Faecal Microbiota Transplants – How are Products Regulated?
Faecal microbiota transplants are quickly gaining popularity around the world. If you have heard of FMT, chances are either you are not particularly squeamish or you have had enough time to digest the concept, pun intended. To put it mildly, FMT is used to repopulate the bacterial microenvironment in a recipient’s bowel with healthy microorganisms.
FMT has been successfully used worldwide to treat recurrent Clostridioides difficile infection (rCDI), an infection that can occur after antibiotic treatment. FMT is also being experimentally used to treat other gastrointestinal (GI) diseases as well as non-GI mental disorders, however, more clinical evidence is still required to assess the efficacy of FMT for these treatments.
Did you know? The first FMT used specifically to treat recurrent CDI was performed in the late 80s in Sydney, Australia.
FMT therapies are showing promise in treating a range of indications, from gut health and links to breast cancer to improved liver function
What are Faecal Microbiota Transplants (FMT) Products?
The Therapeutic Goods Administration (TGA) defines FMT products as things that “comprise, contain, or are derived from donated human stool and are introduced into a recipient person for a therapeutic use”.
Human stool is collected from a screened donor by defaecation and is then processed into an FMT product and provided to the recipient via enema, colonoscopy, nasoenteric tube, or orally (e.g. capsules). FMT products can be manufactured from either frozen or fresh stool.
How are FMT products regulated in Australia?
All FMT products are considered low risk products and are regulated as biologicals, either as Class 1 biologicals or Class 2 biologicals.
|FMT products as Class 1 biologicals||FMT products as Class 2 biologicals|
|Are collected under the supervision or direction of registered medical practitioners, are manufactured in hospitals and used in recipients who are patients of the hospital and who are under the clinical care of the practitioner.||Are manufactured in a facility that is not a hospital or manufactured in one hospital and used in different hospitals or clinics.|
|Have an appropriate level of external governance and clinical oversight.||Have been subjected to only minimal manipulation, such as:
|Do not require GMP licensing.||Must have GMP licensing for all manufacturing and testing facilities.|
FMT products are required to be included on the Australian Register of Therapeutic Goods (ARTG). Currently, there are 3 FMT products on the ARTG, including frozen faecal microbiota and freeze-dried, frozen, encapsulated faecal microbiota.
Donor screening requirements are strictly governed by the Therapeutic Goods (Standard for Faecal Microbiota Transplant Products) (TGO 105) Order 2020, which was published in August 2020 and took effect from 01st July 2021.
From the 01st of July 2021, all FMT products must:
- be included in the ARTG
- comply with advertising prohibitions
- have adverse events reported to the TGA
- comply with the standard for FMT products (TGO 105)
- comply with the labelling standard for biologicals (TGO 87).
The TGA must also be notified if any Class 4 in-house IVDs are used for the screening of FMT donors.
Did you know? Biologicals are prohibited from being advertised to the public as they are only suitable to be supplied and used by appropriately qualified healthcare professionals. However, a statement that is not designed or calculated to draw public attention to and to promote supply, sale or use of FMT is not considered an advertisement.
TGA Licensed FMT facility requirements and tips?
TGA licensed FMT facility requirements in Australia would follow the Australian Code of Good Manufacturing Practice for human blood and blood components, human tissues and human cellular therapy products, and not the PIC/S Guide to GMP.
For further information about GMPs for human blood and tissue and the consultancy services PharmOut can offer in this area please visit the links below:
Blood & Tissue GMP consultants
GMP consulting services for Biologicals, Blood & Tissues
We would like to congratulate Biomebank for becoming the first TGA GMP licensed in Australia last month (as far as we know).
Some of our design tips –
Greater attention should be paid to the environmental controls utilised to minimise the risk of microbiological and particulate contamination. Premises, facilities and equipment that are critical to the control of processing should be formally qualified.
The ventilation in any pass-through hatches should be active, and not passive. Active ventilation uses mechanically introduced air to preserve a pressure regime between adjoining rooms and maintain an area classiﬁcation even during door openings.
Wherever possible, its desirable to make sure personnel and material flows through airlocks are separate and unidirectional.
Any gases used in production, for example, to create anaerobic conditions within a chamber during the processing of stool sample into FMT products, should be risk assessed, typically they should be clinical or medical grade.
A minimum of ISO8 room grade should be maintained for GMP corridors, airlocks and manufacturing areas.
Further suggested reading:
Australian Regulatory Guidelines for Biologicals (ARGB) Appendix 10 – Guidance on TGO 105: Standards for faecal microbiota transplant (FMT) products, Version 1.0, September 2020
Australian Code of Good Manufacturing Practice for human blood and blood components, human tissues and human cellular therapy products, Version 1.0, April 2013