eIFUs Now Allowed for All Professional Use Devices: EU Amending Regulation 2025/1234 Published
26 June 2025
June “In All Other News”: MDCG Q&A on the AI Act, New MDSAP Website, MIR Form Updates & More
3 July 2025Background
The IVDR introduced more stringent requirements for generating clinical evidence, particularly through performance studies. These include new procedural, ethical, and safety requirements that were not present under the IVDD. Manufacturers are now expected to justify the clinical performance of their devices through more robust and transparent data, often involving formal studies with human specimens.
However, the IVDR leaves many important questions unanswered, e.g., when a study actually qualifies as a regulated performance study, what type of studies require submission to competent authorities, and how certain terms (e.g., “interventional” or “left-over samples”) should be interpreted.
Without clear guidance, manufacturers and Notified Bodies may interpret these requirements differently, leading to delays, inconsistent expectations, or unnecessary study submissions. These uncertainties increase both the cost and complexity of bringing an IVD to market and can undermine strategic planning for regulatory and clinical teams.
MDCG 2025-5 was developed to close these gaps and promote a more consistent and predictable application of the IVDR across the EU.
Note: While all IVDR-compliant devices require a performance evaluation, not all performance evaluations require a performance study, i.e., performance studies are one potential source of data within the broader performance evaluation process. That said, most IVDs will require at least analytical performance studies. And many will also need clinical performance studies unless a valid justification is provided for relying on other sources of performance data, such as published literature or routine diagnostic use.
Overview of MDCG 2025-5
MDCG 2025-5 is available: HERE
The guidance provides clarification on the practical application of performance studies under the IVDR, such as the below:
- Unlike the MDR, the IVDR does not distinguish between studies conducted for conformity assessment vs. other purposes.
- When a performance study falls under Article 57 (general requirements), Article 58 (additional risk), or Article 70 (CE-marked device studies). Notably:
- Article 57 applies to all performance studies.
- Article 58(1) applies if the study involves invasive procedures, additional risks, or interventional designs.
- Article 58(2) covers companion diagnostics.
- Article 70(1)-(2) applies to PMPF studies and off-label use of CE-marked devices.
- Provides a decision tree (Appendix I) to determine whether a performance study requires application vs. notification vs. no submission to competent authorities.
- Confirms that analytical performance must always be demonstrated through analytical performance studies. However, the term “study” is used broadly under the IVDR. It can include retrospective or pre-existing data (e.g., internal validation reports or batch testing), provided the data are structured, relevant, and traceable to specific analytical endpoints.
- Distinguishes early design validation (not regulated) from analytical/clinical performance studies (regulated).
- If an RUO product or custom assay is used with a medical purpose in a study, it becomes an IVD under the IVDR, and must meet all the applicable regulatory obligations.
- Performance studies involving companion diagnostics (CDx) are 1) always subject to Article 58(2) if the CDx is investigational, 2) only require notification if left-over samples are used; and 3) otherwise require application (if prospectively collected).
- Both collection and analysis sites are investigational sites; however, only sites involving human subjects require competent authority application/notification.
- Ongoing studies that started before 26 May 2022 don’t need to be resubmitted under IVDR. However, any serious adverse events and device deficiencies that occurred after that date must be reported under IVDR Art. 76.
The guidance also includes a non-exhaustive list of modifications that may be deemed substantial (Appendix II), such as:
- Use of a new mode of measurement for the primary endpoint
- Deletion of an interim analysis
- Change of testing modalities (modification of procedure, techniques, or instructions for use) of the device for performance study
- Changes to the device’s software or firmware
- New insurance policy
- Change in compensation paid to subjects and/or investigators/site
- Modification of the manufacturing site, process of manufacturing including change in supply chain (e.g., antibodies, material of human or animal origin suppliers or their sources, etc.), raw materials, reagent formulation, materials and coating of storage containers (such as tubes, plates and vials), production volume, sterilization method, sterilization or packaging
Note: While the guidance creates a consistent approach to interpreting performance evaluation requirements under the IVDR, it does not harmonize national Competent Authority-specific requirements. Therefore, manufacturers should still check for additional national-level requirements related to ethics review, language, or sample use.
