Updated December 7, 2022
FDA Regulation of Laboratory-Developed Tests (LDTs)
Laboratory-developed tests (LDTs) are a class of in vitro
Diagnostic Multivariate Index Assays (IVDMIAs).
diagnostic (IVD) device that is designed, manufactured, and
IVDMIAs are defined by the FDA as tests that, among
used within a single laboratory. LDTs are often used to test
other things, provide results that are not transparent and that
for conditions or diseases that are either rapidly changing
the end user (usually a physician) could not independently
(e.g., new strains of known infectious diseases) or that are
derive. The FDA never finalized its guidance concerning
the subject of advancing scientific research (e.g., genomic
IVDMIAs, and instead announced its intent to regulate all
testing for cancer). The majority of genetic tests—a type of
LDTs in June 2010.
IVD that analyzes various aspects of an individual’s genetic
material (e.g., DNA, RNA)—are LDTs.
October 2014 Draft Guidance
In July 2014, FDA officially notified Congress of its intent
Federal agencies involved in the regulation of LDTs include
to begin regulating LDTs through draft guidance. This
the Food and Drug Administration (FDA) and the Centers
notification was in fulfillment of a statutory requirement in
for Medicare & Medicaid Services (CMS). FDA regulates
the Food and Drug Administration Safety and Innovation
the safety and effectiveness of the diagnostic test, as well as
Act of 2012 (FDASIA, P.L. 112-144), requiring FDA to
the quality of the design and manufacture of the diagnostic
notify Congress at least 60 days before issuing any draft or
test, pursuant to authorities in the Federal, Food, Drug, and
final guidance on regulation of LDTs. In the October 2014
Cosmetic Act (FFDCA). CMS regulates the quality of
draft guidance, Framework for Regulatory Oversight of
clinical laboratories and the clinical testing process
Laboratory Developed Tests (LDTs), FDA presented the
pursuant to the Clinical Laboratory Improvement
details of a risk-based framework for regulating LDTs. The
Amendments of 1988 (CLIA). This In Focus addresses only
framework generally identified classes of LDTs that would
FDA’s role in the regulation of LDTs.
be (1) exempt from regulation entirely; (2) required to meet
The regulation of LDTs has been the subject of ongoing
only registration and listing (or notification) and adverse
debate over recent decades, driven in large part by the
event reporting requirements; or (3) required to meet
increase in the number and complexity of genetic tests over
registration and listing (or notification), adverse event
this time. In general, the FDA has maintained that it has
reporting, applicable premarket review, and quality system
clear regulatory authority over LDTs, as it does with all
regulation requirements. The determination to continue
IVDs that meet the definition of medical device in the
enforcement discretion—or to enforce certain or all
FFDCA. However, the FDA traditionally exercised
applicable regulatory requirements—for an LDT would be
enforcement discretion over LDTs—choosing not to
based on risk evaluation. The agency collected comments
enforce applicable statutory and regulatory requirements
on the draft guidance document; however, in November
with respect to such tests—meaning that most of these tests
2016 FDA announced that it would be delaying finalization.
have neither undergone premarket review nor received
FDA clearance, authorization or approval for marketing.
January 2017 Discussion Paper
(For more information about FDA regulation of medical
FDA summarized the comments it had received on the 2014
devices, including premarket review, see CRS In Focus
draft guidance in its January 2017 Discussion Paper on
IF11083, Medical Product Regulation: Drugs, Biologics,
Laboratory Developed Tests (LDTs) and noted that it would
and Devices.) Some representatives of clinical laboratories
not be issuing “a final guidance on the oversight of [LDTs]
and manufacturers of LDTs, such as the American Clinical
at the request of various stakeholders to allow for further
Laboratory Association (ACLA), have asserted that LDTs
public discussion … and to give our congressional
are clinical services and not medical products, and therefore
authorizing committees the opportunity to develop a
should be outside of FDA’s regulatory purview. Given the
legislative solution.” The discussion paper included a
growing use and complexity of LDTs and genetic tests,
proposed framework for an approach to LDT oversight that
both Congress and the FDA have once again revisited the
would focus on “new and significantly modified high and
regulation of LDTs.
moderate risk LDTs.” Previously marketed LDTs would be
grandfathered and would not be expected to comply with
FDA Activity on LDT Regulation
most or all FDA regulatory requirements, such as premarket
FDA has, to date, focused its enforcement efforts on
review, unless necessary to protect the public health. In
commercial IVD kits, which are broadly marketed, and has
addition, new and significantly modified LDTs in several
not generally enforced premarket requirements for LDTs. In
specified categories (e.g., LDTs for rare diseases) would
recent years, however, FDA has indicated its intent to
generally not be expected to comply with FDA regulatory
regulate LDTs using a risk-based approach due to the
requirements.
increasing number, significance, and complexity of LDTs.
In 2006 and 2007, FDA published and updated draft
guidance on a specific subset of LDTs called In Vitro
https://crsreports.congress.gov

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FDA Regulation of Laboratory-Developed Tests (LDTs)
Key Issues in FDA Regulation of LDTs
specific medication, but that it may guide discussions with
In recent years, despite the absence of specific agency
health care providers by informing how a patient may
guidance on the regulation of LDTs, FDA has nevertheless
metabolize some medications. FDA released a safety
begun to assert authority over LDTs. This has included
communication in November 2018 warning against the use
direct-to-consumer (DTC) genetic tests that provide
of certain DTC and provider-ordered tests that claim to
information about the risk of developing a disease or
predict response to specific medications, stating that these
condition, or about a patient’s predicted response to
tests’ claims have not been reviewed by FDA and are not
medications (which can facilitate precision medicine).
necessarily supported by evidence. There was concern that
patients and their health care providers may rely on
DTC Genetic Tests
information from these tests, and make adjustments to
Genetic testing has become increasingly available for direct
medication and/or dosing that could be detrimental to
purchase by consumers, generally over the internet, often
patient health. In April 2019, FDA sent a warning letter to
without the involvement of a health care provider and for
Inova Genomics Laboratory for marketing tests without
increasingly complex and common diseases (e.g., cancer).
FDA clearance or approval that claim to predict a patient’s
As FDA has historically exercised enforcement discretion
response to specific medications based on genetic variants.
over LDTs—and because many DTC genetic tests are
Tests that inform the use of a specific medication—termed
LDTs—DTC genetic test companies had generally
“companion diagnostics”—are addressed through FDA
understood that regulatory requirements pertaining to LDT
guidance and are a component of personalized medicine. A
DTC genetic tests were not actively being enforced by the
2014 guidance document, In Vitro Companion Diagnostic
FDA. Notably, however, the FDA stated in its 2014 draft
Devices: Guidance for Industry, defines companion
guidance that “FDA generally does not exercise
diagnostic as “an in vitro diagnostic device that provides
enforcement discretion for [DTC] tests regardless of
information that is essential for the safe and effective use of
whether they meet the definition of an LDT provided in this
a corresponding therapeutic product. The use of an IVD
guidance.”
companion diagnostic device with a therapeutic product
Over past years, FDA has begun to enforce the regulation
(e.g., drug) is stipulated in the instructions for use in the
of certain DTC genetic tests. In November 2013, FDA sent
labeling of both the diagnostic device and the
a warning letter to 23andMe instructing the company to
corresponding therapeutic product, including the labeling of
discontinue marketing of its Personal Genome Service
any generic equivalents of the therapeutic product.” The
(PGS) test until it received FDA clearance for this test.
guidance notes that if scientific evidence is sufficient to
Again in late 2015, FDA sent letters to companies
support the use of a diagnostic with a group of therapeutics,
marketing DTC genetic tests without FDA clearance (e.g.,
then the diagnostic’s intended use/indications for use in its
Pathway Genomics, Inc.). These actions indicated that FDA
labelling should refer to the specific group of therapeutic
is taking steps to enforce regulatory requirements—and
products, rather than to a specific product to increase
specifically, premarket review—for DTC genetic tests that
clinical flexibility. In April 2020 FDA issued final
the agency considers to be higher risk.
guidance—Developing and Labeling in vitro Companion
Diagnostic Devices for a Specific Group or Class of
Alongside these actions, FDA has authorized for marketing
Oncology Therapeutic Products: Guidance for Industry—
some specific DTC genetic tests, reflecting evolution in
elaborating on this point. This guidance notes that
both DTC genetic tests and FDA oversight of these tests. In
developers may consider several factors (e.g., if a specific
2015, FDA cleared a 23andMe PGS Carrier Screening Test
group of oncology therapeutic products can be defined)
for Bloom Syndrome, and in late 2017, FDA provided in
“when determining whether their test could be developed,
the Federal Register its “final determination for autosomal
or the labeling for approved companion diagnostics could
recessive carrier screening gene mutation detection system
be revised through a supplement, to support a broader
devices by exempting this type of device from premarket
labeling claim,” thus increasing clinical flexibility for both
notification requirements, subject to certain limitations.” In
the provider and patient.
April 2017, FDA cleared the first DTC genetic test that
provides information about the risk of developing disease.
Recent Relevant Legislative Activity
This test, 23andMe’s PGS Genetic Health Risk, provides
Since passage of the 21st Century Cures Act, various
consumers information about their likelihood of
legislative approaches to FDA regulation of IVDs and
manifesting 10 diseases or conditions (e.g., Celiac Disease).
LDTs have been considered. A discussion draft circulated
Since then, FDA has cleared additional tests developed by
in early 2017, the Diagnostic Accuracy and Innovation Act
23andMe that assess the risk of developing a disease or
(DAIA), outlined a regulatory approach for IVDs that was
condition.
risk-based and flexible. FDA responded to DAIA in August
Pharmacogenetic Testing
2018 with a proposal for a novel regulatory approach,
including a mechanism for precertifying certain related tests
In the context of asserting its authority over certain LDTs,
to streamline premarket requirements. In December 2018, a
FDA has taken recent action to address DTC—as well as
new draft bill based on DAIA and incorporating FDA’s
health care provider ordered—pharmacogenetic tests (tests
feedback was released, the Verifying Accurate, Leading-
examining genetic variants with a link to metabolism of
edge, IVCT Development (VALID) Act. The VALID Act
medication). Many pharmacogenetic tests are offered as
was first introduced in the 116th Congress (S. 3404/H.R.
LDTs. FDA cleared 23andMe’s PGS Pharmacogenetic
6102) and again in the 117th (S. 2209/H.R. 4128). In 2022,
Reports test in October 2018, stating that the test does not
provide information about a patient’s response to any
it was incorporated into the Senate user fee bill (S. 4348,
Subtitle C—In Vitro Clinical Tests).
https://crsreports.congress.gov

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FDA Regulation of Laboratory-Developed Tests (LDTs)

IF11389
Amanda K. Sarata, Specialist in Health Policy


Disclaimer
This document was prepared by the Congressional Research Service (CRS). CRS serves as nonpartisan shared staff to
congressional committees and Members of Congress. It operates solely at the behest of and under the direction of Congress.
Information in a CRS Report should not be relied upon for purposes other than public understanding of information that has
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https://crsreports.congress.gov | IF11389 · VERSION 2 · UPDATED

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