MDCG 2025-5: New IVDR Guidance on IVD Performance Studies

The Medical Device Coordination Group (MDCG) has published MDCG 2025-5 “Questions & Answers regarding performance studies of in vitro diagnostic medical devices under regulation (EU) 2017/746,” which focuses on Articles 57 to 77 of the IVDR and provides guidance to sponsors of performance studies of IVDs, IVD manufacturers and sponsors of combined studies. It is important to note that this guidance is not meant to be exhaustive and should be utilized along with additional legal requirements, standards and guidance documents relevant to IVDs and performance studies.  

MDCG 2025-5 is Broken Down into Five Sections Covering 54 Questions: 

1.  General questions (Q1-Q14)  

Focus: Definitions, types of performance studies, applicability of IVDR, and investigator roles. 

• Defines performance studies (analytical and clinical) and their role in demonstrating GSPR compliance. 

• Explains when performance studies are needed, and under what circumstances they are regulated by the IVDR. 

• Clarifies the status of RUO products, in-house devices, and CE-marked devices used in studies. 

• Identifies who qualifies as an investigator and the relevance of combined studies. 

• Describes safety reporting requirements and the transition from IVDD to IVDR for ongoing studies. 

2.  Requirements to apply for/notify performance studies (Q15-Q22) 

Focus: Regulatory obligations for submission to competent authorities.  

• Clarifies which studies require application (authorization) or notification based on their risk level and device status. 

• Details Articles 58(1), 58(2), and 70(1–2), which define submission obligations depending on invasiveness, use of companion diagnostics, or whether CE-marked devices are used within or outside their intended purpose. 

• Specifies that specimen collection sites determine jurisdiction for submission, not analysis sites. 

• Offers insight into notification for academic studies and how studies using left-over samples are handled. 

3. Additional requirements for certain performance studies (Q23-Q34) 

Focus: Specific regulatory conditions for high-risk or complex study types.

• Defines surgically invasive sample-taking, interventional studies, and burdensome procedures.

• Explains the use and regulatory treatment of companion diagnostics. 

• Clarifies what qualifies as left-over samples, and under which conditions their use triggers notification or application. 

• Establishes that Article 58 applies only to non-CE marked or off-label use of IVDs, while Article 70 applies to CE-marked devices used within their intended purpose but involving extra procedures. 

4. Application/notification (Q35-Q43) 

Focus: Required content of submissions, documentation, and multilingual obligations. 

• Describes what documents must be included in a performance study application, including references to Annex XIII & XIV of the IVDR. 

• States that the Performance Evaluation Plan (PEP) is not mandatory but should be available upon request. 

• Clarifies language and translation requirements for Instructions for Use (IFU) and related materials, especially at sampling sites. 

• Covers use of CIV-ID as temporary study identifier before EUDAMED is functional. 

5. Timeline considerations, and substantial modifications (Q44-Q54) 

Focus: Timing of study initiation and management of changes. 

• Defines the start date of a performance study and when studies can begin in multi-state trials. 

• Clarifies the authorization vs. acknowledgement requirement depending on the type of submission (application vs. notification). 

• Outlines what constitutes a substantial modification, how to submit such changes, and when a new application is required. 

• Details timelines for implementation (e.g., 38-day period) and exceptions (e.g., for studies using only left-over samples). 

• Discusses handling of combined IVDR/CTR modifications and Member State variations in process. 

MDCG 2025-5 IVDR Performance Study, Includes 2 Appendixes: 

• Appendix I provides a decision tree for determining the regulatory pathway for performance studies. 

• Appendix II lists modifications that may be deemed substantial. 

Key Points 

1. Performance Studies according to the IVDR: 

• A performance study is defined as a study undertaken to establish or confirm the analytical or clinical performance of an IVD. 

• The IVDR does not regulate clinical or laboratory methods, therefore a performance study should generate performance data for a device.  

2. Types of Performance Studies: 

• Analytical Performance Studies: Focus on the ability of an IVD to detect or measure a particular analyte, including parameters like sensitivity, specificity, and accuracy. 

• Clinical Performance Studies: Establish or confirm the ability of an IVD to yield results correlated with a clinical condition or a physiological or pathological process or state in accordance with the target population and intended user. 
  • MDCG 2022-2 provides guidance on general principles of clinical evidence for IVDs. 

3. Regulatory Requirements: 

• All performance studies are regulated by Article 57 of the IVDR, and different types of performance studies are governed by different articles.  

• Performance studies must comply with the General Safety and Performance Requirements (GSPR) set out in Annex I of the IVDR. 

4. Application and Notification: 

• Certain performance studies require an application or notification to the competent authority, depending on the study’s nature and risk level. The related regulatory pathways are included in Appendix I of the MDCG guidance. 

• The guidance MDCG 2022-19 on performance study application/notification documents contains a series of performance study application/notification documents which have been created to support performance study procedures with respect to the IVDR. 

• The related regulatory pathways are included in Appendix I of the MDCG guidance. 

5. Roles and Responsibilities: 

• The manufacturer is responsible for assigning the intended purpose of the IVD. 

• Where a sponsor assigns a medical purpose to a product in a way that fulfils the definition of an IVD as per the IVDR, the sponsor may assume the role of a manufacturer under the IVDR. 

• Investigators must have the necessary scientific knowledge and experience in patient care or laboratory medicine. 

6. Ethics and Safety: 

• The IVDR does not specify details about ethics review; national requirements must be checked. 

• Safety reporting requirements are described in the guidance document MDCG 2024-4, which includes a safety reporting form MDCG 2024-4 Appendix. 

7. Substantial Modifications: 

• Substantial modifications to performance studies must be notified to the competent authority. 

• A non-exhaustive list of potential substantial modifications is provided in Appendix II. 

Learn More About the MDCG 2025-5 IVDR Performance Study with MedEnvoy

MDCG 2025-5 serves as a valuable guide for IVD manufacturers and sponsors of performance studies, providing guidance on the regulatory requirements, responsibilities, and processes under the IVDR.  

MedEnvoy supports clients in navigating IVDR performance study requirements by offering expert guidance on study classification, regulatory pathway determination, and preparation of submission documentation. If you have any questions regarding this summary or the accompanying guidance document, we encourage you to reach out to our regulatory experts here.