RUOs, LDTs, and FDA Enforcement: Just Because They Lost Doesn’t Mean They’re Gone

For years, the FDA has tried, sometimes gently, sometimes aggressively, to bring laboratory developed tests (LDTs) out from under enforcement discretion. Its most recent effort, the LDT Final Rule, was struck down in March 2025 by a federal court that found the agency overstepped its statutory authority under the FDCA and CLIA. But if anyone thought this ruling marked the end of FDA interest in LDTs, they may have misread the situation.

The FDA may have lost this regulatory battle in court, but it still retains powerful tools and is actively using them.

The Quiet Tool: Labeling

In vitro diagnostic (IVD) components labeled “For Research Use Only” (RUO) play a central role in the development of many LDTs. According to FDA’s 2013 guidance, RUO products cannot be marketed, promoted, or distributed with any indication of clinical use.

Despite this, some manufacturers have edged too close to the line. When the FDA finds evidence that RUO-labeled products are being sold for diagnostic purposes, whether through product websites, customer records, or included instructions, it often responds with warning letters.

A recent example is the March 2025 warning letter issued to DRG Instruments. The agency found that DRG’s RUO-labeled salivary cortisol assay included language, instructions, and promotional claims that were clearly intended for clinical use. As a result, the product was considered both misbranded and adulterated under federal law.

This was not a minor infraction. The agency emphasized that changes to the assay’s components and clinical claims required a new 510(k) submission. DRG had not submitted one. Despite the RUO label, the product was being distributed as an unapproved diagnostic device.

Court Ruling Does Not Equal Regulatory Freedom

Although the federal court sided with test developers and vacated the LDT Final Rule, the decision does not eliminate FDA’s existing authorities. It simply reaffirms that LDTs, as services performed in certified labs, are not automatically regulated as devices under the FDCA.

That nuance matters. While FDA cannot impose a comprehensive regulatory framework for all LDTs at this time, it can still take action when products are mislabeled or marketed improperly.

RUO components are often a key part of LDTs. If FDA enforcement causes RUO manufacturers to restrict how their products are sold or used, clinical labs may feel the impact quickly.

A Shift in Strategy, Not a Surrender

The court’s decision may be interpreted by some as a retreat by the FDA, but recent enforcement actions suggest the agency is simply changing its approach. Warning letters and increased scrutiny of RUO misuse show that the FDA is still focused on controlling unregulated diagnostic use wherever possible.

Clinical laboratories and test developers should not assume that a court ruling gives them a free pass. Even without the Final Rule, the FDA continues to regulate:

• • RUO product labeling and distribution
  • Manufacturer intent as demonstrated in advertising and instructions
  • Analyte Specific Reagents (ASRs), which are medical devices under 21 CFR 864.4020
  • Components used in patient care without proper clearance

These regulations remain in effect, and the agency continues to monitor and enforce them.

Final Thoughts

FDA has long sought closer oversight of LDTs. The courts may have blocked the agency’s broader efforts, but that has not changed the agency’s view of the risks posed by unregulated diagnostics.

The FDA will continue to act where it can. RUO labeling and enforcement remain practical ways to curb off-label clinical use. Laboratories and manufacturers that treat the court’s decision as a green light may find themselves facing regulatory consequences.

LDTs may have gained some legal breathing room, but the FDA has been working enhancing LDT regulation for 15 years and is it unlikely they are going to stop now.