The United States Food and Drug Administration (FDA) recently published a final rule, making it explicit that in vitro diagnostic products (IVDs) are considered devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act) – including in situations where the manufacturer of the IVD is a laboratory. The FDA simultaneously issued targeted enforcement discretion policies for certain categories of IVDs manufactured by laboratories as well as a policy to phase out its general enforcement discretion approach for laboratory developed tests (LDTs) over the course of four years.
LDTs are a subset of IVDs that are intended for clinical use and designed, manufactured, and used within a single clinical laboratory that meets certain regulatory requirements. IVDs are used in the collection, preparation, and examination of specimens taken from the human body (i.e., blood, saliva or tissue). They can be used to measure and/or detect substances or analytes, such as proteins, glucose, cholesterol, or DNA, to provide information about a patient’s health.
While the FDA has historically exercised enforcement discretion for most LDTs, the risks associated with more modern LDTs are greater than they had been previously. LDTs were lower risk, used in small volumes, and used for specialized needs of a local patient population. Now that LDTs are used more widely, for a larger and more diverse population, and in situations where critical health care decisions are being made, the FDA believes greater oversight is necessary.
In announcing the Final Rule, the FDA also notes that “there is a growing body of evidence that demonstrates that some IVDs offered as LDTs raise public health concerns; for example, they do not provide accurate test results or do not perform as well as FDA-authorized tests, including from published studies in the scientific literature, the FDA’s own experience in reviewing IVDs offered as LDTs, news articles and class-action lawsuits.” FDA also referenced examples of “potentially inaccurate, unsafe, ineffective or poor quality IVDs offered as LDTs that caused or may have caused patient harm, including tests used to select cancer treatment, aid in the diagnosis of COVID-19, aid in the management of patients with rare diseases and identify a patient’s risk of cancer.”
The agency hopes that with greater oversight of LDTs, patients and health care providers will be in a better position to “have confidence in IVDs regardless of where they are manufactured” and that it can save patients from harm, including worsening illness or death, and unnecessarily increased health care costs.
The phase out of the FDA’s general enforcement discretion approach for LDTs will help to ensure the safety and effectiveness of LDTs while avoiding disruptions to patient care. It may also help to foster test innovation and help the scientific and medical communities identify technologies, therapies, or areas that are worthy of future research. After the phase out, the FDA generally will expect IVDs made by a laboratory or non-laboratory to meet the same requirements, though certain IVDs manufactured by laboratories may fall within a targeted enforcement discretion policy.
“LDTs are being used more widely than ever before – for use in newborn screening, to help predict a person’s risk of cancer, or aid in diagnosing heart disease and Alzheimer’s. The agency cannot stand by while Americans continue to rely on results of these tests without assurance that they work,” said FDA Commissioner Robert M. Califf, M.D. “The final rule announced today aims to provide crucial oversight of these tests to help ensure that important health care decisions are made based on test results that patients and health care providers can trust.”
Additional Guidance Documents
In addition to the Final Rule, the FDA published two draft guidances. The first draft guidance provides insight into the agency’s thinking about an enforcement discretion policy for laboratories that offer certain unauthorized IVDs for immediate response to an emergency situation (i.e., an outbreak of an infectious disease), in the absence of a declaration applicable to IVDs under Section 564 of the FD&C Act. The second draft guidance shows the agency’s thinking about the factors that the agency tends to consider when developing a policy regarding enforcement discretion for certain IVDs during a public health emergency declared under Section 564 of the FD&C Act.