When facing the complexity and cost of a full In Vitro Diagnostic Regulation (IVDR) performance study, it is tempting to consider the in-house device exemption under Article 5(5) as a faster, lighter alternative.
We hear it very often: "We are going to start with an in-house device and then switch to a CE-marked assay later."
In practice, this route comes with its own substantial regulatory obligations, and underestimating them can derail your programme.
In this blog, we explore what Article 5(5) actually requires, why many organisations underestimate the associated obligations, and how an apparently simpler route can ultimately create additional regulatory and operational complexity.
What Article 5(5) Actually Requires
Article 5(5) of the IVDR allows health institutions to manufacture and use devices in-house without obtaining CE marking, provided they meet a strict set of conditions. These include, amongst others:
- Operating under a documented quality management system (QMS)
- Restricting the device to internal use without transfer between legal entities
- Maintaining publicly available declarations of compliance
- Meeting the General Safety and Performance Requirements (GSPR) laid out in Annex I
That last point is where many organisations encounter difficulties.
Annex I compliance means the device's clinical performance must be established and documented. Analytical verification alone is not enough.
If you cannot demonstrate that the test result actually predicts clinical outcomes or informs safe patient care, the exemption does not hold.
Without established and documented performance, the device may no longer qualify for the Article 5(5) exemption and may instead fall within the scope of IVDR performance study requirements, triggering the very regulatory obligations you were trying to avoid.
Who Actually Qualifies as a Health Institution?
It is also important to understand which organisations actually qualify for the exemption.
Article 5(5) applies only to health institutions, meaning organisations whose primary purpose is the care or treatment of patients or the promotion of public health.
This may include:
- Public hospitals
- National reference laboratories
- Private hospitals or laboratories meeting these criteria
It does not generally include:
- Research laboratories
- Universities, unless legally linked to hospitals
- Contract Research Organisations (CROs)
- Laboratories providing diagnostics exclusively to clinical trial sponsors
This distinction is critical and often underestimated early in development planning.
ISO 15189 Is Not Sufficient
A common misconception is that ISO 15189 accreditation satisfies the requirements of Article 5(5).
It does not.
ISO 15189 demonstrates that a laboratory can run a test consistently, but it does not demonstrate whether the test result is clinically meaningful for the intended purpose.
It also does not address device manufacture, which under Article 5(5) must fall within the health institution's quality management system.
A laboratory may prove it can perform an assay with good reproducibility, but that is a question of analytical competence.
Clinical validation, meaning evidence that the test result actually predicts clinical outcomes, is a separate and non-negotiable requirement.
If clinical performance has not been demonstrated, the device cannot rely on Article 5(5), even if:
- The laboratory is ISO 15189-accredited
- The device is used exclusively within a clinical trial
- Assay results are relevant to patient management or safety
Relying on ISO 15189 alone, therefore, leaves a critical gap, as Article 5(5) requires the health institution to control not only how the test is performed, but also how the device is designed, manufactured, maintained, and changed over time.
Additional Obligations Sponsors Often Underestimate
Meeting Article 5(5) is not simply a formal declaration.
The IVDR explicitly requires:
- Manufacture and use under a quality management system
- No transfer of the device between legal entities
- Publicly available documentation and declarations of compliance (including lab details, device identification, and compliance with Annex I or justified deviations)
- Additional documentation for Class D devices
- Incident reporting obligations to the competent authority and within the health institution
- Openness to competent authority oversight and inspections
The exemption also does not apply if manufacturing exceeds what is justified by the needs of the health institution or evolves into industrial-scale manufacturing.
These obligations create a substantial operational and regulatory burden that many sponsors initially underestimate.
The Commercialisation Trap
Another major risk concerns future commercialisation.
Clinical validation data generated under an Article 5(5) exemption may not be directly usable for future commercialisation activities.
If there was no formal performance study application, there may be no formally recognised performance study. And without a performance study conducted under the applicable regulatory framework, the resulting data may not qualify as acceptable performance data for regulatory submissions without additional bridging or validation.
Transitioning from an in-house device to a commercial CE-marked in vitro diagnostic (IVD) often requires:
- Bridging studies
- Additional analytical validation
- Additional clinical validation
- Expanded supporting documentation
This can significantly erode the perceived early advantage.
As Jules Petit from GenDx explained during our recent webinar, even technically identical assays become different devices in the eyes of regulators once moving from an in-house context to a commercial manufacturer.
Everything must be bridged: the analytical validation, the clinical validation, and the supporting documentation.
Inconsistent Interpretation Across Member States
One particularly striking example from a recent industry conference illustrates the practical risks.
A sponsor conducted a clinical trial using an in-house device under the Article 5(5) exemption, and three different national competent authorities provided three different responses:
- One accepted the approach
- One rejected it
- One was still deliberating
This inconsistency reflects the broader reality that local law determines health institution accreditation and oversight.
Laboratories accredited in one Member State may not necessarily be recognised in another.
The Bottom Line
Using an in-house device under Article 5(5) can be a valid route for early-stage development, particularly when future commercialisation remains uncertain.
However, the exemption is not a shortcut.
Any involvement of third parties, such as device manufacturers, must remain strictly limited and may not undermine the health institution's responsibility for manufacturing and use of the in-house device under Article 5(5).
The practical takeaway is clear:
- Plan for full GSPR compliance from the start
- Confirm that your institution genuinely qualifies
- Assess the downstream impact on future regulatory and commercialisation strategy before committing to this pathway
Looking to Go Deeper?
The practical realities of Article 5(5), IVDR grey zones, and drug-diagnostic co-development remain highly complex and often misunderstood.
Watch the webinar: Grey Zones & Growing Pains in Drug-Diagnostic Co-Development
Watch now关于作者
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.
Navigate Regulatory Complexity with Confidence
Navigate complex regulatory landscapes with expert guidance across pharmaceuticals, medical devices, and IVD.
Read more
