Clinical Evaluation of Orphan Medical Devices

What is a Orphan Medical Device?

Orphan devices (ODs) are medical devices or their accessories, which are intended to be used for diseases or conditions affecting only a small number of individuals each year. By their nature, these ‘orphan devices’ are only intended for use in a small number of individuals each year. Many rare diseases have very few diagnostic or therapeutic options and the orphan device can be particularly crucial to fulfil an otherwise unmet medical need.

The MDCG 2024-10 guidance, published in June, provides criteria for determining when a medical device or an accessory for a medical device should be regarded as ‘orphan device’ under the Medical Devices Regulation 2017/745 (MDR).


When a device is an orphan device?

First of all, to qualify as orphan device status, a device need to meet some criteria. The device is specifically intended to benefit patients in the treatment, diagnosis, or prevention of a disease or condition that presents in not more than 12,000 individuals in the European Union per year; and at least one of the following criteria are met:

  • there is insufficiency of available alternative options for the treatment, diagnosis, or prevention of this disease/condition, or
  • the device will offer an option that will provide an expected clinical benefit compared to available alternatives or state of the art for the treatment, diagnosis, or prevention of this disease/condition, taking into account both device and patient populationspecific factors.


What are the clinical evidence requirements for these devices?

Having regard to the challenges to generate clinical data in the pre-market phase, orphan devices may

be granted market access with acceptable limitations in the amount and quality of pre-market clinical

data, provided that appropriate measures are implemented.

As with all devices, orphan devices must meet the General Safety and Performance Requirements that apply to it. When a manufacturer specifies the level of clinical evidence for an orphan device, he needs to include the clinical disease/condition being treated, the anticipated risks, the insufficiency of alternatives and unmet medical need, and the expected clinical benefit that the device offers, balanced against the anticipated risks.

The limitations in the ability to generate pre-market clinical data (it is not feasible or proportionate to generate further clinical data within an acceptable time) increase the importance and relevance of robust, high-quality non-clinical data. All potential sources of non-clinical data should be considered for orphan devices. If the non-clinical data provide substantial high-quality evidence to support the safety and performance of the orphan device and its expected clinical benefit this can reduce the burden of required pre-market clinical data and can help to justify CE marking with limitations in clinical data that can be met through PMCF activities.

If pre-market limitations in clinical data have been identified and deemed acceptable, it is important that these limitations will be filled through well-defined and structured Post Market Clinical Follow-up (PMCF) activities.


How is done the conformity assessment?

The OD status of the device should be checked by the notified body as early as possible, for example

as part of structured dialogue before or during initial conformity assessment activities. When the orphan device status is established, the technical documentation should be assessed following the same principles as for non-orphan medical devices. Taking into account the acceptability of limited pre-market clinical data and appropriate PMCF activities to generate additional clinical data.

The MDCG acknowledged in its position paper MDCG 2022-14, point 17 that the use of certificates

with conditions will contribute to increasing the necessary flexibility to apply the reinforced clinical evidence requirements to devices that have a demonstrable track record of safety. Orphan devices for which the pre-market clinical evidence is deemed sufficient but needs to be completed or confirmed through PMCF, are a good example where notified bodies can make use of the possibility to issue certificates with specific conditions or provisions.

The guidance includes the possibility for manufacturers and notified bodies to seek advice from European Medicines Agency expert panels on the orphan device status and the clinical data needed for their clinical evaluation.