Quality of Fecal Microbiota Transplantation (FMT) Products at the Initial Development Stage — PMDA Early Consideration Summary

In Plain Language

Fecal microbiota transplantation (FMT) products use gut bacteria prepared from the feces of healthy human donors, so donor selection and infection screening are central quality and safety questions. The document describes considerations for the initial development of FMT products intended to be approved as drugs. It says interviews and tests should be used together to assess prospective donors, and that pathogens known to cause human disease should be addressed through a justified testing approach. It also highlights the need to understand the microbiota in the product and maintain treatment-relevant characteristics consistently across lots. Because bacteria are the active substance and sterility testing is not feasible, the manufacturing environment and process controls are important to prevent contamination.

What This Guidance Covers

The document applies to FMT products prepared from the feces of healthy human donors and intended to be regulatorily approved as drugs. Its focus is quality at the initial development stage, especially donor and donor-feces eligibility, infectious risks, microbiota composition, and manufacturing controls.

The document defines FMT as a therapy in which enteric bacteria prepared from healthy human donor feces, rather than specifically identified bacterial strains, are transplanted into patients with the aim of improving the gut microbiota and thereby producing the expected effect. It does not describe a particular clinical trial design or a complete product-development programme. Its stated scope is the quality considerations for the specified FMT products.

Why It Matters

FMT products contain enteric bacteria directly derived from donors and are used without substantial processing, according to the document. This makes it important to assess donor eligibility from multiple safety perspectives and to address the possibility of infection being transmitted through a donor or donor feces. The document identifies interviews, stool testing and blood testing as ways to assess donor eligibility and infectious risks.

A further challenge is that gut microbiota composition can differ by country or region, ethnic group and individual donor, and can vary within the same donor with factors such as diet and lifestyle. The document therefore connects product quality with understanding microbiota composition and investigating which bacterial strains or microbiota characteristics may be effective for the target disease. It also notes a manufacturing challenge: because the active substance is bacteria, adventitious agents introduced during manufacturing are difficult to remove, while sterility testing is not feasible.

Key Recommendations

1. Assess donor eligibility from multiple perspectives. The document says interviews and tests should be used appropriately in combination to determine whether prospective donors are fully qualified. A physician’s interview about health history and lifestyle is important. Interview items should be determined with reference to regulatory guidelines from outside Japan and interview sheets used for blood donation, among other sources.

2. Address pathogens in both donors and donor feces. Donors and donor feces used for FMT products should be tested for infections with pathogenic bacteria, fungi, viruses and other pathogens, and infection with pathogens must be ruled out. The document’s Table 1 presents test items to consider for donor feces, donor blood and other samples. It says tests should be extensive and should use highly sensitive detection methods to assess either the donor or donor feces for pathogens known to cause human disease.

   The pathogens selected for testing should take account of the donor’s country or region, the target disease, and the product’s risk-benefit profile. If a new pathogen causing infection emerges beyond those listed in Table 1, it must also be tested. The sponsor should justify the pathogens tested, test-method details such as detection sensitivity and reference values, and any omission of a pathogen listed in the table.

3. Include specified blood testing and account for the window period. To address donor-mediated infection risk, blood samples should be tested for at least hepatitis B virus, hepatitis C virus and human immunodeficiency virus using both serological testing and nucleic acid amplification testing. The document explains that blood-derived substances could contaminate human feces and that blood samples are favored in terms of detection sensitivity. Testing frequency should be specified with the window period in mind.

   Samples for testing should be collected before feces are provided for FMT products. The document says testing should use methods with adequate performance and be performed within an appropriate period, with periodic retesting reasonably performed to maximize the capability of detecting infectious diseases.

4. Consider biological raw materials carefully. If biological raw materials other than human feces are used in manufacturing, they need to conform to the Standards for Biological Raw Materials. The document states that, as a general principle, use of biological raw materials should be avoided as much as possible, and that such materials should likewise be avoided wherever possible in FMT products.

5. Investigate microbiota characteristics and their consistency. Collecting data on the microbiota composition of FMT products throughout development is important from the perspective of ensuring efficacy and safety. The document says to investigate bacterial strains and microbiota that may be effective for the target disease, including their diversity. This investigation should consider gene analysis results on product microbiota, clinical trial results obtained using FMT products, changes in gut microbiota before and after transplantation in clinical trials, and publicly available information on gut microbiota related to the target disease. The effective characteristics identified should be maintained consistently within a certain range across product lots.

6. Check donor feces at the manufacturing site and control the manufacturing environment. Separately from pathogen tests, appropriate acceptance tests for donor feces conditions should be performed at the manufacturing site before use in manufacturing; the document gives fecal softness and color as examples. Since adventitious agents introduced during manufacturing are difficult to remove and sterility testing is not feasible, the manufacturing process needs to be carried out in an appropriate environment and under control to prevent contamination with adventitious agents.

Practical Implications

Interpretation: For sponsors, the document’s approach points to a need to make donor eligibility and infection-risk decisions traceable: explain how interviews and tests work together, why particular pathogens are included or omitted, and how testing methods and timing support the intended screening. The document does not set one universal pathogen panel or testing frequency for every product; it says these choices should be determined and justified in light of specified considerations.

Interpretation: Clinical and manufacturing teams may need to coordinate so that testing is connected to when donor feces are collected and used, while the testing schedule accounts for the window period and periodic retesting. The document’s Figure 1 illustrates screening and re-donor screening, assessments of donor eligibility, fecal donation, window periods and feces qualified for release. It does not provide numerical time intervals in the extracted figure text, so specific intervals should not be inferred from that schematic.

Interpretation: For quality and analytical teams, the document suggests treating microbiota characterization as an ongoing development activity rather than a one-time description. Investigating potential treatment-relevant characteristics and monitoring whether they remain within a certain range across lots can connect product characterization with clinical observations. The document does not supply a numerical range or a single required analysis method.

Interpretation: Manufacturing teams should distinguish pathogen screening from fecal condition checks: the latter are acceptance tests at the manufacturing site before use. They should also account for the document’s stated limitation that sterility testing is not feasible for these products, placing emphasis on appropriate manufacturing conditions and contamination prevention controls.

Technical Details

Table 1 organizes test items by sample category. The following names reflect the document’s listed items; the document also says the test plan should be justified and should take account of the donor’s country or region, target disease and product risk-benefit profile.

• Donor feces — bacteria and fungi: Aeromonas; Campylobacter; toxigenic Clostridium difficile; enteroinvasive, enteroaggregative, enterotoxigenic, enteropathogenic and enterohemorrhagic Escherichia coli (Shiga toxin-producing Escherichia coli); Shigella; Salmonella; Vibrio; Vibrio cholerae; Yersinia enterocolitica; Plesiomonas shigelloides; Listeria monocytogenes; Helicobacter pylori; toxigenic Staphylococcus aureus; vancomycin-resistant enterococci; extended spectrum beta-lactamase-producing Enterobacteriaceae; carbapenemase-producing Enterobacteriaceae; carbapenem-resistant Enterobacteriaceae; drug-resistant bacteria such as vancomycin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, drug-resistant Pseudomonas aeruginosa and drug-resistant Acinetobacter; enterotoxin-producing Clostridium perfringens; and Microsporidia.
• Donor feces — viruses: Norovirus, rotavirus, adenovirus, astrovirus, sapovirus and enterovirus.
• Donor feces — parasites: Cryptosporidium, Giardia lamblia, Cyclospora, Cystoisosporiasis, Entamoeba histolytica, helminths and parasite eggs.
• Donor blood — bacteria: Treponema pallidum, Chlamydia trachomatis, Coxiella burnetii and Mycobacterium tuberculosis.
• Donor blood — viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, human immunodeficiency virus, human T-lymphotropic virus type I, cytomegalovirus, Epstein-Barr virus and human Parvovirus B19.
• Donor blood — parasites: Toxoplasma and Echinococcus.
• Other samples: SARS coronavirus 2 and Neisseria gonorrhoeae.

The document’s specified minimum blood testing for donor-mediated infection risk is hepatitis B virus, hepatitis C virus and human immunodeficiency virus, with serological testing and nucleic acid amplification testing. This minimum statement is distinct from the broader list of Table 1 test items. The document also says that if any listed pathogen is not tested, the omission should be justified, and that newly emerging pathogens causing infection must be tested as well.

For microbiota quality, the document identifies several information sources to consider together: microbiota gene analysis of FMT products, clinical trial results using those products, changes in gut microbiota from before to after transplantation in clinical trials, and publicly available information related to the target disease. These inform investigation of potentially effective bacterial strains and microbiota, including diversity; the desired characteristics should be consistently maintained within a certain range across lots. No formula or fixed numerical acceptance range is supplied in the document.

Who Should Read It

This document is relevant to sponsors and developers of FMT products made from healthy human donor feces for development as drugs, particularly during initial development. It may also be useful to regulatory affairs and quality professionals preparing the rationale for donor eligibility and pathogen testing, microbiology and analytical teams assessing product microbiota, and clinical and manufacturing teams coordinating donor screening, fecal acceptance and contamination prevention. Investigators involved in FMT development may find its description of donor and product quality considerations useful when considering the safety context of clinical studies.

Official PMDA Source

• Official title: Quality of Fecal Microbiota Transplantation (FMT) Products at the Initial Development Stage (Early Consideration)
• Issuing body: Pharmaceuticals and Medical Devices Agency, Office of Cellular and Tissue-based Products
• Date on cover: October 31, 2025
• Official PMDA PDF: Download the PMDA document
• PMDA list page: PMDA Early Consideration documents

Source: Pharmaceuticals and Medical Devices Agency (PMDA) website, PMDA Early Consideration documents. This page was created by editing and summarising the PMDA document.

Consult the official document; this summary does not replace it. PMDA provides the English version for reference purposes, and the Japanese original prevails if the two versions differ. PMDA describes Early Consideration documents as reference information reflecting the Agency’s views at the time of publication; those views may change as scientific knowledge develops.

Related Clinical Biostats Resources

• All Clinical Biostats tutorials — Browse other plain-language tutorials on clinical research and regulatory topics.
• Statistical Calculators — Find calculators for statistical work that may support clinical research activities.