• FDA goes after 23AndMe. Wow.


    23AndMe is a home genetic test kit that can give you some answers about your DNA. It’s being marketed as a way for people to see if they have certain traits that might be associated with health risks. One of these is an assessment of the BRCA-mutations that might be associated with breast cancer. The FDA is none-too-pleased with this:

    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.

    In other words, the FDA is sorta saying that 23AndMe is going to get women to get treatment, or even a prophylactic mastectomy when one isn’t needed. It appears that this is because the company is ticking them off:

    The Office of In Vitro Diagnostics and Radiological Health (OIR) has a long history of working with companies to help them come into compliance with the FD&C Act. 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 nine 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.

    Overdiagnosis is a real problem. But these are fighting words. Go read the whole thing. There must be quite a story behind all of this.


    Comments closed
    • I’m sure that there is a very interesting back story here which includes the original established purveyor of the BRCA test which was making large profits on its (previously) exclusive ownership of the test. 23andMe is cutting into these profits with an aggressive marketing campaign.
      This reflects the larger problem common to all genetic tests which is that there is very little information for most genes on what to do if you have the gene and that in most cases there is very little that can be done. You end up with a lot of worried people who may not make the best decisions even with medical advice because medical science does not have many good answers.

    • So as the letter says 23andme have been jousting for a while with FDA w/r/t the regulatory clearance process. My guess is the precipitating event was 23andme’s recent all-out national TV ad campaign, which I’m sure did not amuse FDA.

      This strikes me as a fairly typical conflict between Silicon Valley attitudes and regulator attitudes. The Silicon Valley way is to just do it, make mistakes and learn later. Regulations, in this attitude, become something to run into or through rather than negotiated around. (See Uber; or see Larry Page musing that we should have, like, a lawless experimental island where tech companies could just try lots of stuff out.)

      FDA, of course, sees its history as descending from the snake oil salesmen and therefore might take a dim view. The interesting contrast here in terms of FDA’s response is with a company called Biosense Technologies who had released an app called “uChek” — it used a smartphone camera to read urinalysis strips. FDA was super-nice about their warning, probably because an intrepid investigator revealed the company’s regulatory position (and the firm wasn’t exactly flaunting the promotional aspects of FDA rules.) In general the FDA is becoming much more friendly to digital innovation — partially because of Congressional pressure — so I’m sure they’ll be chagrined by the negative press they’re sure to get.

    • A friend said he had thought these tests were exempt from regulation as “homebrew”; I looked it up and found a blog post suggesting the FDA believes this exemption was discretionary on their part and the clinical laboratory industry thinks the FDA has no statutory jurisdiction over them.


      Can anyone comment on whether the ACLA’s interpretation is facially valid or frivolous?

    • I seem to recall there being a similar controversy (although maybe not the same degree of back-and-forth) over home drug testing kits, as well as HIV testing.

      All in all, this looks to be another case of the FDA trying to not only stop directly harmful, defective, or useless treatments from reaching the market, but also trying to stop things that give individuals access to information that they might benefit from under the guise that people are better off ignorant because they might misuse the information. It seems to me there ought to be a very high bar for a federal agency to clear when trying to restrict these sorts of products, and I don’t see anything here that might clear that bar.

    • Sean: the problem isn’t that the kits are “giv[ing] individuals access to information that they might benefit from”. It’s that information from genetic testing can lead to life-changing decisions, and the kits are not giving individuals access to all the information that they need to make those decisions properly. To make those decisions properly, the patients and their doctors need to know how that information was obtained, and most importantly, how accurate it is. The FDA requires the manufacturer of every medical analytical test to report the details of the testing protocol and the accuracy of the results so that people who use the test can have proper context for the results of that test. And in this case, 23AndMe has not provided any of this information, or even shown a good faith intent to provide this information, so the FDA is justifiably pissed off.

    • “but also trying to stop things that give individuals access to information that they might benefit from ”

      The FDA specifically indicated it had concerns with false positives and false negatives. BRCA1/2 mutations are a tiny percentage of the population, so even a nearly perfect test will have the majority of its positives be false, exposing those customers to unnecessary treatment. And false negatives are problematic, too.

      It sounds as though the FDA is on solid scientific ground here.

    • @David:

      -The issue isn’t the accuracy of the sequence-reads generated by 23andMe, it’s that our understanding of the association between particular sequence variants and specific disease states is quite limited. That is – their concern isn’t with the information that people get from 23andMe, it’s what they will do with it.

      Eg.the FDA is concerned that people will spend lots of money and put themselves at risk after learning that they have a variant in a gene that may have an association with an elevated risk for a particular disease – not that 23andMe will send back erroneous sequencing reads.The probability that a random sequencing error will fall into the precise codon associated with a particular gene, and will code for precisely the amino acid associated with a particular mutation is essentially nil. That’s just not a real issue.

      What this comes down to is whether or not a given individual has the right to obtain the information encoded in their own genes or not. The FDA seems to have concluded that that is not the case, and is using assumptions about how the average person will respond to make an argument from “public health” to deny every individual that right.

      A separate question is whether the FDA even has the statutory authority to deny individual access to sequencing data. Evidently they’re declaring that 23andMe is selling an “adulterated product” and asserting the power granted them under the Food, Drug, and Cosmetic Act of 1938 to do so. Here’s to hoping that 23andMe puts that assertion to the test in the courts, and soon.


    • Edit – “Particular mutation associated with a particular mutation known to be associated with a specific disease in a particular gene is essentially nil.”