Regulation, commercialisation and future perspectives on faecal transplantation

Transcription

1 Regulation, commercialisation and future perspectives on faecal transplantation James McIlroy 5 th Year MBChB University of Aberdeen CEO EnteroBiotix

2 From then to now It is suggested that this simple yet rational therapeutic method should be given more extensive clinical evaluation Dr Ben Eiseman, 1958

3 Disclosures and conflict of interest statement Salary, Shareholding and Directorship from EnteroBiotix Limited Consultancy from Biotechspert Limited Grant support from Scottish Enterprise and Opportunity North East

4 Overview and objectives Current regulatory landscape for faecal microbiota Regulatory landscape in UK Establishing a donor programme and GMPmanufacturing facility in the UK Processes and stipulations Future perspectives on faecal transplantation Closed system and encapsulation Using FMT to develop next generation microbial therapeutics Adaptive clinical trial design Landscape of commercial efforts globally

5 Regulatory landscape (UK) On the basis of the legal opinion provided by Sought formal EU legal opinion after NICE the Commission, the HTA does not consider guidance. that FMT is currently within the scope of the Q&S Regulations." (1) Article 1 of Directive 2001/83/EC as amended and Regulation of 2 of S.I 2012/1916 (The Human Medicines Regulations) The commission concluded that in FMT, the Under human Medicines cells are Directive not the active component Any substance of or combination this substance of substances and therefore presented are not as intended having properties for human for applications treating or preventing within the disease meeting in of human beings the EUTCD. 1

6 Regulatory landscape (UK) Licensed faecal microbiota product manufactured by organisation that has obtained a Marketing Authorisation (MA) FMT Unlicensed faecal microbiota produced from an MHRA licensed facility as Specials for a named patient OR as Investigational Medicinal Product (IMP) released by QP Unlicensed faecal microbiota produced from unlicensed facility

7 Overview and objectives Current regulatory landscape for faecal microbiota Regulatory environment in UK Establishing a donor programme and GMPmanufacturing facility in the UK Processes and stipulations Future perspectives on faecal transplantation Closed system and encapsulation Using FMT to develop next generation microbial therapeutics Adaptive clinical trial design Landscape of commercial efforts globally

8 Establishing a GMPmanufacturing centre Quality Management System Good Manufacturing Practice (GMP) Established, clearly defined and validated standards, change controls, incident reporting, dressing, cleaning etc Inspection body (MHRA) checks compliance against current standards Clean room Quality Control Office

9 Controlled donation facility Waiting room Blood samples Donation vessel Fridge

10 Overview and objectives Current regulatory landscape for faecal microbiota Regulatory landscape in UK Establishing a donor programme and GMPmanufacturing facility in the UK Processes and stipulations Future perspectives on faecal transplantation Closed system and encapsulation Using FMT to develop next generation microbial therapeutics Adaptive clinical trial design Landscape of commercial efforts globally

11 Next generation FMT Potential for environmental contamination Invasive mode of delivery Inefficient open air transfer Current problems Unappealing nature No standardisation No donor consideration given to donor patient compatbility

12 Next generation FMT Closed system collection and processing GMP Encapsulation technology GMPcompliant processing Novel QC Assays for safety and quality

13 Next generation FMT

14 Overview and objectives Current regulatory landscape for faecal microbiota Regulatory landscape in UK Establishing a donor programme and GMPmanufacturing facility in the UK Processes and stipulations Future perspectives on faecal transplantation Closed system and encapsulation Using FMT to develop next generation microbial therapeutics Adaptive clinical trial design Landscape of commercial efforts globally

15 Using FMT to develop next generation microbial therapeutics FMT Healthy human Diseased human Healthy human Identify microbes that drive patient outcomes Cocktail of bugs Microbial signatures, colonisation etc Adapted from Lawley and Forster Nature Biotechnology 33, (2015)

16 FMT in UC: Microbiota analysis Moayyedi et al. Rossen et al. (TURN trial) Paramsothy et al. Ruminococcus and Lachanospiraceae (Clostridium cluster IV and XIVa) Clostridium clusters IV, XIVa and XVIII Clostridium cluster IV, Clostridium cluster XVIII IV, XIVa and XVIII are consistently associated with remission McIlroy J, et al. Aliment Pharmacol Ther, 2017;00:117.

17 FMT in UC: Microbiota analysis Cocktails of Clostridial species belonging to clusters XIVa, IV and XVIII promotes an antiinflammatory immune responses by activating regulatory T (Treg) cells in animal models Atarashi K et al., Science Jan 21; 331(6015): Atarash Ki et alnature. 2013; /nature12331

18 Next generation FMT Optimising FMT s efficacy through adaptive donor allocation. Assign patient 1; patient responds Assign patient 2; patient does not respond Change donor; assign patient 2 Adapted from Olsen et al Stat Methods Med Res Jan 1:

19 Landscape and status

20 Thank you, any questions?

21 Overseas regulatory landscape Image courtesy of: Carolyn Edelstein Director of External & Regulatory Affairs, OpenBiome