Understanding the Orphan Device Framework

An Overview of Key Criteria, Regulatory Updates, and Market Comparisons for Manufacturers

The European Union’s regulatory framework for orphan devices has undergone significant refinement with the introduction of new guidance under the Medical Device Coordination Group (MDCG). 

[Download the EU Orphan Device Clinical and Regulatory Playbook]

This update, published in 2024, is designed to address the increasing shortage of medical devices used for rare conditions, particularly in specialized fields such as pediatric cardiology. Historically, manufacturers have withdrawn low-demand devices due to the high costs of compliance under the Medical Device Regulation (MDR). The new framework seeks to prevent further market losses while maintaining strict safety and performance standards.

Defining an Orphan Device

To qualify as an orphan device under the new EU guidance, a medical device must meet three key criteria:

• Prevalence Threshold – The device must address a condition that affects fewer than 12,000 patients per year in the EU. This number is derived from the FDA’s orphan drug definition and adjusted to reflect Europe’s larger population.
• Lack of Sufficient Treatment Options – There must be no adequate treatment currently available for the targeted patient group.
• Superior Benefit Over Existing Treatments – If treatments do exist, the orphan device must offer clear advantages, such as better patient outcomes, fewer complications, or reduced healthcare burdens.

The 12,000-patient threshold is not based on projected device sales but on the total number of patients diagnosed or treated for a specific condition within the EU each year. Manufacturers must provide robust epidemiological data to justify their claims, using registries, clinical studies, and professional society reports.

Key Elements of the New Framework

The MDCG guidance clarifies three core aspects of orphan device approval:

• Clinical Evaluation Requirements – Unlike traditional MDR approvals, orphan devices benefit from reduced clinical evidence requirements. Non-traditional data sources, including real-world evidence, computational modeling, and off-label data from legacy devices, may be considered.
• Procedural Aspects – Notified bodies oversee the approval process, but expert panels play an increasing role in reviewing orphan device applications. Manufacturers are encouraged to seek early-stage engagement with these panels to assess eligibility.
• Application Templates and Justification Guidelines – The guidance provides structured templates to help manufacturers submit comprehensive yet streamlined applications, ensuring transparency and efficiency in the review process.

How Europe Compares to Other Markets

The EU’s orphan device framework aligns with similar programs in other major markets, but with key differences:

• United States – The FDA has a Humanitarian Device Exemption (HDE) program for rare disease devices, but approval rates are low. Since its inception in the 1990s, only 78 orphan devices have been approved.
• Japan – Japan’s orphan device program is even more restrictive, with fewer than 25 approvals in over 30 years.
• Australia – Unlike the EU and the U.S., Australia allows more off-label use of existing devices, making its approach more flexible but less structured.

While orphan device approvals remain rare worldwide, the EU’s updated framework introduces clearer pathways, encouraging manufacturers to leverage structured dialogues and alternative evidence sources.

Why the Regulatory Shift Matters

The introduction of orphan device guidance represents a significant shift in European medical device policy. The framework acknowledges the urgent need to keep critical niche devices available, while balancing regulatory rigor with pragmatism. However, the pathway is still evolving, and early adopters of this designation will play a key role in shaping how regulators interpret and refine these policies in the coming years.

By understanding the nuances of the orphan device framework, manufacturers can strategically position themselves to take advantage of regulatory flexibility and market exclusivity, ensuring both patient access and business sustainability.