FDA Reclassifies Oncology ISH-FISH Companion Diagnostics to Class II, Effective September 16
On August 17, 2026, the U.S. Food and Drug Administration issued a final order that reclassifies a defined family of oncology in situ hybridization (ISH) companion diagnostic assays — including fluorescence ISH (FISH) and chromogenic ISH applications — from Class III (PMA) to Class II (510(k)). The order becomes effective September 16, 2026, and represents the completion of a reclassification proposal first published in June 2025. For the molecular diagnostics community, this is a concrete structural shift in the regulatory pathway for a critical class of biomarker-driven assays, one that should lower barriers to entry and reshape competitive dynamics in the companion diagnostics space.
Regulatory Mechanics and Statutory Basis
The reclassification rests on Section 513(f)(3) of the Federal Food, Drug, and Cosmetic Act, which permits the agency to revisit the classification of postamendments devices when evidence demonstrates that general controls plus appropriate special controls can provide reasonable assurance of safety and effectiveness. Many oncology CDx assays were originally placed into Class III not through an affirmative determination that PMA-level scrutiny was indispensable, but by operation of the 1976 Medical Device Amendments timeline. After decades of accumulated clinical and analytical validation data, the agency concluded that the Class II 510(k) framework — with tailored special controls — is now sufficient for this assay category.
The final order explicitly states that the change is intended to reduce regulatory burden, encourage additional manufacturers to enter the market, and improve patient access to companion diagnostic testing. These are not aspirational language fragments; they reflect a calculated policy decision grounded in the maturity of ISH-based methodologies in clinical oncology workflows.
Context: A Two-Track IVD Policy That Survived Court Scrutiny
The August 2026 final rule sits within a broader, somewhat counterintuitive two-part regulatory policy initiated under the Biden administration. In January 2024, the FDA's Center for Devices and Radiological Health (CDRH) announced its intention to reclassify most IVDs then classified as Class III into Class II, explicitly identifying infectious-disease and companion-diagnostic IVDs as the majority of affected categories. The agency described the contemplated CDx categories broadly, encompassing nucleic acid-based, ISH-based, and immunohistochemistry-based oncology tests, with a target completion timeline of November 2027 for much of the reclassification work.
Simultaneously, the FDA pursued a separate initiative to bring laboratory-developed tests (LDTs) more fully into the device regulatory framework, issuing a final rule in May 2024. The LDT rule subsequently lost in court. The down-classification initiative, however, did not — and it continues to advance. The August 2026 ISH-FISH reclassification is proof of that trajectory. A broader November 2025 reclassification proposal remains pending and awaits its own final order, which would extend similar pathway relief to additional IVD categories including immunohistochemistry-based CDx assays.
Market and Workflow Implications
The operational significance of this shift should not be underestimated. The PMA pathway imposes substantially greater time, cost, and evidentiary requirements on manufacturers compared with 510(k) clearance. For ISH-FISH companion diagnostics — many of which have well-established analytical and clinical validation profiles in oncology practice — PMA-level regulation has functioned as an outsized barrier relative to the residual risk profile of these assays.
The companion diagnostics market for targeted therapies was valued at $5.76 billion in 2025 and is projected to grow to $6.57 billion in 2026, with a compound annual growth rate of 14.1%. By 2030, the market is forecast to reach $11.25 billion. The reclassification is likely to accelerate that growth trajectory by enabling a broader range of manufacturers — particularly smaller, specialized developers — to pursue 510(k) clearance for ISH-based CDx assays without the prohibitive investment that PMA historically demanded.
For clinical laboratories and pathology groups, the downstream effects are twofold: expect greater assay availability and competitive pricing in the ISH-FISH CDx segment, and anticipate that regulatory review timelines for new submissions will compress meaningfully. The stratification of patients based on established FISH biomarkers — HER2 amplification, ALK rearrangement, ROS1 fusions, and others — is unlikely to change, but the pipeline of cleared assays targeting those markers is poised to expand.