Medical device simplification in detail: orphan and breakthrough device designations

We wrote recently about the European Commission’s proposals to simplify the EU Medical Device Regulation (“MDR”)[1] and EU In Vitro Diagnostic Medical Device Regulation (“IVDR”)[2]. That article can be found here.

One of the most striking aspects of the simplification proposal is the introduction of statutory orphan and breakthrough designations for certain categories of medical device and in vitro diagnostic medical device (“IVD”) which serve unmet medical needs in the EU. Under the proposal, devices which obtain orphan or breakthrough designation will be entitled to certain benefits before and during the conformity assessment process which should allow for faster access to the EU market.

In this article, we fully explain the orphan and breakthrough designations set out in the simplification proposal and think through how impactful the proposal is likely to be in this regard.

Breakthrough designation

Under the proposal, a device will be entitled to breakthrough designation if it meets the following criteria:

1. it is expected to introduce in the Union a high degree of novelty with respect to the device technology, related clinical procedure or the application of the device in clinical practice;
2. it is expected to provide a significant positive clinical impact on patients or public health, for a life-threatening or irreversibly debilitating disease or condition, by either of the following:
   1. offering a significant positive clinical or health impact compared to available alternatives and the state of the art;
   2. fulfilling an unmet medical need where there is an absence or insufficiency of available alternative options for that purpose.

To summarise these criteria colloquially, a device will be entitled to breakthrough designation if: 

• it is “highly novel”; and
• it will have a significant positive health impact on a life-threatening or debilitating disease or condition, either:
  • by being better than the available alternatives, or
  • by serving a medical need for which alternatives are non-existent or inadequate.

Further guidance on these concepts is provided in the MDCG guidance on Breakthrough Devices that was issued alongside the proposal in December 2025[3] .

To obtain breakthrough designation for a device, either the manufacturer or the Notified Body responsible for the conformity assessment will need to submit a substantiated request to an expert panel convened by the European Medicines Agency (“EMA”), which will provide its opinion on whether the breakthrough criteria are met. This opinion will be published on a dedicated website.

The opinion of the expert panel will not be binding, but the Notified Body will be obliged to give the opinion “due consideration” and duly justify with reasons any departure from the expert panel’s opinion.

Orphan designation

Under the proposal, a device will be entitled to orphan designation if it meets the following criteria:

1. it is intended for the treatment, diagnosis, or prevention of a disease or condition that presents in not more than 12,000 individuals in the Union per year;
2. at least one of the following criteria are met:
   1. there are insufficient available alternatives;
   2. the device is expected to provide a clinical benefit compared to available alternatives or the state of the art, taking into account both device-specific factors and patient population-specific factors.

The criteria for orphan designation are simpler than for breakthrough designation. Orphan designation is intended for devices targeting rare diseases and conditions, where there is a lack of available alternatives or the device will be better than existing alternatives.

As with breakthrough designation, to obtain orphan designation for a device, either the manufacturer or the Notified Body responsible for the conformity assessment will need to submit a substantiated request to an expert panel, which will provide its opinion on whether the orphan criteria are met. Again, the Notified Body will have to give the opinion “due consideration” and duly justify with reasons any departure from the expert panel’s opinion.

Interestingly, there is already an MDCG guidance document on orphan devices dating from June 2024[4]. The MDCG breakthrough guidance indicates that the MDCG orphan guidance remains relevant to the new scheme under the simplification proposal.

Benefits of orphan or breakthrough designation

The manufacturer of a device that obtains orphan or breakthrough designation will be entitled to the following benefits:

• Access to scientific advice from an expert panel convened by the EMA on clinical development strategy and appropriate preclinical or clinical data for the clinical evaluation of the device.
• “Priority” rolling review from the Notified Body during conformity assessment. According to the MDCG breakthrough guidance, this means that the device should be prioritised “during planning and resource allocation.”
• During conformity assessment, the Notified Body will be obliged to grant the Certificate of Conformity based on limited clinical data (e.g. where long term evidence is lacking) if the benefit of the immediate availability on the market of the device outweighs the risk associated with the limitations of the clinical data, or the benefit-risk-ratio of the device is favourable and the manufacturer commits to providing additional data from post-market clinical follow-up (“PMCF”) activities.
• During conformity assessment, the Notified Body will be obliged to have due regard to any opinion of an expert panel obtained by the manufacturer or Notified Body. This will influence the Notified Body’s assessment of whether the benefit of device availability outweighs limitations in clinical data.

In short, the proposal aims to facilitate market access for breakthrough and orphan devices, including where clinical data is limited. PMCF studies will be used in such cases to generate further clinical data. The MDCG breakthrough and orphan guidance indicate that Notified Bodies should also impose conditions on certificate validity to mitigate the risks associated with limited clinical data. For instance, requiring the manufacturer to disclose on the label that the device has breakthrough or orphan designation, to draw attention to aspects of device use where the risk profile is not well understood (e.g. long term use), and to prominently display to users how safety incidents can be reported to the manufacturer.

There is also an interesting provision for legacy devices (that is, devices with a valid certificate granted under the former medical device directives) that obtain orphan designation. By derogation from the ordinary transition periods under the MDR and IVDR, Certificates of Conformity for legacy orphan devices will remain valid indefinitely, allowing them to continue to be placed on the market in the EU without obtaining a new Certificate under the MDR or IVDR. This will be provided that they maintain their orphan designation and do not undergo any significant changes in their design or intended purpose.

A history lesson

As noted above, while the Commission only now proposes to introduce orphan and breakthrough designations into the MDR and IVDR, there has been MDCG guidance on orphan devices since 2024. Based on the references to this guidance in the new MDCG guidance on breakthrough devices, the Commission still considers the orphan guidance to be relevant to the proposed statutory regime (although some updates might be expected).

What is even more striking is that there was a MEDDEV guidance document on the clinical evaluation of so-called “breakthrough devices” under the former medical device directives as early as 2019[5]. The MEDDEV guidance used a broader definition of a “breakthrough” device to the simplification proposal, asking only whether the device serves a life-threatening or debilitating disease or condition and whether available alternatives are adequate. There was no requirement that the device be novel or serve a rare disease or condition. As such, many devices that would be designated “orphan” or “breakthrough” under the present proposal would have been considered “breakthrough” under the old MEDDEV guidance.

The approach adopted by the MDCG orphan guidance and the MEDDEV breakthrough guidance to expediting market access for designated devices was remarkably similar to the approach adopted under the proposal:

• Where available evidence shows that a device will serve an unmet medical need, the Notified Body should be prepared to accept a lower standard of clinical data, e.g. based on a smaller patient population with a lack of long-term follow-up.
• To compensate for the lower standard of clinical data, the Notified Body should grant the Certificate of Conformity subject to appropriate conditions:
  • use of PMCF studies,
  • special warnings to patients and users, and
  • heightened post-market surveillance.

As such, Notified Bodies have been able to grant Certificates of Conformity for orphan and breakthrough devices on the basis of a lower standard of clinical evidence, and regulatory guidance has encouraged them to do so where justified and subject to appropriate conditions, since at least 2019. If only for legal certainty, it is welcome news that these procedures are codified. Leaving this aside, what is really changing with the simplification proposal?

Assessing the impact of orphan and Breakthrough designation under the simplification proposal

The orphan and breakthrough designations in the simplification proposal are part of a long term trend of seeking to facilitate market access for devices that serve unmet medical needs, and they go further than the previous measures which were only set out in guidance.

Here are some of the key points:

1. Expert panels: determining whether a device qualifies as orphan or breakthrough is reassigned from Notified Bodies to expert panels convened by the EMA. Expert panels already exist under the MDR and IVDR and can provide advice to Notified Bodies on orphan designation and the suitability of clinical evidence, but under the proposal, the manufacturer will be able to apply directly to the expert panel for orphan or breakthrough designation and for scientific advice and will be able to do so earlier in the conformity assessment process.
2. Notified Body obligations: currently, a Notified Body considering whether to grant a conditional Certificate of Conformity for an orphan or breakthrough device must satisfy itself that it is appropriate in the circumstances to grant on the basis of a lower standard of clinical evidence. This carries risk for a Notified Body and there is little incentive for a Notified Body to take such a risk. Under the proposal, the Notified Body will be obliged to grant a Certificate of Conformity for an orphan or breakthrough device where the benefit of the immediate availability of the device on the market outweighs the risks associated with a relative lack of clinical evidence submitted by the manufacturer. The decision whether to grant a Certificate in these circumstances will be informed by opinions issued by the expert panels. In particular, a Notified Body will be required to justify any decision to depart from an expert panel opinion. While it remains to be seen what approach will be adopted, it seems likely that a Notified Body will tend to defer to the opinion of an expert panel, although a Notified Body will be entitled to ask an expert panel to clarify its opinion. The new statutory duties for Notified Bodies and more readily available expert panel opinions should increase the likelihood of Certificates for orphan and breakthrough devices being granted on the basis of limited clinical evidence.
3. Priority rolling review: this is new and in theory should allow faster conformity assessments for breakthrough and orphan devices. However, it is not clear exactly what “priority” means in terms of what a manufacturer is entitled to demand from a Notified Body. The MDCG breakthrough guidance refers to priority rolling review only briefly and does not clarify matters.
4. Transition periods for legacy orphan devices: this is also new and should keep orphan devices the subject of an existing certificate under the former medical device directives on the market indefinitely, provided they undergo no significant change in their design or intended purpose and maintain their orphan designation.

Overall, the breakthrough and orphan designation component of the proposal should provide manufacturers with a fair amount to be excited about. They indicate that the EU is prepared to accept a greater degree of risk in return for ensuring that manufacturers of novel devices and devices serving unmet medical needs choose to launch early in the EU and are not deterred by the regulatory burden.

As ever, caution must be exercised. For instance, it remains to be seen whether or not expert panels will adopt a conservative approach to orphan and breakthrough designation or to clinical data requirements, and how Notified Bodies will work with expert panels. However, this appears to be a step in the right direction, and it will be interesting to see how these proposals develop as they move through the EU legislative process.