On March 6, 2018, the US Food and Drug Administration issued an authorization letter to 23andMe, Inc. that permits marketing of the company’s genetic test for use in screening consumers for select BRCA1/BRCA2 breast cancer gene mutations that are most commonly found in people of Ashkenazi (Eastern European) Jewish descent. The test, which goes by the tradename, “Personal Genome Service (PGS) Genetic Health Risk Report for BRCA1/BRCA2 Select Variants,” was reviewed by FDA under its De Novo medical device marketing pathway, which is primarily used to evaluate and classify novel, low risk medical devices for which a reasonable assurance of safety and effectiveness can be established though the agency’s general regulatory controls and/or by the development of device-specific special controls. The device is the first Direct-to-Consumer (DTC) test to detect breast cancer gene mutations that the agency has authorized for marketing. FDA classified the test as a Class II medical device.
As background, FDA’s authorization of the above genetic tests follows the agency’s similar authorization in 2017 of a 23andMe PGS-marketed genetic test intended to help determine genetic predisposition for 10 different diseases or conditions, including the presence or absence of certain variants believed to be associated with the risk of developing Parkinson’s disease, late-onset Alzheimer’s disease, and others. Prior to obtaining FDA authorization, 23andMe received a Warning Letter from FDA in 2013 asking the company to stop marketing the test for over 250 diseases and conditions until it received marketing authorization from the agency. 23andMe subsequently submitted a De Novo application to FDA covering a test for 10 diseases and conditions and received marketing authorization on April 6, 2017. With this latest test, 23andMe is growing its ability to provide information related to genetic mutations directly to consumers.
Similarly, the most recently FDA-authorized 23andMe genetic test analyzes DNA from a self-collected saliva sample, and the genetic health risk report generated by use of the test describes if a woman is at increased risk of developing breast and ovarian cancer. The test can also determine if a man is at increased risk of developing breast cancer or may be at increased risk of developing prostate cancer. The test only detects three out of more than 1,000 known BRCA mutations and the mutations detected by the test are not the most common BRCA1/BRCA2 mutations in the general population. In fact, the mutations occur in approximately only 0.1 percent of ethnic populations other than Ashkenazi Jewish. Thus, a negative test result does not rule out the possibility that an individual carries other BRCA mutations that increase cancer risk.
FDA has noted that the test provides information to consumers who may be at increased breast, ovarian, or prostate cancer risk and who might not otherwise get genetic screening, and is a considered a step forward in the availability of DTC genetic tests. The labeling for the test notes that it should not be used as a substitute for seeing your doctor for cancer screenings or counseling on genetic and lifestyle factors that can increase or decrease cancer risk. Further, consumers and health care professionals should not use the test results to determine any treatments, including anti-hormone therapies and prophylactic removal of the breasts or ovaries, as such decisions require confirmatory testing and genetic counseling. The test also does not provide information on a person’s overall risk of developing any type of cancer.
FDA’s review of the test determined, among other things, that the company provided sufficient data to show that the test is accurate (i.e., can correctly identify the three genetic variants in saliva samples), and can provide reproducible results. 23andMe submitted data on user comprehension studies, using representative test reports, that showed instructions and reports were generally easy to follow and understood by a consumer. The test report generated for the test provides information describing what the results might mean, how to interpret results, and where additional information about the results may be found.
FDA authorization of the test continues the agency’s use of the De Novo authorization pathway for novel devices. The latest user fee agreement between FDA and industry authorized the first fees for the De Novo program. North of $90,000 for standard filers and nearly $25,000 for small businesses, the user fees also establish performance goals that the agency must meet for these types of submissions that were previously not formally tracked when free. In addition, the authorization of another Direct-to-Consumer medical product continues a growing trend towards making affordable, potentially life-saving medical technologies directly available to consumers.