The FDA has announced its decision to grant a de novo application submitted by 23andMe for the company's direct-to-consumer (DTC) Personal Genome Service Genetic Health Risk ("GHR") tests. The GHR test panel currently includes genetic variants correlating with increased risk for ten serious and complex disorders, among them late-onset Alzheimer's disease and Parkinson's disease.[1]

23andMe's GHR tests are the first DTC genetic tests authorized by FDA that provide individuals with information about their own risk of disease. In 2015, FDA authorized DTC carrier testing for specified autosomal recessive conditions, but such tests offer information about potential disease risk in an individual's offspring and do not inform the individual's own personal health status.

The decision to grant 23andMe's application, announced by the agency in an April 6 press release, is a significant step for FDA, which historically has questioned the accuracy of some DTC genetic tests and has raised concerns about consumers' ability to understand the information that the tests provide. In 2010, Dr. Jeff Shuren, Director of the Center for Devices and Radiological Health (CDRH), presented testimony to Congress highlighting the potential for consumers to make adverse medical decisions based on the results of DTC genetic tests and stressing the need for increased FDA oversight.

While FDA has asserted that the GHR tests are not "diagnostic," the results of such tests, in combination with other medical or family history information, can be the basis for medical diagnosis by healthcare providers. And while risk mitigation measures and treatments are available for some of the diseases in the GHR panel, for others, such as Alzheimer's disease, there currently are no proven means to reduce risk or to cure the disease.

FDA authorized marketing of the GHR tests through the de novo review process. This pathway permits low and moderate risk medical devices that are ineligible for the 510(k) premarket notification pathway − because there is no "predicate" device to which they are substantially equivalent − to gain marketing authorization without the need to submit a premarket approval application (PMA). According to the press release, FDA does not intend to require 23andMe to obtain premarket review before offering additional tests to the GHR panel.

Authorization for 23andMe's GHR tests was supported by a user study demonstrating that the information was understandable and easy to use for consumers. According to the press release, 23andMe's user study indicated that people using the tests understood more than 90 percent of the information presented in the reports. Other companies seeking to market DTC genetic health tests would similarly be required to show that consumers can understand the results of their tests.

Now that FDA has granted the de novo application, the agency will publish a classification regulation in the Federal Register for the general category of device, although the press release does not make the timing of such publication clear. Subsequent applicants may use this classification, and foreseeably may seek to rely on 23andMe's GHR test as a "predicate" in their 510(k) premarket notification submissions for the purposes of  demonstrating substantial equivalence. FDA will also establish special controls − a set of criteria that must be met to ensure the tests' accuracy, reliability  and clinical relevance.

Other than requiring companies to show that the test results are understandable, it is unclear what specific special controls FDA will require for this new class of genetic tests, since the classification order to 23andMe has not yet been made publicly available. In the case of FDA's 2015 de novo classification order for 23andMe's Bloom Syndrome carrier test, and the agency's subsequent issuance of a classification regulation covering "autosomal carrier screening gene mutation detection systems," special controls included the requirement to provide potential customers and test recipients with information about pre and post-test genetic counseling; the use of an FDA-compliant specimen collection device; the inclusion of specified warnings and limitation statements in labeling; and certain performance specifications, such as demonstrating a high degree of analytical validity and user comprehension.

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[1] The other diseases or conditions covered in the GHR test are 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.