FDA issues another safety alert related to fecal transplants, as data suggest coronavirus lingers in poop
Since 2013, the FDA has implemented a policy of “enforcement discretion” regarding fecal microbiota transplants (FMT) to treat refractory C. diff: While biopharma companies work on developing standardized products, physicians can conduct FMT’s after securing reasonable consent from patients. But since last summer, a handful of safety issues have caused a stir in the field.
Earlier this week, the FDA issued a safety alert highlighting the risk of potential transmission of the new coronavirus from fecal matter derived from donors used in FMT, and said that additional safety measures are necessary.
“Several recent studies have documented the presence of SARS-CoV-2 ribonucleic acid (RNA) and/or SARS-CoV-2 virus (which causes Covid-19) in stool of infected individuals. This information suggests that SARS-CoV-2 may be transmitted by FMT, although the risk of such transmission is unknown,” the regulator said in a statement.
Earlier this month, an international panel of experts in FMT stressed in an article in The Lancet Gastroenterology and Hepatology, that updating (at least temporarily) the screening of stool donors is imperative — as the risk of transmitting SARS-CoV-2 by FMT might be higher than that in other tissue transplants. A 98-patient study in China yielded data that suggested the possibility of extended duration of viral shedding in feces, for nearly 5 weeks after the patients’ respiratory samples tested negative for SARS-CoV-2 RNA.
Designed to replenish gut microbes, FMT has shown high rates of efficacy in the treatment of recurrent C. difficile, a stubborn infection that has grown resistant to existing antibiotics and kills more than 29,000 Americans each year.
FMT requires a stool sample to be screened, liquefied and delivered to the colon by nasal or rectal tube. Patients must either find their own donor, obtain viable stool from a licensed health care provider, or turn to a stool bank, such as OpenBiome. Fewer than 3% of the population qualify as healthy donors, according to the Fecal Transplant Foundation.
On Monday, the FDA issued recommendations to mitigate the risk of serious adverse events for any fecal material that has been donated since December 1, 2019 and is being considered for use in an FMT procedure, including testing donors and donor stool for SARS-CoV-2 if feasible and developing criteria to exclude of donors and donor stool based on screening and testing.
Earlier in March, the FDA issued a separate safety alert after E. coli-tainted stool from the non-profit stool bank OpenBiome made six patients sick, four of whom were hospitalized. Two other FMT recipients whose transplants comprised OpenBiome’s product also died. Last summer, the death of an immuno-compromised elderly patient in an FMT trial at the Massachusetts General Hospital — due to a stool donation that contained a rare type of E. coli bacteria — sent shivers across the field.
“These safety alerts point to the fact that donor screening is…necessary but insufficient to minimize the infection risk for donor-derived microbiome, and fecal transplant products,” said Eric Shaff, CEO of Seres Therapeutics, in an interview.
A few years ago, the spectacular failure of Seres Therapeutics’ seminal Phase II trial testing its “crapsule” — donor-derived processed fecal material encapsulated in a pill — derailed the emerging field.
Now, as Seres awaits the results of a key study, the company was keen to point out in a statement that its manufacturing process involves multiple layers of testing of samples, including the use of ethanol, beyond the initial screening of fecal matter.
What these FDA alerts show is that with FMT, there will always be an issue that must be chased, said Seres’ chief technology officer John Aunins in an interview.
“You didn’t test previous agents, or you use the test that wasn’t sensitive enough or a pathogen emerges and you don’t have a test for it. So it’s, it’s just an inherent situation with that kind of a product.”
Seres’ analysis suggests that in the case of C. diff, for instance, the most benefit can be derived from bacterial spores, and Seres’ manufacturing apparatus isolates these spores from donor stool.
To be sure, experts acknowledge that in the gut, it has still not really been established what it means to be healthy. The interaction between the microbes and the host happens in many different dimensions, on an anatomical level as well as in terms of metabolites and immunology — making the determination rather complex.
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