In a warning letter, that expressed frustration as the overwhelming emotion more than anything else, the FDA asked 23andMe, the much-talked about genomics testing company, to immediately stop selling its Personal Genomics Service (PGS) and Saliva Collection Kit.
The letter, dated Nov. 22, narrates the length of time FDA officials have tried to work with the company to bring what the agency deems as diagnostic services under the law.
It acknowledges that 23andMe filed 510(k) applications for the tests but has failed to demonstrate adequately that the tests conform to come predicate device. Aside from that, the firm has also not made additional submissions as the tests have expanded for other indications.
The letter underscores FDA's biggest fear - that inaccurate results such as false positives may lead patients to choose unnecessary procedures while false negatives will lead to inaction on the patients' part.
Some of the uses for which PGS is intended are particularly concerning, such as assessments for BRCA-related genetic risk and drug responses (e.g., warfarin sensitivity, clopidogrel response, and 5-fluorouracil toxicity) because of the potential health consequences that could result from false positive or false negative assessments for high-risk indications such as these. For instance, if the BRCA-related risk assessment for breast 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 that may exist.
It goes on to say:
Since July of 2009, we have been diligently working to help you comply with regulatory requirements regarding safety and effectiveness and obtain marketing authorization for your PGS device. FDA has spent significant time evaluating the intended uses of the PGS to determine whether certain uses might be appropriately classified into class II, thus requiring only 510(k) clearance or de novo classification and not PMA approval, and we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification. Further, we provided ample detailed feedback to 23andMe regarding the types of data it needs to submit for the intended uses of the PGS. 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 (including reasonable submission timelines), provided statistical advice, and discussed potential risk mitigation strategies. As discussed above, FDA is concerned about the public health consequences of inaccurate results from the PGS device; the main purpose of compliance with FDA’s regulatory requirements is to ensure that the tests work.
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 from the uses that the firm identified in its submissions.
In your letter dated January 9, 2013, you stated that the firm is “completing the additional analytical and clinical validations for the tests that have been submitted” and is “planning extensive labeling studies that will take several months to complete.” Thus, months after you submitted your 510(k)s and more than 5 years after you began marketing, you still had not completed some of the studies and had not even started other studies necessary to support a marketing submission for the PGS. It is now eleven months later, and you have yet to provide FDA with any new information about these tests. You have not worked with us toward de novo classification, did not provide the additional information we requested necessary to complete review of your 510(k)s, and FDA has not received any communication from 23andMe since May. Instead, 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 from FDA.
In response to the warning letter, 23andMe, the company backed by Google, issued this statement without challenging any of the agency's conclusions:
We have received the warning letter from the Food and Drug Administration. 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 committed to fully engaging with them to address their concerns.
This is a classic example of technological innovation that appears to have gotten ahead of regulatory concerns. It also shows how FDA officials are trying to balance the need to allow new innovations reaching the market and the requirement to maintain public health.
Earlier this year, FDA slapped a warning letter to another novel diagnostic tool - the uCheck urine analyzer, a smartphone app, but the letter was much shorter, more clipped. In that case, however, the company concerned - Biosense Technologies Private Ltd. - had not even applied for regulatory clearance of any kind.