Medical Devices

Laboratory Developed Tests

A laboratory developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured and used within a single laboratory.

LDTs can be used to measure or detect a wide variety of analytes (substances such as proteins, chemical compounds like glucose or cholesterol, or DNA), in a sample taken from a human body. Some LDTs are relatively simple tests that measure single analytes, such as a test that measures the level of sodium. Other LDTs are complex and measure or detect numerous analytes. For example, DNA variations can be detected from a blood sample, which can be used to help diagnose a genetic disease. Various levels of chemicals can be measured to help diagnose a patient’s state of health, such as levels of cholesterol or sodium.

While the uses of an LDT are often the same as the uses of FDA-cleared or approved in vitro-diagnostic tests, some labs may choose to offer their own test. For example, a hospital lab may run its own vitamin D assay, even though there is an FDA-cleared test for vitamin D currently on the market.

The FDA does not consider diagnostic devices to be LDTs if they are designed or manufactured completely, or partly, outside of the laboratory that offers and uses them.

LDT’s are important to the continued development of personalized medicine, but it is important that in vitro diagnostics are accurate so that patients and health care providers do not seek unnecessary treatments, delay needed treatments, or become exposed to inappropriate therapies.  

The FDA has generally not enforced premarket review and other applicable FDA requirements because LDTs were relatively simple lab tests and generally available on a limited basis. But, due to advances in technology and business models, LDTs have evolved and proliferated significantly since the FDA first obtained comprehensive authority to regulate all in vitro diagnostics as devices in 1976. Some LDTs are now more complex, have a nation-wide reach and present higher risks, such as detection of risk for breast cancer and Alzheimer’s disease, which are similar to those of other IVDs that have undergone premarket review.

The FDA has identified problems with several high-risk LDTs including: claims that are not adequately supported with evidence; lack of appropriate controls yielding erroneous results; and falsification of data. The FDA is concerned that people could initiate unnecessary treatment or delay or forego treatment altogether for a health condition, which could result in illness or death. The FDA is aware of faulty LDTs that could have led to: patients being over- or undertreated for heart disease; cancer patients being exposed to inappropriate therapies or not getting effective therapies; incorrect diagnosis of autism; unnecessary antibiotic treatments; and exposure to unnecessary, harmful treatments for certain diseases such as Lyme disease.

To help health care providers and patients better rely on the thousands of laboratory tests that are used every day to diagnose disease or other conditions or guide treatment and to encourage the advance of personalized medicine, on July 31, 2014 the FDA notified Congress of the Agency’s intent to issue a draft oversight framework for LDTs based on risk to patients rather than whether they were made by a conventional manufacturer or a single laboratory. This draft oversight framework includes pre-market review for higher-risk LDTs, like those used to guide treatment decisions, including the many companion diagnostics that have entered the market as LDTs. In addition, under the draft framework, the FDA would continue to exercise enforcement discretion for low-risk LDTs and LDTs for rare diseases, among others. The framework would be phased in over many years.

A webinar will be held on October 23, 2014 at 2:00 p.m. EST during which FDA will address clarification questions on the proposed framework. To participate, one must both dial into the conference call for audio and connect to the MyMeetings website to view the slide presentation:

No registration is required; however, participants are encouraged to connect and dial in no later than 1:45 p.m. The webinar is intended to provide clarification on the proposed framework only; comments on the framework should be submitted to the docket (instructions for submitting comments are provided in the notice that is published in the Federal Register) and/or presented at the January 2015 public meeting described further below.

Commenting on the Proposed LDT Regulatory Oversight Framework

As required by the 2012 FDA Safety and Innovation Act, on July 31, 2014 the FDA provided 60-day notice to Congress of its plan to issue draft guidance on the regulation of laboratory developed tests. At the same time, the FDA posted, for public viewing, the notification provided to Congress regarding LDTs that included the anticipated details of the draft guidances (Notification to Congress: FDA’s Laboratory Developed Tests Framework - July 31, 2014).

Following this 60-day notice, on September 30, 2014, the FDA posted both draft guidances on its website. On October 3, 2014, the FDA published notices in the Federal Register formally announcing their release and the beginning of a 120-day public comment period. This comment period will last until February 2, 2015. Electronic comments on the draft LDT framework and notification guidances should be submitted through www.regulations.gov. Written comments may be submitted to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Identify comments with the docket number found in brackets in the heading of the appropriate Federal Register notice for the draft guidance document (Docket No. FDA-2011-D-0360 for Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs), and Docket No. FDA-2011-D-0357 for Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs)).

The FDA welcomes comments on all aspects of these draft guidances, as well as on the following specific issues for the oversight framework draft guidance:

  • Traditional LDTs: In Section D.5.(a) of the draft guidance, FDA has proposed continued enforcement discretion for premarket review and quality system requirements for a category of LDTs called “Traditional LDTs” based on whether the device is: 1) an LDT (designed, manufactured and used within a single laboratory); 2) manufactured and used by a health care facility laboratory (such as one located in a hospital or clinic) for a patient that is being diagnosed and/or treated at that same health care facility or within the facility’s healthcare system; 3) comprised only of components and instruments that are legally marketed for clinical use; and 4) interpreted by qualified laboratory professionals without the use of automated instrumentation or software for interpretation. FDA believes that these factors appropriately mitigate risks associated with Traditional LDTs being used on patients so that continued enforcement discretion with respect to premarket review and quality system requirements is appropriate. However, FDA is seeking public feedback as to whether the following three factors may be sufficient to appropriately mitigate risk for this category of tests and whether they may also be sufficient to support continued enforcement discretion in full (i.e., for all regulatory requirements rather than just for premarket review and quality system requirements): 1) the test is an LDT (designed, manufactured and used within a single laboratory); 2) the test makes use of only components and instruments that are legally marketed for clinical use, which have a number of regulatory controls in place, including reporting of adverse events; and 3) the test is interpreted by laboratory professionals who are appropriately qualified and trained as required by the CLIA (Clinical Laboratory Improvement Amendments) regulations (see, e.g., 42 CFR 493.1449), without the use of automated instrumentation or software for interpretation.
  • LDTs Used for Rare Diseases: In Section D.5.(a) of the draft guidance, FDA has proposed continued enforcement discretion for premarket review and quality system requirements for LDTs used for rare diseases, which are those tests that meet the definition of LDT in the guidance (designed, manufactured and used within a single laboratory) and meet the definition of a Humanitarian Use Device (HUD) under 21 CFR 814.102(a)(5). With these factors, FDA has attempted to balance the need to mitigate the risks associated with these tests with their potential benefit for patients. FDA invites stakeholders to provide feedback on the suitability of these factors for LDTs for rare diseases. Further, FDA is seeking feedback on whether a factor other than the HUD definition should be considered, such as a factor based on the number of tests for a rare disease or condition that would likely (based on the prevalence of the condition) be conducted annually in the United States, and if so what the annual number of tests should be for the purpose of defining an LDT as an LDT for a rare disease. FDA also seeks feedback on whether enforcement discretion should be limited to tests that are designed, manufactured and used within a single laboratory.
  • Healthcare System: In Section D.5. of the draft guidance, for the categories of tests called “Traditional LDTs” and “LDTs for Unmet Needs,” FDA has identified factors it intends to consider in continuing to exercise enforcement discretion for premarket review and quality system requirements. One such factor is whether the LDT is both manufactured and used by a healthcare facility laboratory (such as one located in a hospital or clinic) for a patient that is being diagnosed and/or treated at that same health care facility or within that facility’s healthcare system. To further clarify this factor, the guidance document explains that “healthcare system” refers to a collection of hospitals that are owned and operated by the same entity and that share access to patient care information for their patients, such as, but not limited to, drug order information, treatment and diagnosis information, and patient outcomes. While FDA invites feedback on all factors described in Section D.5. of the draft guidance, FDA specifically requests feedback on whether enforcement discretion should be limited, as proposed, to those LDTs that are both manufactured and used by a healthcare facility laboratory.  FDA also invites the public to provide feedback to the Agency on which types of facilities would or would not be considered within a healthcare system, or to offer an alternative description of healthcare system for Agency consideration.
  • Quality System (QS) Phase-in: In Section D.6. of the draft guidance, FDA has proposed to continue to exercise enforcement discretion with respect to QS regulation requirements, codified in 21 CFR Part 820, until a manufacturer of a given LDT submits a PMA or FDA issues a 510(k) clearance order for the LDT. Under this enforcement policy, the clinical laboratory manufacturing and using the LDT will be responsible for having a quality system in place that meets the minimum requirements codified in 21 CFR Part 820, either at the time of PMA submission (the facility that makes the device must pass an inspection as a condition of PMA approval as a matter of law (21 CFR 814.45(a)(3))), or prior to market launch for cleared devices, as applicable. FDA invites feedback on the timeframe for phase-in enforcement of QS regulation requirements. Specifically, FDA is considering whether those LDTs in the highest-risk category of devices (described in section D.5.(c)), which FDA intends to generally enforce premarket review requirements 12 months following publication of the final Framework guidance, should remain under enforcement discretion for the design control requirements (21 CFR 820.30(a-h) and (j)) of the QS regulation for up to 24 months after publication of the final guidance.
  • Notification: FDA notes that some laboratory networks (i.e., more than one laboratory under the control of the same parent entity) offer the same test in multiple laboratories throughout their network.  Although devices in this scenario do not meet FDA’s definition of an LDT (i.e., they are not designed, manufactured and used within a single laboratory), FDA would like feedback on whether a single notification from the laboratory network for that test is sufficient, provided that the laboratory network indicates in the notification to FDA that the test is offered at multiple sites. In addition, FDA seeks comment on whether there are certain types of LDTs for which the Agency should neither enforce requirements for registration and listing nor request notification in lieu of registration and listing.
  • FDA understands that members of the public may want more clarity around specific issues, such as how laboratory sponsors could interpret what elements make up a medical device, what might constitute the label or labeling for their device, whether or not unique device identifier requirements apply to LDTs, and how laboratory-physician communication about a test and its result would be viewed by FDA, among others. We invite public comment on these issues and any other issues or questions that should be addressed in the guidance, including how that issue or question should be addressed.

The agency also intends to hold a public meeting in early January 2015 to collect additional input during the comment period. When the FDA schedules the public meeting it will be announced in the Federal Register notice and on this website.

Page Last Updated: 10/03/2014
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