Commercial In Vitro Diagnostic Devices (IVDs) And How They Are Regulated

An IVD is a device commonly used to test samples of human saliva and blood by analyzing and detecting the presence or absence of certain markers (or set of markers, e.g., genetic mutation, immune response to infections, etc.), as well as the concentration of specific analytes (cholesterol, sodium, etc.), among other substances. Medical practitioners also use these devices to diagnose, guide treatment decisions and even prevent future diseases or a recurrence of the same. Clinical doctors can also use IVDs in screening tests to determine if a patient is at risk of developing a particular condition.

Since the Medical Device Amendment bill was passed in 1976, all medical devices have been regulated by the FDA. This includes products meant to be used to diagnose diseases and other health issues. The FDA is particularly keen on regulating these devices compared to diagnostic tests and components related to the same, e.g., reagents. For this reason, all IVDs developed for commercial use (market) are subject to regulatory requirements of the FDA. This is to help ensure the devices are effective and safe.

The regulation of IVDs is based on managing possible risks, which fall under 3 regulatory categories. Class I category encompasses tests that pose minimal risk to patients and public health if inaccurate (e.g., cholesterol tests). Class II categories cover moderate-risk tests such as pregnancy tests. Class III or high-risk, categories cover all tests that hold the greatest risk should there be inaccuracies and inconsistencies. Genetic tests are an example of tests that fall under the Class III category. The 3 categories align with increasing regulatory scrutiny on Classes I and a few classes II, which may be exempt from premarket requirements. However, the larger percentage of Class II and Class III tests need to have decent levels of premarket review before they can be introduced to the market. If you are looking to bring new experimentation into your research lab, I would recommend creating a project on ivd assay development.

The FDA has set two primary premarket review pathways for IVD tests. The PMA (premarket approval) pathway is the strictest, requiring manufacturers to demonstrate the effectiveness and safety of their IVDs before approval. PMA mostly applies to Class II tests as they don’t have a known equivalent on the market, hence posing a high degree of risk. The 510(k) or premarket notification pathway isn’t as strict and is described by a section of the Food, Drug, and Cosmetic Act. This is because these tests are considered/described as ‘considerably equivalent to products already on the market. Additional tests may be required if the devices are considered to be of moderate risk. The manufacturer may have to file a petition with the agency to reclassify their product.

Laboratory developed tests (LDTs) are more popular today and are developed for a broader range of conditions such as cancers and infectious diseases (e.g., Lyme disease, HPV, and whooping cough). LDTs are commonly marketed by large companies and laboratories, which potentially affect more than just local populations. It’s worth noting that LDTs may be made with components and instruments that haven’t been approved or legally marketed for clinical use. Some companies may also use complex software and algorithms to generate clinical interpretations and results. The companies however have to run numerous simulations and tests before arriving at a concrete result.

With these tests developed and used within the company (or single entity), they are often considered LDTs despite being quite similar to commercial IVDs (cleared by the FDA). Although the FDA may have waived regulatory requirements for most LDTs, there are times when it has to intervene, especially when the patient’s health and wellbeing are at risk.

Author: Transen