The FDA has authorized the marketing of the first direct to consumer (DTC) genetic health risk reports, offered by 23andMe, a California corporation offering genetic testing services. These are their Personal Genome Service Genetic Health Risk (GHR) products. The company describes the tests:
A genetic health risk report offers customers the opportunity to see whether they have genetic variants that increase their chances of developing certain health conditions. Not everyone with a risk variant will develop the health condition. And for most of these conditions, not having a genetic variant does not eliminate the risk of the health condition.
The FDA described the approval of the tests:
The U.S. Food and Drug Administration today allowed marketing of 23andMe Personal Genome Service Genetic Health Risk (GHR) tests for 10 diseases or conditions. These are the first direct-to-consumer (DTC) tests authorized by the FDA that provide information on an individual’s genetic predisposition to certain medical diseases or conditions, which may help to make decisions about lifestyle choices or to inform discussions with a health care professional.
The FDA reviewed data for the 23andMe GHR tests through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device. Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the tests’ accuracy, reliability and clinical relevance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for these and similar GHR tests.
In addition, the FDA intends to exempt additional 23andMe GHR tests from the FDA’s premarket review, and GHR tests from other makers may be exempt after submitting their first premarket notification. A proposed exemption of this kind would allow other, similar tests to enter the market as quickly as possible and in the least burdensome way, after a one-time FDA review.
The FDA requires the results of all DTC tests used for medical purposes be communicated in a way that consumers can understand and use. A user study showed that the 23andMe GHR tests’ instructions and reports were easy to follow and understand. The study indicated that people using the tests understood more than 90 percent of the information presented in the reports.
The Federal Trade Commission has published consumer protection materials relevant to purchasing DTC testing products. 23andMe has had a number of regulatory encounters with the FDA over the last several years (see earlier post here), and is slowly achieving more official recognition of their health-related testing products. However, the DTC dimension of these products is still a source of professional concern and caution among genetics professionals (see here).
Market reception for these products will indicate whether a cohort of consumers develops which can be studied for their use and satisfaction with these testing services.
In a move that will significantly impact the field of genetic testing, the FDA has notified Congress that it intends to issue a formal draft guidance that will detail the agency’s plan for formal regulation of laboratory-derived tests (LDTs). LDTs are biochemical or genetic tests that are offered as services by commercial laboratories, whether to medical personnel or directly to consumers (DTC). Over the years, the FDA has sent mixed signals over its regulatory posture for these tests, which constitute the majority of commercially available genetic tests offered in the U.S. (an estimated 11,000 tests offered by 2,000 laboratories). Now, in letters sent to the Senate Committee on Health, Education, Labor and Pensions and the House Committee on Energy and Commerce, the FDA announced that the draft guidance, Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs), will be published within 60 days. The FDA defines LDTs as medical devices, falling within the subset of devices known as in vitro diagnostics (IVDs). As medical devices, the LDTs are subject to the agency’s existing authority under the 1976 Medical Device Amendments (MDA) to regulate such items. To date, the FDA has asserted that it exercised “enforcement discretion” for LDTs – which generally meant no regulation. That will now change. The FDA will design a risk-based classification system for LDTs (Class I-III), which parallels the existing medical device regulatory structure. For the highest-risk LDTs (Class III), the FDA will require premarket approval, phasing that requirement in over four years, while existing tests stay on the market. Moderate-risk LDTs (Class II) will be subject to registration, listing and adverse reporting requirements. The FDA will regard companion diagnostic tests, genetic tests that are used in tandem with an approved therapeutic drug to assess patient suitabiltity (e.g., the genetic test for the HER-2 gene that determines whether Herceptin should be administered to breast cancer patients) as high-risk Class III devices. The FDA describes the factors that will be used to assess LDT risk and classification:
FDA will rely upon the existing medical device classification system to evaluate the risk of a category of LDTs and, informed by the industry’s expressed interest in participating in the discussion of the classification process, will use expert advisory panels to help classify devices not previously classified by FDA, as appropriate. In determining the risk an LDT poses to the patient and/or the user, FDA will consider several factors including whether the device is intended for use in high risk disease/conditions or patient populations, whether the device is used for screening or diagnosis, the nature of the clinical decision that will be made based on the test result, whether a physician/pathologist would have other information about the patient to assist in making a clinical decision (in addition to the LDT result), alternative diagnostic and treatment options available to the patient, the potential consequences/impact of erroneous results, number and type of adverse events associated with the device, etc.
Risk will correlate with the likelihood that a genetic test result will deliver information that will be used by a patient to make significant medical decisions (e.g., as illustrated by a BRCA1/2 genetic test result that some patients rely on to elect prophylactic mastectomy based on breast cancer risk). Although the FDA’s move is not a complete surprise, it will significantly alter the business landscape for the LDT genetic testing industry as it contends with formal approvals and regulatory compliance measures for lab tests that have been or will be developed. Not all stakeholders are pleased with the FDA decision. The American Clinical Laboratory Association (ACLA) represents the nation's leading providers of clinical laboratory services and filed a citizen petition in 2013 with the FDA, asking it to refrain from imposing new regulations on LDTs, asserting that existing regulations are adequate; the FDA denied the request. Just last month, a coalition of academic lab directors filed a statement of opposition with the Office of Management and Budget (OMB), disputing the FDA’s jurisdiction and alleging that new regulations on LDTs would stifle the innovate environment that has produced the thousands of LDTs already available. The FDA will proceed on its schedule, as announced, and public comments will be sought and public hearings will be held. The industry was braced for the FDA's action: a leading genetic test provider, 23andMe, had already anticipated the FDA moves and initiated its own regulatory relationship with the agency.
The FDA has approved a rapid, in-home test for Human Immunodeficiency Virus (HIV), the virus that causes AIDS. This is an approval of the premarket approval application (PMA) by the FDA's Center for Biologics Evaluation and Research, which oversees the review of devices that involve the use of a biologic reagent. This is the first in-home test for HIV infection that produces immediate results, and will be sold over the counter (OTC) by pharmacies. The single-use test, OraQuick, detects antibodies to viral strains HIV-1 and HIV-2, and allows an individual to take an oral swab (no blood required) and receive results at home in 20-40 minutes. The package insert instructs users that this test be a predicate to confirmation by a physician. This is the first at-home test for an infectious disease, and the need (and potential market) for such a test is supported by HIV statistics from the CDC, which suggest that at least 20% of those infected with HIV are unaware of their status. Several developments in the last several decades suggest that this test might be useful to some who suspect possible HIV infection – decreased stigma over HIV-positive status, coupled with the availability of more effective antiviral treatments. However, the cost of the test will be over $17.50 (current price to clinics), which will be pricey for many, and, furthermore, to note that antiviral regimens for HIV have improved over time does not mean that access to treatment is universal. The test is only approved for sale to those 17 and older, and pharmacies may screen for verified age in selling the product. There are other FDA-approved HIV home tests available, but they require sending a sample to a laboratory. While this test expands options for those at risk of HIV infection, it is a relatively straightforward application of long-existing technologies; the FDA resisted the approval of other HIV home test applications for years. The CDC estimates that approximately 50,000 people are newly infected with HIV each year in the United States. Although some of the stigma associated with HIV has decreased, there is still a visible effort to encourage testing for high-risk groups (or those engaged in high-risk behaviors); National HIV Testing Day was just observed on June 27 of this year.
