Providing health reports on an individual’s specific diseases and conditions, carrier status, health risks and drug responses are medical device uses, requiring either premarket approval or 510(k) clearance, FDA tells the Personal Genome Service testing provider 23andMe Inc. in a Nov. 22 warning letter.

“We have become aware that you have initiated new marketing campaigns, including television commercials that, together with an increasing list of indications, show that you plan to expand the PGS’s uses and consumer base without obtaining marketing authorization.

“Therefore, 23andMe must immediately discontinue marketing the PGS until such time as it receives FDA marketing authorization” the agency writes to 23andMe in the warning letter.

Consumers can purchase a saliva sampling kit online from 23andMe for $99 and mail in the sample for analysis of a broad range of genetic traits, including risk status for various diseases and drug-response information.

The company launched a national TV ad campaign for its Personal Genome Service test kit Aug. 5. 23andMe told “The Gray Sheet” at the time that it had submitted a 510(k) to FDA in 2012, and as of the summer of 2013 was “continuing to work together with the FDA towards that goal.”

At the time, FDA’s Director, Office of In Vitro Diagnostics and Radiological Health, Alberto Gutierrez said he was aware of, and reviewing, the firm’s activities. (See Also see "23andMe Launches TV Ad Campaign For DTC Gene Testing Service While Seeking 510(k)" - Medtech Insight, 12 August, 2013..)

“Even after these many interactions with 23andMe, we still do not have any assurance that the firm has analytically or clinically validated the PGS for its intended uses, which have expanded...,” the warning letter says.

But in the Nov. 22 warning letter, Gutierrez says that the 510(k)s submitted July 2, 2012 and Sept. 4, 2012, “failed to address the issues described during previous interactions with the Agency or provided the additional information identified…”

Further, the director notes, “As part of our interactions with you, including more than 14 face-to-face and teleconference meetings, hundreds of email exchanges, and dozens of written communications, we provided you with specific feedback on study protocols and clinical and analytical validation requirements, discussed potential classifications and regulatory pathways … and discussed potential risk mitigation strategies.

“…However, even after these many interactions with 23andMe, we still do not have any assurance that the firm has analytically or clinically validated the PGS for its intended uses, which have expanded…,” Gutierrez says.

In its Nov. 25 response to queries about the warning letter, 23andMe responds: “We recognize that we have not met the FDA’s expectations regarding timeline and communication regarding our submission. Our relationship with the FDA is extremely important to us and we are committee to fully engaging with them to address their concerns.”

Company CEO Anne Wojcicki also addressed the situation in a Nov. 26 blog post on the company’s website. “This is new territory for both for 23andMe and the FDA,” Wojcicki wrote. “This makes the regulatory process with the FDA important because the work we are doing with the agency will help lay the groundwork for what other companies in this new industry do in the future.”

FDA first sent a letter in 2010 to 23andMe similarly noting that the firm did not have a PMA approval or 510(k) clearance for its services, despite what appeared to be medical claims on its website. That earlier letter was part of a broader effort by the device center to contact direct-to-consumer genetic testing firms and inform them of their regulatory responsibilities. (See Also see "FDA To Regulate Direct-To-Consumer Genetic Tests" - Medtech Insight, 14 June, 2010..)

Broader Message Or Targeted Enforcement?

The warning letter was particularly strongly-worded, observers suggested.

“The FDA is clearly frustrated with 23andMe’s failure to cooperate,” said Marcy Darnovsky, director of the Center for Genetics and Society. “The public agency charged with protecting public health has finally lost patience with a private company that seems to think it doesn’t have to play by the rules.”

But the letter has implications that go beyond 23andMe, suggested Bradley Merrill Thompson, an FDA attorney with Epstein, Becker and Green.

“The 23andMe warning letter is as much a guidance document as it is a warning letter,” Thompson said in an interview. “I think it was deliberately written to start putting companies on notice to where FDA is planning to draw the line … [on] the difference between disease and wellness,” he explained.

“I think it was deliberately written to start putting companies on notice to where FDA is planning to draw the line … [on] the difference between disease and wellness” – attorney Bradley Thompson

“That said, we really still need that guidance, because there’s a ton of very nuanced details about whether something is truly a disease, or wellness.”

For example, Thompson explains, the agency and industry could argue over advice on cholesterol, and in FDA’s mind, “managing a cholesterol level, is disease management,” while others could look at managing cholesterol and say: “Well, you are just trying to manage your overall health.”

FDA recently listed a guidance on “general wellness topics” as among ones that it could get to drafting in fiscal year 2014 if resources permit. (See Also see "510(k) Program, Companion Dx Among Top FDA Guidance Priorities For FY 2014" - Medtech Insight, 8 November, 2013..)

But Sheila Walcoff, principal at the personalized-medicine consultancy Goldbug Strategies LLC, said that while the letter from FDA will certainly serve as a “warning” to other DTC genetics companies, it also reads like a “very targeted response resulting from a series of factors that are likely atypical in regulatory compliance interactions.”

The letter may provide some insight into FDA’s thinking into the direct-to-consumer space, but “I do not believe that FDA would consider it a reliable ‘guidance’ for other areas, such as clinical information tools (used by physicians) or clinical laboratory testing itself.”

Specific Health Claims

23andMe, which has generated popularity through its own marketing and its pedigree (it is financially backed by Google), might be a particularly high-profile target for FDA to use to attract others’ attention, Thompson suggested.

The 23andMe warning letter alerts the industry, “They said it – and the rest of us now have that as guidance, and if we didn’t know it, we certainly know it now,” he notes.

Among the 23andMe marketing claims made for its PGS that FDA cites in the warning letter:

Health reports on 254 diseases and conditions, including carrier status, health risks and drug responses
Providing the “first step in prevention” and enabling users to “take steps toward mitigating serious diseases” including diabetes, coronary heart disease and breast cancer
Assessments for breast cancer-related genetic risk (BRCA) and drug responses, e.g., warfarin sensitivity, clopidogrel response and 5-fluorouracil toxicity

Gutierrez says in the letter that some of the personal genome service’s intended uses “are particularly concerning,” because of the potential health consequences resulting from false positive or false negative assessments for high-risk indications.

“For instance, if the BRCA-related risk assessment for breast cancer or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk,” he states.

Gutierrez asks 23andMe to notify FDA within 15 working days from Nov. 22 of “specific actions you have taken to address all issues noted...,” and warns that failure to do so could result in seizure, injunction and civil money penalties.

FDA Comes Down Hard On 23andMe, Putting Consumer-Directed Genetic Testing On Notice

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