Inside the FDA's Final Rule On LDTs
The FDA has finally released its highly-awaited final rule for regulating laboratory developed tests.
This special edition of our newsletter is available in full for all subscribers. If you’re not already a paid subscriber, you can upgrade here. The following piece incorporates original analysis from our consulting team and wonderful reporting from Citeline’s Brian Bossetta. If you haven’t already downloaded our white paper on preparing for the first stage of the LDT enforcement discretion, you can grab it here.
On April 29th, the FDA announced its long-awaited final rule on lab-developed tests (LDTs), marking a new era for in vitro diagnostics. This 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.
But the rule does not provide specific exemptions for academic medical centers except for a broad exemption covering tests that address "unmet needs." FDA Commissioner Robert Califf said despite his preference for a legislative approach, this rulemaking was driven by Congressional inaction.
“LDTs are being used more widely than ever before — for use in newborn screening, to help predict a person’s risk of cancer, or aid in diagnosing heart disease and Alzheimer’s. The agency cannot stand by while Americans continue to rely on results of these tests without assurance that they work.” … “The final rule announced today aims to provide crucial oversight of these tests to help ensure that important health care decisions are made based on test results that patients and health care providers can trust.”
The extensive exemptions for current LDTs likely reflect the FDA's recognition of its limited capacity to handle the large volume of submissions that the new rule would bring.
Under the final rule, LDTs will now be explicitly classified as medical devices, phasing out the FDA's previous leniency. This change follows the Congressional failure to pass the VALID Act, which would have reformed diagnostic oversight in the U.S. Again, although the FDA favored legislative action, it resolved to use its rulemaking powers amidst ongoing delays from Congress.
When the FDA proposed this rule in September, it faced criticism from the industry and Republican lawmakers, who argued it would curb innovation and questioned the FDA's authority to enact such regulations.
Senator Bill Cassidy (R-LA), a physician, responded critically to the announcement, contending that the FDA does not have the authority to increase its regulatory jurisdiction unilaterally. He also said the rule will undermine access to essential laboratory tests, increase health care costs, and ultimately harm patients.
Conversely, Representative Anna Eshoo (D-CA) noted during a March House committee meeting that Congress has repeatedly failed to pass the VALID Act despite broad bipartisan support. "This is the sixth year for Congress to be grappling with the VALID Act. And we have not acted. We have to accept that.”
The final rule at a glance
The FDA states that the final rule on LDTs is based on “years of study and deliberation.” It contends that the public will benefit as LDT manufacturers must now adhere to foundational FDA standards when new IVDs are introduced or substantially modified. These standards include adverse event reporting, establishment registration, device listing, labeling requirements, investigational use requirements, good manufacturing practices, and premarket review.
The rule asserts that complying with these established regulatory measures will enhance patient confidence and understanding of IVDs, regardless of their origin. Over time, as more IVDs enter the market and the FDA narrows its enforcement discretion, the FDA says the benefits of this rulemaking will become increasingly apparent.
The rule outlines targeted enforcement discretion policies for certain categories of IVDs, particularly for tests serving urgent public health needs or those with no feasible alternatives. This ensures that critical diagnostic needs continue to be met without unnecessary regulatory barriers.
The agency refutes claims from stakeholders that IVDs produced by labs are inherently different or superior to warrant exclusion from FDA oversight, stating that such positions lack logical support. Notably, the FDA acknowledges that while the Department of Defense (DoD) and Veterans Health Administration (VHA) have specific mandates to serve their populations, additional oversight in these contexts would not be a prudent use of government resources. The rule also clarifies that the Clinical Laboratory Improvement Amendments (CLIA) of 1988 do not replace FDA oversight.
The phase-out plan
The final rule details a phased implementation approach over a four-year period (ending in 2028), specifying the types of requirements that will be enforced at each stage. This includes medical device reporting, quality system regulations, and premarket review requirements for high, moderate, and low-risk IVDs at different stages.
This gradual approach is designed to give laboratories sufficient time to adapt to new regulatory demands without causing disruption to their operations.
Stage 1: One year post-publication, FDA will enforce medical device reporting requirements for LDTs.
Stage 2: Two years post-publication, the agency will fully apply requirements such as corrections, removal reporting, and premarket reviews.
Stage 3: Three years post-publication, enforcement of quality system regulations will commence.
Stage 4: Three and a half years post-publication, premarket review requirements for high-risk IVDs will be enforced.
Stage 5: By the fourth year, the FDA will cease using enforcement discretion for all moderate and low-risk LDTs requiring premarket submissions.
Incorporation of public input
In drafting the final rule, the FDA considered over 6,500 comments and adapted the phase-out policy accordingly. The rule highlights broader exemptions for currently marketed LDTs and those approved by New York State. It also outlines the FDA's intent to "generally not enforce" certain requirements for LDTs within the VHA and DoD. The FDA maintains that it will not apply its discretionary enforcement to tests intended for blood donor screening, emergency use, or direct-to-consumer tests.
Despite these changes, the final rule may lead to legal challenges due to perceived FDA overreach. Congress could eventually address these issues. The rule will become effective 60 days after its publication in the federal register, which is projected to be around July 5th.
How to prepare and act on the final rule
Read our full white paper on LDT compliance preparation:
As the initial phase of enforcement discretion concludes one year after the rule's publication, labs will need to work somewhat quickly to implement systems to begin filing medical device reports (MDR) under 21 C.F.R. Part 803 and notices of correction and removal under 21 C.F.R. Part 806.
Here’s the high-level implementation strategy we’re planning to deploy with our clients before the phase one deadline:
Review current incident and adverse event reporting mechanisms.
Identify gaps in capturing data required for FDA medical device reporting.
Create or refine procedures for reporting adverse events and corrections or removals in compliance with FDA requirements. Train on those procedures.
Set up systems for capturing, documenting, and reporting relevant information to the FDA.
Establish a timeline for regular review and updates.
Ensure proper documentation of all reports and actions taken for compliance and future audits.
Beyond the current requirement under CLIA for demonstrating analytical validity, labs will need to establish the clinical validity of their LDTs. This involves substantiating the test's ability to accurately identify, measure, or predict clinical conditions or predispositions in patients. Gathering this evidence early can streamline later stages of regulatory scrutiny. Although the pathways for complying with FDA requirements on evidence generation for premarket reviews are well-established for other IVDs, the volume of LDTs entering this regulatory framework poses a significant challenge. Laboratories should leverage existing regulatory experiences to develop efficient compliance strategies.
Critically important, labs should not defer preparations for compliance with quality system regulations, which become enforceable in the third year after the rule's publication. Developing and implementing a quality system is a complex process that typically requires 8 to 10 months to complete all documentation and register the facility. Given the involved nature of QS development, starting early can prevent rushed implementations and ensure compliance readiness.
How The FDA Group can help
We’re here to turn uncertainty into a pathway for growth and compliance in what will most likely be a more highly regulated future. Our tailored services are designed to navigate the complexities of this rule, ensuring your LDTs meet regulatory expectations without losing the innovative edge that sets you apart.
Here's how we’re helping firms take action now:
Regulatory gap assessment and strategic planning: Identifying areas where existing practices may not align with the forthcoming LDT regulations is a foundational step toward compliance. We perform thorough gap analyses, identifying discrepancies and developing strategic plans to address them, ensuring a smooth transition to full compliance.
QMS development: Adapting to the FDA's regulatory requirements for LDTs will involve significant updates to a laboratory's quality management systems. We provide expert advice on integrating comprehensive quality management practices, ensuring that laboratories meet the high standards expected by the FDA.
Documentation and process improvement: Compliance will require meticulous documentation and process management, from test design and validation to post-market surveillance. We assist in reviewing and updating these processes, ensuring they adhere to the new regulatory requirements, thereby streamlining operations and enhancing overall test quality and reliability.
Training and staff development: Understanding and adapting to new regulations is a collective effort. We plan to develop and deliver targeted training to staff across all levels, ensuring everyone understands the regulatory changes, their impact, and their roles in maintaining compliance well after the consultant is gone.
Preparation for inspections and audits: With the expectation of increased FDA oversight, preparing for inspections and audits is paramount. We simulate FDA inspection scenarios through mock audits, helping laboratories identify potential areas of non-compliance and advising on corrective actions to mitigate risks before they become regulatory issues.
The new FDA rules for LDTs encompass a broad range of compliance requirements, from test validation to quality management systems. Consultants specializing in LDT regulation and FDA processes offer invaluable guidance, ensuring laboratories navigate these complexities effectively and meet all regulatory standards.
The demand for specialist RA/QA consultants will far exceed its supply in the coming months. If you know you'll need LDT compliance support, please contact us to express your interest now so we can ensure specialists are available when you need them.
Correction: We had initially reported tests approved by the New York State Clinical Lab Association were exempt from the FDA’s new rulemaking. In fact, LDTs approved by the New York State Department of Health’s Clinical Laboratory Evaluation Program are excluded from the FDA’s premarket review requirements.
Who is The FDA Group?
The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on Quality Assurance, Regulatory Affairs, and Clinical Operations.
With thousands of resources worldwide, hundreds of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee. Learn more.