FDA Quietly Moves Oncology ISH/FISH Companion Diagnostics From PMA to 510(k)
A Biden-era deregulatory promise survives the LDT court loss — and continues under the Trump FDA
On August 17, 2026, FDA did something that should matter to almost anyone following oncology companion diagnostics: it reclassified a defined family of oncology in situ hybridization (ISH) companion diagnostic tests from Class III/PMA to Class II/510(k).
The category includes important FISH applications as well as chromogenic ISH. The final order becomes effective September 16, 2026 [eg at 30 days]. FDA/Federal Register: August 2026 Final Order
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Kudos to Julie Ramage for highlighting this news on Linked In - here - it's gotten little trade press so far. The big picture - the August 2026 final rule for FISH, finishes a June 2025 proposal. A broader November 2025 proposal is still waiting for its release as final.
This blog generated by Chat GPT.
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Little Early Press, and an interesting "Big Picture"
The action has attracted surprisingly little visible trade-press attention. Yet it is more than a housekeeping exercise. FDA is converting a group of oncology companion diagnostics from the agency's most burdensome device pathway — PMA approval — to the much more familiar Class II pathway of special controls plus 510(k) clearance. FDA explicitly says the change should reduce regulatory burden, encourage additional manufacturers and improve patient access. (Federal Register)
And it sits inside a particularly interesting bit of FDA history: the Biden FDA simultaneously moved toward much broader regulation of laboratory-developed tests while promising that many high-risk IVD categories would be down-classified. The LDT initiative subsequently lost in court. The down-classification initiative did not.
The Odd Policy Pairing: Regulate More Tests, but Make More Tests Class II
The story actually begins in January 2024.
On January 31, 2024, while the Biden administration's LDT initiative was moving toward a final rule, CDRH announced that it intended to initiate reclassification of most IVDs then classified as Class III into Class II. FDA specifically said that the majority were infectious-disease and companion-diagnostic IVDs. The rationale was straightforward: where general controls plus appropriate special controls could assure safety and effectiveness, manufacturers should be able to use a 510(k) rather than PMA. FDA: January 2024 High-Risk IVD Reclassification Announcement
FDA later described the contemplated companion-diagnostic categories quite broadly, including nucleic acid-based, ISH-based, and immunohistochemistry-based oncology CDx tests, and at the time aimed to complete much of the reclassification work by November 2027. (U.S. Food and Drug Administration)
Thus, there was always a somewhat counterintuitive two-part policy. On one hand, the May 2024 LDT final rule sought to bring laboratory-manufactured IVDs much more fully into FDA's device framework and phase out enforcement discretion for most LDTs. On the other hand, FDA was simultaneously saying that the device framework itself had become unnecessarily stringent for many mature IVD categories: Class III did not necessarily have to mean Class III forever. (U.S. Food and Drug Administration)
That latter point is grounded in device law. Many "postamendments" devices were automatically placed into Class III because they entered the market after the 1976 Medical Device Amendments, not because FDA had affirmatively concluded after decades of experience that PMA was the only adequate regulatory pathway. Section 513(f)(3) expressly allows FDA to revisit those classifications when evidence shows that Class II general and special controls can provide reasonable assurance of safety and effectiveness. FDA's current reclassification page emphasizes exactly this mechanism.
Then the LDT Rule Fell — but Reclassification Kept Going
The major LDT policy did not survive.
On March 31, 2025, the U.S. District Court for the Eastern District of Texas vacated FDA's LDT final rule, holding that FDA had exceeded its statutory authority. FDA subsequently amended its regulation in September 2025 to restore the pre-2024 regulatory language. Federal Register: FDA Reverts the LDT Regulation After the Court Decision
But that litigation concerned FDA's claimed authority over laboratory-developed testing services. It did not eliminate FDA's established statutory power to classify and reclassify medical devices that are within FDA jurisdiction.
And the latter process continued under the Trump administration.
For example, FDA finalized Class III-to-II reclassification of three hepatitis B diagnostic categories in September 2025. FDA's live reclassification table now also records multiple 2026 downward reclassifications, including all four product codes covered by the new oncology ISH order.
In other words, the expansive LDT portion of the Biden-era IVD agenda disappeared, while an important deregulatory component of the same broader IVD modernization effort has continued apace under Trump.
November 2025: FDA Goes After the Big Molecular CDx Category
Another important marker came on November 25, 2025, when FDA issued a much broader proposed order and request for comments for oncology therapeutic nucleic-acid tests. Technically, the Federal Register document was a proposed order/request for comments rather than a freestanding "RFI."
FDA proposed moving four product-code families — OWD, PJG, PQP and SFL — from Class III to Class II. These encompass oncology therapeutic tests using nucleic-acid amplification technologies such as PCR as well as sequencing technologies such as NGS. The proposed new regulation, 21 CFR 866.6075, would retain FDA premarket review but replace PMA with 510(k). Federal Register: November 2025 Nucleic-Acid Oncology CDx Proposal
This was not a small evidence exercise. FDA reported that between 2011 and September 2025 it had approved 35 original PMAs and 403 PMA supplements across these product codes. For its reclassification analysis, FDA was able to use information from 17 original PMAs and one panel-track supplement under the statutory provisions allowing certain older PMA information to be considered, together with published literature and postmarket safety data.
There was also an interesting industry catalyst. Foundation Medicine had petitioned FDA in July 2024 to reclassify NGS oncology panels carrying companion-diagnostic indications under product code PQP. FDA effectively went further: rather than dealing only with Foundation's requested category, the agency proposed on its own initiative to reclassify the broader family of related nucleic-acid oncology therapeutic tests.
Comments on that proposal closed January 26, 2026. As of early September 2026, the broader nucleic-acid CDx proposal does not yet appear as a final action on FDA's live reclassification table. (GovInfo)
That makes the August ISH action especially worth noticing: one important oncology-CDx reclassification has now actually crossed the finish line.
August 2026: ISH and FISH CDx Move to Class II
The August order is narrower than the November molecular proposal, and there is an important procedural distinction.
The August final order does not finalize the November 2025 PCR/NGS proposal. Rather, it finalizes a separate proposal FDA published on June 11, 2025, for oncology therapeutic ISH-based test systems. Federal Register: June 2025 ISH Proposed Order
The final order covers four existing FDA product codes:
MVD — System, Test, HER-2/Neu, Nucleic Acid or Serum
NYQ — Chromogenic In Situ Hybridization, Nucleic Acid Amplification, HER2/Neu Gene, Breast Cancer
OWE — Fluorescence In Situ Hybridization, Anaplastic Lymphoma Kinase, Gene Rearrangement
PNK — Fluorescence In Situ Hybridization, Chromosome 17p Deletion (TP53)
FDA now groups these under the new classification regulation 21 CFR 864.1890, "In Situ Hybridization Test Systems for Use With a Corresponding Approved Oncology Therapeutic Product." FDA's own reclassification table explicitly lists all four as 2026 Class III-to-II reclassifications. FDA: Live Reclassification Table (U.S. Food and Drug Administration)
So, while "FISH CDx reclassification" is a useful shorthand, the regulatory category is slightly broader: it is oncology therapeutic ISH, including FISH and other ISH technologies.
PMA Is Out; 510(k) Is In — but This Is Not an Exemption
The practical change is substantial.
For a new oncology therapeutic ISH device entering the market after the September 16 effective date, the manufacturer will no longer need an approved PMA. It must instead submit a 510(k) and obtain FDA clearance.
Existing products with prior PMA approval do not suddenly need another application. FDA states explicitly that they may remain marketed under their existing authorization. But when an existing device undergoes a modification that could significantly affect safety or effectiveness, or undergoes a major change in intended use, FDA expects the manufacturer to submit a 510(k) rather than a PMA supplement.
That last point may prove nearly as important as the pathway for brand-new products.
There is also the predicate effect. Reclassified devices can potentially support future substantial-equivalence determinations. FDA cautions that ordinary 510(k) standards still apply — same intended use and either the same technology or technological differences that do not raise different questions of safety and effectiveness. But FDA specifically acknowledges that an appropriate predicate may support devices involving, for example, a new clinical cutoff or a new therapeutic indication when adequate supporting data are supplied.
That begins to create something oncology CDx developers historically have had little opportunity to exploit: a genuine 510(k) predicate ecosystem.
Class II Does Not Mean "Easy"
FDA has not turned FISH companion diagnostics into lightly regulated tests.
The new special controls in §864.1890 are extensive. They require validation of test interpretation and clinical cutoffs; analytical sensitivity and specificity; precision and reproducibility, including major sources of variability and inter-reader effects; multisite reproducibility where applicable; robustness; linearity for quantitative tests where applicable; specimen stability; and clinical performance in appropriately representative specimens.
Required labeling must summarize relevant performance studies, address appropriate interpretation by qualified readers in conjunction with other laboratory, pathology and clinical information, and remain consistent with labeling of the corresponding FDA-approved oncology therapeutic.
FDA did make several changes in response to comments. Most notably, it expressly allowed appropriate surrogate specimens to supplement clinical specimens for some precision and reproducibility studies, where FDA agrees they adequately represent the intended specimen and biomarker. FDA also dropped a separately proposed requirement for reagent-stability performance data.
Interestingly, the docket itself was hardly a regulatory food fight. FDA says it received comments from fewer than five commenters, mostly from the device industry, and all supported reclassification, although several proposed modifications. (Federal Register)
Perhaps the scarcity of trade coverage has a companion phenomenon: there was remarkably little controversy in the formal docket as well.
Why Policy Mavens Should Care
The most important conceptual point may be that "companion diagnostic" and "Class III/PMA" are no longer synonyms.
FDA is explicitly recognizing that decades of experience can change the appropriate regulatory classification of a technology. A high-consequence clinical use still requires substantial evidence and meaningful controls, but PMA need not remain the permanent regulatory answer when risks are well characterized and can be handled through Class II special controls.
Second, the episode shows an unusual degree of policy continuity across administrations. The Biden FDA launched a sweeping effort to bring LDTs into FDA's regulatory system and, at roughly the same time, began an equally deliberate project to reduce the classification of many mature high-risk IVDs. The first policy was struck down in court. The second has survived the change in administration and is producing final orders.
Third, the ISH order provides a concrete preview of what a much larger change could look like if FDA finalizes its November 2025 proposal for PCR- and NGS-based oncology therapeutic tests. Moving major molecular companion-diagnostic categories from PMA to 510(k) would affect development strategies, modification pathways, predicate planning, co-development with pharmaceutical companies, timelines and ultimately the economics of entering the CDx market.
The August FISH/ISH order is therefore narrow in subject matter but potentially quite broad in implication.
The Bottom Line
FDA's August 2026 action is easy to miss in the Federal Register, but it is consequential. Oncology ISH companion diagnostics — including established FISH categories — are moving from Class III/PMA to Class II/510(k), effective September 16, 2026.
The change does not eliminate FDA review. It replaces PMA with a special-controls-plus-510(k) framework that FDA believes can manage the known risks while reducing burden and encouraging competition.
There is also a striking regulatory irony. The Biden administration's effort to extend FDA device regulation broadly across LDTs is gone. But its promise to make the FDA pathway itself less onerous for many mature IVD categories is alive and well under the Trump administration.
For oncology diagnostics, the deregulatory half of that earlier agenda may ultimately prove to be the part that lasts.
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Key Primary Sources
FDA/Federal Register — August 17, 2026 Final ISH Reclassification Order
FDA/Federal Register — June 11, 2025 ISH Proposed Order
Federal Register — November 25, 2025 Nucleic-Acid Oncology CDx Proposed Order
FDA — Current Medical Device Reclassification Table
FDA — January 2024 Announcement on Reclassifying Most High-Risk IVDs
FDA/Federal Register — September 2025 Reversion of the Vacated LDT Rule
