23andMe is not a traditional diagnostics company. Rather than seeking to directly sell its services to health care professionals, 23andMe went straight to the consumer, offering genetic screening and analysis in a mail-order fashion. For ninety-nine dollars, customers only needed to send in a saliva sample and the company would analyze the customer’s genetic information, interpret and report the results directly to the consumer, bypassing the physician or genetic counselor.

In November of 2013 the U.S. Food and Drug Administration sent 23andMe a warning letter instructing the company cease offering its services as a predictive genetic test. The FDA advised that the test was considered a medical device and thus, was being offered without regulatory clearance or approval. The FDA’s letter stated in part:

“This product is a device within the meaning of section 201(h) of the FD&C Act, 21 U.S.C. 321(h), because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body. For example, your company’s website at www.23andme.com/health (most recently viewed on November 6, 2013) markets the PGS for providing “health reports on 254 diseases and conditions,” including categories such as “carrier status,” “health risks,” and “drug response,” and specifically as a “first step in prevention” that enables users to “take steps toward mitigating serious diseases” such as diabetes, coronary heart disease, and breast cancer. Most of the intended uses for PGS listed on your website, a list that has grown over time, are medical device uses under section 201(h) of the FD&C Act. Most of these uses have not been classified and thus require premarket approval or de novo classification, as FDA has explained to you on numerous occasion.

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. Assessments for drug responses carry the risks that patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment. For example, false genotype results for your warfarin drug response test could have significant unreasonable risk of illness, injury, or death to the patient due to thrombosis or bleeding events that occur from treatment with a drug at a dose that does not provide the appropriately calibrated anticoagulant effect. These risks are typically mitigated by International Normalized Ratio (INR) management under a physician’s care. The risk of serious injury or death is known to be high when patients are either non-compliant or not properly dosed; combined with the risk that a direct-to-consumer test result may be used by a patient to self-manage, serious concerns are raised if test results are not adequately understood by patients or if incorrect test results are reported.”

Shortly after receiving the FDA’s Warning Letter, 23andMe revised the way in which it marketed its test. Rather than offering its services for “genetic analysis”, 23andMe’s web site then characterized its test as “ancestry-related genetic reports and uninterrupted raw genetic data only.” The web site goes on to report that “[w]e intend to add some health-related genetic reports in the future once we have a comprehensive product offering. At this time, we do not know which health reports might be available or when they might be available.”

That time is now, at least for one particular inherited disorder. On February 19, 2015, the company received notice from the FDA that it may offer its test for Bloom Syndrome – a rare inherited genetic disorder. Individuals suffering from the disease are small in stature and have an increased risk of developing any one or more of several diseases such as diabetes, chronic obstructive pulmonary disease (COPD), recurrent infections of the upper respiratory tract and cancer. The FDA stated that it was was classifying carrier screening tests such as the Bloom Syndrome test as class II and that it intends to exempt these devices from FDA premarket review. The agency also will issue a notice announcing its intent to exempt these tests and that a 30-day period will be provided for public comment.

The FDA noted that 23andMe had performed two separate studies to demonstrate the accuracy of its tests (using a total of 123 samples, including some with the disease), along with a 295-person usability study and a study of 302 randomly recruited participants to show that the tests were easy to follow and understand.

FDA’s decision is interesting in light of recent controversy over the agency’s proposed regulation of high risk laboratory developed tests (“LDTs”), reviewed in my prior posts of October 6, 2014; September 23, 2014; and August 4, 2014. Here, FDA determined that 23andMe’s test for Bloom Syndrome was not in fact a medical device requiring a licensed practitioner to interpret the test results. In addition to having evidence of the accuracy and validity of the test, there is no specific therapeutic consequence associated with a positive result for Bloom Syndrome. For example and in contrast to a test for BRCA1/2 mutations, a patient receiving a positive result for having a high risk BRCA1/2 mutation has several readily available therapeutic interventions, e.g., prophylactic surgery, chemoprevention, intensive screening, while a false negative could result in a failure to recognize an actual risk that may exist. Thus, the Bloom Syndrome test is not a “high risk” test that may require increased regulatory oversight.

Nevertheless, FDA’s action signals a commitment to a risk-based approach, with lower risk devices requiring little or no regulatory oversight.