In vitro diagnostic (IVD) tests must show they are safe and effective. Understanding how IVD tests are regulated helps differentiate IVD uses and risks.

When translated literally from Latin, “in vitro” means “in glass.” While the term has gained broad recognition in the context of reproductive health, many medical tests or procedures done outside the body are referred to as “in vitro.” This includes tests conducted using medical devices known as in vitro diagnostic (IVD) tests. IVDs may be instruments, reagents, or systems that help diagnose diseases or identify other medical conditions, so medical professionals can treat illness or prevent diseases and their aftereffects. Understanding how IVD tests are regulated provides insight into the different types and uses of IVDs and their effect on patient care.

Three Classifications

The Food and Drug Administration (FDA) divides IVDs into three classes, based on what the device is supposed to do and the amount of regulation needed to be reasonably sure that the device is both safe and effective. The class determinations are based on the level of risk to patients and public health if the device returns inaccurate results. The amount of control the FDA exerts through regulation increases along with the classification.

Class I IVDs are deemed low to moderate risk. These include things like cholesterol tests. Outside the testing realm, Class I devices include things like non-powered wheelchairs and stethoscopes.

Class II devices involve moderate to high risk and include IVD tests like pregnancy tests or tests for sexually transmitted diseases. Many home-diagnostic tests purchased over the counter (OTC) fall into Class II. Tests that a doctor prescribes but are performed at home (home use by prescription) may also fall into this category. An inaccurate result of such a test carries a greater risk for the patient and, in many cases, for public health.

Class III devices are the highest risk. These are things like tests to determine what kind of cancer therapy might be effective for a patient based on genetic screening.

How Classification Affects Regulation

The FDA imposes “general controls” defined by the Food, Drug, and Cosmetic act on all medical devices. “Special controls” apply to Class II devices. General controls address things like adulteration, misbranding, and adverse event reporting. Special controls involve performance standards, patient registries, and special labeling.

Understanding how IVD tests are regulated helps diagnostic product development by distinguishing the two routes by which the FDA conducts “premarket review” of IVDs. The route a given IVD takes depends on its classification. Lower risk Class I and some Class II devices must meet the criteria for “premarket notification,” also known as the 510(k) pathway, named after the section of the Food, Drug, and Cosmetic Act that defines it. Under premarket notification, the IVD must be “substantially equivalent” to a product that is already available on the market. If it is, it is exempt from stricter evidence requirements.

By contrast, high-risk Class II and Class III devices must undergo premarket approval (PMA). This process requires a demonstration of safety and effectiveness before the product may be introduced to the market.

To achieve FDA clearance either through the “substantial equivalence” track or the PMA track, devices must show they can accurately identify and measure the presence of a chemical, hormone, or marker in a sample or that they can predict or find a medical condition. Tests should also provide improved patient outcomes when weighed against the risks the tests impose.