Definitions and General Oversight: Laboratory Developed Tests FAQs
General
A: In general, FDA regulatory requirements are not impacted by the frequency or volume a test is used. However, we note that devices that are designed to treat or diagnose a disease or condition that affects not more than 8,000 individuals in the United States on an annual basis may be eligible for a different type of pre-market submission, called a humanitarian device exemption. In the case of devices used for diagnostic purposes, humanitarian device exemptions are limited to devices for which not more than 8,000 individuals per year would be subject to diagnosis by the device in the United States. You may find more information on the HDE program, including a link to the HDE guidance, on FDA's HDE webpage.
For IVDs offered as LDTs, please refer to the preamble to the LDT final rule and FDA's Laboratory Developed Tests website for additional information regarding applicable requirements and FDA's policy for phasing out the general enforcement discretion approach for LDTs.
A: As discussed during the webinar presentation "FDA's Total Product Lifecycle Approach to IVDs", the analytical and clinical validation for each submission may depend on a number of factors, including the analyte detected, the technology used to measure it, the specific claims made by the manufacturer and the risks of wrong results. To understand the type of validation information FDA may expect to review, FDA encourages the use of the resources in the presentation such as recognized consensus standards, including many CLSI guidelines (the searchable database for FDA recognized consensus standards can be found at Recognized Consensus Standards: Medical Devices, as well as decision summaries that show the type of information that FDA has previously found appropriate to support a 510(k), PMA, or De Novo submission for similar test systems. FDA also issues a number of guidance documents that may be helpful in gathering data and preparing for a premarket submission, which can be found on our website as well. These can be located at Guidance Documents (Medical Devices and Radiation-Emitting Products). When manufacturers have specific questions that are not addressed by any of the publicly available resources, they may submit a pre-submission, as described in the FDA guidance "Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program."
What is an LDT?
A: Laboratory developed tests, or LDTs, are in vitro diagnostic products (IVDs) that are intended for clinical use and designed, manufactured, and used within a single clinical laboratory that is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and meets the regulatory requirements under CLIA to perform high complexity testing.
IVDs are devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act) including when the manufacturer of the IVD is a laboratory. IVDs are intended for use in the collection, preparation, and examination of specimens taken from the human body, such as blood, saliva, or tissue. IVDs, including LDTs, can be used to measure or detect substances or analytes in the body, such as proteins, glucose, cholesterol, or DNA, to provide information about a patient's health, including to diagnose, monitor, or determine treatment for diseases and conditions.
A: The final rule, including the phaseout policy described in the preamble to the final rule, is intended to better protect the public health by helping to assure the safety and effectiveness of IVDs offered as LDTs, while also accounting for other important public health considerations such as patient access and reliance. The FDA is phasing out the general enforcement discretion approach for LDTs so that IVDs manufactured by laboratories will generally fall under the same enforcement approach as other IVDs.
Compliance with device requirements under the FD&C Act will help assure IVDs offered as LDTs are appropriately safe and effective and put patients in a better position to have confidence in IVDs regardless of where they are manufactured. Device requirements include, among others:
- adverse event reporting,
- establishment registration,
- device listing,
- labeling requirements,
- investigational use requirements,
- quality system requirements, and
- premarket review.
A: The LDT final rule amends the FDA's regulations to make explicit that IVDs are devices under the FD&C Act including when the manufacturer of the IVD is a laboratory. This amendment is not specific to certain types of LDTs, but rather relates to all IVDs manufactured by laboratories. In addition, the preamble to the LDT final rule describes a tailored phaseout policy under which the FDA will provide greater oversight of IVDs offered as LDTs through a phaseout of its general enforcement discretion approach for LDTs over the course of four years. The phaseout policy includes targeted enforcement discretion policies for specific categories of IVDs, including policies for currently marketed IVDs offered as LDTs and LDTs for unmet needs under certain circumstances.
As described in the preamble to the final rule, the FDA intends to exercise enforcement discretion with respect to premarket review and most Quality System (QS) requirements for currently marketed IVDs offered as LDTs that were first marketed before the LDT final rule issued. Additionally, as described in the preamble to the final rule, the FDA intends to exercise enforcement discretion with respect to premarket review and most QS requirements for LDTs manufactured and performed by a laboratory integrated within a health care system to meet an unmet need of patients receiving care within the same health care system. FDA expects compliance with other device requirements for IVDs falling within these policies.
A: The phaseout policy is intended to better protect the public health by helping to assure the safety and effectiveness of IVDs offered as LDTs, while also accounting for other important public health considerations such as patient access and reliance. The targeted enforcement discretion policies described in the preamble to the LDT final rule for certain categories of IVDs, such as the policies for IVDs marketed at the time of issuance of the final rule and LDTs for unmet needs, for example, will help to facilitate patient and health care professionals' access to certain IVDs.
A: The FDA believes that by applying the same general oversight approach to laboratories and non-laboratories that manufacture IVDs, the FDA will reduce regulatory uncertainty, which will give stakeholders more stability, clarity, and confidence, and facilitate investment in the development of innovative IVDs.
A: As discussed in the preamble to the LDT final rule, an LDT is an IVD that is intended for clinical use and that is designed, manufactured, and used within a single laboratory that is certified under CLIA and meets the regulatory requirements under CLIA to perform high complexity testing. This definition does not exclude previously FDA-authorized IVDs that are modified by a laboratory for a use that is outside the IVD's original authorization. Please refer to the preamble to the final rule for a discussion of the phaseout policy, including targeted enforcement discretion policies such as those relating to modifications of an FDA-authorized IVD and to LDTs for unmet needs.
When a healthcare provider orders an IVD for a use that is outside the IVD's authorization, that does not dictate whether the IVD is an LDT or not – i.e., whether it is designed, manufactured, and used within a single laboratory that is certified and meets the regulatory requirements under CLIA to perform high complexity testing. We note that under the FD&C Act, a healthcare practitioner may prescribe or administer a legally marketed device to a patient for any condition or disease within a legitimate healthcare practitioner-patient relationship (see section 1006 of the FD&C Act (21 U.S.C. 396)). This could include situations where the healthcare practitioner specifically orders the use of an IVD outside of its original authorization for an individual patient.
A: LDTs are IVDs that are intended for clinical use and that are designed, manufactured, and used within a single CLIA-certified laboratory that meets the regulatory requirements under CLIA to perform high complexity testing. If an IVD is designed, manufactured, or used in more than one laboratory, it is not an LDT.
FDA's phaseout policy in the final rule applies to "IVDs offered as LDTs.&qout; These are IVDs that are manufactured and offered as LDTs by laboratories that are certified under CLIA and meet the regulatory requirements to perform high complexity testing, even if those IVDs do not fall within FDA's traditional understanding of an LDT because they are not designed, manufactured, and used within a single laboratory. FDA adopted this scope because it recognizes that not all laboratories have understood the limited nature of FDA's general enforcement discretion approach and have been offering IVDs based on the approach even when those IVDs do not fit what FDA generally considers to be an LDT.
The targeted enforcement discretion policies for certain new LDTs introduced after May 6, 2024 are all limited to LDTs as defined by FDA in the preamble to the final rule.
IVD Classification
A: FDA classifies IVDs manufactured by laboratories, including laboratory developed tests, in the same way it does other IVD test systems.
Test systems are a set of components--such as reagents, instruments, and other articles--that function together to produce a test result. Test systems include components and are accompanied by instructions for use for sample preparation and pre-analytical processing. Classification of the test system is based on the intended use and risk of the test system.
The most efficient method for an IVD manufacturer to determine the classification of a device type that has already been classified by FDA is by searching the product classification database, included on the resources and references page of the webinar slide deck. Searching FDA's 510(k), PMA, and De Novo databases may also be helpful in understanding what specific IVDs fall within a given device type and how such IVDs are regulated.
An IVD may be of a type that has not already been classified by FDA and, therefore, would not be in the product classification database. As a reminder, device types that have not been classified by FDA previously, and that were not on the market prior to the enactment of the Medical Device Amendments on May 28, 1976, are automatically Class III unless they are reclassified by FDA. If an IVD has not been classified, manufacturers should assess the risk of their IVD and submit the appropriate premarket submission based on the assessed risk. If the manufacturer believes their IVD is high risk, a PMA is likely required. If the manufacturer believes their IVD is low or moderate risk, the IVD may be eligible for de novo classification. The de novo process provides a pathway to class I or class II classification for medical devices for which general controls or general and special controls provide a reasonable assurance of safety and effectiveness, but for which there is no legally marketed predicate device.
A: In general, yes. However, where differences in specimen type or technology between a subject IVD test system and those specified in a classification regulation raise different questions of safety and effectiveness, the classification regulation describing use for a specific specimen type or technology would not be appropriate for a different specimen type or technology.
If you have questions regarding the classification of a specific test, you can submit a pre-submission or 513(g) request.
A: As discussed previously, FDA classifies LDTs the same way it does other IVD test systems. If a laboratory chooses to use one or more components labeled for research use only (RUO) by another manufacturer in its IVD offered as an LDT, then the laboratory is responsible for qualifying such components in its IVD and appropriately listing their IVD test system. As long as the laboratory has implemented a quality system that meets the QS requirements, as applicable, and is able to appropriately manage the quality of these components under that quality system, then the components may be incorporated as part of an IVD offered as an LDT. The RUO-labeled component(s) will be reviewed in the premarket submission for the IVD offered as an LDT, if applicable.
A: In general, LIMS are not included as part of IVD test systems. Rather, LIMS are generally regulated under their own classification regulation (refer to 21 CFR 862.2100, product code JQP) and are Class I, exempt from 510(k) subject to the limitations to exemption under 21 CFR 862.9. In addition, to better understand FDA's regulatory approach for Device Software Functions, see Section V of FDA's Guidance document, Policy for Device Software Functions and Mobile Medical Applications.
A: We recommend laboratories start by searching the product classification database to see if the device type has already been classified by FDA.
If the IVD is of a type that has already been classified by FDA, the database includes the device Class (I, II, or III), the type of submission required (if any), and if applicable, the classification regulation number.
If the IVD is not of a type listed in the classification database, you should assess the risk of your IVD to determine the premarket submission type that is most likely appropriate based on the assessed risk.
- If you believe the IVD is high risk, a PMA is likely required. As a reminder, only about 5% of IVDs currently listed with FDA require a PMA.
- A moderate or low risk device may be eligible for de novo classification.
If after searching FDA's medical device databases and assessing the risk of your IVD you have questions regarding the classification of your IVD, you can seek feedback from FDA via a pre-submission or 513(g) request.
A: As described in the webinar, low risk devices are those that pose minimal potential for harm. Although there are exceptions, the classification of a device generally correlates with its risk category with most Class I devices being low risk.
A: A product code identifies the generic category of a device for FDA. A classification regulation may have multiple product codes associated with it. In this case, classification product codes help to delineate technology and indication subgroups within a regulation. However, a product code is only associated with one classification regulation or no regulation at all. In the latter case, they serve to categorize unclassified or Class III (PMA) devices. Classification product codes are assigned and maintained by the Agency.
For non-510(k)-exempt devices, the submitter of the premarket submission identifies a product code they believe to be appropriate for their device. The proposed product code is reviewed by FDA staff for accuracy during the premarket review. If the proposed product code is incorrect, or a more appropriate product code should be used, the FDA reviewer will change the product code and notify the submitter.
The reviewer will assign a classification product code based on the regulation (if relevant) or the device intended use, indications for use or technology. The most common method of assignment is to use an existing product code from the product classification database. A device will be assigned an existing classification product code when it has the same intended use, indications for use, and relies on technology that does not raise new safety and effectiveness questions. In other words, if the device is determined to be substantially equivalent to the predicate device, it will typically be assigned the predicate device's product code. However, if the proposed device differs significantly from the predicate device with respect to technology, intended use or indications for use or is found not substantially equivalent (NSE), a new product code should be assigned.
In some cases, product code definitions may be updated to accommodate new technology. Additionally, new product codes may be created for tracking purposes for a specific technology or device area.
For additional information on product codes, refer to FDA guidance on Medical Device Classification Product Codes.
A: The original classification of a device can be changed through reclassification, for which multiple processes exist in the FD&C Act. In general, the FDA follows a process for reclassification that includes issuing a proposed order(s), convening a classification panel as appropriate, receiving and considering public comment, and issuing a final order(s).
A: As discussed in the preamble to the LDT Final Rule, FDA’s device classification processes focus on the risk of the IVD itself and availability of controls to address such risk. In classifying devices, FDA considers, among other things, the device’s intended use and indications for use, which includes consideration of the intended patient population. The risk the device poses to the patient and/or the user is a major factor in the class it is assigned. Therefore, FDA considers the risk of a device as it is intended to be used. A manufacturer may design a device in many ways, including as a single test that provides a single result or as a panel of tests that collectively provide a single result.
For example, if a test is intended to detect troponin to aid in the diagnosis of myocardial infarction (MI), the risk would be assessed based on the use of the test in aiding the diagnosis of MI. However, if the troponin test is combined with NT-proBNP and CRP to collectively aid in diagnosing the risk of future MI, the risk would be assessed based on the combined use of the tests in aiding the diagnosis of future risk of MI (even though some of the analytes in the panel are not traditionally associated with assessment for MI).
Laboratories
A: As stated in the preamble to the final rule, FDA recognizes that some small laboratories may be disproportionately impacted by the phaseout of the general enforcement discretion approach for LDTs from a financial perspective. However, the final phaseout policy includes several enforcement discretion policies that the Agency anticipates will reduce costs for laboratories, including small laboratories. For example, FDA intends to exercise enforcement discretion and generally not enforce premarket review and QS requirements (except for requirements under part 820, subpart M (Records)) for "currently marketed IVDs offered as LDTs" (i.e., those that were first marketed prior to May 6, 2024) that are not modified or that are modified as described in section V.B.3 of the preamble to the final rule and for LDTs manufactured and performed by a laboratory integrated within a healthcare system to meet an unmet need of patients receiving care within the same healthcare system.
We note that premarket submission requirements for IVDs do not depend on the manufacturer of the IVD (i.e., whether they are a laboratory or non-laboratory manufacturer, the size of the manufacturer).
A: FDA appreciates the important role public health laboratories play in our healthcare system. While the Final Rule does not provide a separate policy for LDTs manufactured and offered by public health laboratories, various enforcement discretion policies detailed in the preamble to the final rule may be applicable to IVDs offered as LDTs by public health laboratories. For example, FDA intends to exercise enforcement discretion and generally not enforce premarket review and QS requirements (except for requirements under part 820, subpart M (Records)) for "currently marketed IVDs offered as LDTs&qout; (i.e., those that were first marketed prior to May 6, 2024) that are not modified or that are modified as described in section V.B.3 of the preamble to the final rule, including those manufactured by public health laboratories. FDA also intends to exercise enforcement discretion for premarket review requirements for LDTs approved, conditionally approved, or within an approved exemption from full technical documentation, under NYS CLEP.
We have also issued draft guidance describing a proposed enforcement discretion policy for certain immediate response tests designed, manufactured, and used within State or local public health laboratories, among other entities. We are seeking comment on this proposal prior to issuing final guidance.
Laboratory Changes
A: If the same laboratory is offering the same LDT before and after publication of the final rule, the LDT generally would fall within the "currently marketed IVDs offered as LDTs&qout; (i.e., those that were first marketed prior to May 6, 2024) policy so long as the IVD is not modified or modified in a way that does not change the indications for use, alter the operating principle, include significantly different technology, or adversely change the performance or safety specifications of the IVD.
Registration & Listing
A: FDA is generally phasing out the general enforcement discretion approach with respect to registration and listing requirements under 21 U.S.C. 360 and part 807 (excluding subpart E). FDA generally expects compliance with R&L requirements by May 6, 2026. Comprehensive registration and listing is critical to inform FDA's understanding of the universe of IVDs offered as LDTs and to help FDA identify, monitor, and address any issues with IVDs offered as LDTs.
We note, however, that tests for public health surveillance are outside the scope of the phaseout policy and that enforcement discretion policies for the following tests extending to R&L requirements: 1976-type tests, certain HLA tests for transplantation, forensic tests, and DoD and VHA LDTs.
Inspections & Audits
A: All domestic and foreign device establishments, including those manufacturing IVDs offered as LDTs, are subject to inspection by FDA. Section 704(a) of the FD&C Act provides FDA authority for inspections, specifically providing authority for duly designated officers or employees of FDA to enter and inspect facilities subject to regulation under the FD&C Act. FDA uses a risk-based evaluation to select device manufacturing facilities for inspection and prioritizes device surveillance inspections that are deemed high-risk based on a variety of specific criteria, including facility compliance history, hazard signals, and inherent risks of the device manufactured at the facility. FDA does not intend to have a different approach for selecting laboratory manufacturing facilities for inspection. Although CLIA inspections occur for laboratories, such inspections do not verify that the tests themselves comply with the requirements of the FD&C Act that are designed to ensure that tests have appropriate assurance of safety and effectiveness for their intended purpose.