MDCG 2024-10: Clinical evaluation of orphan medical devices, explained

Who this applies to

This guidance applies to MDR medical devices and accessories of any risk class that serve a qualifying orphan population or have a distinct orphan indication. It is particularly relevant to rare diseases, paediatric populations and devices for which conventional study recruitment is difficult.

IVDs, custom-made devices, in-house devices and Annex XVI products are outside this guidance's scope.

The orphan-device criteria

A device qualifies under MDCG 2024-10 when it is specifically intended to benefit patients through treatment, diagnosis or prevention of a disease or condition that presents in no more than 12,000 individuals in the EU per year, and at least one of these is true:

• available alternatives are insufficient; or
• the device is expected to provide a clinical benefit over available alternatives or the state of the art.

The threshold may apply to a clinically valid subpopulation within a more common condition. Support the incidence estimate with authoritative EU-relevant literature or health statistics, explain any extrapolation and define the subpopulation without post-hoc commercial slicing.

Orphan status does not create market exclusivity. More than one device can qualify in the same therapeutic area.

Limited pre-market data can be acceptable—not absent evidence

The MDR requirements remain applicable. The manufacturer must identify which GSPRs and clinical-evidence requirements are met, what the current evidence cannot answer and why any remaining uncertainty is acceptable in light of the population, unmet need, state of the art and expected benefit.

Use all suitable existing evidence: non-clinical testing, prior investigations, compassionate or derogation use, legacy-device experience, literature, registries and use outside the EU. The clinical evaluation report should make the evidence gaps visible and connect each accepted limitation to a concrete post-market activity.

Expert panels and notified bodies

Manufacturers and notified bodies may seek expert-panel advice on orphan status and the clinical-evidence strategy. Engage early enough for the advice to influence the plan, not after the evidence package is fixed.

The notified body assesses the technical documentation under the normal MDR framework while considering the justified evidence limitations and PMCF commitments. Certification may include specific provisions, such as defined post-market studies, milestones and transparent information for users.

PMCF carries more weight

Where pre-market limitations are accepted, the PMCF plan must state what remains unknown, what data will resolve it, the expected patient numbers and timing, and when accumulated data will be analysed. Clinical investigations, registries and other real-world data can contribute; the plan must justify which sources are suitable.

For small populations, representative capture matters. The guidance encourages broad enrolment where feasible, long-term follow-up where benefits or risks develop slowly, and use of suitable national or professional registries.

What this means for you, practically

1. Prove status separately from conformity. Prepare the epidemiology, unmet-need and expected-benefit case before arguing about evidence sufficiency.
2. Inventory every evidence source. Include non-clinical, historical, off-label, registry and post-market data, with limitations stated.
3. Design around the population. Involve clinical experts, patients or caregivers and multiple centres where proportionate.
4. Make uncertainty traceable. Map each accepted pre-market gap to PMCF endpoints, recruitment assumptions, milestones and escalation criteria.
5. Seek dialogue early. Align orphan status and the evidence strategy with the notified body and, where useful, the expert panel before pivotal work begins.

Read the official MDCG 2024-10 guidance.