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The FDA final LDT rule and new guidance

- by James Lappin

The Food and Drug Administration (FDA) releases its final rule for Laboratory Developed Tests (LDT) and publishes new guidance

On Monday 29th April, the FDA released its Final LTD Rule. This rule outlines how the agency will end its long-standing ‘enforcement discretion’ in regards to LDTs. The primary goal is to ensure (or improve) the safety and effectiveness of the LDT tests. The release  was followed up by the publication of the  “Laboratory Developed Tests: Small Entity Compliance Guide - Guidance for Laboratory Manufacturers and Food and Drug Administration Staff” on 25th June. This guidance provides more information on the FDA’s amendment and phaseout policy for LDTs.

How does the FDA final LDT rule expand oversight and increase compliance?

The LDT final rule widens the scope of FDA oversight to include tests manufactured and offered by laboratories and significantly increases the regulatory requirements for compliance. However, the FDA, has taken a ‘targeted enforcement discretion’ approach regarding premarket review and most quality system requirements for certain tests. This targeted approach includes:

  • currently marketed in vitro diagnostics (IVDs) offered as LDTs, that were first marketed prior to the final rule
  • LDTs, used to meet unmet need within a healthcare system.

Phased implementation

The FDA has implemented a staged approach to ending its enforcement discretion over a period of 4 years. Of particular interest to ARC and its  clients, compliance of LDTs with investigational use requirements (21 CFR 812) is included in stage two that begins on the 6th of May 2026 – two years after the final rule publication date. However, within the Final LDT Rule, the FDA has reiterated that it has always generally expected compliance with Investigational Device Exemption (IDE) requirements for all clinical investigations of LDTs conducted under clinical protocols requiring Institutional Review Board (IRB) approval.

The Food and Drug Administration (FDA) also notes that it is aware that some laboratories are currently conducting clinical investigations using LDTs without complying with IDE requirements. And that these investigations, may lack key human subject protections, including appropriate informed consent, evaluation of data to justify use in the study population, and inadequate analytical validation.

How does the FDA addresses clinical investigation concerns within the LDT final rule?

Within the rationale discussing clinical investigations, the FDA agency cites a Memorandum that highlights numerous examples of inadequate analytical validation of data provided within IDE applications for LDTs used in clinical investigations. The FDA has also responded to comments made on the proposed rule regarding LDTs used in clinical investigations, refuting most of the arguments made against compliance with the IDE and reiterating that these requirements have aways applied in the context of a clinical investigation, including when used in conjunction with an Investigational New Drug (IND) trial:

“As FDA has explained, sponsors should already be aware that all investigational IVDs used in therapeutic product trials are subject to IDE requirements, and may require the submission of an IDE application separate from an investigational new drug application (IND) to the extent an IDE application is required under part 812…. When an IDE application is not required, a therapeutic product trial that uses an investigational IVD must still comply with other IDE requirements as applicable under part 812…”   

FDA June LDT's guidance 

The June 2024 guidance reinforces the FDA’s position on regulating LDTs. It also provides a helpful table outlining  the compliance requirements for various test that, falling in the scope of the phaseout policy, are expected to meet the IDE requirements by May 2026. These test include:

  • ‘LDTs for unmet needs manufactured and performed by labs integrated in the healthcare system treating the patient’,
  • ‘Currently marketed IVDs offered as LDTs first marketed prior to rule publication date and not modified beyond scope’, and
  • ‘Modified versions of another manufacturer’s 510(k) cleared or De Novo authorized test within the scope described in the preamble’

Considerations

Finally, the recent decision by the US Supreme Court to overturn the ‘Chevron doctrine’ may pave the way for more legal challenges to the FDA’s Final LDT Rule and suggests that there may be more uncertainty ahead.

IND Sponsors utilizing LDTs within their clinical trials should conduct appropriate due diligence of partner labs to ensure that the tests used within the trial comply with regulatory requirements, and ultimately, are safe and effective for their intended use

To learn more about how to prepare for the changes and guidance on planning your clinical trials, contact ARC experts.

James Lappin
Article written by James Lappin
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