U.S. FDA Final Rule Published on Laboratory Developed Tests (LDTs)

By Harrison Emery, Sarah Fitzgerald and Evangeline Loh

Laboratory Developed Tests (LDTs) are IVDs that are designed, manufactured and used within a single clinical laboratory. The FDA estimates that there are about 80,000 LDTs in use and approximately 8,000 new LDTs introduced each year. 

Background on the regulation of LDTs in the U.S.

Historically, the FDA has exercised enforcement discretion for most LDTs. While these laboratories have been certified by the Clinical Laboratory Improvement Amendments of 1988 (CLIA), the IVD has not been subject to further regulatory review.

Since at least 2006, the FDA has been actively assessing how to best regulate LDTs. Multiple draft guidance documents (2006, 2010), a framework document (2014) and a discussion paper (2017) have all been issued. In September 2023, the FDA announced its intent ( proposed rule) to regulate LDTs: LDTs would now require premarket authorizations analogous to IVDs.

Rudimentary regulatory primer

Most Class III medical devices, including IVDs, (high risk) are subject to Pre-Market Approvals (PMA) and most Class II (moderate risk) devices, including IVDs, require Pre-Market Notifications or 510(k)s. Novel devices are automatically considered  Class III but if not truly high risk, may utilize a special submission to reach market called a de novo classification request.

At the end of January, the FDA shared the intended proposal to reclassify most IVDs currently classified as Class III to Class II devices.

FDA publishes final rule on LDTs

On April 29, the FDA released the text of the Final Rule for LTDs. It was officially published May 6. The requirements will be phased in over the next four years.

• Stage 1 (May 6, 2025): Complaint management and adverse event, correction and removal of reporting requirements
• Stage 2 (May 6, 2026): Establishment registration and device listing, labeling, investigational use requirements
• Stage 3 (May 6, 2027): Complete compliance to 21 CFR 820 (Note Quality Management System Regulation (QMSR) ISO 13485 incorporated effective February 2, 2026)
• Stage 3.5 (November 6, 2027): LDTs subject to PMA, de novo and CBER licensing must be submitted
• Stage 4 (May 6, 2028): LDTs subject to 510(k)s must be submitted

Are all LDTs now subject to this final rule?

The Federal Register document is a tome of 160 pages. As such, it includes brief FDA responses to the many comments the agency typically receives. See Frequently Asked Questions for more.

The FDA will continue enforcement discretion for a subset of LDTs placed on the market before the Final Rule: 1976-Type LDTs, certain HLA tests, tests for law enforcement and LDTs manufactured and used within the Department of Defense or Veteran Hospital Administration and LDTs approved by New York State CLEP.

Otherwise, the laboratory and the LDT are subject to this rule based on the stages and dates. The FDA also has a webinar on this topic (May 14).

What do we recommend?

We at Emergo by UL recommend that laboratories assess the LDTs designed, developed and used within their institution. As a first step, laboratories should assess their quality management system and the processes and procedures that currently exist, as well as the expected risk classification of the LDTs (gap assessment). A strategic plan should be developed to understand the requirements and how these stages will be addressed.  

Additional elements to be considered: design and development of the LDT, risk management manufacturing and verification and validation of performance characteristics.

The first deadline requires a system for complaint management and adverse event reporting. It would benefit your laboratory to adopt these procedures and train employees on this topic.

Impact on U.S. market

The Final Rule impacts all LDTs in the U.S. unless described as under enforcement discretion.

We at Emergo by UL will continue to monitor developments and share these. We are available to provide medical device, IVD and pharma regulatory consulting support whenever and wherever you need it.