The US Food and Drug Administration today issued two reports, both of a type called a Form 483, which documented the problems the agency found at Theranos, the notoriously secretive blood testing company. The forms date from an inspection from the period of August 25th to September 16th. In the documents, the FDA observes a number of concerns, including that lots of Theranos' activity hasn't been documented, the design process for one of its devices was inadequate, and that no quality audits have been performed in 2015. "Specifically," the document states, "you have not monitored your Quality Management System through internal quality audits; you had no documented internal quality audit schedule to monitor your Quality Management System until after the start of this inspection."
At least one of Theranos' devices "was not validated under actual or simulated use conditions."In one of the forms, the FDA documented a number of complaints, including that a Theranos device (it's not clear in the form, due to redactions, which one) had a design evaluation that didn't ensure the device "conforms to defined user needs and intended uses." A Theranos spokesperson confirmed that the device referred to in this document is the Nanotainer, which is used to contain the blood samples from a finger prick. Additionally, the Nanotainer "was not validated under actual or simulated use conditions," and the risk analysis for the device hasn't been adequately documented. In another form from the same inspection period, FDA said that there were inadequate procedures for logging customer complaints, and that complaints that Theranos' technology didn't work weren't reviewed or investigated.
Theranos, a privately held company that has been valued at $9 billion, has at least two proprietary technologies: the Edison machine, for analyzing samples, and the Nanotainer device, which is used to contain the blood samples from a finger prick. On October 15th, Theranos announced it would stop using the Nanotainer after the FDA said the device needed regulatory approval. At that time, the company's lawyer, David Boies, told The New York Times that "we haven’t had any indication about a problem of the accuracy of the test." Today's FDA documents suggest that may be in part because there hasn't been a process for complaints, and no complaints appear to have been evaluated by the company.
"The FDA is dealing with Theranos as a device manufacturer," says Stephen Master, chief of clinical chemistry at Weill Cornell Medical College. "Clinical labs are not typically device manufacturers and obviously once you step into the field of being a device manufacturer, then the FDA will look more closely."
This is Theranos' first FDA inspection, according to an emailed statement from the company. "We believe that we addressed and corrected all the observations at the time of, or within a week of, the inspection," Theranos said in an emailed statement. The company has "submitted documents to FDA that say so, including extensive documentation." The statement goes on to say that over 120 tests developed for use with Theranos's devices "have been submitted in pre-submissions to the FDA."
"The FDA is dealing with Theranos as a device manufacturer."
That's not all. The inspection found Theranos hadn't documented the validity of the software for the quality system or of the company's evaluation of potential suppliers. (One supplier, the inspection says, "had no documented approved supplier qualification until after the start of this inspection" but Theranos apparently purchased something — what, specifically, is redacted — for use in July.) Nor had Theranos kept records of acceptable suppliers.
The Form 483 documents notify a manufacturer of objectionable conditions, though it's not an all-inclusive list of every violation. The observations are serious, though — FDA inspectors make them when "conditions or practices observed would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health." The findings are discussed with senior management — and the forms themselves are addressed to Theranos' chief executive officer, Elizabeth Holmes and Ramesh Balwani, the company's president and chief operating officer. Holmes last night compared scrutiny of her company to a witch hunt.
These letters do not represent the FDA's final conclusions of the Theranos' facilities. "These are the thoughts of the inspector at the point in time that they were reviewing their facility," says James Nichols, a pathologist at Vanderbilt University and the government relations committee chair for the American Association for Clinical Chemistry. Depending on how Theranos responds to these letters, the FDA could back off or ask for more data, and even take some sort of action against the company. But that hasn't happened yet. "I just wouldn't over-interpret it," Nichols says. "Let's wait and see what the FDA says; if they walk in and shut Theranos down, then that's something to take note of."
"Let's wait and see what the FDA says."Theranos, founded in 2003 by a then-19-year-old Holmes, has been selling its tests through a legal loophole; not all tests require evaluation by the FDA, provided those tests are manufactured and performed in a single lab. Because Theranos operates this way, it hasn't had to seek FDA approval for its proprietary technology. Today's report stems from the first FDA inspection of Theranos' labs, as the company is trying to transition from its loophole status to FDA's framework, the company said in an e-mailed statement. One test made by Theranos is approved: a herpes test received FDA approval in July. The Nanotainer is still used in this test.
One of Theranos' much-touted partnerships is with the pharmacy chain Walgreens — Theranos operates out of 41 Walgreens stores in California and Arizona. On Friday, The Wall Street Journal reported that Walgreens learned from a WSJ article that only a small fraction of tests performed by Theranos were on their proprietary technology; and that Walgreens hadn't been told Theranos was no longer collecting vials of blood from finger pricks for all but one of its tests until the WSJ wrote about it. Walgreens is now reviewing the partnership, and won't open any new Theranos testing centers until the review is complete.
Last night, Holmes said Theranos would publish data, though she did not say when or where And though several newspaper articles have noted partnerships Theranos has with Pfizer and GlaxosmithKline, Pfizer told the Financial Times that its involvement with Theranos was minimal and GSK denied any partnership existed. "GSK has not done any business with Theranos in the past two years," Mary Anne Rhyne, a spokeswoman for GSK, told The Verge in an email today. We responded by asking if GSK had dealings with Theranos before that period; Rhyne answered that she didn't "have more information to share." A Theranos spokesperson said that Theranos had engaged in clinical trial testing for GSK starting in 2008, but before Theranos opened its retail business.
Last night, Holmes made a public about-face on whether Theranos would publish its data: it would, she told an audience at a Cleveland Clinic conference, though she did not say when or where the data would appear. (Cleveland Clinic is another of Theranos' partners.) Publishing one's data in a peer-reviewed journal is standard practice in the medical industry; Theranos has not done this. Last week, she told The New York Times the company had no immediate plans to publish any data to convince the company's skeptics, and called criticism of the company "a few people who want to say bad things about us."
The Form 483 documents also have attached responses. On the first — regarding the device, which may or may not be the Nanotainer — the inspector said that the company had reported the problems were corrected, though the inspector hadn't verified this. On the second, most responses are that the company "promised to correct" the issues within seven days.
Update October 27, 2:12PM ET: This story has been updated to add statements from Theranos.
Update October 27, 4:13PM ET: This story was updated with a second statement from GSK.