Dr. Oliver Eikenberg breaks down the European Commission’s new MDCG 2025-5 guidance on IVD performance studies under the IVDR. He highlights how the document clarifies when studies require ethics and authority submissions, what qualifies as a substantial modification, and how to ensure data quality and compliance. For manufacturers and sponsors preparing for CE marking, these insights are essential to avoid costly delays and rejections.
In June 2025, the European Commission’s Medical Device Coordination Group (MDCG) released new guidance that summarizes the obligations and information on how performance studies for in vitro diagnostic devices (IVDs) are regulated under the EU’s In Vitro Diagnostic Regulation (IVDR). Published as MDCG 2025-5, the guidance takes a practical, Q&A-style approach and outlines when performance studies require notification or application to the Ethic Committees (EC) and National Competent Authority (NCA), what counts as a substantial modification, and how to ensure data quality and compliance throughout performance studies.
Most of this information is not new, as it is addressed in the IVDR, standards, and other MDCG documents, including:
However, the summarized information is very helpful for all sponsors and IVD manufacturers when planning their performance studies conducted within the scope of the IVDR. It is designed to prevent rejections and delays caused by noncompliance with fundamental requirements or by misunderstandings due to incorrect terminology or misinterpretation. For performance studies sponsored by other parties, including combined studies, lack of awareness of IVDR obligations has been a major cause of delays and rejections. Here are the highlights of the MDCG guidance.
Respect national EU Member State legislation
The guidance emphasizes that manufacturers and sponsors must comply with national requirements of each EU Member State when submitting documentation to ECs and NCAs. This is critical, as some countries may require additional documents and translations into the local language where the performance study is being conducted.
Definition of performance study
Questions 1–3 clarify that a performance study refers to an analytical or clinical investigation conducted to establish or confirm the performance of an IVD, in line with the relevant General Safety and Performance Requirements (GSPR) outlined in Annex I of the IVDR.
Definition of intended purpose
The guidance clarifies that the intended purpose of an IVD must be defined by the manufacturer in line with the criteria set out in the IVDR (Annex I, 20.4.1c). Conducting a performance study without a clearly defined intended purpose and clinical indication is no longer acceptable, even though it was common under the IVDD where manufacturers often relied solely on analytical purposes. This presents a major challenge for those now trying to use legacy clinical data, as they may be unable to demonstrate how those studies support current clinical claims under the IVDR.
Responsibility for performance study
Performance studies can be initiated without the legal manufacturer’s direct involvement. However, if a sponsor assigns a medical purpose that meets the definition of an IVD under Article 2 of the IVDR, the sponsor may be considered the manufacturer under the regulation. In other words, performance studies should typically involve the actual manufacturer; otherwise, the resulting data may not be accepted for CE marking.
Decision tree for performance study regulatory pathways under IVDR
Appendix I includes a straightforward decision tree to help manufacturers determine whether a planned performance study falls under notification, application, or no submission at all, with a structured path based on “yes” or “no” responses.
Application of IVDR for performance study types
To prevent misinterpretation, the guidance reaffirms the principle—carried over from the IVDD—that any study meeting the IVDR definition of a "performance study" is subject to Article 57, regardless of who conducts it or who the sponsor is. Additional requirements apply to certain performance studies according to Article 58(1), Article 58(2), Article 70(1), and Article 70(2) in the IVDR:
Study modifications that may be deemed substantial changes
Changes inside performance studies may bring new risks to patients, which is why most of them require an official amendment and approval from the involved ECs and the NCAs. MDCG 2025-5 outlines how sponsors of IVD performance studies must handle substantial modifications. Appendix II includes a non-exhaustive list of substantial modification scenarios. Sponsors must determine if a modification is substantial and notify the relevant NCA in the Member State(s) within one week of issuing updated documents. Once notified, you typically must wait at least 38 days (potentially longer if expert consultation is triggered) to implement the change. Sponsors must respect EU Member State-specific requirements for modification reporting and documentation.
Qualification as a clinical performance study for final acceptance for CE Marking
Under the IVDR, any performance study that fulfills the definition of a performance study can contribute to the clinical evidence needed for CE marking, if it meets Article 57 requirements. GSPR compliance must be documented for each study, and full supporting data must be made available to competent authorities on request. This typically includes the official favorable opinion from the EC established under IVDR and the approval from the NCAs.
Emphasis on Good Study Practice Principles (ISO 20916)
EN ISO 20916:2024, first published in 2019, is the EU state-of-the-art standard for Good Study Practice and is referenced throughout the guidance. Submissions for IVD performance studies must align with fundamental Good Study Practice principles by adhering to the general requirements of IVDR Article 57, ensuring subject protection, generating robust and reliable data, and fulfilling detailed documentation requirements. Under IVDD, these Good Study Practice Principles must follow EN 13612:2002 and the ethical and clinical principles in the EN ISO 14155 standard version. It’s important to note that Good Study Practice differs from Good Clinical Practice (GCP). Performance studies conducted under GCP or other unrelated standards may raise serious concerns and risk being rejected for CE marking.
Final thoughts
MDCG 2025-5 is a welcome summary of basic principles for conducting IVD performance studies under the IVDR. Because these principles are fundamental for the acceptance by Notified Bodies for clinical evidence and final CE Marking, every manufacturer and sponsor should carefully follow this guidance document to avoid rejections of performance study submissions or other problems during CE Marking. National EU Member state legislation may pose practical challenges, too.
Pure Global supports IVD manufacturers through every step of the performance study lifecycle, from study design and protocol development to GSPR documentation and regulatory submissions. If you're preparing for IVDR CE marking or facing compliance gaps, we can help. Learn more about IVDR consulting services.
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