One of the unique aspects of Finch Therapeutics is that although its product does not fall easily into any regulated category and thus is not FDA-approved, the company has been working closely with the agency for at least five years. The FDA has broad jurisdiction to regulate all health products, and it also has the freedom to not exercise that authority (enforcement discretion) as it sees fit. This puts Finch in the delicate position of providing a product that is regulated by the FDA, yet isn’t actually bound by any existing regulatory statutes, such as 21 CFR.

Finch is a clinical-stage microbiome therapeutics company dedicated to developing novel microbial therapies to serve patients with serious unmet medical needs. Built on 30 years of translational research at OpenBiome, MIT, the University of Minnesota, the Center for Digestive Diseases, and Crestovo, Finch uses its unique Human-First Discovery approach to develop therapies from microbes that have demonstrated clinically significant impacts on patient outcomes.

At the MasterControl Summit 2018 in Utah, I had the pleasure of sitting down with Kurt Warren, quality systems manager and system administrator of MasterControl at Finch, to discuss what Finch does and how it manages to execute stringent quality assurance protocols when none of the regulations are an exact match for the company’s unusual business model.

Quality Digest: You said Finch’s products primarily target Clostridium difficile (C. diff) infections in patients and are currently involved in research projects targeting inflammatory bowel disease (IBD) and other indications. What are some of the Finch therapies that people would recognize?

Kurt Warren: Our most recognizable treatment/product is the fecal microbiota transplants (FMT) that are distributed by a separate nonprofit company called OpenBiome. A lot of people have heard of them because of articles in  The New York Times and Huffington Post. FMT is processed very minimally and derived from stool that has a very high concentration of microorganisms. So, FMT is designed to leverage those good bugs to repopulate the gut flora in patients to displace the bad bacteria.

QD: And C. diff is the bad bugs?

KW: Right. C. diff is a particularly gnarly bacteria that’s incredibly difficult to get rid of. Treatments right now are primarily Vancomycin and Ciprofloxacin, but they’re not always effective at killing all the bugs.

The caveat, with Vancomycin in particular, is that although they are very effective at killing bugs, they are non-targeted. You’re trying to kill the bad bugs, but there’s a lot of sacrifice to do that. You’re wiping out vast majorities of all bugs, both good and bad. Now, if there’s any bad seed left over, then it can repopulate even more quickly because there’s a lot less of the good bacteria.

QD: How do FMTs with Finch products help?

KW: FMT is not designed to kill the C. diff. The intent is to just repopulate the patient with a tremendous number of healthy bacteria from a healthy person. We’re taking those bacteria from poop with very minimal processing, so we’re not killing off a lot of the good bugs [in the stool]. What we’re trying to put into patients is the entire community of healthy microbes from a healthy person.

QD: So, if your products are not FDA approved, how do you get them to the patients who need them?

KW: Clinicians are only allowed [by the FDA] to treat patients with OpenBiome FMT if those patients are not responding to standard therapy. That’s the circumstance where the FDA has exercised enforcement discretion and where healthcare providers are not required to complete an investigational new-drug application.

QD: And that’s how you find yourselves in FDA’s enforcement discretion category. Your quality control/quality assurance protocols must be pretty stiff to keep the agency happy.

KW: Yes, they’re very robust. We’re constantly improving them, just like any other company, but we’re starting from a very high starting point. We obviously work with the FDA quite a bit, and the microbiome space, in general, is so new that there’s no significant regulations that speak directly to us. So, it’s a lot of analyzing the regulations and really figuring out how it translates to our business model. For example, a blood bank doesn’t follow GMPs necessarily, but we do because we make a treatment. Nonetheless we follow a very similar business model to a blood bank because we have donors that provide us their stool. What I do day-to-day is study the regulations and translate them into what it means for us. Once we get into the manufacturing side of things, it becomes very standard; we have change controls and CAPAs, and all that good stuff, but everything surrounding the donors is very complex.

We really apply risk to everything. So as far the donors go, not only do we screen their stool, we screen their blood. Prospective donors also fill out a questionnaire with something like 150 questions [which must be done with the supervision of a nurse]. The nurses review it, and then MDs will review it. There’s a tremendous amount of control in each step. We’re in Boston, so we always say it this way: It’s easier to get into Harvard than it is to become a stool donor for us; we have a lower acceptance rate!

QD: How does your QMS help you operate in that oddball regulatory and compliance area?

KW: We have a very large quality group, and really what it comes down to is, all changes go through quality, and we have that independent body to really do risk assessments and change management effectively. Our strategy is to have quality’s eyes on absolutely everything to make sure that all changes are worthwhile, and we assess the risk effectively.

It all kind of just falls in line with 21 CFR 211. The FDA doesn’t make regulations specific to one company. There really aren’t too many microbiome companies in general, so it really is picking apart the regulations that do exist and applying them to us. It also comes down to applying risk to make sure that we’re doing everything we can to prevent and mitigate any issues that present themselves.

We operate under this paradigm of enforcement discretion where the FDA is not holding us to the same standard as a commercially FDA-approved drug, but they do establish controls that we need to put in place in order to have our product go into patients.

QD: Now that the FDA is revealing that it’s supplanting 21 CFR 820 with ISO 13485, is that something you guys are looking at?

KW: Currently, we don’t hold ourselves to the medical device regulations, whether it’s ISO 13485 or 21 CFR 820. But we consider those to be relevant in the sense that they have good best practices that we believe we can and should leverage to mitigate any risk.

QD: Is that just being proactive on your part so that when you do get to a point, or when you become FDA approved/regulated, you can say, “This is the approach; this is the logic here?” After all, Finch is a life science pioneer.

KW: Yeah, that’s the standpoint that I’m taking. But we’ve worked with the FDA for five years on this, so they know exactly what we’re doing, and they make recommendations. We also do have a biologics master file that we submit that tells the FDA everything that we do when it comes to our donors and general manufacturing processes and stuff like that.

We are pursuing an FDA-approved product, and there are a few other companies that are doing a similar thing.

Parting thought

The nature of Finch’s business model tends elicit both humor and wonder.

“I’ve heard all the jokes about our treatments and my work with poop,” admits Kurt. “Everyone giggles about it. Then when they learn [how much of our health and well-being is affected by a healthy microbiome], everyone is like, ‘That’s so cool!’ Which it is.”