	Introduction

In vitro diagnostic (IVD) devices, including genetic tests, provide information that is used to inform health care decision making. Federal oversight of IVDs spans several federal agencies, including the Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS). The use of an IVD companion diagnostic device to select the best therapy, at the right dose, at the correct time for a particular patient is often referred to as personalized medicine. Traditionally, most genetic tests have not been subject to premarket review by the FDA. It has been noted that, in the past, genetic tests were developed mostly by academic or research laboratories primarily for in-house use—tests referred to as laboratory-developed tests (LDTs)—to diagnose rare diseases and were highly dependent on expert interpretation. In recent years, LDTs have been developed to assess relatively common diseases and conditions, such as various cancers. The extent to which all LDTs should be regulated by the FDA has been a subject of debate. On July 31, 2014, the FDA officially notified the Senate Committee on Health, Education, Labor and Pensions and the House Committee on Energy and Commerce that it would be issuing draft guidance on LDT regulation; on October 3, 2014, the agency published a notice in the Federal Register announcing the availability of the guidance documents and requesting comments within 120 days to ensure their consideration in the development of final guidance. The agency announced in November 2016 that it would be delaying finalization of the draft guidance. In January 2017, FDA released a discussion paper on LDTs that included a possible approach to LDT oversight (for more detail, see " FDA's January 2017 Discussion Paper: A Possible Approach to LDT Oversight "). Genetic testing has become increasingly available for direct purchase by consumers, generally over the Internet. This report provides an overview of federal regulation of IVDs by FDA, through the Federal Food, Drug, and Cosmetics Act (FFDCA) and the Public Health Service Act (PHSA), and by CMS, through the Clinical Laboratory Improvement Amendments (CLIA) of 1988. FDA's Authority to Regulate In Vitro Diagnostic (IVD) Devices

IVDs that are used in the clinical management of patients generally fall under the definition of medical device and therefore are subject to regulation by the FDA. The FDA derives its authority to regulate the sale and distribution of medical devices from the Medical Device Amendments of 1976 (MDA, P.L. Commercial Test Kits vs. Examples include tests for infectious disease, blood glucose tests, and pregnancy tests. FDA regulation "addresses the safety and effectiveness of the diagnostic tests themselves and the quality of the design and manufacture of the diagnostic tests." Agency Activity

On July 31, 2014, the agency officially notified Congress of its intent to begin regulating LDTs in fulfillment of a statutory requirement in the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA, P.L. In the lead paragraph of the discussion paper, the agency states that it would not be issuing "a final guidance on the oversight of laboratory developed tests (LDTs) at the request of various stakeholders to allow for further public discussion on an appropriate oversight approach, and to give our congressional authorizing committees the opportunity to develop a legislative solution." On the other hand, some representatives of clinical laboratories and manufacturers of LDTs, such as the American Clinical Laboratory Association (ACLA), have asserted that LDTs should be outside of the FDA's regulatory purview. In June 2010, FDA announced it would hold a public meeting the following month to allow stakeholders the opportunity to discuss the agency's decision to exercise its regulatory authority over all LDTs. Section 1143 of FDASIA 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." The framework generally identifies classes of LDTs that will be (1) exempt from regulation entirely; (2) only required to meet registration and listing (or notification) and adverse event reporting requirements; and (3) required to meet registration and listing (or notification), adverse event reporting, applicable premarket review (PMA or 510(k) notification), and quality system regulation requirements. Once classification has taken place, the FDA will enforce premarket review requirements, prioritizing the highest risk class III tests. The agency anticipates the entire process of bringing all LDTs into compliance will take nine years to complete.
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 would 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 would 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 would classify LDTs, based on risk, using information obtained through the notification process. Next FDA would enforce premarket review requirements, prioritizing the highest-risk tests. Bringing all LDTs into compliance was estimated to take nine years.
However, in November 2016 the agency announced it will be delaying finalization of the guidance indefinitely "to allow for further public discussion on an appropriate oversight approach and to give our congressional authorizing committees the opportunity to develop a legislative solution." In January 2017, FDA released a discussion paper on LDTs that included a possible approach to LDT oversight.