Regulatory Q&As – Derogations and Exceptional Mechanisms

Under the EU Medical Device Regulation (MDR) 2017/745 and the EU In Vitro Diagnostic Regulation (IVDR) 2017/746, Competent Authorities may grant derogations allowing a device to be placed on the market or put into service without full conformity assessment procedures in specific circumstances, on a duly justified request.

According to Article 59 MDR and Article 54 IVDR, a national Competent Authority may authorise the placing on the market or putting into service of a specific device within the territory of a Member State in the interest of public health or patient safety or health, even if the conformity assessment procedures have not been fully completed.

This mechanism may be particularly relevant for devices addressing serious or life-threatening rare conditions where no alternative treatment options are available.

The European Commission, in exceptional cases relating to public health or patient safety or health, may, by means of implementing acts, extend for a limited period of time the validity of an authorisation granted by a Member State in accordance with paragraph 1 of the Article 59 MDR and Article 54 IVDR to the territory of the Union and set the conditions under which the device may be placed on the market or put into service.

This mechanism allows a device that has been authorised at national level to be made available in other Member States, provided that the conditions set by the Commission are met.

Although not specific to orphan devices, this provision may be relevant when a device addresses rare diseases affecting small patient populations across several Member States.

More information:

Regulation (EU) 2017/745 on Medical Devices (MDR) – Article 59

Regulation (EU) 2017/746 on In Vitro Diagnostic Medical Devices (IVDR) – Article 54

Under the EU Medical Device Regulation (MDR) 2017/745 and the EU In Vitro Diagnostic Regulation (IVDR) 2017/746, orphan medical devices are subject to the same post-market surveillance (PMS) obligations as other medical devices.

Manufacturers must establish and maintain a PMS system to actively and systematically collect, analyse and review data on the quality, performance and safety of the device once it has been placed on the market (Article 83 MDR; Article 78 IVDR).

Key elements of the PMS system include:

• Post-Market Clinical or Performance Follow-up (PMCF/PMPF) activities, as described in Annex XIV Part B MDR and Annex XIII Part B IVDR, aimed at continuously updating the clinical/performance evaluation and confirming the safety and performance of the device.
• Periodic Safety Update Reports (PSUR) for higher-risk devices, including Class IIa, IIb and III devices (Article 86 MDR) and Class C and D IVD devices (Article 81 IVDR).
• Vigilance reporting, including the reporting of serious incidents and field safety corrective actions to Competent Authorities in accordance with Article 87 MDR and Article 82 IVDR.

For orphan medical devices, PMS and PMCF are particularly important, because the limited size of the patient population may restrict the amount of clinical evidence that can be generated during the pre-market phase. This aspect is recognised in the guidance document MDCG 2024-10.

Where limitations in pre-market clinical data have been identified and considered acceptable, manufacturers should ensure that these gaps are addressed through well-defined and structured PMCF activities.

According to MDCG 2024-10, the PMCF plan for orphan devices should clearly describe:

• the limitations in clinical data identified during the pre-market phase;
• the justification for the proposed PMCF activities and how these activities will address the identified evidence gaps;
• the type of clinical and performance data to be generated in the post-market phase;
• the methodology and timelines for data generation, including expected numbers of patients treated with the device and predefined milestones for periodic analysis.

PMCF activities may include PMCF investigations, patient registries, observational studies, and other sources of clinically relevant real-world data collected in the post-market setting.

These activities support the continuous confirmation of the device’s safety, clinical performance, and benefit-risk profile throughout its lifecycle.

More information:

MDCG 2024-10

Regulation (EU) 2017/745 on Medical Devices (MDR) – Articles 83, 86, 87; Annex XIV

Regulation (EU) 2017/746 on In Vitro Diagnostic Medical Devices (IVDR) – Articles 78, 81, 82; Annex XIII

MDCG 2025-10

For orphan devices, patient registries are considered a valuable tool for building a comprehensive knowledge base on rare and often heterogeneous conditions and for supporting post-market surveillance (PMS) and PMCF activities. MDCG guidance recommends:

• Enrolling orphan devices in registries as part of the PMCF plan, where feasible.
• Using registries to collect representative data (ideally >90%) on patients with the disease/condition, including those receiving the orphan device.
• Preferably using registries established by national bodies or specialty medical associations.
• Justifying the choice of registry, addressing limitations in pre-market clinical data, and demonstrating sufficient access and data quality to confirm safety and performance throughout the device’s lifecycle.

Registries support continuous monitoring, help generate real-world evidence, and are particularly important for rare diseases where clinical data are limited.

More information:

MDCG 2024-10