Onsite with OpenBiome

Issue: January 2017

**Process:** “First, we invite people who qualify for a clinical interview to undergo a full medical history that looks for known risk factors and conditions that can be potentially mediated by the microbiome. Those who pass undergo stool and blood tests,” Edelstein said. “Once they qualify, we collect stool material for 60 days and hold it in quarantine. Donors undergo health checks with every donation, and random exams throughout the collection window. At the end of the 60-day period, each donor is fully rescreened, and if they pass, their material gets released according to a schedule that accounts for seroconversion windows.”

“Donor stool is brought into the lab, weighed, logged, and then the lab technician will bring the container into the biosafety cabinet to assess stool pathology and Bristol stool type.”

“We’ve been inspired by how quickly the field has brought this treatment from what was considered a fringe therapy half a decade ago to something that’s now fairly standardized and has been broadly adopted in the clinic,” said **Mark Smith, PhD.**

“If we accept a sample, the lab technician will transfer it into a homogenizing filter bag,” Edelstein said. “We add cryopreservatives, a saline and glycerol solution, and homogenize the sample and filter out any large, fibrous material. Then we pipette it into bottles or emulsify it and put it into capsules. And that’s it. The samples are transferred to a –80°C freezer and await their release from quarantine. It’s a relatively simple manufacturing process.”

“We also freeze and store a safety aliquot from every stool we collect. Each treatment can be traced to the stool and donor from which it came. If need be, we can run testing on a particular sample from a particular donor, for example, to investigate an adverse event,” Edelstein said.

“Treatments are available in three formats. The most commonly used is the preparation for delivery by the lower GI tract, by colonoscopy, sigmoidoscopy or enema,” Edelstein said.

“An alternative is delivery through an EGD or nasoenteric tube, which is a route of administration that infectious disease physicians often use. The upper delivery FMT is a more concentrated 30 CC formulation, to reduce a patient’s risk of aspiration. Then there’s capsules, which are administered in one dose of 30 capsules taken in succession,” Edelstein said.

“We’re seeing early wins, but what is so exciting about FMT is that we’re just at the starting line. The field is very much in its infancy, so gastroenterologists have the chance to be architects of change and not be trapped by dogma. With nimble thinking and rigorous methods, we have the potential to transform human disease linked to the microbiome,” said **Zain Kassam, MD, MPH, FRCPC.**

“We send material to clinical sites overnight on dry ice with temperature verification. Sites can store the material in a standard medical-grade freezer at –20°C for up to 6 months or –80°C for up to 2 years. We send the full donor screening history, patient education material, and other resources, and each treatment also comes with a checklist to help guide clinical use, from the patients’ first assessment through 8-week follow-up,” Edelstein said.

**Marketing Outreach:** OpenBiome recruits donors through social media, publications, and advertising on college campuses, as people in their late 20s tend to be good donors, but “by far, our most successful recruitment tool is a media story going viral,” Edelstein said. “In the early days, when we were just getting off the ground, we’d try community-based recruiting methods like tabling drives at the gym across the street from our lab, but now viral coverage is the most effective way to get a lot of attention and ultimately, prospective donors in the door. We pay our donors $40 a sample to reimburse them for the headache of coming in here and subjecting themselves to our screening and collection protocols.”

“It’s been really impressive how the GI community has harnessed the microbiome and taken ownership over opportunities to engineer and manipulate the microbiome to improve many aspects of health,” said **James Burgess.**

**Research:** In addition to providing safe access to FMT, OpenBiome is committed to catalyzing microbiome research, and is currently supporting 14 enrolling clinical trials and helping to develop 35 other trials across numerous indications.

Since OpenBiome — the first nonprofit public stool bank — launched in 2012, it has provided fecal microbiota transplantation preparations to treat more than 13,000 patients with recurrent Clostridium difficile infection.

CDI is the most common microbial cause of health care-associated infections in U.S. hospitals, affecting about 450,000 patients per year, of whom nearly 30,000 die within 30 days, according to recent statistics from the CDC. However, one in five patients with CDI do not respond to antibiotics.

Recently, FMT has emerged as a highly effective treatment for recurrent CDI, with 80% to 90% success rate, and thus, OpenBiome’s mission has been to provide safe access to FMT and catalyze microbiome research.

The team at OpenBiome welcomed Healio Gastroenterology to their facility in Somerville, Mass., just outside of Boston, where we had the opportunity to speak with Carolyn A. Edelstein, MPA, OpenBiome’s director of policy and communications, Zain Kassam, MD, MPH, FRCPC, OpenBiome’s chief medical officer, and co-founders James Burgess, and Mark Smith, PhD, who was recently named to Forbes ‘30 Under 30’ for Science.

“At this point, we work with over 800 medical facilities in the U.S. in all 50 states, and our last mapping assessment showed that close to 99% of the population is within a 4-hour drive of a provider, and about 97% are within a 2-hour drive of a provider,” Edelstein said.

This rapid expansion of OpenBiome has contributed to the organization’s ability to set the standard for safety in FMT, she explained.

“The scale we’ve achieved — having provided more than 20,000 treatments so far — allows us to be far more conservative than providers and patients could accomplish on their own. Between our screening process, which eliminates about 97% of candidates ... and our GMP [Good Manufacturing Processes] lab, we can bring a heightened level of rigor to the quality of the material.”

Despite the high success rate and rigorous safety protocols, several barriers to FMT access remain, all of which OpenBiome is working to address.

“At conferences, we hear about all kinds of barriers clinicians face when trying to bring an FMT program into their hospital, but at least patients are now within striking distance of an FMT provider,” Edelstein said.

One such barrier is that “the regulatory environment still contains some uncertainties,” she explained. “In May 2013, the FDA announced that FMT will be regulated like an investigational drug, so it would need to be performed in clinical trials registered with the agency. There was pushback at that announcement, with medical societies and practitioners arguing that it would be overly restrictive for patients with recurrent CDI, given available evidence on safety and efficacy. Clinical guidelines from gastroenterology and infectious disease societies in the U.S. and abroad have recommended FMT for patients who have failed two or more rounds of antibiotics. Two months later, the FDA issued the current prevailing guidance, which says that to treat CDI that’s not responsive to standard antibiotics, you can use FMT outside of a clinical trial framework as long as you obtain informed consent. Still, some sites struggle with whether or not to allow the investigational treatment without an IRB or without an [investigational new drug designation].”

Another barrier is variation in protocols, Edelstein said. “We are working on developing protocols for hospitals that they can adapt for their purposes. It can take a long time to build up a program, and we sit at the center of 800 medical facilities who have already solved these problems, so we’re consolidating best practices and we’ll be sharing a protocol soon.”