The Harmonisation Gap: Managing EU Performance Study Submissions

Two Regulatory Worlds, One Combined Study

In a combined drug-diagnostic study, the pharmaceutical side benefits from a centralized submission through the Clinical Trial Information System (CTIS).

One application covers all participating Member States, supported by a coordinated review process and defined timelines. The system is designed for efficiency, even if not always perfect in practice.

The IVD side does not yet benefit from a comparable centralised submission system.

In the absence of a fully functional European Database on Medical Devices (EUDAMED), performance study applications must still be submitted individually to each participating Member State, including countries where samples are collected.

Each country has:

• Its own expectations
• Its own format requirements
• Its own operational process

Some countries use dedicated e-portals. Others accept submissions by email. Some still require printed binders shipped physically by post.

This divergence creates substantial administrative complexity that can catch sponsors off guard.

It is also important to understand that the diagnostic submission remains entirely separate from the clinical trial application for the drug.

You cannot assume that completing the pharma submission covers the device.

Even within authorities themselves, different departments handle the two frameworks. They are fundamentally separate systems.

Sample Origin Triggers Obligations

One important and frequently misunderstood point is that IVDR applicability is driven by:

• The origin of the patients
• The intended use of the assay

It is not determined solely by where testing takes place.

If samples are collected from EU patients, the IVDR will generally apply, even if analysis takes place outside the EU.

This also applies to companion diagnostic studies using leftover samples.

Under Medical Device Coordination Group (MDCG) 2025-5 guidance, notification under Article 58(2) is required in all Member States participating in the performance study where the study falls within IVDR scope.

This may include:

• Countries where samples are collected
• Countries where analysis takes place
• Countries where relevant performance study activities occur

The practical implication is clear: sponsors must assess obligations across the full operational footprint of the study, not only where laboratory testing occurs.

Timelines That Vary Widely

While the IVDR defines indicative review timelines for competent authorities, there are no harmonised timelines for ethics committee reviews.

Depending on the country and the submission strategy used, approval timelines may range from three to nine months.

This is a planning reality that must be incorporated from the outset.

Different Member States apply different procedural approaches:

Strategic Submission Approaches

Smart sequencing can significantly improve timelines.

Countries with consolidated review systems often provide faster pathways to first patient in.

Starting with these "easier" countries and onboarding more complex Member States later can help maintain overall programme timelines.

Similarly, some sponsors first initiate studies in the United States (US), where approval timelines for performance studies are often shorter, while EU submissions continue in parallel.

Another critical consideration is the coordination between:

• The pharmaceutical clinical trial application
• The IVD performance study submission

Several competent authorities increasingly expect the pharmaceutical dossier to be submitted before accepting the IVD application.

Submitting the performance study too early may result in:

• Requests to withdraw
• Application holds
• Delayed review timelines

This is not theoretical. We have seen this happen in practice.

Plan for the Patchwork

The current lack of harmonisation is unlikely to disappear overnight.

Initiatives such as the COMBINE programme are actively exploring whether performance study applications can eventually be integrated into CTIS workflows.

Meanwhile, EUDAMED is expected to streamline submissions and support more coordinated assessments in the future.

For now, however, regulatory intelligence remains a critical success factor.

Sponsors must understand:

• Which portals each Member State uses
• Which formats are expected
• How national review processes function
• How submission strategies impact timelines

This is where experienced regulatory support can make a measurable difference to programme execution and approval timelines.

Looking to Go Deeper?

Combined drug-diagnostic studies continue to expose operational and regulatory grey zones across Europe.

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