The FDA's final rule on laboratory-developed tests (LDTs) introduced a significant regulatory shift. It will now regulate these tests as well as other medical devices and in vitro diagnostics.
Released on April 29, 2024, this rule aims to enhance patient safety by ensuring LDTs, traditionally developed and used within single laboratories, meet the same stringent standards as diagnostics used across various healthcare settings.
The final rule, set to be published in the Federal Register on May 6, 2024, and effective 60 days thereafter, expands the FDA’s oversight over a rapidly growing category of tests. The rule offers wider exemptions than previously anticipated for LDTs on the market by May 6th and tests approved by the New York State Department of Health’s Clinical Laboratory Evaluation Program. Notably, it does not offer specific carve-outs for academic medical centers, except for a general exemption for tests addressing "unmet needs."
FDA Commissioner Robert Califf expressed a preference for a legislative solution but noted that this regulatory step was necessitated by a lack of Congressional action. Despite the intent to protect patients from inaccurate test results while preserving access to crucial diagnostics, the rule has stirred controversy within the industry.
Some experts are concerned that the enhanced requirements may restrict test availability and predict potential legal challenges to the new framework. As the rule transitions into effect, the balance between regulatory oversight and innovation in healthcare diagnostics will be a key area of focus and debate.
In February 2024, we examined the FDA's proposed rule closely, which still stands as an informative deep dive with many points of relevance to the final rule. Watch our analysis below via our Insider Newsletter, a Substack publication.
[February 2024 Issue] FDA Finalizes Guidance on DSCSA Verification Systems, a Closer Look at FDA's Proposed LDT Rule + Warning Letter Breakdown by The FDA Group
We dive into the FDA's final guidance on DSCSA verification systems, lay out what the agency's proposed LDT rule could mean for labs, and dissect a CGMP warning letter.
Read on SubstackWhat's Inside the Final Rule?
The recently released pre-publication version of the FDA's LDT Final Rule represents a significant shift in the regulatory landscape for LDTs. Spanning 528 pages, the document notably enacts a singular yet pivotal amendment to the codified regulations concerning in vitro diagnostic products.
Specifically, the rule modifies the definition at 21 C.F.R. § 809.3(a) to explicitly include laboratory-produced tests under the umbrella of "devices" as defined by section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (FDCA). This adjustment ensures that all LDTs are recognized as "devices," thereby subjecting them to FDA's regulatory authority.
This alteration, though seemingly minor with the addition of a few critical words, marks a substantial expansion of the FDA's oversight by clarifying that LDTs, regardless of their manufacturing environment, are to be regulated as medical devices. This change was proposed in the initial LDT draft and has now been formally adopted in the final rule.
The rule comes in response to over 6,500 comments from stakeholders during the public consultation phase, reflecting widespread interest and concern. Most of the final rule's preamble addresses these comments, providing the FDA's justifications for this broad assertion of regulatory power.
Historically, when the Medical Device Amendments were added to the FDCA in 1976, laboratory operations were not explicitly excluded from these regulations. The FDA interprets this as indicating that Congress did not intend to exempt LDTs from the same regulatory standards applied to other medical devices. Previously, the FDA exercised enforcement discretion as outlined in their 2014 Draft Guidance, which acknowledged the regulatory oversight of LDTs but often refrained from stringent enforcement.
This new rule underscores a shift from discretionary enforcement to a more definitive regulatory stance, applying not only to traditional LDTs designed, manufactured, and used within a single laboratory but also extending to all tests developed by laboratories, even those that might not fit the traditional LDT definition. Thus, the FDA is setting a clear regulatory framework encompassing all laboratory-developed in vitro diagnostics, irrespective of their specific characteristics or the context of their use.
The 5-Stage "Phase-Out" of Enforcement Discretion
The FDA has outlined a structured "phase-out" policy for its enforcement discretion for LDTs, transitioning towards full regulatory oversight. This gradual shift, scheduled over a four-year period, is structured into five distinct stages, each imposing increasingly stringent requirements. The FDA's intention behind this phased approach is to ensure a manageable transition for laboratories to comply with the statutory and regulatory device premarket and postmarket requirements.
Here's a closer look at each of the five stages.
Stage 1Starting one year after the publication of the LDT Final Rule, the FDA will require laboratories to comply with Medical Device Reporting (MDR) requirements under 21 C.F.R. Part 803, correction and removal reporting requirements under 21 C.F.R. Part 806, and complaint handling requirements under 21 C.F.R. § 820.198. Notably, the final rule has shifted the requirement for complaint handling from Stage 3 (as initially proposed) to Stage 1, emphasizing its importance for effective MDR compliance. |
Stage 2Two years post-publication, laboratories must adhere to additional regulatory requirements not covered in other stages, including registration and listing under 21 C.F.R. Parts 607 and 807, labeling requirements under 21 C.F.R. Parts 801 and 809, and investigational use requirements under 21 C.F.R. Part 812. This stage now explicitly includes investigational use requirements, addressing past confusion and non-compliance in this area as recognized by the FDA. |
Stage 3Three years after the rule's publication, compliance with 21 C.F.R. Part 820 is expected, except for complaint handling requirements, which are moved to Stage 1 from the original proposed rule. By the effective date of this stage, the Quality System Regulation (QSR) will transition to the revised "Quality Management System Regulation" (QMSR), effective from February 2, 2026. The FDA also notes the expectation for laboratories to retain relevant manufacturing records created before this stage, particularly those pertinent to validation and other topics under recordkeeping requirements in 21 C.F.R. Part 820, Subpart M. |
Stage 4At 3.5 years after publication, the FDA expects laboratories to meet premarket review requirements for high-risk IVDs classified as Class III devices. Laboratories that submit a premarket review by the beginning of this stage will continue to benefit from the FDA's enforcement discretion during the review process. This stage remains unchanged from the proposal. |
Stage 5Four years following publication, the FDA will enforce compliance with premarket review requirements for moderate-risk and low-risk IVDs that are non-510(k)-exempt Class I and II devices. Similar to Stage 4, if a premarket submission is made by the onset of this stage, the FDA will maintain its enforcement discretion during the review period. This final stage also remains consistent with the proposed rule. |
The Carve-Outs
Regulators landed on a number of significant carve-outs, which are detailed in the preamble to the LDT Final Rule. These carve-outs indicate areas where the FDA will continue to exercise enforcement discretion by not applying certain statutory requirements. However, the preamble notes that the FDA can modify these exceptions at its discretion. This creates a degree of regulatory uncertainty, reflecting the challenges in transitioning all LDTs to full regulatory oversight.
The FDA acknowledges that it currently lacks the resources necessary for comprehensive premarket and postmarket oversight of all LDTs. The carve-outs are partly intended to mitigate the new rule's immediate budgetary impact and prevent potential harm to patients from the unavailability of essential LDTs. They also aim to lessen administrative burdens on the Agency. To compensate, the FDA plans to enhance the Third Party 510(k) review program to handle about 50% of reviews for low- and moderate-risk LDTs — and to adjust Medical Device User Fee Amendments (MDUFA) during its next reauthorization to cover IVD and LDT premarket submissions.
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Significant carve-outs include:
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Enforcement discretion will continue for:
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What's Next for the Rule?
With the release of the LDT Final Rule, the FDA continues to assert that laboratory-developed tests fit within the statutory definition of a "device," a legal stance also taken in the proposed rule. This position holds that LDTs, as part of the broader professional laboratory testing services industry, are subject to the FDA's medical device jurisdiction, akin to manufactured medical devices. This interpretation, however, is contentious and has been historically disputed by the laboratory community, which argues that the statutory definition of a manufactured "device" should not extend to professional "services" such as clinical testing conducted by laboratories.
The laboratory community's argument centers on the claim that Congress did not intend for LDTs to fall under the FDA's device jurisdiction when the relevant legislation was enacted in 1976 and that the FDA's own enforcement discretion policy, introduced over two decades later, was the first public indication of such an intent. This interpretation suggests a disconnect between the original legislative purpose and the FDA's later regulatory approach.
As a result, the finalization of the LDT Rule does not put an end to the debate but rather shifts the venue from regulatory discussions within the FDA to potential legal battles in the courts. The rule's controversial nature and its broad implications for the industry make it a likely candidate for multiple legal challenges. These challenges will test the validity of the FDA's jurisdictional claim over LDTs and could influence how laboratory testing services are regulated in the future.
Furthermore, regardless of the outcome of these legal challenges, the issue is expected to return to the legislative arena. Previous efforts by Congress to explicitly regulate LDTs, such as the Verifying Accurate, Leading-edge IVCT Development (VALID) Act, have failed to pass. However, the concessions and carve-outs included in the FDA's LDT Final Rule, which were necessary for the FDA to maintain a practical regulatory authority over laboratories, are likely to serve as a baseline for any future legislative efforts. These elements reflect the complex interplay between regulatory intent, industry capability, and legislative action in the ongoing governance of LDTs.
Preparing for the End of LDT Enforcement Discretion
If the FDA's rulemaking survives its legal tests and we transition out of its enforcement discretion for laboratory-developed tests, affected laboratories will face significant regulatory requirements over a four-year phase-out period.
Here’s a step-by-step guide on how laboratories can prepare for each stage, including recommended timelines for planning and execution, as well as how The FDA Group can assist in these efforts.
Stage 1 PreparationImmediate Preparations for MDR and Corrections or Removals Reporting (1 Year Post-Publication)
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Stage 2 PreparationRegistration and Listing, Labeling, and Investigational Requirements (2 Years Post-Publication)
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Stage 3 PreparationCompliance with Quality System Regulation (3 Years Post-Publication)
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Stage 4 PreparationPremarket Approval for High-risk LDTs (3.5 Years Post-Publication)
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Stage 5 PreparationPremarket Notification for Low and Moderate-risk LDTs (4 Years Post-Publication)
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How The FDA Group Can Help
The FDA Group is equipped to support laboratories throughout this transitional period with tailored services designed to navigate the complexities of the new regulatory framework.
Here's how we're preparing to guide impacted firms through the phase-out period.
- Regulatory Gap Assessment and Strategic Planning: Early engagement to conduct gap analyses and develop strategic plans to address compliance needs.
- QMS Development and Compliance Framework Setup: Expert guidance on developing robust quality management systems and other compliance frameworks well ahead of deadlines.
- Submission and Registration Guidance/Support: Assistance with the preparation and submission of all required FDA documentation.
- Training and Continuous Regulatory Vigilance: Implementation of comprehensive training programs and ongoing regulatory updates to ensure sustained compliance.
By planning early and engaging with expert regulatory consultants like The FDA Group, laboratories can ensure they meet each regulatory milestone effectively and continue to provide safe and effective diagnostic tools under the new LDT regulations.
The FDA Group is more than a consultancy; we are your partners in regulatory excellence. We commit to transforming these regulatory changes from hurdles into stepping stones towards greater innovation, safety, and market success. Let’s start a conversation about your laboratory’s future.
Contact us and get the conversation started about LDT compliance support.
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