FDA to Formally Regulate Laboratory-Derived Tests; Genetic Tests to be Classified by Risk

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will significantly impact the field of genetic testing, the FDA has notified Congress that it intends to issue a formal draft guidance that will detail the agency’s plan for formal regulation of laboratory-derived tests (LDTs).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on Health, Education, Labor and Pensions and the House Committee on Energy and Commerce, the FDA announced that the draft guidance, Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs), will be published within 60 days.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.