New regulatory requirements for faecal microbiota transplant (FMT) products commenced on 1 July 2021. FMT products supplied in Australia must be included in the Australian Register of Therapeutic Goods and comply with all applicable standards.
What are FMT products?
FMT products are defined in the Therapeutic Goods Regulations 1990 as a thing that:
- comprises, contains or is derived from human stool; and
- is for introduction into a person for a therapeutic use.
FMT products are manufactured from stored (frozen) stool or fresh (non-frozen) stool, and are introduced to the bowel for therapeutic use by a range of methods including rectal enema, sigmoidoscopy, colonoscopy, and nasogastric or nasoduodenal tube.
FMT products can also be made from stool that has been processed (e.g. encapsulated) to allow for oral ingestion.
What are FMT products used for?
FMT products are typically used to repopulate the bacterial microenvironment in a recipient's bowel with healthy microorganisms. Currently, FMT products have sound clinical evidence of efficacy for the treatment of recurrent Clostridium difficile infection (CDI), an often serious bacterial infection of the gut.
There is also emerging evidence of efficacy for treatment of ulcerative colitis (UC), a chronic relapsing-remitting mucosal inflammatory bowel disease (IBD), and increasing interest in the use of FMT products for a range of other conditions.
Products that contain only microorganisms derived from sources other than stool are not FMT products.
Commencement of FMT product regulation
On 1 January 2020, TGA provided clarity for the new regulatory model for FMT products. Following an 18-month transition period, the new regulatory requirements for FMT products commenced on 1 July 2021.
Most FMT products are regulated as biologicals. This includes significantly processed products (e.g. capsules) that are derived from stool. How your FMT product will be regulated by TGA depends on the level of clinical oversight and external governance in its preparation.
As a general principle, most FMT products will currently be regulated as either Class 1 or Class 2 biologicals depending on whether or not they are:
- manufactured in a hospital
- minimally manipulated
However, where a strain(s) of microorganisms, known to be present in stool, is characterised and grown from established isolates with standardised consistency, it may be regulated as a medicine rather than a biological.
What action do you need to take as a provider or manufacturer of FMT products?
From 1 July 2021, FMT products must comply with all of the following requirements:
- inclusion in the Australian Register of Therapeutic Goods (ARTG)
- advertising prohibitions/requirements
- reporting adverse events to TGA
- all applicable standards, including:
- notify TGA of any Class 4 in-house IVDs being used for the screening of FMT donors
From 1 July 2021, the supply of FMT products can only occur in Australia where:
- TGA has included the product in the Australian Register of Therapeutic Goods (ARTG); or
- TGA has granted approval or been notified utilising the 'unapproved' product pathways (e.g. clinical trials, Special Access Scheme), where specific criteria are met; or
- a supplier is complying with the transition arrangements
- this requires TGA to receive and accept an application for inclusion of an FMT product in the ARTG on or before 30 June 2021, and allows ongoing supply until a final decision is made on the application by TGA
How can you source FMT products?
From 1 July 2021, if you are a gastroenterologist or infectious disease specialist, FMT products can be best sourced from TGA-approved providers or manufacturers as either a:
- Class 1 biological, which is manufactured and used in the same hospital (essentially an in-house FMT product) following submission of a statement of compliance to TGA; or
- Class 2 biological included in the ARTG from a third party supplier or supplying under the transition arrangements
Schedule 16 of the Therapeutic Goods Regulations 1990 defines a Class 1 biological. We have published guidelines describing how to apply for inclusion of a Class 1 biological in the ARTG.
FMT products cannot otherwise be supplied directly to the public.
Where can you find further information?
More information about how TGA regulates FMT products and the regulatory requirements for sponsors is described in the Australian Regulatory Guidelines for Biologicals (ARGB).
How can you get further specific advice?
If you would like further advice, the following options are available:
- Download and complete a Request for advice - Biologicals form and send to bloodandtissues@health.gov.au
- Request a pre-submission meeting with TGA
- Meet us at your local SME Assist workshop. Alternatively, you can subscribe to the SME Assist email list to stay up to date with the latest SME information from TGA.
If you have any questions or feedback, please contact us at bloodandtissues@health.gov.au.
Standards applicable to FMT products
Therapeutic Goods Order No. 105 – Standard for Faecal Microbiota Transplant Products (TGO 105)
TGO 105 commenced on 1 July 2021 and is a legislative instrument that specifies the minimal requirements for stool donor and FMT product screening to ensure the quality, safety and efficacy of FMT products.
This new FMT product standard was drafted based on feedback received through public consultation, collaboration with Australian providers of FMT products, specialist clinical working groups, and reference to numerous recent international published consensus statements.
TGO 105 contains sections outlining:
- General manufacturing requirements
- Requirements relating to screening of stool donors
- Medical and social history
- Taking and testing of samples
- Physical assessment
- Requirements following collection
- Microbial control procedures
Accompanying technical guidance documents has been published on:
- Interpretation of the requirements in TGO 105; and
- Good Manufacturing Practice (GMP) licensing requirements for an FMT manufacturing facility.
Therapeutic Goods Order No. 107 - General requirements for the labelling of biologicals (TGO 107)
FMT products must comply with TGO 107, which applies to all steps in the manufacturing process of biologicals. All labelling requirements apply from the point of stool collection, through processing and release of the final FMT product.
An accompanying technical guidance document is also available for TGO 107.
Regulation of in vitro diagnostic medical devices (IVDs) for screening stool donors
IVD test kits used to screen stool, blood and other samples taken from potential stool donors for the manufacture of FMT products must be validated for the purpose for which they are intended (i.e. their intended use), and testing must be carried out in accordance with test kit instructions. When an IVD test kit is used by a laboratory outside of the manufacturer's intended use, it becomes an in-house IVD and further validation data must be generated to support the extended use. This occurs, for example, when an IVD is only approved for diagnostic rather than screening purposes (but is used for the purpose of donor eligibility selection), or when a different sample type is being tested from what is listed in the instructions for use.
Under the TGA's IVD Framework and as detailed in IVD guidance documents, an IVD intended to detect the presence of, or exposure to, transmissible agents in blood, stool or other samples in order to assess suitability for FMT transplant is regulated as a Class 4 IVD (or Class 4 in-house IVD). This applies to serological tests and nucleic acid amplification testing (NAAT), although an exception to this rule is microbial culture media which are considered Class 1 IVDs. For the majority of blood tests being proposed for FMT donors, there are already Class 4 IVDs included in the ARTG that are intended for screening purposes (exceptions include Hepatitis A IgM antibodies and Strongyloides serology). However, there are currently no Class 4 IVDs included in the ARTG that are approved for testing of stool specimens for the purpose of screening donors for the manufacture of FMT products.
Following public consultation on this requirement, it was determined that a change to the legislation was required to introduce an exemption for Class 4 in-house IVDs that are intended by its manufacturer to be used to detect the presence of, or exposure to, transmissible agents in blood, stool or other specimens from a person's body in order to assess the suitability of the person to be a donor of human stool for use in the manufacture of a faecal microbiota transplant product. Amendments in the Therapeutic Goods (Medical Devices) Regulations 2002 (see Schedule 4, Part 2, item 2.10A) exempt laboratories who develop and use these types of Class 4 in-house IVDs from the requirement to include them in the ARTG.
The exemption was intended to allow laboratories time to work with the TGA to establish processes that allow adequate data to be generated which supports their performance as Class 4 in-house IVDs. This data will contribute to the clinical evidence needed to address some of the residual risks associated with detection of specific organisms in the stool samples of healthy donors, and their relevance to potential transmission. The amendments also provide for a requirement for these laboratories to notify the TGA so that we are aware of the tests being used for donor screening purposes. The TGA will monitor and review this exemption to determine if it is still needed in the future.
Guidance will soon be published by the TGA Medical Devices Authorisation Branch to assist laboratories to meet the new IVD regulatory amendments. These will outline TGA's expectations around the technical considerations for these tests, in line with the conformity assessment procedures and National Pathology Accreditation Advisory Council (NPAAC) requirements.
Transition period for compliance with the FMT regulatory requirements
Following public consultation in 2019, TGA provided clarity with regard the regulatory requirements for FMT products. These new regulatory requirements for FMT products were implemented on 1 January 2020, with most FMT products regulated as Class 1 or 2 biologicals by TGA. The requirements were introduced with a 12-month transition period to allow time for current providers of FMT products to understand how the changes would impact them, to ensure there is no loss of access for patients, and to allow manufacturers time to comply with the new requirements.
Initially, the new regulatory requirements were to commence on 1 January 2021 following the 12-month transition period. However, due to delays caused by the COVID-19 pandemic in Australia during the first half of 2020, there was a 6-month extension granted for FMT products to 1 July 2021.
Additional safety protections relating to COVID-19 for FMT products
In April 2020, TGA provided advice on safety protections to FMT providers in Australia due to the potential to transmit the SARS-CoV-2 virus and COVID-19 disease via FMT through shedding in stool.
Details of this safety advice are published.
Other useful links
- Commencement of new regulatory framework for FMT products (January 2020)
- Consultation on draft standards for faecal microbiota transplant (FMT) products (January 2020)
- Consultation on regulatory framework for FMT products (September 2019)
- Outcomes from FMT products stakeholder forum (October 2018)