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Faecal microbiota transplant (FMT) products regulation

14 September 2020

Faecal microbiota transplant (FMT) products are defined in the Therapeutic Goods Regulations 1990 as a thing that:

  1. comprises, contains or is derived from human stool and
  2. is for introduction into a person for a therapeutic use

These include products manufactured from stored (frozen) stool or fresh (non-frozen) stool, introduced to the bowel for therapeutic use by a range of methods including rectal enema, sigmoidoscopy, colonoscopy, and nasogastric or nasoduodenal tube. It also includes stool that has been processed (e.g. encapsulated) to allow oral ingestion.

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, and emerging evidence of efficacy for treatment of ulcerative colitis (UC), a chronic relapsing-remitting mucosal inflammatory bowel disease (IBD). There is also 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.

On 1 January 2020, TGA provided clarity for the new regulatory model for FMT products. Most FMT products are regulated as biologicals. This includes significantly processed products that are derived from stool. 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.

More information about how TGA regulates FMT products and the regulatory requirements for sponsors is described in the Australian Regulatory Guidelines for Biologicals (ARGB).

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 outbreak of COVID-19 disease in Australia during the first half of 2020, there will be a 6-month extension to the transition period for these FMT products, i.e. commencement of the requirements from 1 July 2021.

Therapeutic Goods Order No. 105 – Standard for Faecal Microbiota Transplant Products (TGO 105)

This standard specifies the minimal requirements for donor and product screening, to ensure the quality, safety and efficacy of FMT products.

This standard was drafted based on feedback from a public consultation, collaboration with Australian providers of FMT products and specialist clinical working groups, and reference to numerous recent international published consensus statements.

The new FMT product standard is written as a legislative instrument and known as the Therapeutic Goods (Standard for Faecal Microbiota Transplant Products) (TGO 105) Order 2020. 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:

TGO 105 is now published but has a transition period, i.e. with commencement from 1 July 2021. The commencement date for the new FMT regulatory requirements thus now coincides with the commencement of the new standard for FMT products.

Therapeutic Goods Order No. 87 – General requirements for the labelling of biologicals (TGO 87)

The requirements for FMT products include the Therapeutic Goods Order No. 87 General requirements for the labelling of biologicals applies to all steps in the manufacturing. The labelling requirements apply from the point of stool collection, through processing and release of the final FMT product.

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, 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 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, TGA has made changes to the Therapeutic Goods (Medical Devices) Regulations 2002 through legislative amendments to introduce a temporary exemption for Class 4 in-house IVD medical devices that are intended to be used in the screening of stool donors for the purpose of FMT product manufacture. These amendments provide an exemption for laboratories who develop and use these types of IVDs from the requirement to include them as IVD medical devices in the ARTG. The exemption is intended to be in place for a period (up to 4 years) to allow providers to work with 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 to notify TGA so that we are aware of the unapproved tests being used for donor screening purposes.

The amended regulatory obligations commenced on 1 July 2020. Guidelines will soon be prepared 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.

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.