Clinical Evaluation of Orphan Devices: Navigating MDCG 2024-10

July 2, 2024

The Medical Device Coordination Group (MDCG) recently released guidance MDCG 2024-10, focusing on the clinical evaluation of orphan medical devices. This comprehensive guidance aims to address the unique challenges and regulatory requirements for orphan devices under the Medical Device Regulation (MDR) 2017/745. Orphan medical devices are intended for rare diseases or conditions, affecting a small patient population. This article delves into the key aspects of the new guidance, emphasizing the clinical evaluation processes and the implications for manufacturers.

Introduction to Orphan Devices

Orphan medical devices play a crucial role in providing diagnostic or therapeutic solutions for rare diseases or conditions, which often lack adequate medical alternatives. The MDR has stringent requirements for clinical evidence, which pose significant challenges for orphan devices due to their limited patient population and the ethical concerns surrounding clinical investigations in vulnerable groups, such as children.

Defining Orphan Devices

Orphan devices (OD) are defined as medical devices or accessories intended for the treatment, diagnosis, or prevention of diseases or conditions that affect no more than 12,000 individuals annually in the European Union. To qualify as an orphan device, the device must meet one of the following criteria:

  • There is an insufficiency of available alternative options for the treatment, diagnosis, or prevention of the disease or condition.
  • The device provides an expected clinical benefit compared to available alternatives or the current state of the art, taking into account both device-specific and patient population-specific factors.

Scope of Applicability for MDCG 2024-10

The MDCG 2024-10 guidance does not apply to the following types of devices:

  • Custom-made devices: According to EU MDR Article 2(3).
  • In-house devices: According to EU IVDR Article 5(5).
  • Products without an intended medical purpose: According to EU MDR Annex XVI.
  • In vitro diagnostic medical devices: Devices covered under the In Vitro Diagnostic Medical Devices Regulation (IVDR) 2017/746.

Evaluating Clinical Data Limitations

For orphan devices, it is acknowledged that the scarcity of available patients and the nature of the conditions often limit the amount of comprehensive clinical data that can be gathered pre-market. Therefore, the MDCG allows for certain limitations in pre-market clinical data under specific conditions:

  • There must be enough existing non-clinical and clinical data to suggest that the device can perform its intended purpose with an acceptable level of safety.
  • Any limitations in the clinical data must be transparently communicated to healthcare professionals and users.
  • The manufacturer must implement an effective post-market surveillance (PMS) strategy and post-market clinical follow-up (PMCF) plan to gather further data and validate the clinical performance and safety of the device post-launch.

Importance of Non-clinical Data for OD

Non-clinical data play a pivotal role in supporting the safety and efficacy of orphan devices, especially when clinical data are limited. This data can include:

  • Laboratory and animal studies that provide preliminary safety and performance insights.
  • Engineering and bench tests that demonstrate the device’s mechanical and functional integrity.
  • Computational modeling that predicts device behavior in various scenarios.

Manufacturers are encouraged to utilize robust non-clinical data to justify the safe use of their devices, reducing the reliance on extensive pre-market clinical trials which may not be feasible for orphan devices.

Expert Panel Consultation: Enhancing the Orphan Device Certification Process

Section 11 of the MDCG 2024-10 guidance outlines the role of expert panels in the evaluation process of orphan medical devices. This section emphasizes the importance of obtaining external expert advice to ensure that orphan devices meet stringent safety and efficacy standards before they reach the market. The involvement of expert panels is particularly crucial given the unique challenges associated with the development and evaluation of devices intended for rare diseases.

Purpose of Expert Panel Consultation

The consultation with expert panels serves multiple purposes:

  • Verification of Orphan Device Status: Expert panels assist in verifying the orphan status of a device, ensuring that the manufacturer’s justification aligns with the regulatory definitions and requirements.
  • Assessment of Clinical Evidence: Panels review the sufficiency and appropriateness of both clinical and non-clinical data to support the intended use of the device. This is especially critical when traditional clinical trial routes are impractical due to the rarity of the condition the device is designed to treat.
  • Guidance on Regulatory Compliance: Expert panels provide guidance on whether the device meets the overall regulatory requirements, including safety and performance standards outlined in the MDR.

Process of Expert Panel Involvement

  1. Early Engagement: It is recommended that notified bodies engage with expert panels as early as possible, ideally during the pre-assessment phase of the device certification process. This early engagement allows for a structured dialogue between the manufacturer, the notified body, and the expert panel, facilitating a thorough and informed evaluation.
  2. Review of Manufacturer’s Submission: The expert panel reviews the documentation provided by the manufacturer, focusing on the justification for the orphan device classification and the adequacy of the clinical and non-clinical evidence.
  3. Issuance of Recommendations: Based on their review, the expert panel issues recommendations that can significantly impact the certification process. These recommendations might pertain to additional data requirements, modifications to the device or its intended use, or specific post-market surveillance strategies.
  4. Influence on Notified Body Decisions: The advice provided by the expert panel is taken into consideration by the notified body in their final decision-making process. While the notified body is not bound to follow the panel’s recommendations, any deviations must be well justified in the assessment report.

Benefits of Expert Panel Consultation

The involvement of expert panels in the certification process of orphan devices brings several benefits:

  • Enhanced Device Safety and Efficacy: Expert panels contribute to a higher level of scrutiny, potentially increasing the safety and efficacy of devices approved for rare conditions.
  • Reduced Risk of Post-Market Issues: By addressing potential issues during the pre-market phase, expert panels help reduce the risk of significant complications once the device is in clinical use.
  • Increased Confidence Among Stakeholders: The input from expert panels can increase confidence among healthcare providers, patients, and regulatory bodies regarding the reliability and effectiveness of orphan devices.

Notified Bodies

Notified bodies play an essential role in determining whether a device qualifies as an orphan device before its certification. This critical initial assessment should be conducted as early as possible to ensure compliance and readiness for market entry:

  1. Verification of Orphan Device Status:
    • The orphan status of the device should be verified at the earliest opportunity, ideally during a structured dialogue before or during the initial conformity assessment activities. This verification involves a thorough assessment of the evidence provided by the manufacturer, which must justify the classification of the device as an orphan, as detailed in section 4.2 of the guidance.
  2. Assessment of Clinical and Non-clinical Data:
    • Notified bodies are tasked with evaluating the sufficiency and quality of both clinical and non-clinical data submitted by the manufacturer. This evaluation is crucial to ensure that, despite the acknowledged limitations typically associated with clinical data for orphan devices, there is robust evidence to demonstrate that the device can perform safely and effectively.
  3. Compliance with Regulatory Requirements:
    • The review process must confirm that the device complies with all relevant regulatory requirements, with a focus on safety and performance standards as specified in the Medical Device Regulation (MDR).

Additionally, if applicable, notified bodies may take into consideration advice provided by an expert panel. This advice can significantly influence the assessment, particularly regarding the device’s status as an orphan and the adequacy of the clinical evidence. This expert input ensures a comprehensive review process, aligning the device assessment with the highest standards of regulatory compliance and patient safety.

Conclusion for the Clinical Evaluation of Orphan Devices

The MDCG 2024-10 guidance provides a structured approach for the clinical evaluation of orphan medical devices, balancing the need for clinical evidence with the practical challenges of studying rare conditions. By allowing for limitations in pre-market clinical data and emphasizing robust non-clinical evidence and post-market follow-up, the guidance aims to facilitate the market access of orphan devices, ultimately improving patient care for rare diseases. Manufacturers must navigate these requirements carefully, leveraging robust non-clinical data and detailed documentation, to ensure that orphan devices meet regulatory standards while addressing the unique needs of patients with rare conditions.

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