FDA Proposes Moving Oncology IHC Companion Tests From Premarket Approval to 510(k) Clearance
A Nov. 12 proposal would put PD-L1, HER2, MMR and nine other immunohistochemistry test types tied to cancer drugs in class II. Our count: 23 original approvals and 292 supplements so far.
In 28 years of use, immunohistochemistry tests tied to cancer drugs have generated 48 adverse event reports in the Food and Drug Administration's MAUDE database, no class I recalls, one class III recall and 10 class II recalls. On that record, the FDA proposed on Nov. 12, 2026, to stop requiring premarket approval for them.
The proposed order would move oncology therapeutic IHC test systems in 12 product codes, including PD-L1, HER2, mismatch repair and claudin 18, from class III into class II with special controls. New tests would need 510(k) clearance instead of a premarket approval application. Comments are due Jan. 11, 2027.
What would change
The proposal creates a new classification regulation, 21 CFR 864.1895, titled "Immunohistochemistry Test Systems for Use with a Corresponding Approved Oncology Therapeutic Product." It covers both true companion diagnostics, whose use is essential for a drug's safe and effective use, and tests referenced in a drug's labeling that inform benefit and risk without being required. FDA says the two groups share the same risks: false positive or false negative results, a test that does not perform as intended, and misinterpretation of results.
The special controls would require analytical validation, including precision, sensitivity, specificity and cut-section stability, and clinical data from a population representative of the intended use. That clinical evidence may come from the drug's own trial enrollment assay or from "a method comparison study to an appropriate FDA-authorized device." Labeling would have to state that results are to be read by a qualified reader alongside other pathology results, clinical information and proper controls.
FDA started this on its own initiative after announcing on Jan. 31, 2024 that it intended to reclassify most high-risk in vitro diagnostics. Ventana Medical Systems, Roche's tissue diagnostics unit, petitioned on Jan. 7, 2026, to reclassify PD-L1 assays alone. FDA chose to cover all 12 product codes in one regulation.
How many tests are affected?
The rule does not count them. We queried FDA's premarket approval database through openFDA on Nov. 12 for each of the 12 product codes, separating original approvals from supplements, and set the totals beside the adverse event counts FDA reports.
| Code | Biomarker | Original PMAs | Supplements | First approved | MAUDE reports |
|---|---|---|---|---|---|
| MVC | HER2 | 4 | 96 | 1998 | 7 |
| NKF | c-KIT | 2 | 34 | 2004 | 0 |
| NQF | EGFR | 1 | 7 | 2004 | 0 |
| PKW | ALK | 1 | 22 | 2015 | 4 |
| PLS | PD-L1 | 6 | 88 | 2015 | 35 |
| QNH | Mismatch repair | 3 | 27 | 2021 | 1 |
| QQT | Ki-67 | 1 | 3 | 2021 | 0 |
| QUL | FOLR1 | 1 | 6 | 2022 | 1 |
| SBL | MAGE-A4 | 1 | 5 | 2024 | 0 |
| QZJ | Claudin 18 | 1 | 1 | 2024 | 0 |
| SER | MET | 1 | 3 | 2025 | 0 |
| SHF | PTEN | 1 | 0 | 2026 | 0 |
| Total | 23 | 292 | 48 | ||
Two things stand out. Supplements outnumber original approvals almost 13 to one, because each new drug indication, cutoff or instrument change has required its own PMA supplement. HER2 and PD-L1 alone account for 184 of the 292. And nine of the 23 original approvals came in 2021 or later, covering seven biomarkers whose first approvals all fall in that period: mismatch repair, Ki-67, FOLR1, MAGE-A4, claudin 18, MET and PTEN.
Those newer tests matter for how the evidence was built. Under the FD&C Act's six-year rule, FDA may use data from a PMA only after six years. So the proposal rests on 14 older PMAs from five product codes, HER2, c-KIT, EGFR, ALK and PD-L1, approved between 1998 and 2017. The seven newest biomarker categories would be reclassified on evidence drawn from the older five, which FDA justifies by saying the risks do not differ by antibody, biomarker or tumor type.
Class II does not lower the bar for a test's accuracy. It changes who can try to clear it, and how fast.
What it means for pathologists and oncologists
FDA's stated aim is more manufacturers and quicker review. In practice, a lab could see more FDA-cleared PD-L1 or HER2 kits validated against an existing assay rather than in a drug trial. That could widen platform choice, and it puts more weight on method-comparison data and scoring concordance, a known problem for PD-L1, where the 22C3, 28-8, SP142 and SP263 assays already use different scoring systems. Earlier Script Pad coverage of pembrolizumab in mismatch-repair-deficient endometrial cancer and adjuvant atezolizumab in dMMR colon cancer shows how often treatment now turns on these stains.
Nothing changes for tests already on the market until a final order is published, which FDA proposes would take effect 30 days later. Previously approved tests would move to class II automatically. Pathology groups, oncology practices and lab directors with views on concordance or labeling can comment on Docket No. FDA-2026-N-12508 at regulations.gov until Jan. 11, 2027.
Reported, fact-checked and edited by The Script Pad's editorial staff. See How we use AI.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
