In vitro diagnostic (IVD) devices are used in the analysis of human samples, such as blood or tissue, to provide information in making health care decisions. Examples of IVDs include (1) pregnancy test kits or blood glucose tests for home use; (2) laboratory tests for infectious disease, such as HIV or hepatitis, and routine blood tests, such as cholesterol and anemia; and (3) tests for various genetic diseases or conditions. More recently, a specific type of diagnostic test—called a companion diagnostic—has been developed that may be used to select the best therapy, at the right dose, at the correct time for a particular patient; this is often referred to as personalized or precision medicine.
Federal agencies involved in the regulation of IVDs include the Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS). FDA derives its authority to regulate the sale and distribution of medical devices, such as IVDs, from the Federal Food, Drug, and Cosmetics Act and the Public Health Service Act. CMS’s authority to regulate IVDs is through the Clinical Laboratory Improvement Amendments of 1988. FDA regulates the safety and effectiveness of the diagnostic test, as well as the quality of the design and manufacture of the diagnostic test. CMS regulates the quality of clinical laboratories and the clinical testing process.
Traditionally, most genetic tests have not been subject to premarket review by the FDA. This is because in the past, genetic tests were developed by laboratories primarily for their in-house use—referred to as laboratory-developed tests (LDTs)—to diagnose mostly rare diseases and were highly dependent on expert interpretation. However, more recently, LDTs have been developed to assess relatively common diseases and conditions, thus affecting more people, and direct-to-consumer (DTC) genetic testing has become more available over the Internet. The extent to which LDTs should be regulated by the FDA, in conjunction with CMS, has traditionally been a subject of debate. Some clinical laboratories and manufacturers of LDTs have maintained that LDTs should be outside of the FDA’s regulatory purview. Legislation was introduced in the 110th and 112th Congresses with the aim of clarifying regulatory oversight and supporting innovation.
In June 2010, FDA announced its decision to exercise its authority over all LDTs. A provision in the Food and Drug Administration Safety and Innovation Act of 2012 stipulates that the agency “may not issue any draft or final guidance on the regulation” of LDTs without, “at least 60 days prior to such issuance,” first notifying Congress “of the anticipated details of such action.” On July 31, 2014, in fulfillment of this statutory requirement, the FDA officially notified the Senate Committee on Health, Education, Labor and Pensions and the House Committee on Energy and Commerce that it will issue draft guidance on the regulation of LDTs, and included the anticipated details of that regulatory framework. On October 3, 2014, the FDA formally issued these documents as draft guidance in the Federal Register, giving 120 days for comment.
The draft guidance identifies groups of LDTs that will be (1) exempt from regulation entirely; (2) only required to meet notification and adverse event reporting requirements; and (3) required to meet notification, adverse event reporting, applicable premarket review, and other regulatory requirements. FDA will use the information obtained through the notification requirement to classify LDTs, based on risk, using a public process involving advisory panels and public comment. Once classification has taken place, the FDA will enforce premarket review requirements, prioritizing the highest-risk tests. The agency anticipates the entire process of bringing all LDTs into compliance will take nine years to complete.