Microbiome Treatment Centre
Dr Victoria L McCune, (Clinical Scientist and Honorary Research Fellow)
Professor Tariq H Iqbal (Consultant Gastroenterologist)
Professor Peter M Hawkey (Consultant Microbiologist)
Dr Victoria L McCune (Clinical Scientist and Honorary Research Fellow)
Dr. Mohammad Nabil Quraishi (Gastroenterology SpR and Clinical Research Fellow)
Dr Susan Manzoor (Production Manager)
Miss Sahida Shabir (MTC Manager)
Mr Shankar Seetharaman (Qualified Person)
Mrs Carol Evans (Quality Manager)
Mrs Jane Steel (Director Advanced Therapies Facility)
Summary of the service story
- Clinical need to provide FMT for routine treatment and use in clinical trials
- Evidence of poor availability of FMT across UK1
- Change in the FMT regulatory landscape
- No UK precedent for central stool bank for supra-regional delivery
- No precedent for running an NHS FMT service from a university facility
- Faecal Microbiota Transplant (FMT) is the transfer of processed faeces from a healthy person to someone with disease. A handful of FMT services were developed under Human Tissues Authority review2 3. However, in June 2015 FMT became regulated as a medicinal product in the UK. As such, supply between institutions could only be undertaken under the provisions of an MHRA Specials license and supply for clinical trial use required an Investigational Medicinal Product (IMP) license.
- In the absence of a UK licensed service, these changes directly limited the availability of FMT for NHS patients suffering from Clostridium difficile infection (CDI). Equally FMT research in the UK was restricted by the lack of IMP suppliers. As a pre-existing supplier of FMT and the only service supplying on a regional level, we needed to develop to meet the regulatory changes and ensure continuity of supply in the NHS.
- The regulatory framework of FMT was, at the time, in its infancy, and much development was needed to establish acceptable standards for production, storage and supply. Applying the regulations for the production of drugs, to that of a biological product was a challenge and required careful consideration and risk assessment to adapt pathways appropriately.
How we managed the challenges
- Firstly, by building a multidisciplinary team with the appropriate knowledge and skills, bringing together microbiology and gastroenterology experts with colleagues (Facilities Management, Legal Services, Qualified Person) with the necessary Good Manufacturing Practice (GMP) andcell therapy production experience. This enabled us to integrate our existing Standard Operating Procedures into an appropriate Quality Management System and develop our pathways and procedures to meet GMP guidelines, leading to successful MHRA licensing.
- Wider stakeholder engagement also enabled our success. For us, close collaboration with the MHRA Inspectorate Strategy and Innovation Unit was pivotal in understanding the evolving regulatory framework to ensure our service met requirements. NHS England and the BSG sponsored Gut Microbiome for Health Expert Panel, gave us wider perspective of the national challenge.
- We also fostered new relationships with external partners to support our service and minimise cost. For example, working with the Shropshire, Staffordshire and Cheshire Blood Bikes Association, enables the transport FMT to service users for the treatment of CDI on a voluntary basis.
Evaluation and Outcomes
- The first UK licensed FMT service was created at the Microbiome Treatment Centre, University of Birmingham in November 2017 (holding both Specials and IMP licenses).
- >63 FMTs have been supplied to 25 NHS Trusts across England for the treatment of CDI.
- Successful supply of >360 FMT samples to the pilot stage of STOP Colitis (ISRCTN74072945).
- Feedback of our experience, in collaboration with colleagues across the UK, to develop National guidelines regarding the practice of FMT for CDI4 5.
- Team work was essential and detailed forward-planning maintained efficiency of the project
- Early identification and engagement of the key stakeholders was critical to success
- Problem solving and adaption of processes was consistently required throughout
- Environmental control of the production facility and equipment was key to risk management of FMT production
- Validation, traceability and document control of methodology was essential for licensing
- Clinical and Information Governance structures must be considered
- Service level agreements for 3rd party services should include quality indicators
1. Quraishi et al., (2016) J Hosp Infect. 2016;95(4):444–5.
2. Quraishi et al., (2015) BSG Conference (PG-S641-S642): S641–2.
3. Bicknell, et al., (2017) Gut;66(Suppl 2): A7–8.
4. Mullish, et al., (2018) Gut 0:1–22. doi:10.1136/gutjnl-2018-316818
5. Mullish et al., (2018) Journal of Hospital Infection100, S1-S31
Contact details for members interested in getting more information
Microbiome Treatment Centre
IBR West Link Level 2
College of Medical and Dental Sciences
University of Birmingham
- A flow plan which presents the FMT service implementation process
- Figure 1 to present the geographic distribution of supply of FMT for the treatment of CDI to the NHS from the Microbiome Treatment Centre University of Birmingham
- The UoB FMT Request form and order form