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Sunsetting FDA Enforcement Discretion of Laboratory Developed Tests

Diagnostic assays serve as pivotal tools in healthcare, enabling timely and accurate identification of diseases and guiding clinical decision-making. The CDC estimates 70% of medical decisions are based on laboratory test results.[i] However, if the results of assays are not safe and effective, they can pose serious risks to patients. Prior to the 21st century, the risks of assays were limited by the scope of technology. However, in a relatively short amount of time, the technology of assays, such as rapid gene sequencing and point-of-care testing, created a boom of industry, expanding the potential utility and risk of these tools. Due to several factors, oversight did not keep up. The rapid expansion in assay technology and the rush of healthcare providers to use these tests created a Wild West-like environment that is seeing its last days.

The FDA plays a crucial role in overseeing the development, manufacturing, and distribution of devices, which includes in-vitro and other diagnostic assays. This is not a recent development. In 1976, the Medical Device Amendments to the Food, Drug, and Cosmetic Act made explicit that FDA’s responsibility includes devices. At that time, FDA carried over a risk-based framework in use at the time and put certain in-vitro diagnostic assays into the category of laboratory developed tests (LDT). Specifically, these are in-vitro diagnostic assays intended for clinical use, designed, manufactured, and used within a single certified laboratory that meets the regulatory requirements under Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high complexity testing. LDTs at that time were manufactured in small volume and used in a local population or for rare diseases. They also used simple technology with manual methods and without automation.[ii] Within that risk environment, FDA took an enforcement discretion approach.

Since that time, and most notably over the past 15 years, technological and global use of assays have expanded into the open prairies of assays. LDT’s were a gold rush of information, providing important medical information. Complex instrumentation, computerized and automated devices, immunologic and DNA-based testing have stampeded into the market. While run in a single laboratory, these are not for a local population. These tests are much different than the LDTs from the 1970s, and FDA has oversight responsibility. FDA’s previous attempts at less burdensome oversight and gentle regulation proved untenable. After about a decade of waiting, the FDA is preparing to implement its plan for the oversight of laboratory developed tests.  

Like the federal marshals riding into a gold-boom town or cattle rancher’s territory, the FDA announcement that it will fully embrace its responsibilities in regulating the assay area was met with resistance. The first draft guidance published in 2014 described a framework for addressing the oversight for these tests. There was no distinction for assays made by conventional device manufacturers and those manufactured by laboratories.[iii] An avalanche of comments poured in response. On November 16, 2015 FDA published the public health evidence for the need for FDA oversight of laboratory developed tests, which included 20 case studies that specifically highlighted the need for effective oversight.[iv] Then, in 2017, FDA announced they would not issue a final guidance, ostensibly to allow “congressional authorizing committees the opportunity to develop a legislative solution.”[v] Since that time, FDA has been working with industry, academia, and other stakeholders to address the issues. Finally, almost a decade since its first announcement, FDA will phase out enforcement discretion. The plan is to do so in five stages over the next four years. Key dates include premarket review requirements for high-risk assays not before October 1, 2027, and for low-risk assays not before April 1,2028.[vi]

Some argue there are better ways to regulate these tests, including CLIA or the College of American pathologist (CAP) accreditation. However, even these arguments support awareness of the problems with unregulated testing and that additional regulation or oversight is needed and merely propose other ways to do it. Arguments for CLIA-only oversight are undermined by the overt support for FDA’s proposed rulemaking by the Centers for Medicare and Medicaid Services (CMS), who regulate laboratories through the CLIA standards.[vii] The 2015 testimony by the Chief Medical Officer of CMS specifically notes that they do not have the expertise to assure that tests work while FDA does.[viii] Proposals for amendments to CLIA to require further CAP oversight belabors that argument. Adding additional layers to an existing framework would require resources that are already being given to FDA.

The idea that innovation would be stifled, or necessary tests would be unavailable for patients and participants is a real concern. Additionally concerns about smaller companies not being able to produce the results FDA requires, or shoulder the burdens needed to produce the evidence for tests of rare diseases also need careful consideration.[ix] At the same time, arguing for the need of such testing and the imperative importance of its impact on health care only further underlines the need for accurate and reliable tests in those spaces. FDA’s phase-out plan includes provisions to address both concerns. Further mechanisms in place to both effect quick and specific review include expanded access[x] and the humanitarian use device pathway.[xi] Pre submission review and predicate device (e.g., 510K) pathways should also further decrease the burdens over time.

The pandemic provided good evidence of FDA’s ability to address the issues directly. The need for COVID tests right after the pandemic started and the processes for addressing the need prior to FDA approval showed that there are mechanisms to address concerns even in the worst case. The number of COVID molecular tests that applied to obtain Emergency Use Authorization (EUA) and the subsequent number that were identified as having major issues shows FDA can rapidly deploy tests and that FDA can quickly and effectively work with those that have issues. For example, in 2020, FDA reviewed 125 EUA requests for COVID tests. Of those, 82 (66%) had major issues while 43 had no issues and moved forward. Notably, of those 82 that had major issues, there was no clear distinction between hospital or commercial laboratories. Of the 82 that had major issues, six were withdrawn and FDA worked with the submitters until all but 28 were able to successfully manage to produce the data necessary to show that they were effective enough for the specific EUA requirements for their test.[xii]

FDA oversight instills confidence and trust in diagnostic assays among healthcare providers, patients, and other regulatory agencies. FDA evaluation encompasses the assessment of both analytical and clinical performance, including accuracy, precision, sensitivity, specificity, and potential risks associated with assays’ use. By establishing clear regulatory pathways, the FDA helps support accurate diagnoses and mitigate the harm to patients from inaccurate or unreliable diagnostic results. These assays are part of modern healthcare, and ever-increasing in importance. Other solutions are not tenable. Furthermore, even if those solutions might work, FDA still has the responsibility to oversee these tests. Those and similar arguments are just as irrelevant as arguing if cowboys actually needed the assistance of federal marshals in keeping the peace. The railroad has come through. Enforcement of regulation is overdue.


[i] FDA’s Proposed Rule Regarding Laboratory Developed Tests. Accessed 24 Mar 2024.

[ii] FDA’s Proposed Rule Regarding Laboratory Developed Tests. Accessed 24 Mar 2024.

[iii] Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs). October 2014.

[iv] Accessed 20 Mar 2024.

[v] Discussion Paper on Laboratory Developed Tests (LDTs). January 13, 2017.

[vi] FDA’s Proposed Rule Regarding Laboratory Developed Tests. Accessed 24 Mar 2024.

[vii] Accessed 20 Mar 2024.


[ix] JR Caldera, Hannah K. Gray, Omai B. Garner, Shangxin Yang, “FDA trial regulation of laboratory developed tests (LDTs): An academic medical center’s experience with Mpox in-house testing,” Journal of Clinical Virology,

Volume 169, 2023.

[x] Expanded Access for Medical Devices. Accessed 24 Mar 2024.

[xi] Humanitarian Device Exemption Accessed 24 Mar 2024.

[xii] Memorandum from Elizabeth Hillebrenner, Associate Director for Scientific and Regulatory Programs Center for Devices and Radiological Health (CDRH). Summary of 2020 Assessment of the First 125 EUA Requests from Laboratories for Molecular Diagnostic Tests for SARS-CoV-2.

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