Recapturing the Current State of LDT Regulation in the United States

There has been a longstanding discussion regarding the oversight and regulation of laboratory developed tests (LDTs). The Clinical Laboratory Improvement Amendments (CLIA), which was enacted by Congress in 1988, governs the accreditation, inspection, and certification process for laboratories. Under CLIA, the Centers for Medicare & Medicaid Services (CMS) has oversight of clinical laboratories and LDTs (note that Washington State and New York State have their own laboratory standards and labs are required to receive a valid permit from the state itself). The United States Food and Drug Administration (FDA) states that the Medical Device Amendments Act of 1976 provides the agency with the authority to regulate LDTs to ensure safety, effectiveness, and design and manufacture quality. However, the FDA has used “enforcement discretion”, allowing laboratories to use LDTs that have not been approved or cleared by the FDA. The FDA, however, has continuously voiced to reconsider its role in regulating LDTs, as evidenced by the FDA’s related draft guidance in 2014.

The focus of LDT regulatory authority is now the topic of two opposing bills in Congress. The Verifying Accurate Leading-Edge IVCT Development (VALID) Act of 2021 would authorize FDA to regulate in vitro clinical tests (IVCTs), unifying oversight over LDTs and in vitro diagnostics (IVDs). In contrast, the Verified Innovative Testing in American Laboratories (VITAL) Act of 2021 would strengthen CLIA and empower CMS to continue to regulate LDTs.

There are countless publications and opinions on the VALID or VITAL act. For example, the American Association for Clinical Chemistry (AACC) has published multiple articles on the topic. To understand the debate, let’s take a refresher on all the requirements and steps a laboratory must undertake to implement and offer an LDT under the current regulations. 

High-level overview of LDT regulations and requirements 

This high-level overview is not a comprehensive summary of regulations and requirements for diagnostics / medical devices. Its sole intention is to provide a basic understanding of the current regulatory environment. Also, it is important to note that this is an evolving process with ongoing changes.

What is an LDT under the current regulation?

The FDA and CMS both agree that an LDT is “a type of in vitro diagnostic test that is designed, manufactured, and used within a single laboratory.” As discussed above, LDTs are currently governed through CLIA and regulated by CMS while FDA exercises “enforcement discretion.” Any in vitro diagnostic test that does not conform to the definition above is considered an IVD medical device, and subject to FDA regulations and oversight.

Many laboratories develop LDTs out of necessity and market need. LDTs often cover areas, such as rare diseases, that lack commercially available IVDs. LDTs are often the fastest option to respond to new developments and needs. It is also important to mention that, under current laws and regulations, any modification to the approved workflow of an IVD device will render the test as an LDT. In other words, if a laboratory is performing an IVD assay using a non-IVD-approved instrument, the assay will be considered an LDT.

LDTs can utilize a wide variety of applications with different complexities, ranging from molecular diagnostics to immunoassays and mass spectrometry. It must be pointed out that by default - independent of the design - all LDTs fall into the CLIA “high complexity” test category. Tests can be designed to detect a single biomarker or multiple analytes, targeting small molecules, proteins, cells, DNA or RNA. Assays can be developed to identify a wide spectrum of targets, such as pathogens, pharmacogenomic and companion diagnostic markers, oncology markers, genes or proteins linked to rare diseases, or the presence/absence of specific antibodies.