When and how to conduct IVD performance studies under EU IVDR

Under the In Vitro Diagnostic Regulation (EU) 2017/746 (IVDR), manufacturers must gather comprehensive clinical evidence for their devices comprising of scientific validity, analytical performance, and clinical performance, and identify, appraise, and document this data in a robust and ongoing manner. Clinical evidence can be gathered by conducting analytical or clinical performance studies as well as from scientific literature, and post-market surveillance. The IVDR sets out requirements that apply to all performance studies, along with additional specific rules for performance studies under certain conditions.

The transition from the In Vitro Diagnostic Directive 98/79/EC (IVDD) to the IVDR has brought substantial changes to the regulatory landscape for IVD devices in Europe, especially regarding performance study requirements. Unlike the broader framework of IVDD, the IVDR sets forth rigorous and precise expectations for conducting and documenting performance studies, making compliance more demanding and critical for manufacturers.

Understanding these requirements is crucial, particularly during the ongoing IVDR transition period, which has set deadlines for compliance that are rapidly approaching for many products. Without a solid grasp of performance evaluation obligations and the potential need for additional studies, manufacturers risk delays in placing their devices on the EU market, or even device withdrawal. IVDR demands thorough and scientifically robust performance studies, supported by current clinical evidence. Therefore, manufacturers should proactively identify gaps in their performance data and prepare accordingly. Focusing on these requirements not only ensures regulatory compliance but also strengthens patient safety and product reliability as the regulatory environment evolves.

In this blog post, we offer practical guidance on the IVD performance study requirements necessary for IVDR compliance. Through a clear breakdown of requirements and expectations, this blog aims to help manufacturers understand IVDR study requirements to prepare robust clinical evidence and navigate the transition period to maintain market access and uphold patient safety. Previously, we described the overall performance evaluation process and the different elements of clinical evidence. In a later blog post, we offered more detailed guidance about the performance evaluation documentation requirements necessary for compliance.

When are performance studies needed?

Analytical performance of a device is typically proven through analytical performance studies. For new markers, or those lacking certified reference materials or measurement procedures, demonstrating trueness may not be possible. If there are no comparative methods available, alternative approaches can be used, such as comparing results to other well-established methods or using a composite reference standard, provided their appropriateness is demonstrated. If these options are unavailable, a clinical performance study that compares the new device with existing clinical practise is necessary.

Clinical performance studies should be carried out unless there is a strong justification for relying on other sources of clinical performance data. These studies aim to verify aspects of device performance that cannot be determined through analytical performance studies, literature, or previous routine diagnostic testing experience. The information gained helps to demonstrate compliance with the general safety and performance requirements (GSPRs) outlined in IVDR Annex I concerning clinical performance. When clinical performance studies are conducted, the data collected contributes to the device’s performance evaluation and forms part of its clinical evidence.

What are the general requirements for conducting a performance study?

• Performance studies need to be designed and conducted in such a way that the rights, safety, dignity and well-being of the subjects participating in such performance studies are protected and prevail over all other interests and the data generated is scientifically valid, reliable and robust.
• Devices for performance studies must comply with the GSPRs apart from the aspects covered by the performance study. Every precaution needs to be taken to protect the health and safety of the patient, user and other persons with regard to the aspects of the GSPRs covered by the performance study.
• Where appropriate, performance studies should be performed in circumstances  similar to the normal conditions of use of the device.
• Performance studies, including performance studies that use left-over samples, must be conducted in accordance with applicable law on data protection.
• Each step of a clinical performance study, from the initial consideration of the need for and justification of the study to the publication of the results, must be carried out in accordance with recognised ethical principles.

For which performance studies do additional requirements apply to?

• Studies involving surgically invasive sample-taking only for the purpose of the performance study.
  • Surgically invasive sample-taking includes:
    • sample-taking that penetrates inside the body through the surface of the body, including through the mucous membranes of body orifices, and
    • using a device which produces penetration other than through a body orifice for sample taking.
  • Examples of surgically invasive sampling include:
    • blood sampling (arterial, venous or capillary),
    • puncture (body liquids, incl. cerebrospinal fluid or abscess), and
    • collection of fresh tissue biopsy.
• Interventional clinical performance studies, meaning clinical performance studies where the test results may influence patient management decisions and/or may be used to guide treatment.
• Studies involving additional invasive procedures (like imaging) or other risks for the subjects of the studies.
• Performance studies involving companion diagnostics.
  • The additional requirements don’t apply to performance studies involving companion diagnostics which utilise left-over samples only. Such studies still need to be notified to the competent authority.
• Post-market performance follow-up (PMPF) studies (studies assessing a CE-marked device within the scope of its intended purpose) involving submitting subjects to additional invasive or burdensome procedures that are not performed under the normal conditions of use.
• Studies assessing a CE-marked device outside the scope of its intended purpose.

Which additional requirements apply to certain performance studies?

Regulatory approval and ethical aspects

• The studies need scientific and ethical review by the competent authority and an ethics committee. The performance study is the subject of an authorisation by the Member State(s) in which the performance study is to be conducted.
• Where the sponsor of the study is not established in the EU, that sponsor must ensure that a natural or legal person is established in the EU as its legal representative. 
• Benefit-risk analysis has been conducted.
  • The performance study must be designed to involve as little pain, discomfort, fear, and any other foreseeable risk as possible for the subjects, and both the risk threshold and the degree of distress must be specifically defined in the performance study plan and monitored constantly.
  • Where appropriate, biological safety testing reflecting the latest scientific knowledge or any other test deemed necessary in the light of the device’s intended purpose has been conducted.
  • In the case of clinical performance studies, the analytical performance, and in the case of interventional clinical performance studies, the analytical performance and scientific validity have been demonstrated, taking into consideration the state of the art. Where, for companion diagnostics, the scientific validity is not established, the scientific rationale for the use of the biomarker must be provided.
  • The anticipated benefits to the subjects or to public health must justify the foreseeable risks and inconveniences.

Informed consent process

• The subject or, where the subject cannot give informed consent, their legally designated representative, must give informed consent and be provided with the contact details of an entity where further information can be received in case of need. The informed consent can be revoked at any time.
• Vulnerable populations and subjects including minors as well as pregnant or breastfeeding women must be appropriately protected.
• The rights of the subject to physical and mental integrity, to privacy, and to the protection of the data concerning them are safeguarded.
• No undue influence, including that of a financial nature, is exerted on the subject, or, where applicable, on their legally designated representatives, to participate in the performance study.

Safety aspects

• The sponsor of the study must ensure that adverse events and device deficiencies are reported and notified to authorities as required during performance studies.
• The investigator must be a person exercising a profession which is recognised in the Member State concerned, as qualifying for the role of investigator on account of having the necessary scientific knowledge and experience in patient care or laboratory medicine. Other personnel involved in conducting a performance study must be suitably qualified, by education, training or experience in the relevant medical field and in clinical research methodology, to perform their tasks.
• The medical care provided to the subjects is the responsibility of an appropriately qualified medical doctor or, where appropriate, any other person entitled by national law to provide the relevant patient care under performance study conditions.
• The technical safety of the device with regard to its use has been proven, taking into consideration the state of the art as well as provisions in the field of occupational safety and accident prevention.
• Where appropriate, the facilities where the performance study involving subjects is to be conducted must be suitable for the performance study and must be similar to the facilities where the device is intended to be used.
• The sponsor and the investigator must ensure that the performance study is conducted in accordance with the approved performance study plan and there is sufficient insurance coverage in place.
• The sponsor is responsible for the accountability of IVD medical devices under investigation throughout the study.
• The accountability, traceability, suitability, and quality of all specimens must be ensured throughout the study.
• In order to verify that the rights, safety and well-being of subjects are protected, that the reported data is reliable and robust, and that the conduct of the performance study is in compliance with the requirements of the IVDR, the sponsor must ensure adequate monitoring of the conduct of a performance study.  A monitoring plan is established for that purpose.

Where can I get more information or help with conducting IVD performance studies?

The performance evaluation process and study requirements are demonstrated in detail in IVDR Articles 56-77 and Annexes XIII and XIV. Additionally, the following documents give additional guidance on the study requirements:

• IVDR harmonised standard EN ISO 20916:2024 In vitro diagnostic medical devices – Clinical performance studies using specimens from human subjects – Good study practice (ISO 20916:2019)
• MDCG 2022-2 Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs)
• MDCG 2025-5 Questions & Answers regarding performance studies of in vitro diagnostic medical devices under regulation (EU) 2017/746
• MDCG 2024-4 Safety reporting in performance studies of in vitro diagnostic medical devices under Regulation (EU) 2017/746
• Commission Implementing Regulation (EU) 2022/1107 laying down common specifications for certain class D IVDs.
  • Following these common specifications is a mandatory requirement for those certain class D devices, but they can also be used as guidance when conducting performance evaluations for other devices
• CLSI guidelines
  • These guidelines should be referenced when planning performance studies. Although following them is not mandatory under IVDR, they help to generate robust and consistent data across studies.

Medfiles provides comprehensive support for IVD performance evaluations, covering everything from writing performance evaluation plans, managing performance study applications and notifications, planning, monitoring, and documenting clinical performance studies, as well as writing comprehensive performance evaluation reports. Working with our experts ensures that all study protocols and documentation meet IVDR requirements and the performance studies are tailored to address your device’s risk classification, intended use, and specific performance attributes. If you lack the time or internal resources/expertise to conduct performance studies, Medfiles can step in to support your project efficiently, offering expert assistance throughout all stages of the process.

Author: Emma Talvitie 
Regulatory Affairs Expert, Medical Devices and IVDs  

Emma Talvitie is a medical device and in vitro diagnostic (IVD) regulatory affairs professional with a Master of Science (Tech.) degree in biotechnology, who has over 4 years of professional experience in MD and IVD regulatory affairs. Emma has a strong background in IVD regulatory affairs and assay development. During her studies she focused on assay development, especially in molecular diagnostics and immunoassays. She started her career by updating the IVDD compliant technical documentation of an IVD analyser to be compliant with the IVDR. She has also been responsible for planning, executing, data analysis and reporting of IVD assay verification and validation studies and contributed to writing and reviewing IVDR and FDA 510(k) documentation for IVD assays.

Since April 2023, as a Regulatory Affairs Expert at Medfiles, Emma has worked in varying projects helping clients with regulatory issues and compiling technical documentation for multiple medical devices and IVDs. Emma is excited about contributing to the development of innovative, high-quality devices that meet both regulatory requirements and user needs.  

Author: Essi Sarkkinen 
Director, Clinical Research and Medical Device  

Since joining Medfiles in 2014, Essi Sarkkinen has held several leadership positions. She led the Food, Feed, and Medical Device Regulatory Unit, and later the Clinical Unit. In March 2025, she was appointed Director of Clinical Research and Medical Device.

Essi has a PhD in clinical nutrition and she is an adjunct professor at the University of Eastern Finland. Essi has published dozens of scientific articles in peer-reviewed journals and supervised four academic dissertations. After her academic career, she has worked for over 15 years managing and leading contract research in the field of food and nutrition. In the beginning of the 2000s, Essi started working with clinical trials for medicinal products and good clinical practice (GCP), as well as regulatory affairs concerning food product, like health claims and novel foods.

Essi has over 30 years of experience in clinical trials and medical writing as well as know-how of R&D and regulatory affairs in the fields of food, medical devices and pharmaceuticals. All in all, she has worked in various leadership positions in contract research organisations for over 25 years.

See also:

• How to document IVD performance evaluations under EU IVDR
• How to gather clinical evidence for IVD performance evaluation under EU IVDR
• EU MDR and IVDR notified body processes and transition periods
• EU IVDR: Compliance with technical documentation, notified body processes and transition periods
• What to know about medical device and IVD class changes and transition periods