The development of a companion diagnostic (CDx) alongside a medicinal product brings together complex regulatory, clinical, and analytical considerations. While the US and EU share the fundamental concept of a companion diagnostic, the regulatory frameworks and expectations are not identical, and these differences can have a significant impact on clinical trial planning, evidence requirements, timelines, and overall development strategy.
In this blog, we explore key similarities and differences between the US and EU approaches to companion diagnostics, including how a test may be classified, how clinical evidence is considered, and how regulatory interactions can influence development timelines. We also examine practical considerations for planning CDx clinical trials and discuss scenarios that illustrate where differences between the two jurisdictions can create challenges, as well as opportunities to address them early in development.
This content was originally presented as a Solution Circle during the RAPS Convergence 2026.
The core idea is the same for both the US and the EU. A companion diagnostic (CDx) provides information that is essential, not merely helpful, for the safe and effective use of a corresponding drug. FDA sets this out in its 2014 guidance, In Vitro Companion Diagnostic Devices, and the EU defines it at Article 2(7) of the IVDR (Regulation (EU) 2017/746).
Unfortunately, the details are not identical.
Where they align - Both definitions cover the two classic use cases: selecting patients likely to benefit and identifying patients at increased risk of serious adverse reactions. This shared core is why most biomarker-driven oncology eligibility tests are treated as CDx in both the US and EU without much friction.
Where they differ - Four gaps matter in practice:
A key takeaway from this discussion is that a device's US classification does not automatically travel to the EU. A single asset can end up on a PMA track in the US and a different conformity route in the EU, with differing levels of evidence, timelines, and engagement strategies. A documented, defensible rationale for each jurisdiction protects you in due diligence and inspection.
United States - Companion diagnostics typically follow the PMA (Class III) pathway. FDA expects the CDx to be approved, cleared, or granted De Novo contemporaneously with the therapeutic. FDA's 2020 class-labeling guidance also supports a single test labeled across a group of oncology drugs (one diagnostic test, many drugs), which is relevant for NGS panels and multi-drug tests.
European Union - Under IVDR, companion diagnostics default to Class C and require notified body conformity assessment. Under Article 48(3)/(4), the notified body must seek a scientific opinion from EMA (for centrally authorized medicines) or a national competent authority on the suitability of the device for use with the specific medicinal product. This step has no direct FDA comparison.
The structural difference that drives most timeline friction is FDA's culture of parallel, coordinated drug and device review versus the EU's sequential loop for the CDx: notified body, then medicines authority opinion, then CE mark with a completely separate review of the drug. This can make planning key milestone dates difficult when submitting in multiple jurisdictions.
A few principles that we touched on during the Solutions Circle:
We worked through two scenarios in the Solution Circle:
Compressed timeline scenario - Breakthrough Therapy designation pulls the filing date forward by six months while the CDx is mid-way through analytical validation and bridging specimens are still being collected. Meeting the new date would mean finalizing the cutoff before the full precision and reproducibility dataset is available.
Divergent requirement scenario - A sponsor pursues simultaneous US and EU approval. The PMA is already submitted, but the IVDR consultation process surfaces a request for additional clinical performance data that was not required in the US, putting EU launch timing at risk.
The questions raised by these scenarios are worth considering early in any companion diagnostic development program: At what point could a different regulatory decision have changed the development path? Are the right perspectives represented across clinical, regulatory, biostatistical, and diagnostic teams? And what decisions or regulatory interactions should be prioritized in the next 30 days?
For companies developing companion diagnostics for both the US and EU markets, understanding the differences between the two regulatory frameworks early can help reduce avoidable delays and support a more coordinated development strategy. Building regulatory considerations into clinical trial planning from the outset, establishing clear communication between the drug and diagnostic teams, and engaging with the relevant regulatory bodies early can help identify potential challenges before they become obstacles to development.
Companion diagnostic development continues to evolve, and regulatory expectations can vary depending on the specific drug, diagnostic technology, intended use, and development pathway. The resources below provide further guidance for those looking to explore the regulatory framework and clinical evidence considerations in more detail.
Contact us to discuss the possibilities.
Further reading