As the field of genomics advances, genetic and genomic tests are becoming more common in, and out of, the clinic. Yet most genetic tests today are not regulated, meaning that they go to market without any independent analysis to verify the claims of the seller.
Two federal agencies have the primary authority to regulate genetic tests: the Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS). In the past, the Federal Trade Commission (FTC) has also played a role in regulating genetic testing companies who advertised false and misleading claims about their products, but this agency currently plays a more minor role in this space.
Genetic and Genomic tests, like other types of diagnostic tests, can be evaluated and regulated on the following three criteria, adapted from the National Library of Medicine's Genetics Home Reference.
Analytical Validity: Refers to how well the test predicts the presence or absence of a particular gene or genetic change. Can the test consistently and accurately detect whether a specific genetic variant is present or absent?
Clinical Validity: Refers to how well the genetic variant(s) being analyzed is related to the presence, absence, or risk of a specific disease. Has having a specific genetic variant been conclusively shown to increase the risk or likelihood of having a disease or eventually developing a disease?
Clinical Utility: Refers to whether the test can provide information about diagnosis, treatment, management, or prevention of a disease that will be helpful to patients and their providers. Will use of the test lead to improved health outcomes
CMS implements regulations to control the analytical validity of clinical genetic tests, but there is no federal oversight of the clinical validity of most genetic tests. In light of this, FDA has proposed new policies to enhance analytical validity regulation and expand oversight of the clinical validity of genetic tests. Neither agency has issued formal plans to regulate the clinical utility of genetic tests, but typically, health care insurers like CMS draw on data from the research and medical communities to determine the clinical utility of medical treatments and procedures. Since clinical genomics is a relatively new field, frameworks to evaluate the clinical utility of genetic tests are still being developed. With time and experience, researchers, clinicians, health insurance companies, and regulators will have better information with which to establish the clinical utility of genetic tests.
CMS regulates clinical laboratories, including laboratories conducting clinical genetic testing, through its CLIA program. CLIA refers to the "Clinical Laboratory Improvement Amendments" of 1988, which established a certification process laboratories must pass in order to legally conduct clinical testing. The objective of CLIA is to determine clinical testing quality, including verification of the procedures used and the qualifications of the technicians processing the tests. It also comprises proficiency testing for some tests. More information about CLIA is available in this factsheet.
Though CLIA does look at the analytical validity of genetic tests, it does not examine whether the tests performed are clinically valid. Since the 1990s, expert panels and members of Congress have expressed concern about this regulatory gap and the need for FDA to address it. In response, in 2010 the FDA announced plans to move away from a policy of "enforcement discretion" (see next section, "FDA Regulation", for an explanation of the term "enforcement discretion") and expand its regulation to all genetic tests; this expansion has yet to take place due to the complexity of the task at hand.
Part of the FDA's mission is to protect public health by ensuring the safety, efficacy, and security of drugs, biological products, and medical devices. The agency considers genetic tests to be a special type of medical device, and therefore these diagnostic tools fall within FDA's regulatory purview. Until recent years, FDA chose to apply "enforcement discretion" to the vast majority of genetic tests. The FDA can use "enforcement discretion" when it has the authority to regulate tests but chooses not to. In the current regulatory landscape, whether FDA regulates a test is determined by how it comes to market. A test may be marketed as a commercial test "kit," a group of reagents used in the processing of genetic samples that are packaged together and sold to multiple labs. Test kit manufacturers must receive approval from FDA before selling their products on the market. More commonly, a test comes to market as a laboratory-developed test (LDT), where the test is developed and performed by a single laboratory, and where specimen samples are sent to that laboratory to be tested. To date, FDA has practiced enforcement discretion for LDTs. This means that LDTs are being used in the clinic without the FDA's assessment of their analytical and clinical validity.
FDA initially applied enforcement discretion on LDTs T because clinical genetic testing was not very widespread in the past - however, due to the rapid advances in next-generation sequencing (NGS) technology, the pervasiveness of clinical genetic testing today, the growth of direct-to-consumer (DTC) genomic testing, and FDA's mounting concern that unregulated tests pose a public health threat, FDA is modifying its approach. To this end, FDA has drafted new guidance to describe how it intends to regulate NGS genetic tests and verify their analytical and clinical validity. The agency has also drafted guidance proposing a new regulatory framework for LDTs. FDA "guidance" is different from laws and regulation in that it only represents the FDA's "current thinking" on a topic and is not legally binding for FDA or the parties it regulates. In practice, however, adhering to FDA guidance is beneficial because it can streamline the regulatory process. The draft guidances are listed below. Since they are in draft form, they are not currently being implemented.
List of FDA Draft Guidance on Genetic Tests
- LDT Draft Guidance
- Framework for Regulatory Oversight of Laboratory Developed Tests (2014)
- FDA Notification and Medical Device Reporting for Laboratory Developed Tests (2014)
- In 2017, FDA released a discussion paper on LDTs to provide an informal update to the 2014 guidance: Discussion Paper on Laboratory Developed Tests
- Next-generation sequencing (NGS) Draft Guidance
- Use of Standards in FDA Regulatory Oversight of NGS-Based In Vitro Diagnostics Used for Diagnosing Germline Diseases
- LDT Draft Guidance
Last updated: November 20, 2019