The MDCG 2024-10 guidance provides detailed instructions on the clinical evaluation of orphan medical devices under the EU Medical Device Regulation (MDR). It addresses the unique challenges posed by the rarity of conditions treated by these devices and offers tailored regulatory pathways to ensure these essential products reach the market. Here’s a detailed summary focusing on the criteria for orphan devices and orphan indications, how to navigate the regulatory landscape, and procedural considerations for marketing these devices.
1. Criteria for orphan device and orphan indication
- Orphan device:
An orphan device is specifically designed to benefit patients by treating, diagnosing, or preventing a disease or condition that affects no more than 12,000 individuals per year in the European Union. The orphan device must address an unmet medical need, meaning there is either an insufficiency of available alternative treatments, diagnostics, or preventive options for the condition, or the device offers a significant expected clinical benefit over existing alternatives. This could be in terms of improved safety, efficacy, or ease of use.
These criteria reflect the quantitative and qualitative characteristics of an orphan device, referring respectively to the relevant epidemiology, and to the insufficiency of alternatives and expected clinical benefit.
- Orphan indication:
It refers to a specific use within a subpopulation, i.e., a device may have a specific intended purpose (indication) for an orphan population or subpopulation even if it also has broader applications. For example, a device designed for use in a rare pediatric condition may also be applicable to a larger adult population but still qualifies as an orphan device when used in the pediatric subgroup.
2. Navigating the regulatory landscape for orphan devices
Given the stringent requirements of the EU MDR, orphan devices face specific challenges in meeting pre-market clinical evidence standards. The MDCG 2024-10 guidance outlines a pathway to navigate these clinical challenges, ensuring that the regulatory process does not unduly delay access to these crucial devices.
- Tailored clinical evaluation- adaptation to rarity
Due to the limited number of patients, generating robust clinical data for orphan devices can be difficult. The guidance allows for flexibility in the type of evidence used, such as real-world evidence, patient registries, and data extrapolation from similar conditions or devices. Manufacturers are encouraged to justify any limitations in their clinical data by providing a thorough risk-benefit analysis.
Risk-benefit analysis must demonstrate that the benefits of the device outweigh the risks, taking into account the specific needs of the patient population, which may lack other treatment options.
- Use of alternative data sources- extrapolation and real-world evidence
The guidance supports the use of data from similar conditions or devices to extrapolate expected outcomes for the orphan condition. This approach helps overcome the challenge of small patient populations.
Additionally, real-world data can be crucial for demonstrating the device’s safety and performance, especially when clinical investigation are not feasible due to the rarity of the condition.
- Pre-market clinical investigation exceptions
While clinical investigations are generally required for Class III and Class IIb implantable devices, Article 61(4) of the MDR allows for exemptions in specific cases, such as when clinical data is already available, or the device is a modification of an existing device. These exemptions are particularly relevant for orphan devices, where generating new clinical data may not be practical.
3. Regulatory procedural considerations for orphan devices
- Market access with limitations
Despite the flexibility in data requirements, orphan devices must still comply with the general safety and performance requirements (GSPRs) of the EU MDR. The focus is on ensuring that the device’s safety and performance are adequately demonstrated, even if the evidence comes from alternative sources. Orphan devices may still be granted market access even with certain limitations in the pre-market clinical data, after a thorough evaluation of all clinical and non-clinical data, provided robust post-market surveillance is in place to monitor safety and effectiveness.
Manufacturers are required to set up an extensive Post-Market Clinical Follow-up (PMCF) plan to continuously assess the device’s performance and manage any emerging risks.
- Transparency and documentation
Instructions for Use (IFU) and Summary of Safety and Clinical Performance (SSCP) for implantable and Class III devices must clearly communicate the orphan status, limitations in pre-market clinical data, and provide guidance on reporting incidents and complaints.
- Collaboration and expert consultation
Manufacturers should engage with notified bodies early in the development process to align on clinical evaluation strategies and address potential challenges. For complex cases, especially with innovative orphan devices, consultation with expert panels can provide valuable insights into the clinical evaluation process and help tailor the evidence requirements to the specific context of the orphan condition.
The MDCG 2024-10 guidance offers a structured yet flexible approach for the clinical evaluation and regulatory approval of orphan medical devices under the EU MDR. By allowing for alternative data sources, accepting certain limitations in pre-market evidence, and emphasizing the importance of post-market surveillance, the guidance aims to balance the need for rigorous clinical evaluation with the challenges of developing devices for rare diseases. Manufacturers are encouraged to work closely with notified bodies to navigate the complex regulatory landscape and ensure that orphan devices reach the market without unnecessary delays.