23andMe green light is a shift for FDA

The Federal Drug Administration recently authorized the marketing of a medical device that permits ordinary Americans to gain valuable insight into our genetic predisposition for certain diseases, at home and without a prescription. But in the era of big data, common questions remain - can the data be trusted and what do we do with that information? Much of the FDA's concern with medical technology that provides information about genetics revolves around the latter question.

The April authorization for the genetic health test 23andMe to help determine genetic predisposition for 10 different diseases or conditions represents a dramatic shift in FDA's longstanding policy on consumer-oriented genetic testing. As many may recall, in 2013 FDA sent that same company a warning letter to stop marketing its test on the basis that the results from the test could be inaccurate and therefore required regulatory approval. In contrast to four years ago, along with the current approval, FDA now states the agency intends to authorize similar tests in the future but without premarket review.

The "23andMe Personal Genome Service Genetic Health Risk" test works by isolating DNA from a saliva sample which is then assayed for genetic variants. According to the labeling, the presence or absence of certain variants is believed to be associated with the risk for developing the following 10 diseases or conditions: Parkinson's disease, late-onset Alzheimer's disease, celiac disease, Alpha-1 antitrypsin deficiency, early-onset primary dystonia, factor XI deficiency, Gaucher disease type 1, glucose-6-phosphate dehydrogenase deficiency, hereditary hemochromatosis and hereditary thrombophilia.

Although testing positive or negative for these variants can provide individualized clues regarding a person's propensity to ultimately develop these diseases, the 23andMe device is not a diagnostic test and the results are not intended to be dispositive as to whether the individual will ultimately develop the disease or condition so they should not be used to inform treatment decisions. For instance, it is not certain that someone will develop Parkinson's disease if they are genetically predisposed to it and, conversely, someone not genetically predisposed to the disease could still develop it. However, because environmental and lifestyle factors often play a significant role in the onset or progression of disease, the results of the test are intended to help make decisions about these everyday choices.

FDA reviewed the 23andMe device through its maturing de novo program - a path to market reserved for those devices that are not high risk and not comparable to other legally marketed class II devices. The de novo program has the potential to introduce innovative, game-changing technologies to the American public since eligible devices are, by definition, novel.

Based on an evaluation of the device's safety and efficacy, the 23andMe test was classified as class II - signifying a moderate level of risk. Contrast that with low risk class I devices such as elastic bandages and tongue depressors or high risk class III devices like implantable pacemakers and automated external defibrillators (AEDs). By virtue of the class II designation, the 23andMe test can be leveraged by other companies as a comparator to market similar devices via the 510(k) program which requires a determination of substantial equivalence as opposed to the more demanding safety and efficacy standard.

For class II devices, the agency establishes specific requirements, or special controls, that must be met prior to commercialization in order to mitigate the risks to health. Two central risks of the 23andMe test identified by FDA are incorrect test results (false negatives and false positives) and incorrect understanding of the device and test system. That is, in addition to the technical concern that the test will not provide accurate results, there exists an operational concern that users will treat the test result as a diagnosis and take potentially harmful action based on that belief.

To address concerns regarding the device's ability to properly indicate a genetic predisposition to the diseases, 23andMe provided information to support the clinical performance of each variant reported by the test. Specifically, the FDA was provided with peer-reviewed, scientific literature demonstrating a link between specific gene variants and each of the 10 health conditions, as well as studies that demonstrated 23andMe test correctly and consistently identified these variants.

The concern regarding how users interpret and make use of the information is, however, quite complicated and therein lies the significance of FDA's recent decision. In the 2013 warning letter, FDA asserted that the company's genetic test required review because the implications of the consumer's reactions to the results of the test such as prophylactic surgery, chemoprevention or other morbidity-inducing actions. FDA resolved this perceived issue by imposing special controls on the 23andMe test that require the device's labeling to state the limitations of the test and the important role of a healthcare professional.

Now that the FDA has reviewed the data concerning the test and determined that the risks can be properly mitigated through controls, the agency is faced with determining whether premarket review of future tests for these indications is warranted or whether review could be limited or avoided altogether through special controls. This is a critical decision for FDA and industry alike for slightly different reasons. For FDA, an agency with a mission to protect the public health, it is a broad declaration that the test is safe and carries some level of efficacy for their intended use. For industry, any reduction of regulatory burden translates directly to reduced costs and speedier time to market.

Premarket review and compliance with special controls are distinct aspects of marketing a medical device and manufacturers must nevertheless comply with special controls and other regulatory requirements even if the FDA elects to forego or truncate premarket review. Moreover, FDA can mandate additional special controls if new information suggests they are required for public health, so in order to facilitate innovative devices to market, FDA may exempt certain genome kits from premarket review with the understanding it can apply additional requirements postmarket if warranted.

Since the original 23andMe test that was subject to the 2013 FDA warning letter offered genetic services for more than 250 diseases and conditions, it's reasonable to expect that 23andMe will expand the types of genetic screening offered. FDA and the manufacturer may have negotiated these first 10 indications as probes to assess how users will respond to the personalized genetic information based on the factors related to the diseases such as the epidemiology, ability to be clinically diagnosed and the side effects of current treatment options. How users incorporate the information provided by the test into their personal health decision-making could dictate the level of oversight FDA will apply to in-home genetic tests going forward. Speculating further, given the Trump administration's stated desire to create a regulatory environment that fosters business development and market competition, we should expect other companies to take advantage of the trail blazed by 23andMe.