The proposed order would shift these test systems to Class II with special controls, replacing the current PMA requirement for companion diagnostics and related oncology assays.
The US Food and Drug Administration (FDA) has proposed reclassifying oncology therapeutic nucleic acid-based test systems from Class III to Class II medical devices, a move the agency says would reduce regulatory burden on manufacturers while maintaining safety and effectiveness standards.
The proposed order, published Tuesday, would establish a new device classification regulation titled “Nucleic Acid-Based Test Systems for Use with a Corresponding Approved Oncology Therapeutic Product” under 21 CFR 866.6075. The reclassification would apply to companion diagnostic tests and related systems that use nucleic acid amplification technology or sequencing technology to detect genetic variants and biomarkers for oncology therapeutic decisions.
Under the proposed change, manufacturers would submit 510(k) premarket notifications instead of premarket approval applications, which are more burdensome and typically require longer review timelines. The agency expects this shift could enable more manufacturers to develop these types of devices and provide patients with increased access to appropriately safe and effective tests.
Scope of the Reclassification
The proposed reclassification covers prescription in vitro diagnostic devices that detect specific genetic variants or other nucleic acid biomarkers in human clinical specimens using nucleic acid amplification technology and sequencing technology. These systems include companion diagnostic devices that provide information essential for the safe and effective use of corresponding approved oncology therapeutic products, as well as test systems that provide information about known benefits or risks related to approved therapeutic products but are not essential for their safe and effective use.
The devices currently fall under product codes OWD, PJG, PQP, and SFL. Since the initial approval of the cobas 4800 BRAF V600 Mutation Test in 2011, FDA has approved 35 premarket approval applications and 403 supplements for oncology therapeutic nucleic acid-based test systems under these product codes.
Safety Profile and Risk Assessment
FDA’s analysis of postmarket data indicates a generally good safety record for these device types. A search of the agency’s Manufacturer and User Facility Device Experience database revealed 147 reported events for oncology therapeutic nucleic acid-based test systems as of Sept 8, 2025, with more than 95% of medical device reports listing no clinical signs, symptoms, or conditions and no known impact or consequence to patients.
The agency identified 27 recalls involving these devices: four Class III recalls, 23 Class II recalls, and no Class I recalls. False positive results accounted for device problems associated with more than 80% of reported events.
FDA identified three primary risks to health associated with these devices: false negative or false positive test results, failure of the test system to perform as intended, and failure to correctly interpret test results. The agency believes these risks can be effectively mitigated through proposed special controls combined with general controls.
Special Controls Requirements
The proposed special controls include design verification and validation requirements covering analytical quality metrics, performance data demonstrating appropriate analytical and clinical performance, and specifications for risk mitigation elements. Manufacturers would need to provide data demonstrating precision, analytical accuracy, analytical sensitivity, analytical specificity, and sample and reagent stability.
Labeling requirements would include device descriptions with biomarkers detected, relevant limitations regarding target regions that cannot be detected, descriptions of analysis algorithms, and summaries of performance studies. For companion diagnostic tests essential for safe and effective use of corresponding therapeutic products, labeling must indicate the test system’s indication for use with FDA-approved oncology therapeutic products and be consistent with the corresponding therapeutic product labeling.
The proposed order is open for public comment until Jan 26, 2028. If finalized, the order would become effective 30 days after publication in the Federal Register. Persons intending to market these types of devices would need to submit a 510(k) to the FDA and receive clearance prior to marketing.
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