Navigating IVDR Performance Studies: Key Insights from MDCG 2025-5 Q&A

The European Medical Device Coordination Group (MDCG) has released its latest guidance, MDCG 2025-5, a comprehensive Questions & Answers document addressing performance studies for in vitro diagnostic medical devices (IVDs) under Regulation (EU) 2017/746 (IVDR). This document, published in June 2025, aims to clarify various aspects of performance studies, providing essential insights for manufacturers, sponsors, and other stakeholders in the IVD sector. This article summarizes the key takeaways from MDCG 2025-5, offering a concise overview for professionals navigating the complexities of IVDR compliance.

Understanding Performance Studies under IVDR

MDCG 2025-5 reiterates the IVDR's definition of a performance study as an undertaking to establish or confirm the analytical or clinical performance of an IVD. It clarifies that performance studies are distinct from clinical or laboratory methods, focusing solely on device performance. The guidance emphasizes that not all performance studies require fresh human specimens; data can be sourced from curated databases, registries, or previously collected patient material, and even contrived samples may be used for certain studies.

Analytical vs. Clinical Performance Studies

The document distinguishes between analytical and clinical performance studies:

• Analytical Performance Studies: These studies aim to establish or confirm an IVD's ability to detect or measure a specific analyte. This includes evaluating parameters such as analytical sensitivity, specificity, trueness (bias), and precision (repeatability and reproducibility).
• Clinical Performance Studies: These studies focus on establishing or confirming the clinical performance of an IVD, often involving human subjects and clinical outcomes.

Crucially, the MDCG 2025-5 clarifies that it is not always required to perform both analytical and clinical performance studies. The necessity depends on the specific IVD and its intended purpose.

Regulatory Pathways: Application and Notification

The Q&A document provides much-needed clarity on when performance studies require an application to or notification of the competent authority. Not all performance studies necessitate submission. Key considerations include:

• Application Requirements: Certain performance studies, particularly those involving surgically invasive sample-taking solely for the study's purpose (Article 58(1)(a)), interventional clinical performance studies (Article 58(1)(b)), or those involving invasive procedures (Article 58(1)(c) and Article 70(1)), require an application to the competent authority.
• Notification Requirements: Other studies, such as those involving companion diagnostics using only left-over samples (Article 58(2)), may only require notification. The document also addresses whether comparisons of CE-marked IVDs or studies initiated by academic researchers require notification or application.

Substantial Modifications

MDCG 2025-5 dedicates a section to substantial modifications, defining what constitutes a substantial change to a performance study and outlining the notification requirements. It clarifies the timeline for notifying Member States of such modifications and addresses whether changes to the device under study are considered substantial modifications or necessitate a new application.

Key Takeaways for Professionals

This MDCG guidance is a vital resource for anyone involved in IVD development and regulatory compliance. It underscores the importance of:

• Clear Intended Purpose: The responsibility for assigning the intended purpose of an IVD lies with the manufacturer, which dictates the scope of required performance studies.
• National Requirements: While the IVDR provides a framework, national requirements regarding ethics committee submissions must also be considered.
• Documentation: The document details the documentation required for both applications and notifications, including the performance evaluation plan and data supporting compliance with General Safety and Performance Requirements (GSPR).
• Timeline Considerations: Guidance is provided on when performance studies can commence, especially when multiple Member States are involved in specimen collection and analysis.

Conclusion

MDCG 2025-5 serves as an indispensable guide for navigating the intricate landscape of IVDR performance studies. By providing clear answers to frequently asked questions, it aims to streamline the regulatory process and ensure the continued safety and performance of IVDs within the European Union. Professionals in the IVD industry are strongly encouraged to review the full document for detailed guidance and to ensure ongoing compliance with the IVDR.

Reference

European Commission. (2025, June). MDCG MDCG 2025-5 - Questions & Answers regarding performance studies of in vitro diagnostic medical devices under regulation (EU) 2017/746. Retrieved from https://health.ec.europa.eu/latest-updates/mdcg-2025-5-questions-answers-regarding-performance-studies-vitro-diagnostic-medical-devices-under-2025-06-18_en