When Does Your Diagnostic Become an IVD in a…

One of the most fundamental questions in drug-diagnostic co-development is deceptively simple: when does the assay you are using in your clinical trial actually become a regulated IVD?

The answer has major implications for your timelines, your submission strategy, and your budget. Yet despite its importance, this question is often addressed too late, or not at all.

In this blog, we explore how intended use determines whether an assay falls within the scope of the IVDR and what this means for clinical trial strategy and compliance planning.

Understanding the Combined Study Ecosystem

When an investigational drug is combined with a diagnostic device in a clinical trial, we are often operating beyond a pharmaceutical study or a device investigation alone.

We are operating in a combined ecosystem.

That means:

Two regulatory frameworks, the Clinical Trials Regulation (CTR) and the In Vitro Diagnostic Regulation (IVDR)
Two studies
Two sponsor perspectives
One common goal: generating robust evidence to support approval of the drug and, where applicable, the device

This ecosystem includes:

The pharma sponsor, focused on the investigational medicinal product and CTR compliance
The device sponsor, focused on performance study and IVDR compliance
Sites and investigators implementing aligned but distinct requirements
Regulators and ethics committees reviewing the study under separate legal frameworks

The complexity is built into the structure. Recognizing it early is the first step toward managing it effectively.

It All Comes Down to How You Use It

Under the IVDR, it is not the device itself that determines regulatory status. Rather, it is how the device is used within the clinical trial. Where an assay is used in patient management decisions, it may fall within the scope of the IVDR.

Patient management decisions may include, for example:

Patient selection (inclusion or exclusion from a trial)
Allocation to treatment arms
Monitoring of drug safety or efficacy
Situations where assay results directly inform medical decisions

If your diagnostic drives these decisions, it is likely to fall within the scope of the IVDR.

In line with IVDR principles and related guidance, this assessment becomes relevant when European Union (EU) patients or EU-origin patient samples are involved. The regulatory assessment focuses on patient origin and intended use, rather than solely on where testing is performed.

When IVDR Does Not Apply

Not every use of a diagnostic in a clinical trial triggers IVDR obligations.

If an assay is used purely for patient stratification or exploratory endpoint analysis and does not inform medical management or treatment decisions, it may fall outside the scope of the IVDR.

Where such uses do not involve medical management decisions, the assay is generally not considered an IVD for that specific use within the clinical trial context.

The key reference here is Medical Device Coordination Group (MDCG) 2022-10, the Q&A document clarifying the interface between the CTR and the IVDR.

The guidance helps clarify the distinction between assays that influence patient care and those used purely for statistical or exploratory analyses.

For example, deciding to stop a drug, escalate therapy, or schedule extra visits based on assay results is clearly a medical management decision and triggers IVDR.
By contrast, assigning patients to "high biomarker expression" or "low biomarker expression" cohorts for exploratory efficacy analysis does not alter patient care and falls outside the regulation.

Your Options When Using an IVD in a Clinical Trial

Once you have established that the IVDR applies, several possible pathways depend on the device's regulatory status.

CE-marked device within intended purpose

If the device is CE-marked and used within its intended purpose without introducing additional risk, no additional IVDR performance study application is typically required, although sponsor oversight responsibilities remain. If there is additional risk, a notification under Article 70 is required.

CE-marked device outside intended purpose

If you are using a CE-marked device outside its intended purpose, for example, for a different patient population or clinical condition, it is no longer considered CE-marked for that use. It must be treated as a device for performance study.

Non-CE-marked device or research-use-only (RUO) assay

For non-CE-marked devices, including research-use-only assays or devices still in full development, the applicable pathway under the IVDR is generally to conduct a performance study, unless an in-house device exemption under Article 5(5) applies.

This requires full compliance with the IVDR's performance study requirements, regardless of whether you intend to commercialize the device. There is no "light" or simplified performance study pathway available under the IVDR.

Why This Matters Early

Getting this regulatory assessment wrong is costly.

If you assume your assay is exempt when it is not, you risk non-compliance and delays during authority review. On the other hand, taking an unnecessarily conservative approach may lead to avoidable regulatory activities and additional costs.

The practical advice is simple: map out the intended use of every assay in your protocol as early as possible. Determine which assays may cross into patient management territory based on their intended use and study design and plan the regulatory strategy accordingly.

Looking to Go Deeper?

The interface between the Clinical Trials Regulation (CTR) and the In Vitro Diagnostic Regulation (IVDR) remains one of the most complex aspects of drug-diagnostic co-development.

关于作者

Kirsten Van Garsse

MSc Biomedical Sciences · Business Unit Manager RA IVD & Representative Services

With over 20 years of experience in the diagnostics industry, Kirsten leads the IVD Regulatory Affairs business unit at QbD Group, guiding regulatory strategy and compliance across all IVDs with a focus on companion diagnostics.

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