OpenBiome Announces Enhanced Donor Screening Protocols Following FDA Alert

Press Release

CAMBRIDGE, Mass—On March 12, 2020, the U.S. Food and Drug Administration (FDA) issued a safety alert regarding the possible transmission of diarrheagenic E. coli in patients who were treated by fecal microbiota transplant (FMT) from three OpenBiome donors. Across more than 55,000 treatments shipped since 2013, the six cases covered in this safety alert are the first reports of likely transmission of pathogens by FMT from OpenBiome.

We are immediately implementing changes to our screening program in collaboration with FDA to ensure all FMT material is appropriately screened for these pathogens. Through our Quality and Safety Program, we screen for blood-borne and stool-borne pathogens or signs of illness through serological and stool testing, and clinical risk factors through a 200-point clinical assessment. Our first priority is always patient safety, and our safety and screening programs are continuously updated to account for new and emerging risks.

The safety alert describes six patients across two different types of cases:

**(1) Shiga Toxin-Producing E. coli (STEC)**

Safety Event Summary

We received four reports of patients who were treated with investigational FMT for recurrent Clostridioides difficile infection (rCDI) who later tested positive for STEC. All were treated with material from one donor. Two were hospitalized and have since been discharged; two were treated as outpatients and their symptoms have resolved.
STEC is a type of E. coli that can produce a toxin called Shiga toxin. Shiga toxin can cause symptoms like abdominal pain, diarrhea (often bloody), vomiting, and mild fever. Most people develop symptoms within 3-4 days of acquiring the bacteria, and most get better within 5-7 days. More information can be found on the CDC website.

OpenBiome Response

All unused material from this donor has been recalled and destroyed. The donor has been permanently excluded from any future donations.
When we received the first patient report, we immediately placed material from the donor on inventory hold and initiated an investigation. When we received the second report, we immediately initiated a recall of all material from that donor. After our recall notification, we received two additional reports of patients who had tested positive for STEC after receiving FMT material from the same donor.
Consistent with CDC guidelines, OpenBiome has previously screened donors for STEC via enzyme immunoassay (EIA). The donor tested negative for STEC at all screens and the material involved in these cases passed all other quality and safety checks.
We retain safety aliquots from every FMT unit that is produced. Aliquots from the units used to treat these four patients tested negative for STEC by EIA, but positive for STEC by nucleic acid testing (polymerase chain reaction, PCR). EIA tests for the presence of Shiga toxin, while PCR tests for the presence of bacterial genes required for Shiga toxin production.
As a result of this investigation and in collaboration with FDA, we are immediately implementing a change to our donor screening process by adding PCR testing for STEC to improve detection of asymptomatic carriage of STEC, and to protect against similar possible transmission events in the future.
We received two additional adverse event reports for patients who received material from this donor that are likely unrelated to their FMT. Both had multiple pre-existing conditions. Both have passed away from unrelated causes.

**(2) Enteropathogenic E. coli (EPEC)**

Safety Event Summary

We received two reports of immunocompromised patients who were treated with investigational FMT for rCDI who later tested positive for EPEC by PCR. The patients were treated with material from two different donors. One was hospitalized for related symptoms; one was hospitalized for unrelated causes. Both have been discharged.
EPEC is a type of E. coli that is generally carried asymptomatically but can sometimes cause transient watery diarrhea, similar to traveler’s diarrhea. Symptoms typically resolve in a matter of days.

OpenBiome Response

All unused material from these two donors has been recalled and destroyed. These donors have been permanently excluded from any future donations.
When we received these patient reports, we immediately placed material from the donors on inventory hold and initiated an investigation.
Consistent with international and national guidelines, OpenBiome has not previously screened donors for EPEC. The material shipped from these donors passed all quality and safety screens.
We retain safety aliquots from every unit that is produced. We performed follow-up testing on these safety aliquots, which tested positive for EPEC by nucleic acid testing (PCR). Upon confirmation of these positive test results, we immediately issued a recall of unused material from each donor.
As a result of this investigation and in collaboration with FDA, we are immediately implementing EPEC screening by PCR into our donor screening protocol.

Prioritizing Patient Safety

In addition to updating and implementing STEC and EPEC screening into our quality and safety protocols, OpenBiome is also working with FDA to implement retrospective screening of units to ensure that available material meets these new standards. We will provide an update on the results of that testing as soon as possible. In the meantime, treatment units not previously recalled are not on hold and may continue to be used.

All facilities that received units impacted by the recalls have confirmed that they received our recall communication and have confirmed the destruction of impacted units.

Notice of these rare safety events should be used by physicians to inform discussions with their patients. FMT remains an investigational product, and patients should give informed consent after a discussion of potential benefits and risks, including potential transmission of multi-drug resistant and/or pathogenic organisms, and alternative treatments.

Detection and response to reported safety events is one of our most important roles as a stool bank.

In collaboration with our network of clinical partners, who provide important follow-up information on the patients they treat, we work to identify and respond quickly to any emerging safety signals. We are currently conducting a full investigation and will share the results to inform safety in the field more broadly. You may find the most up-to-date information on our donor screening program, which qualifies 2.5% of prospective donors, at www.openbiome.org/safety.

As a nonprofit organization, our mission is to enable safe access to FMT. We exist for the patients we serve, and to support the work of the healthcare providers who oversee their care. Please do not hesitate to reach out to us with any questions, concerns, or feedback.

Updates from March 13, 2020:

FDA released an update to their March 12 safety alert with additional information about the relatedness of patient deaths.

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We have been getting some questions about the two patient deaths reported in FDA’s safety alert. We wanted to share additional facts about these cases here:

In the first case, an elderly patient with congestive heart failure and other medical comorbidities including type 2 diabetes and severe chronic kidney disease (stage 4) died due to decompensated congestive heart failure more than 3 weeks post-FMT. The treating clinician determined that the patient’s death was due to the patient’s underlying cardiac causes. Given a clear cause of death, STEC was not tested in this patient. Overall, the clinician determined the death was unrelated to STEC (the type of E. coli under investigation).

In the second case, we have confirmed by both highly-sensitive (PCR) and highly-specific (EIA) testing methods that the donor material that the patient received was negative for STEC. Therefore, it was determined that the death was unrelated to STEC. The safety alert was written prior to the release of this result.

Our material is used to treat a lot of extremely ill patients, and we have always asked our partners to report serious adverse events (including deaths) to us – even when it’s from a seemingly unrelated cause or health event such as cancer or a heart condition. We take every report very seriously and investigate it, and we report it to the FDA so that they can investigate it as well. We have never received a report of a patient’s death definitively caused by OpenBiome material.

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