Ethicolegal framework for the regulation of human faecal microbiota transplants in South Africa: Progress, challenges and recommendations
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This article examines the ethicolegal challenges in regulating faecal microbiota transplantation (FMT) in South Africa (SA), where a regulatory vacuum under the National Health Act 61 of 2003 (NHA) and Medicines and Related Substances Act 101 of 1965 (MRSA) hinders the implementation of FMT. FMT effectively treats recurrent Clostridioides difficile infection by restoring gut microbiome balance, with potential for broader applications, but lacks clear classification as human tissue, biological material, or a medicine under the existing framework. The article suggests regulatory classifications for the different types of human stool under both the NHA and the MRSA. Drawing on relevant guidelines issued by the Food and Drug Administration in the USA and the European Medicines Agency, including the 2024 European Union’s Substances of Human Origin (SoHO) Regulation, which standardises microbiota safety and traceability, the article concludes with recommendations aimed at closing the existing regulatory vacuum concerning FMT in SA.
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1. Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 2021;19(1):55-71. https://doi.org/10.1038/s41579-020-0433-9
2. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464(7285):59-65. https://doi. org/10.1038/nature08821
3. Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: A new clinical frontier. Gut 2016;65(2):330-339. https://doi.org/10.1136/ gutjnl-2015-309990
4. Lloyd-Price J, Mahurkar A, Rahnavard G, et al. Erratum: Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 2017;551(7679):256. https://doi.org/10.1038/nature24485
5. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature 2012;489(7415):220-230. https://doi.org/10.1038/nature11550
6. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity- associated gut microbiome with increased capacity for energy harvest. Nature 2006;444(7122):1027-1031. https://doi.org/10.1038/nature05414
7. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014;157(1):121-141. https://doi.org/10.1016/j.cell.2014.03.011
8. Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 2010;107(26):11971-11975. https://doi. org/10.1073/pnas.1002601107
9. Pannaraj PS, Li F, Cerini C, et al. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr. 2017;171(7):647-654. https://doi.org/10.1001/ jamapediatrics.2017.0378
10. Jernberg C, Löfmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J 2007;1(1):56-66. https://doi.org/10.1038/ismej.2007.3
11. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505(7484):559-563. https://doi. org/10.1038/nature12820
12. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature 2012;486(7402):222-227. https://doi.org/10.1038/ nature11053
13. Falony G, Joossens M, Vieira-Silva S, et al. Population-level analysis of gut microbiome variation. Science 2016;352(6285):560-564. http://www.jstor.org/ stable/24744864
14. Cryan JF, Dinan TG. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 2012;13(10):701-712. https://doi.org/10.1038/nrn3346
15. Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368(5):407-415. https://doi. org/10.1056/NEJMoa1205037
16. Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut 2017;66(4):569-580. https:// doi.org/10.1136/gutjnl-2017-314049
17. Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol 2021;116(6):1124-1147. https://doi.org/10.14309/ajg.0000000000001278
18. Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol 2011;9(12):1044-1049. https://doi.org/10.1016/j.cgh.2011.08.014
19. Chen J, Zaman A, Ramakrishna B, Olesen SW. Stool banking for fecal microbiota transplantation: Methods and operations at a large stool bank. Front Cell Infect Microbiol 2021;11:622949. https://doi.org/10.3389/fcimb.2021.622949
20. South African Gastroenterology Society. SAGES clinical guidelines for faecal microbiota transplantation (FMT). 27 August 2015. https://www.sages.co.za/ content/images/FMT_guidelines_(003).pdf (accessed 7 April 2026).
21. Nana T, Moore C, Boyles T, et al. South African Society of Clinical Microbiology Clostridioides difficile infection diagnosis, management and infection prevention and control guideline. S Afr J Infect Dis 2020;35(1):219. https://doi.org/10.4102/ sajid.v35i1.219
22. Labuschaigne M, Slabbert M, Budree S, Hoosien E, Brink A, Blockman M. The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 1. A legal vacuum. S Afr Med J 2020;110(8):812-815. https://doi. org/10.7196/SAMJ.2020.v110i8.14563
23. Labuschaigne M, Slabbert M, Budree S, Hoosien E, Brink A, Blockman M. The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 2. Human stool as tissue? S Afr Med J 2020;110(8):816-818. https://doi. org/10.7196/SAMJ.2020.v110i8.15069
24. Labuschaigne M, Slabbert M, Budree S, Hoosien E, Brink A, Blockman M. The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 3. Stool as a ‘drug’ or medicine. S Afr Med J 2020;110(8):819-821. https://doi.org/10.7196/SAMJ.2020.v110i8.15070
25. Kao D, Roach B, Silva M, et al. Effect of oral capsule- vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: A randomized clinical trial. JAMA 2017;318(20):1985-1993. https://doi.org/10.1001/ jama.2017.17077
26. Ng RW, Dharmaratne P, Wong S, et al. Revisiting the donor screening protocol of faecal microbiota transplantation (FMT): A systematic review. Gut 2024;73(6):1029-1031. https://doi.org/10.1136/gutjnl-2023-329515
27. Mehta N, Wang T, Friedman-Moraco RJ, et al. Fecal microbiota transplantation donor screening updates and research gaps for solid organ transplant recipients. J Clin Microbiol 2022;60(2):e0016121. https://doi.org/10.1128/JCM.00161-21
28. Ng RWY, Dharmaratne P, Wong S, Hawkey P, Chan P, Ip M. Revisiting the donor screening protocol of faecal microbiota transplantation (FMT): A systematic review. Gut 2024;73:1029-1031. https://doi.org/10.1136/gutjnl-2023-329515
29. Peery AF, Kelly CR, Kao D, et al. The AGA clinical practice guideline on fecal microbiota-based therapies for select gastrointestinal diseases. Gastroenterology 2024;166(3):409-434. https://doi.org/10.1053/j.gastro.2024.01.008
30. Hoffmann DE, Palumbo FB, Ravel J, Roghmann MC, Rowthorn V, von Rosenvinge E. Improving regulation of microbiota transplants. Science 2017;358(6369):1390- 1391. https://doi.org/10.1126/science.aaq0034
31. South Africa. National Health Act 61 of 2003. https://www.gov.za/sites/default/ files/gcis_document/201409/a61-03.pdf (accessed 7 April 2026).
32. South Africa. Medicines and Related Substances Act 101 of 1965. https://www. sahpra.org.za/wp-content/uploads/2019/09/Medicines-and-Related-Substances- Act_101-of-1965_Act_GG-40869_2017-05-26.pdf (accessed 7 April 2026).
33. National Department of Health, South Africa. National Health Act, 2003. Regulations Relating to the Use of Human Biological Material. Regulation R177. Government Gazette No. 35099, 12 March 2012. Published under Government Notice R177. https://www.gov.za/sites/default/files/gcis_document/201409/350 99rg9699gon177.pdf (accessed 7 April 2026).
34. NationalDepartmentofHealth,SouthAfrica.NationalHealthAct,2003.Regulations Relating to Tissue Banks. Government Gazette No. 35099, 2 March 2012. Published under Government Notice R182. https://www.gov.za/sites/default/files/gcis_docu ment/201409/35099rg9699gon182.pdf (accessed 7 April 2026).
35. Cockeran R, Glatt T, Barrow P, Karlsson K, van den Berg K. Faecal microbiota transplant and the benefit of a national faecal microbiota bank in South Africa. S Afr Gastroenterol Rev 2022;20(1):9-10. https://www.ajol.info/index.php/sagr/ article/view/244757 (accessed 7 April 2026).
36. South African Health Products Regulatory Authority. Biological medicines. 2025. https://www.sahpra.org.za/biological-products/ (accessed 7 April 2026).
37. Department of Health, Republic of South Africa. South African Ethics in Health Research Guidelines: Principles, Processes and Structures. 2024. https://www. health.gov.za/wp-content/uploads/2025/07/SA-Ethics-in-Health-Research-2024. pdf (accessed 7 April 2026).
38. US Food and Drug Administration. Guidance document: Enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies. November 2022. https://www.fda.gov/media/86440/download (accessed 7 April 2026).
39. US Food and Drug Administration. Summary basis for regulatory action. 30 November 2022. https://www.fda.gov/media/163879/download (accessed 7 April 2026).
40. US Food and Drug Administration. Vowst. 2023. https://www.fda.gov/vaccines- blood-biologics/vowst (accessed 7 April 2026).
41. Jain N, Umar TP, Fahner AF, Gibietis V. Advancing therapeutics for recurrent Clostridioides difficile infections: An overview of Vowst’s FDA approval and implications. Gut Microbes 2023;15(1):2232137. https://doi.org/10.1080/19490 976.2023.2232137
42. US Food and Drug Administration Center for Biologics Evaluation and Research. Warning Letter. MG infusions: MARCS-CMS 696890. 10 March 2025. https://www. fda.gov/inspections-compliance-enforcement-and-criminal-investigations/ warning-letters/mg-infusions-696890-03102025 (accessed 6 April 2026).
43. Karimi M, Shirsalimi N, Hashempour Z, et al. Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: A comprehensive literature review. Front Immunol 2024;15:1439176. https://doi.org/10.3389/fimmu.2024.1439176
44. Rodriguez J, Cordaillat-Simmons M, Pot B, Druart C. The regulatory framework for microbiome-based therapies: Insights into European regulatory developments. NPJ Biofilms Microbiomes 2025;11(1):53. https://doi.org/10.1038/s41522-025- 00683-0
45. Hoffmann DE, Javitt GH, Kelly CR, et al. Fecal microbiota transplantation: A tale of two regulatory pathways. Gut Microbes 2025;17(1):2493901. https://doi.org/10.1 080/19490976.2025.2493901
46. European Union, EUR-Lex. Consolidated text: Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. https://eur-lex.europa.eu/legal-content/EN/ TXT/?uri=CELEX%3A02001L0083-20250101 (accessed 6 April 2026).
47. European Medicines Agency. Faecal microbiota transplantation EU-IN horizon scanning report. June 2022. https://www.ema.europa.eu/en/documents/ report/faecal-microbiota-transplantation-eu-horizon-scanning-report_en.pdf (accessed 6 April 2026).
48. Mullish BH, Quraishi MN, Segal JP et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: Joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut 2018;67(11):1920-1941. https://doi.org/10.1136/gutjnl-2018-316818
49. Cammarota G, Ianiro G, Tilg H et al.; European FMT Working Group. European Consensus Conference on Faecal Microbiota Transplantation in Clinical Practice. Gut 2017;66(4):569-580. https://doi.org/10.1136/gutjnl-2023-331550
50. Riva L, Petrini C. Regulation (EU) 536/2014 and the role of ethics committees: A proposal for a review system model. BMJ Open 2024;14(11):e073451. https:// doi.org/10.1136/bmjopen-2023-073451
51. European Union, EUR-Lex. Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC Text with EEA relevance. 2014. https://eur-lex.europa.eu/eli/reg/2014/536/oj/eng (accessed 7 April 2026).
52. European Union, EUR-Lex. Regulation (EU) 2024/1938 of the European Parliament and of the Council of 13 June 2024 on Regulation (EU) 2024/1938 of the European Parliament and of the Council of 13 June 2024 on standards of quality and safety for substances of human origin intended for human application and repealing directives 2002/98/EC and 2004/23/EC (text with EEA relevance). 2024. https:// eur-lex.europa.eu/eli/reg/2024/1938/oj/eng (accessed 7 April 2026).
53. European Union, EUR-Lex. Regulation (EC) 1394/2007 of the European Parliament and of the Council of 13 November 2007 on Advanced Therapy Medicinal Products and amending Directive 2001/83/EC and Regulation (EC) No. 726/2004). https:// eur-lex.europa.eu/eli/reg/2007/1394/oj/eng (accessed 7 April 2026).
54. Pokharel S, Adhikari B, Johnson T, Cheah PY. Interventions to address antimicrobial resistance: An ethical analysis of key tensions and how they apply in low-income and middle-income countries. BMJ Glob Health 2024;9(4):e012874. https://doi. org/10.1136/bmjgh-2023-012874