On August 17, 2026, the US Food and Drug Administration published a final order reclassifying in situ hybridization (ISH) test systems indicated for use with a corresponding approved oncology therapeutic product from class III (premarket approval, PMA) into class II (special controls), subject to premarket notification under section 510(k) of the FD&C Act. The order, issued by FDA's Center for Devices and Radiological Health and codified at a new 21 CFR 864.1890, takes effect on September 16, 2026. It covers product codes NYQ, MVD, OWE, and PNK, the postamendments class III companion diagnostic assays that identify biomarkers tied to approved cancer therapies.
In concrete terms, manufacturers of these oncology therapeutic ISH-based test systems will no longer file a PMA to bring a new device to market. After the effective date, they submit a 510(k) premarket notification and obtain FDA clearance against the new special controls, a pathway FDA notes typically results in a shorter premarket review timeline than a PMA. The move follows a proposed order FDA published on June 11, 2025 (90 FR 24540) under docket FDA-2025-N-1243; FDA received comments from fewer than five parties, a majority from the medical device industry, all supporting reclassification.
Who has to change pathway, and by when?
The order binds any US manufacturer or importer developing an oncology therapeutic ISH-based test system falling under product codes NYQ, MVD, OWE, or PNK, the assay families used to detect companion-diagnostic biomarkers that gate access to approved oncology drugs. The exposed commercial audience spans established IVD and companion-diagnostic developers (Abbott, Roche/Ventana, Agilent/Dako, Leica, Biocartis) and laboratories building these assays. The effective date is September 16, 2026, 30 days after Federal Register publication. From that date, a 510(k) demonstrating substantial equivalence to a predicate, plus conformity to the 864.1890 special controls, replaces the PMA for this device type.
What are the new special controls at 21 CFR 864.1890?
For class II clearance, manufacturers must meet the special controls FDA finalized at 21 CFR 864.1890, which FDA determined, together with general controls, provide reasonable assurance of safety and effectiveness. The controls center on analytical and clinical performance testing and labeling. Performance testing must address precision and reproducibility, and FDA modified the final control (864.1890(b)(1)(v)) to permit surrogate samples that adequately represent the intended-use specimen type and biomarker where sufficient clinical specimens are unavailable, for example in rare tumor types, subject to FDA's case-by-case determination.
Labeling must comply with the general IVD labeling requirements at 21 CFR 809.10, supplemented by the special-control labeling elements. FDA declined industry requests to add a separate "device description and principle of operation" paragraph and a dedicated companion-diagnostic labeling sub-control, concluding the existing 809.10 and part 801 requirements already capture the necessary intended-use and operational information. FDA also declined to insert the word "companion" into the identification language, finalizing it as proposed.
Two structural changes from the proposed order matter for planning. First, FDA removed the proposed reagent-stability special control (former 864.1890(b)(1)(viii)), judging that general controls, 510(k) requirements, and the quality system rules at 21 CFR Part 820 (now aligned with QMSR) already cover reagent stability. Second, FDA confirmed manufacturers may use a Predetermined Change Control Plan (PCCP) under section 515C to implement future device modifications, including AI/ML-enabled digital pathology algorithms, without a new 510(k) for each change, with FDA reviewing the PCCP inside the marketing submission and encouraging pre-submission alignment via the Q-Submission program. At publication, FDA had not authorized any oncology therapeutic ISH device incorporating digital pathology or AI/ML algorithms.
| Dimension | Before (class III) | After September 16, 2026 (class II) |
|---|---|---|
| Submission type | PMA (premarket approval) | 510(k) premarket notification |
| Review standard | Valid scientific evidence of safety and effectiveness | Substantial equivalence to a predicate plus special controls |
| Controls | PMA conditions of approval | Special controls at 21 CFR 864.1890 plus general controls (Part 820/QMSR, 809.10 labeling) |
| Reagent stability data | Required as proposed special control | Removed; covered by Part 820 general controls |
| Future modifications | New PMA supplement per change | PCCP permitted, including AI/ML digital pathology, reviewed in submission |
| Review timeline | Longer PMA track | Shorter 510(k) track |
What should manufacturers do now?
Regulatory affairs and submission leads should re-baseline pipeline plans immediately. Confirm which of your pipeline and on-market assays map to NYQ, MVD, OWE, or PNK and whether they fall under the 864.1890 identification. For devices already PMA-approved, the new regulation applies, and a PCCP can govern planned modifications, including AI/ML-enabled digital pathology features, through the Q-Submission alignment route. For new devices, shift the regulatory strategy from PMA to 510(k), map your analytical validation to the 864.1890 performance-testing special controls, and document any surrogate-sample justification where clinical specimens are scarce. The rule's effective date is September 16, 2026.
Continuous, per-jurisdiction monitoring surfaces this kind of pathway change the moment it publishes in the Federal Register, rather than at the next quarterly review. Obsidian tracks US FDA device reclassifications alongside the underlying CFR parts so compliance teams can re-plan submissions without delay.
Take advantage of this real-time watch
Next steps for affected teams: verify applicability against your product codes and the 864.1890 identification, brief regulatory affairs and clinical operations on the PMA-to-510(k) switch, and confirm analytical validation and labeling align with the finalized special controls before the September 16, 2026 effective date.
