FDA Eases Path for Cancer Companion Diagnostics

A class of cancer companion diagnostics just moved out of FDA's most demanding regulatory tier. On 17 August 2026 the agency published a final order reclassifying in situ hybridization (ISH) test systems — used alongside a corresponding FDA-approved oncology drug — from Class III to Class II, replacing full premarket approval with a 510(k) clearance backed by special controls. The change takes effect 16 September 2026.

What an ISH companion diagnostic actually does

In situ hybridization is a laboratory technique that uses a labeled probe to bind to a specific DNA or RNA sequence directly inside a tissue sample, making that genetic feature visible under a microscope. As a companion diagnostic, an ISH test is not a general screening tool: it is validated alongside one specific FDA-approved oncology therapeutic, and its result — positive or negative for a defined genetic marker — is what tells a clinician whether that particular drug is an appropriate choice for that particular patient. The test and the drug are reviewed as a linked pair, which is why the diagnostic side has historically carried Class III's PMA burden even though the therapeutic decision it informs, not the test itself, is where the clinical risk actually sits.

From PMA to 510(k)

Class III is FDA's highest-scrutiny device tier, reserved for products that support or sustain life, are implanted, or present a potential unreasonable risk of illness or injury — and it requires a premarket approval application, the device world's closest analog to a full drug NDA, complete with its own clinical evidence package and, frequently, an advisory panel review. Class II drops that requirement in favor of a 510(k) premarket notification: a manufacturer demonstrates its device is substantially equivalent to an already-cleared predicate, and special controls tailored to the device type — rather than a bespoke approval each time — carry the safety and effectiveness burden going forward. For sponsors developing a new ISH companion diagnostic, that swaps a multi-year PMA track for the comparatively faster 510(k) pathway, provided a suitable predicate exists.

A decade-plus of Class III precedent, ending now

• The reclassification applies specifically to ISH systems tied to an FDA-approved oncology therapeutic — not ISH tests generally, and not companion diagnostics for non-oncology indications.
• Four product codes are named in the order: NYQ, MVD, OWE, and PNK.
• FDA proposed the change in a June 2025 Federal Register notice, alongside a new device classification regulation and special controls specific to this test type.
• The final order closes that process after notice-and-comment, rather than introducing a new proposal.

What happens 16 September

Once the order takes effect, new ISH companion diagnostics of the covered types can be submitted as 510(k)s rather than PMAs. It does not automatically strip PMA status from a device already approved under the old framework — existing approvals are not retroactively converted — but it changes the calculus for every sponsor now deciding whether developing a new ISH-based companion diagnostic for an approved cancer drug is worth the investment. A faster, cheaper regulatory path is also a lower barrier to a crowded field: more entrants competing on the same paired-drug indication, tested against the same special controls FDA has now finalized.