FDA announces public hearing in Maryland on Nov 4, 2019 to obtain input on the use of fecal microbiota transplantation (FMT) to treat Clostridium difficile infection not responsive to standard therapies. Electronic submissions accepted. (2019)

Michael Harrop

Active member
Jul 6, 2023
They're still only getting input for c.diff... what about FMT clinical trials for other conditions... those need regulation too.

Direct link for docket to comment on: https://www.regulations.gov/document?D=FDA-2019-N-3631-0001

Here's what I'm writing up to submit. Feel free to give me your feedback.
For FDA doc, 2019:
FMT should be first line treatment for C. Difficile. Antibiotics have a wide range of collateral damage and are not a solution to gut dysbiosis https://forum.humanmicrobiome.info/threads/while-antibiotic-resistance-gets-all-the-attention-the-damage-being-do.50/. FMT standards, oversight, and transparency need to be significantly improved. Patients need to be given adequate proof of donor safety and efficacy. Current standards are severely inadequate for both safety and efficacy. There seems to be widespread ignorance in the medical and research communities in regards to the gut microbiome's impacts on the entire body, and FMT donor quality. Thus it is vital that things not be left up to these individuals, but rather they must conform to strict guidelines and standards.

For example, the current use of blood donor questionnaires for screening stool donors is extremely deficient, inappropriate, and dangerously negligent. Here is an example of an appropriate questionnaire for FMT donors: https://humanmicrobiome.info/fmt-questionnaire/. Various answers to that questionnaire by applicants should be mandatory disqualification, and patients should be able to see anonymous donor questionnaires.

Due to the current significant limitations of testing https://humanmicrobiome.info/testing/, testing alone cannot be relied upon for safety or efficacy, and it seems that many doctors and researchers do not recognize this.

There is an urgent need for similar regulation and oversight for FMT clinical trials for conditions other than C. Difficle.

The EU had guidelines up in 2017 https://gut.bmj.com/content/66/4/569. The fact that there are still no mandatory guidelines similar to that in the US is negligent, and already confirmed to have cost at least one life.

Regarding transparency, in 2015 Openbiome reported that donor 102 has a 100% efficacy rate after 129 patients https://archive.fo/py71w#selection-1861.203-1861.204, while their average efficacy rate for c.diff is less than 90%.

That completely contradicts their recent (June 2019) public statement that there are no donor-dependent differences https://archive.fo/BvuHK#selection-2659.177-2659.178

It would be very useful to both the research community, and to patient transparency, if they provided a chart that listed every donor (anonymously - IE: donor 102), their cure rate, their rates of AEs and SAEs, most recent antibiotic use, stool type, etc.. And such a chart should be sort-able by each factor, so that we can sort by highest cure rates and then compare the various characteristics of those donors.

If a donor took antibiotics after becoming a donor, then their stats should be separated between before & after the antibiotic to see if their efficacy & safety rate changed. If a donor had a 100% cure rate then that cure rate declined, that should be distinguishable in the chart, ideally along with factors that may have caused it.

This type of data should already be mandatory to track and report to the FDA for regulatory purposes.

Such a chart could/should be listed on their safety page https://www.openbiome.org/safety.

The study they cite here https://www.openbiome.org/publications/#stool-donors is only an abstract https://sci-hub.tw/10.1016/S0016-5085(18)30564-X, and thus missing statistical information on the 51 donors they looked at.

For such data to be most useful though would require that their questionnaire be better than it currently is. For example, they're only asking donors about antibiotic use within the past 2 months. Whereas I asked my 9 donors about lifetime antibiotic use. Therefore I had more data to work with.

This might be a reason why they haven't been able to figure anything out so far in regards to what makes higher quality donors - they're not gathering enough data to work with.

Additionally, there is still no mention on their safety page of their donors causing IBS in 30% 10% of their patients https://archive.fo/eIm25. That seems like a severely negligent omission, and makes me wonder what else is being omitted.

The same requirements should be made of any doctor or hospital providing stool for FMT.

Further comments and citations in regards to FMT regulation:

To address some of your specific questions:
  • Mixing donations:
This increases risk due to not being able to determine which donor caused what outcome. Mixing should only be done after individual donors have a proven safety track record. But even then it does carry increased risk in cases where one donor contracts an acute infection/pathogen and may not be aware of it. Mixing may not even be necessary. One study showed greater benefits when two individually effective donor stools were combined, however, it's likely possible to get the same benefits by alternating donors or using them consecutively.
  • Synthetic FMT and future risk of disease development:
Previous comment: https://www.regulations.gov/document?D=FDA-2013-D-0811-0151

Original 12 Sep 2019.