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The Food and Drug Administration (FDA) provided notice to Congress on July 31, 2014 of its intent to issue draft guidance regarding regulatory oversight of laboratory developed tests (LDTs), including reporting and premarket submission requirements. The FDA treats LDTs as a subset of in vitro diagnostic (IVD) devices, which are currently regulated as medical devices under the Federal Food, Drug, and Cosmetic Act. According to the FDA, it has always had the authority to regulate LDTs, but has chosen to exercise its enforcement discretion.

An LDT is defined by the FDA as “an IVD that is intended for clinical use and designed, manufactured and used within a single laboratory.” The FDA notes that there are likely tests being marketed as LDTs that are not truly LDTs based on this definition, but in order to maintain access to these tests the FDA will be applying the same framework to any IVD offered or marketed as an LDT by a laboratory.

The FDA will use the existing classification system for medical devices and will consider many factors to determine each LDT’s appropriate classification. Such factors include:

  • The risk level of the disease involved
  • The type of clinical decision involved
  • If the test is for screening or diagnosis
  • If the LDT is the sole information upon which a decision will be made, as well as whether or not there are any other available testing options

An LDT’s classification will determine what compliance process it will be subject to.

The FDA will continue to exercise its enforcement discretion and not impose certain regulatory requirements on certain LDTs that have a low risk associated with their use or where there is a risk that regulatory requirements would stifle patient access to important testing. However, high and moderate risk LDTs will be expected to comply with the registration, adverse event reporting, premarket review and quality system requirements. 

Notifications and adverse event reporting

The notification system will take effect six months after the final guidance is published. Establishments that produce and distribute medical devices for use in the United States are required to annually register with the FDA and to list the devices that are produced. If a laboratory does not provide notification, as set forth in the guidance, then it will be immediately subject to the more extensive registration and listing requirements, including registering each of its establishments (“a place of business under one management at one general physical location at which a device is manufactured, assembled, or otherwise processed”).

The FDA also published the anticipated details of guidance it intends to issue regarding the notification requirements for manufacturers of LDTs. The FDA expects laboratories to electronically submit certain data about each LDT, including the monthly test volume, intended use, testing method, sample type, analytes that are measured or organisms that are detected, clinical use of the test, and patient population.

If a laboratory complies with the notification requirements for existing LDTs, new LDTs and significant changes to existing LDTs, the FDA will not enforce the registration and listing requirements with respect to the LDTs until the laboratory submits a premarket submission.

Six months after issuing the final guidance, the FDA will also expect laboratories manufacturing LDTs to comply with the medical device reporting requirements. This includes reporting any deaths or serious injuries caused or contributed to by the LDTs or any malfunctions likely to cause or contribute to death or serious injury if the malfunction were to occur again. As a “user facility,” laboratories have already been required to comply with certain medical device reporting (MDR) requirements related to adverse event reporting. The FDA will now enforce the manufacturer reporting requirements for laboratories manufacturing LDTs.

Premarket review requirements

Compliance with the premarket review requirements will begin 12 months after the final guidance is issued and will be phased-in over several years, starting with the highest risk LDTs. The FDA considers the highest risk LDTs to be those with the same intended use as a cleared or approved companion diagnostic or an FDA-approved Class III medical device, as well as LDTs used to determine the safety or efficacy of blood or blood products.

Premarket review for moderate-risk (Class II LDTs) will begin after the premarket review of high-risk LDTs is completed. The FDA will provide advance notice to manufacturers (laboratories) of the timing of enforcement with respect to their respective LDTs. It expects the phased-in enforcement for Class III LDT devices to take five years, and the phasing in of Class II LDT devices to take an additional four years.

Additional considerations touched upon by the FDA include the clinical investigation requirements. It is the FDA’s opinion that many LDTs already have documentation of clinical validity in the literature that can be utilized rather than requiring a new study. However, it will likely be important for all laboratories manufacturing LDTs to become familiar with the investigational device requirements in order to assess compliance. Further, LDT manufacturers will be expected to comply with the quality system requirements upon submission of a premarket approval application.

The FDA views its premarket approval process as evaluating medical devices to confirm analytic validity (accuracy) and clinical validity, as well as the design, manufacturing, safety and effectiveness of medical devices.

Laboratories should: 

  1. Determine which LDTs they currently offer or may begin to offer as of the effective date of the regulatory oversight.
  2. Determine which category each LDT is likely to fit into. 
  3. Identify the specific requirements that each such test will be subject to and the timing thereof, as well as how ready they are to meet such requirements. 
  4. Determine what personnel and external resources are available to undertake all obligations required for the laboratory’s LDTs. This may necessitate hiring of new personnel with FDA experience. 
  5. Assess the implications of the FDA oversight program on the laboratory’s business plan, and LDT development, and marketing timetable.
  6. Track developments in the roll-out of the FDA oversight program.

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