-transplant-products-regulation
How your FMT product will be regulated by TGA depends on the level of clinical oversight and external governance in its preparation.
"Minimally manipulated" FMT is
Class 2, and subject to GMP licensing.
https://www.tga.gov.au/resources/resource/guidance/faecal-microbiota-transplant-fmt-product-regulation
Donor screening requirements
https://www.legislation.gov.au/F2020L01011/latest/text
Highly overreliant on testing. Blood & stool testing every 90 days. A stool sample must be taken from each stool; must be stored at or below minus 70°C.
Faecal Microbiota Transplant (FMT) - Outcomes from the FMT Stakeholder Forum (Sep 2019)
https://www.tga.gov.au/resources/publication/publications/faecal-microbiota-transplant-fmt-outcomes-fmt-stakeholder-forum
Contact TGA https://www.tga.gov.au/get-in-touch
They use https://
consultations.tga.gov.au/ to take
feedback prior to changing regulations. The last round was in 2019-2020. There are some interesting ones that disagree with the current regulations:
Submissions received: Options for the regulation of Faecal Microbiota Transplantation materials (
Sep 2019)
https://www.tga.gov.au/resources/publication/publications/submissions-received-options-regulation-faecal-microbiota-transplantation-materials
Biomebank says "Regulatory focus on safety not standardisation of product".
CDD says "It is well known that the FDA rule of initially using antibiotics for C. diff is not evidence-based."
"There are no drugs nor biologics tested for decades before marketing."
"FMT does not meet the current definition of a biological"
Makes some arguments against GMP, at least for hospitals.
FMT Consensus Group says Australia is one of the leaders in this field.
FMT is not a drug. FMT has been conducted at home by consenting adults for many years. Over-regulation would not change this or might increase home-FMT.
Given the complexity of FMT, we formed a multidisciplinary steering committee that I chair that aims to
discuss and recommend donor selection and screening, indications, development of FMT centres and
future research. Members include Dr Sudarshan Paramsothy, Dr David Andresen, Dr Viraj Kariyawasam and Dr Craig Haifer. We have decided on a working timetable, criteria for panel nominees, and proceeded to nominate panel members. We have sought endorsement from the Gastroenterological Society of Australia,
Australian Society of Infectious Diseases and The Royal College of Pathologists of Australia and have
representatives from each of these organisations. Panel nominees include gastroenterologists, infectious diseases specialists and pathologists from across Australia and overseas. We have invited the TGA to
participate and will involve a consumer/ patient representative.
Fiona Stanley Hospital says we do not think it logical for FMT to be considered a biological, or regulated as such.
St Vincent's Hospital, Department of Gastroenterology:
We recognise that FMT involves the transfer of human cells from donor to recipient, and therefore requires stringent donor screening for infections and medical co-morbidities. However, regulation of FMT as a Class 2 biologic or higher under the current biologic regulatory framework would impose Good Manufacturing Practice (GMP) requirements, and would be excessively onerous.
In contrast to the biologic and pharmaceutical agents regulated under GMP, there is no logical requirement for FMT to be produced in a sterile environment as faecal matter is not sterile.
There are further risks of imposing GMP approved FMT processing facilities, for the preparation of FMT: [lists financial and regulatory burdens, and DIY without supervision]
Furthermore, consideration should be given as to how a national registry could be developed to facilitate tracking donor and recipient health long term.
Many of the positions of these groups align quite well with what I've suggested, and with what Human Microbes already does. I think the majority of the groups above would agree with allowing access to our donors, as is, if they knew we existed and read the recent blog posts.
Submissions received: Draft standards for faecal microbiota transplant (FMT) products (
Aug 2020)
https://www.tga.gov.au/submissions-received-draft-standards-faecal-microbiota-transplant-fmt-products
Anon 2 says: As researchers, infectious diseases physicians and microbiologists we have concerns that the TGA’s plans to regulate some FMT products as Class 2 biologicals and impose the requirement that all screening tests used on donors be validated for screening purposes will ultimately result in reducing the safety and availability of FMT in Australia.
Biomebank says We have already spent $710,000 during 2019 with the aim of equipping our laboratory to meet the GMP standard. This does cost does not include TGA fees for GMP inspection or dossier assessment. We believe that the costs of TGA assessment and producing a dossier for a biological agent are too high. The regulatory costs will increase the price of FMT product to the point where it may limit access to the therapy.
Fiona Stanley Hospital and the
FMT consensus group challenge the class IV IVD test validation standards.
Gastroenterological Society of Australia (GESA) argues that over-regulation of FMT severely limits availability/affordability and makes patients resort to unsupervised DIY at home. They argue against GMP standards.
The
Microbiology Histopath Diagnostic Specialists one is interesting and has
many disagreements, such as: freezing stool to test it later. Norovirus and Rotavirus. H.pylori.
FMT in Canada:
https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/regulation-fecal-microbiota-therapy-treatment-difficile-infections.html
"Right now, FMT is only approved for use outside of clinical trials for the treatment of a single condition — C. difficile infection that hasn't responded to other therapies."
https://www.cbc.ca/news/canada/british-columbia/bc-naturopath-fecal-transplants-autism-1.5420048
https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/regulation-fecal-microbiota-therapy-treatment-difficile-infections.html
Contact https://www.canada.ca/en/health-canada/corporate/contact-us.html
Health Products and Food Branch https://www.canada.ca/en/health-canada/corporate/about-health-canada/branches-agencies/health-products-food-branch/biologic-radiopharmaceutical-drugs-directorate.html#Contact
FMT in Germany:
Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective (2023)
https://www.researchgate.net/publication/370802057_Fecal_Microbiota_Transfer_FMT_in_Germany_-_Status_and_Perspective "One application hurdle is the regulatory classification of FMT as a non-approved drug. The European Commission recently proposed a regulation to classify FMT as a transplant."
FMT in Finland:
Fimea - The Finnish Medicines Agency
https://fimea.fi/en/about_us
Fees chargeable
https://fimea.fi/en/-/the-new-decree-on-fees-chargeable-by-the-finnish-medicines-agency-into-force-on-1-january-2024 -
19,000 EUR for first marketing authorization application.
Marketing authorisation application
https://fimea.fi/en/marketing_authorisations/marketing_authorisation_application - The processing times for marketing authorisation applications are
210 days.
The classification process takes about
1 to 6 months and the decision is subject to a fee.
Academic Dissertation by Professor Perttu Lahtinen, Helsinki University Hospital (2023)
https://helda.helsinki.fi/server/api/core/bitstreams/9d3aab93-b705-4c10-805c-b537b692d991/content
Page 24: In Finland, Fimea, the national competent authority for regulating pharmaceuticals and blood and tissue products, has stated that stool is not a drug, and FMT does not fall under their regulation. Therefore, FMT does not have specific regulations in Finland thus far and is therefore governed by the existing rules and regulations affecting health care.
