FDA Proposes Down-Classifying Companion Diagnostics

How could FDA's proposal to reclassify nucleic acid-based test systems for oncology therapeutics reduce regulatory burden for manufacturers?

On Nov. 25, the Food and Drug Administration proposed an order to reclassify certain types of companion diagnostic tests, specifically oncology nucleic acid-based tests used in conjunction with gene-specific therapies, from Class III to Class II. If finalized, this order could reduce the regulatory burden on the medical testing industry, eliminating the need to submit lengthy Premarket Approval (PMA) applications for these types of tests. Instead, manufacturers would submit device review applications under the streamlined and more cost-effective 510(k) process to obtain clearance to market their devices.

Public comments on the proposal can be made here until 11:59 p.m. ET Jan. 26, 2026.

What do oncology nucleic acid-based companion diagnostic tests do?

Physicians use these companion diagnostics to identify the genotypes in cancer specimens, enabling the selection of specific therapies and reducing the likelihood of failed treatment strategies and side effects associated with less-specific approaches. These tests are typically fast and effective, but they are currently in FDA's "Premarket Approval" classification (Class III), requiring manufacturers to submit lengthy, detailed PMA documentation before marketing. 

If finalized, this order would establish a new device regulation under 21 CFR 866.607: "Nucleic Acid-Based Test Systems for Use with a Corresponding Approved Oncology Therapeutic Product." As Class II tests, they would not require PMA documentation, resulting in shorter premarket review timelines and more timely patient access to tests, FDA has said. 

Why is FDA reclassifying some companion diagnostics now?

FDA states that oncology nucleic acid-based tests are eligible to be reclassified due to a wealth of currently available PMA data and peer-reviewed literature demonstrating their safety. From the FDA Proposal:

Based upon the extensive PMA data available to FDA in accordance with section 520(h)(4) of the FD&C Act, published peer-reviewed literature studying the longstanding and well-understood technologies, and data available to the Agency demonstrating a lack of significant postmarket safety signals with oncology therapeutic nucleic acid-based test systems, FDA believes there is sufficient information to reclassify these devices from class III (Premarket Approval) into class II (special controls).

FDA has previously approved several PMAs for oncology therapeutic nucleic acid-based test systems, including: 

• 2012: cobas 4800 BRAF V600 Mutation Test (P110020) (product code OWD), a real-time polymerase chain reaction (PCR) in vitro diagnostic (IVD) device intended for the qualitative detection of the BRAF V600E mutation in DNA extracted from human melanoma tissue and intended to be used as an aid in selecting melanoma patients for treatment with Zelboraf (vemurafenib).
• 2014: BRACAnalysis CDx under product code PJG (P140020), an oncology therapeutic nucleic acid-based test intended for the qualitative detection of PARP inhibitor vulnerable variants of certain cancers. Genomic DNA obtained from whole-blood specimens is used to definitively classify the protein-coding regions and intron-exon boundaries of the BRCA1 and BRCA2 genes for deleterious mutations; the test is approved for use in breast, ovarian, pancreatic, and prostate cancer patients treated with Lynparza (olaparib), Talzenna (talazoparib), or Zejula (niraparib).
• 2016: FoundationFocus CDxBRCA Assay under the product code PQP (P160018), an oncology therapeutic nucleic acid-based test system using next-generation sequencing (NGS) technology, intended for the qualitative detection of BRCA1 and BRCA2 alterations in formalin-fixed paraffin-embedded (FFPE) ovarian tumor tissues, with results of the test intended to be used as an aid in identifying ovarian cancer patients for whom treatment with Rubraca (rucaparib) is being considered.

What does this mean for test manufacturers?

If approved, this order will significantly decrease timelines for FDA clearance of and market entry for oncology nucleic acid-based tests used as companion diagnostics. Manufacturers will still need to complete the 510(k) process for review, but that process is much faster and more cost-effective than the full PMA submission. This order could speed the process for getting therapeutics to market that require genotyping to assess whether a therapy should be prescribed.

Manufacturers can still conduct thorough testing and documentation of their systems under the PMA process until a decision has been reached, as many of the processes will apply to the 510(k) process.