On September 30, 2014, the Food and Drug Administration (FDA) announced the availability of two draft guidances intended to implement a new regulatory oversight framework for LDTs, which are defined by the FDA as "a type of in vitro diagnostic test that is designed, manufactured and used within a single laboratory" and which are intended for clinical use. Release of the documents follows on the heels of FDA’s notification to Congress in late July of its intent to issue draft guidance in this area. The first draft guidance, "Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)" (Framework Guidance), describes a risk-based framework for addressing the regulatory oversight of LDTs. The Framework Guidance also describes FDA’s priorities for enforcing pre- and post-market requirements for LDTs, and the process by which FDA intends to phase in enforcement of FDA regulatory requirements for LDTs over time. The second draft guidance, "FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs)" (Notification and Reporting Guidance), describes the process for clinical laboratories to notify FDA of the LDTs they manufacture as well as the Medical Device Reporting (MDR) requirements for clinical laboratories that manufacture LDTs. Both draft guidances reflect the FDA’s effort to take steps to encourage the advancement of personalized medicine by helping to ensure the reliability of certain diagnostic tests. The guidances are neither final nor in effect at this time.  

The following is an overview of the specific issues addressed in the draft guidances:

  • Low-Risk LDTs (Class 1 Devices), LDTs for Rare Diseases, LDTs for Unmet Needs and Traditional LDTs: FDA proposes to continue to exercise enforcement discretion for premarket review and quality system requirements, but will enforce other regulatory requirements, including registration and listing (or notification) and adverse event reporting for Low-Risk LDTs (Class 1 Devices), LDTs for Rare Diseases, Traditional LDT Oversight, and LDTs for Unmet Needs.
    • LDTs used for rare diseases are tests that meet the both the definition of LDT and the definition of a Humanitarian Use Device (HUD). FDA proposes factors to balance the need to mitigate the risks associated with these tests and their potential benefit for patients, and invites feedback on the proposed factors. FDA also seeks feedback as to whether a factor other than the HUD definition should be considered in defining these tests.
    • LDTs used for unmet needs are tests used when no FDA-cleared or -approved alternative exists. FDA proposes factors to determine whether an LDT is an “LDT for Unmet Needs,” and notes that the Agency does not intend to consider factors such as whether the LDT is comprised of only legally marketed components and instruments or whether the LDT is interpreted by qualified laboratory professionals, without the use of automated instrumentation or software for interpretation. FDA believes that greater flexibility is appropriate for LDTs for Unmet Needs because there is no FDA-cleared or approved alternative for the device on the market.
    • Traditional LDTs refer to in vitro devices that reflect the types of LDT available when FDA began its policy of generally exercising enforcement discretion over LDTs in 1976. FDA’s policy of enforcement discretion is based on a number of existing factors that the FDA believes appropriately mitigate risks associated with Traditional LDTs being used on patients. In the Framework Guidance, FDA also proposes, and requests feedback on, three new factors it believes mitigate risk for Traditional LDTs.
  • High and Moderate Risk LDTs: FDA intends to enforce all applicable regulatory requirements for these LDTs.
  • Forensic LDTs and LDTs for Transplant: FDA proposes to continue to exercise enforcement discretion for all regulatory requirements for these types of LDTs.
  • Defining Healthcare System: With respect to Traditional LDTs and LDTs for Unmet Needs, FDA proposes that enforcement discretion should be limited to those LDTs that are both manufactured and used by a healthcare facility laboratory, which are defined in the guidances as 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. FDA seeks public feedback on which types of facilities would or would not be considered within a healthcare system, or an alternative description of healthcare system for Agency consideration.
  • Timing on Quality System (QS) Enforcement: FDA proposes continued enforcement discretion over QS regulation requirements until a manufacturer of a given LDT submits a Premarket Approval (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 certain requirements either at the time of PMA submission or prior to market launch for cleared devices, as applicable. FDA proposes a timeframe for phase-in enforcement of QS regulation requirements, including enforcement of premarket review requirements for high-risk LDTs 12 months following publication of the final Framework guidance, and enforcement of design control requirements 24 months after publication of the final guidance.
  • Notification: FDA proposes that the Agency will collect information regarding LDTs currently being used by laboratories through a notification process. Specifically, laboratory owners/operators with LDTs currently being used in their labs should begin to notify FDA no later than 6 months after publication of the final Notification and Reporting Guidance. Starting 6 months after the publication of the final Notification and Reporting Guidance, laboratories that intend to offer new LDTs should provide notification to FDA prior to offering the LDT. FDA notes that when laboratories make a significant change to the marketed intended use of an LDT for which they have previously provided notification, the LDT will be considered a new LDT subject to a new notification. FDA intends to continue to exercise enforcement discretion for laboratories manufacturing only LDTs (and no other medical device) with respect to registration and listing requirements provided that such laboratories notify FDA of their LDTs. FDA will consider laboratories that do not notify the Agency that they are manufacturing LDTs within the required timeframes to have opted not to be within the scope of FDA’s enforcement discretion policy with respect to the registration and listing requirements.
  • Multiple Site Test Notification: FDA seeks comments on its proposal to allow a single notification from laboratory networks (i.e., more than one laboratory under the control of the same parent entity) that offer the same test in multiple laboratories throughout their network.

FDA will hold a webinar on October 23, 2014 on the Framework Guidance. For more information on accessing the webinar and its materials, click here.

Comments to the draft guidances should be submitted by February 2, 2015. FDA also intends to hold a public meeting in early January 2015 to collect additional input during the comment period.