Table 3.

Comparative overview of orphan medical device frameworks: EU vs. US.

Dimension	EU (EU MDR 2017/745)	US (HUD/HDE framework)
Legal orphan designation	No. Defined only in MDCG 2024–10 (non-binding guidance).	Yes. Humanitarian Use Device (HUD) designation, legally defined since 1990.
Prevalence threshold	≤ 12,000 individuals/year across the EU (guidance only). Definition differs from orphan-drug criteria (≤ 5 in 10,000) and from US device thresholds, creating cross-sector inconsistencies.	≤ 8,000 individuals/year in the US (statutory). Threshold distinct from the US orphan-drug definition (≤ 200,000 patients), highlighting the absence of a uniform standard across product types.
Regulatory pathway	MDR conformity assessment; possible Article 59 derogation (case-by-case, no market status).	Humanitarian Device Exemption (HDE) pathway.
Evidentiary standard	“Expected clinical benefit” + PMCF; allows extrapolation (MDCG 2024).	“Probable benefit” without full demonstration of effectiveness.
Post-market obligations	High: ≥ 90% of eligible patients in PMCF recommended.	Required: IRB oversight and annual reporting to FDA.
Economic incentives	Limited and structurally insufficient. Orphan medical devices may rely on intellectual property rights (IPRs), yet securing and maintaining patents is challenging due to stringent regulatory standards, software–hardware updates, and exclusions under Art. 53(c) EPC (28). In the absence of a legal orphan-device framework, no complementary incentives (such as data exclusivity, fee waivers, or market protection) exist (30, 34)	Restricted incentives. IPRs available, but profit prohibited except for pediatric uses; capped annual distribution (8,000 units). HDE status nonetheless provides a legal route with predictable evidentiary flexibility and limited commercial feasibility.
Reimbursement pathway	National-level, heterogeneous; no EU-wide orphan-specific HTA framework.	Case-by-case; no automatic CMS coverage for HDE devices.
Supply continuity measures	Six-month notice before withdrawal (MDR Art. 123); no obligation to maintain availability.	No obligation to continue supply once commercially non-viable.
Binding legal status	Soft law (guidance); no statutory recognition of orphan status.	Binding statute under Safe Medical Devices Act.
Integration with rare-disease strategy	Fragmented; not aligned with EU rare-disease plans or drug incentives.	Partial alignment; HUD/HDE recognized in rare-disease policy but not fully integrated.
Alignment of incentives for small vs large firms	Structure disproportionately favors large diversified manufacturers able to absorb compliance and IP costs. SMEs (the main innovators in rare-disease devices) face prohibitive regulatory and financial barriers.	More balanced: centralized FDA guidance and predictable criteria allow smaller innovators to engage earlier, though profit restrictions still limit investment sustainability.