Last spring, we wrote about a warning letter the United States Food & Drug Administration (“FDA” or the “Agency”) issued to Agena Bioscience Inc. (the “Agena Warning Letter”)[1] for allegedly promoting its diagnostic product (which was labeled for research use only “RUO” and therefore, not cleared or approved by FDA) for clinical purposes in violation of the U.S. Food, Drug, and Cosmetics Act (the “FDCA”).[2] The Agena Warning Letter – the first issued to an RUO product manufacturer in over five years – left the industry wondering whether FDA intended to ramp up enforcement against manufacturers who improperly utilize the regulatory carve-out for RUO diagnostic devices.[3] However, after the issuance of that Agena Warning Letter last April, all had been quiet on the enforcement front in the RUO space and, given the priorities of the new administration, we expected it to remain that way. But surprisingly, last month, FDA posted yet another warning letter to DRG Instruments GmbH (“DRG”) alleging failure to qualify for the RUO carve-out (the “Warning Letter”), potentially signaling the Agency’s intention to increase, or at least maintain, oversight for RUO-labeled products.[4]

In the Warning Letter, FDA concluded that DRG’s product was inappropriately labeled “ROU” – and, therefore, was not exempt from FDA’s in vitro diagnostic (“IVD”) regulations, including premarket clearance and/or approval – based on evidence that, in FDA’s view, showed the product was intended for clinical use. According to FDA, such evidence included (a) distribution records showing that DRG sold the product to “companies in the business of performing clinical analysis” with “no indication that these companies also conduct research,” and (b) claims made on DRG’s website suggesting that the product may be appropriate for clinical use (e.g., “can be performed also by patients”). Interestingly, FDA reached this conclusion despite the existence of certification letters from the purchasing companies acknowledging that the product was to be used for research purposes only.

The Warning Letter does not add any new parameters to the current regulatory framework for marketing RUOs, which consists of only a single regulation, two relatively dated guidance documents, and the Agena Warning Letter.[5] For instance, we already knew that making “device” claims (i.e., claims suggesting that a product could be intended to diagnose, cure, mitigate, treat, or prevent a disease or condition) and selling RUO products to clinical entities with no research operations are two factors that tend to prove that a product is intended for clinical – as opposed to research – use.[6] Likewise, we already knew that certification letters are not enough to offset evidence otherwise suggesting that a product is intended for clinical use.[7]

However, the issuance of the letter itself is significant. Although it may have been surprising at first glance – given the new administration’s publicized preference for deregulation of drugs and devices generally – it may be part of a larger scheme for FDA to retain at least some patient safety assurances for a smaller subset of exempt diagnostics (i.e., RUO products) in light of its recent decision not to oversee a larger subset of exempt diagnostics (i.e., laboratory developed tests (“LDTs”)) directly.[8] Given the regulatory context, it remains to be seen whether the Warning Letter indicates an intention by the new administration to keep a closer eye on the regulatory carve-out for RUO products and/or components – despite its decision not to regulate one of its most significant policy carve-outs (LDTs) – or whether this Warning Letter will ultimately be an outlier like the Agena Warning Letter. We’ll keep an eye out for further enforcement in the space.

FOOTNOTES

[1] Letter to Agena Bioscience, Inc., MARCS-CMS 665159 (2024).

[2] See FDA Warning Letter Tightens Reins On ‘Research Only’ Labels, Law360 (Apr. 22, 2024).

[3] We remind readers that diagnostic products properly labeled “RUO” are exempt from most FDA regulations, including premarket clearance and/or approval. See 21 CFR 812.2(c)(3); Guidance For Industry, Distribution of In Vitro Diagnostic Products Labeled ‘RUO’ or “IUO’, FDA (2018).

[4] See Letter to DRG Instruments GmbH, MARCS-CMS 700918 (Mar. 31, 2025).

[5] See 21 CFR 812.2(c)(3); FDA Guidance, supra FN 3; Draft Guidance for Industry, Commercially Distributed In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only: Frequently Asked Questions, FDA (2011).

[6] See Agena Warning Letter, supra FN 1.

[7] See FDA Guidance, supra FN 3, at p. 11.

[8] On May 30, FDA’s deadline to appeal the Eastern District of Texas decision vacating the controversial “LDT Rule” issued under the Biden administration lapsed, meaning that the LDT Rule is permanently vacated in its entirety. The LDT Rule (which we wrote about here, here, here, and here) would have required LDTs to comply with the full scope of FDA’s IVD regulations, including premarket clearance and/or approval, ending FDA’s long-standing policy of enforcement discretion for LDTs.