HHS Announcement on FDA Premarket Review of Laboratory-Developed Tests (LDTs)

INSIGHTi

HHS Announcement on FDA Premarket
Review of Laboratory-Developed Tests (LDTs)
December 3, 2020
Regulation of laboratory-developed tests (LDTs)—a class of in vitro diagnostic (IVD) device that is
designed, manufactured, and used within a single laboratory—by the Food and Drug Administration
(FDA) has been the subject of ongoing discussion, driven in part by an increase in the number and
complexity of LDT genetic tests for common conditions. FDA has traditionally exercised enforcement
discretion over LDTs, meaning that most of these tests have neither undergone premarket review nor
received FDA clearance or approval for marketing. To date, FDA has focused its oversight on IVD test
kits or components, which are commercially marketed as opposed to developed and carried out in a single
laboratory. In recent years, despite the absence of broader agency guidance on the regulation of LDTs,
FDA has asserted authority over certain LDTs that it considers to be higher risk.
HHS Announcement
On August 19, 2020, the Department of Health and Human Services (HHS) announced that, effective
immediately, it was rescinding all guidance, compliance manuals, website statements, or other informal
issuances concerning FDA premarket review of LDTs. The announcement applies to all LDTs—including
COVID-19 LDTs—and states that FDA may not require premarket review for these tests absent a notice-
and-comment rulemaking process. Per the announcement, premarket review includes premarket approval
(PMA), premarket notification (510(k) notification), and Emergency Use Authorization (EUA). HHS
notes that laboratories may voluntarily submit an EUA request, PMA, or 510(k) for LDTs.
FDA responded to this change in policy in early October, noting that it would “declin[e] to review EUA
requests for LDTs at this time,” including new EUA submissions and those already in the process of being
reviewed. In response, HHS directed the agency to review all voluntarily submitted EUA applications for
COVID-19 LDTs, noting that submissions will be referred to the National Institute of Health’s National
Cancer Institute for review if the FDA’s timeframe for review exceeds 14 days. Therefore, clinical
laboratories may voluntarily submit EUA applications for COVID-19 LDTs to FDA—and FDA must
review them—but FDA may not require submission of such applications absent rulemaking.
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FDA Regulation of LDTs During a Public Health Emergency
The FDA has maintained that it has clear regulatory authority over LDTs, as it does with all in vitro
diagnostics (IVDs) that meet the definition of medical device in the Federal Food, Drug, and Cosmetic
Act (FFDCA), although it has not generally enforced requirements for LDTs. LDTs that are developed for
and used during a public health emergency have usually not come under the auspices of this exercise of
enforcement discretion, and FDA has stated previously that these LDTs should not be used clinically
without approval, clearance, or authorization from the agency. The EUA process is usually used to
expedite access to medical products during an emergency that would otherwise require premarket
approval. However, because premarket requirements for LDTs are generally waived through enforcement
discretion by the agency, the EUA represents additional regulatory requirements for the clinical use of an
LDT in an emergency. In contrast, for commercial test kits, the EUA represents an abbreviated review
mechanism that allows the unapproved product to be used during an emergency without undergoing the
full FDA premarket review typically required.
FDA Regulation of COVID-19 Diagnostics
Numerous COVID-19 tests have received EUA, allowing for their marketing and clinical use during the
COVID-19 emergency with abbreviated review and data requirements. Through guidance dated May 11
(initially published February 29), FDA allows for modifications to the usual EUA process to facilitate a
more rapid scale-up of testing. Specifically, FDA allows certain COVID-19 diagnostics—both LDTs and
test kits—to be manufactured and used clinically prior to EUA authorization, but after test validation and
agency notification. For molecular and antigen tests, the guidance allows laboratories and commercial
manufacturers to perform and manufacture their tests prior to receiving EUA, as long as they validate the
test, notify FDA, and submit EUA materials within 15 days. For serology tests, manufacturers (but not
clinical laboratories developing LDTs) have 10 days to submit EUA materials to the agency, and may
similarly manufacture and distribute their test in the interim after validation and agency notification.
During the pendency of agency review, tests are to be performed only in high complexity clinical
laboratories; upon EUA authorization, a test may be carried out in settings specified in the Letter of
Authorization, including high or moderate complexity laboratories or waived settings (for use at the
point-of-care).
Issues for Consideration
The HHS announcement clarifies that entities using an LDT that is not approved, cleared, or EUA
authorized would not be eligible for coverage under the Public Readiness and Emergency Preparedness
(PREP) Act, which provides certain liability protections for covered persons administering covered
medical countermeasures. Clinical Laboratory Improvement Amendments (CLIA) requirements apply to
clinical laboratories using LDTs, irrespective of a test’s EUA or approval status.
Several issues are raised by the HHS announcement and its accompanying FAQ, including, but not
limited to the following:
 The announcement does not provide a definition for LDT, raising possible questions
about the scope of its applicability.
 The announcement does not note if, and if so to what extent, other FDA regulatory
requirements—for example, postmarket requirements—may apply to LDTs.
 It is not clear how or if this change in policy will apply to requests for modifications of
EUA authorized LDTs (e.g., adding a new sample type).
 Coverage of COVID-19 diagnostics pursuant to requirements in the Families First
Coronavirus Relief Act (FFCRA) may be affected by this new policy. The requirements

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 apply to COVID-19 IVDs that are FDA approved, cleared, authorized for marketing
pursuant to de novo classification, or EUA authorized. In addition, the statute requires
coverage of tests that are being used clinically or marketed per state authorization or in
the interim between notifying the FDA of test validation and the agency granting EUA,
pursuant to FDA guidance. It is unclear whether LDTs being used without EUA (or state
authorization or pursuant to agency notification) would similarly be required to be
covered under FFCRA requirements.


Author Information

Amanda K. Sarata

Specialist in Health Policy



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