FDA Warnings Shed Light on Theranos' Problems

FDA inspection documents describe the young blood testing company's nanotainer as an "uncleared medical device."

Chris Newmarker and Brian Buntz

Theranos' woes continued to mount on Tuesday, with new evidence of just how much FDA has been pressuring the company to validate what it claims is cutting-edge blood-testing technology.

FDA inspection reports to the multibillion-dollar Silicon Valley-based company and to its founder and CEO Elizabeth Holmes describe the company's capillary tube nanotainers for collecting blood from finger pricks as an uncleared Class II-device, versus a Class I-device as claimed by Theranos.

The Form 483 reports, from inspections conducted in late August and early September, also list a host of other observations: design validation problems, inadequate documentation of design inputs, inadequate procedures for handling complaints, complaints not being investigated where necessary, corrective and preventative actions not being documented, not documenting software validation activities, not documenting evaluation of potential suppliers, not adequately establishing records of acceptable suppliers, not adequately establishing procedures for device history records, and not performing quality audits.

The Wall Street Journal claims the reports confirm what the newspaper had previously reported, citing a "person familiar with the inspection," that Theranos stopped using the vials for all but one test under pressure from FDA.

Theranos responded that none of the observations in the two Form 483s pertain to Theranos' analytical devices or chemistries, or the manufacturing infrastructure.

'All observations were specific to the nanotainers operating under the CLIA lab quality framework. The correction to the observations was to cut over to the FDA Quality Systems framework," Theranos said in a statement shared with Qmed.

Said Theranos: "We believe that we addressed and corrected all the observations at the time of, or within a week of, the inspection and have submitted documents to FDA that say so, including extensive documentation, as well as outlining our path to the whole QSR transition going forward. Their observations are, by their very nature, preliminary and as this is a time of evolving policy, we have advocated for the transition from the LDT framework to the FDA quality systems framework."

Many of the problems listed in the Form 483s are actually very basic mistakes, according to regulatory consultant Mike Drues. "It means the company doesn't have its ducks in a row, so to speak. All of these mistakes could easily be avoided by using competent regulatory professionals, people who understand not only what the regulation says but more importantly what we're trying to do," says Drues, who is president of Vascular Sciences (Grafton, MA).

Jon Speer, founder of Creo Quality and co-founder of greenlight.guru (Indianapolis, IN), has a similar take. "These issues are all too common from many medical device companies--not just startups," Speer says. "I'm noticing an increasing and alarming trend that there is a huge misconception about getting FDA 510(k) market clearance without the company documenting Design Controls and Risk Management and establishing a QMS."

"It's clear from the 483 observations issued that the company had some major systemic breakdowns," Speer says. "Establishing and following a quality management system per FDA 21 CFR part 820 is required and just makes good business sense for medical device companies. These observations also emphasis how important it is to establish and document Design Controls and Risk Management."

The news about the inspection reports comes on the heels of a WSJ report that Walgreens--a major Theranos partner that uses the company for blood testing in about 40 Arizona Walgreens as well as a Palo Alto, CA, location-- is scrutinizing Theranos' blood testing technology, and has no concrete plans to expand it into more Walgreens pharmacies. Walgreens spokesman Jim Cohn said Monday that Walgreens and Theranos are "currently in discussions about the next phase of our relationship;" Cohn had nothing to add on Tuesday.

For its part, Theranos has been pointing to FDA clearance of its test and system that can detect herpes simplex 1 virus with but a drop or two of blood; it is seeking FDA clearance for additional tests to prove its technology. Holmes even told the New Yorker last year that "FDA's stamp of approval is seen as an indicator of the quality of a product."

Because the Theranos technology is a blood test, FDA clearance was voluntary. Regulation of laboratory developed tests (LDTs) is a gray area, Drues says. "LDTs typically made by hospitals are practice of medicine, something FDA does not regulate."

When asked what medical device professionals could learn from Theranos' woes, Drues recommends that medical device professionals be proactive, seeking a collaborative relationship to identify problems and potential resolutions to them as early as possible. "Lead, don't follow. Tell, don't ask. It's our job to figure out what to do," Drues said. Working with FDA is a highly strategic process, he added.

On Monday evening, the company's CEO Elizabeth Holmes announced that it would be releasing data that it says will support the its accuracy claims for the technology, reported The New York Times.  

Chris Newmarker is senior editor of Qmed and MPMN. Follow him on Twitter at @newmarker.