Under the In Vitro Diagnostic Regulation (EU) 2017/746 (IVDR), manufacturers are required to plan, conduct, assess, report and update a performance evaluation. Through the performance evaluation process, manufacturers must identify, appraise, and document comprehensive clinical evidence for their device in a robust and ongoing manner. The clinical evidence comprises of scientific validity, analytical performance, and clinical performance, and is gathered from scientific literature, performance studies and post-market surveillance.
The transition from the In Vitro Diagnostic Directive 98/79/EC (IVDD) to the IVDR has significantly increased the regulatory requirements for IVD devices in Europe with a particular emphasis on how performance evaluations are documented and maintained. While the IVDD provided a general framework, the IVDR requires manufacturers to provide detailed documentation that captures both favourable and unfavourable data and actively update the performance evaluation as new evidence emerges.
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 the need for rigorous, methodologically sound performance evaluations, and the importance of proactively updating their records, manufacturers risk delays in placing their devices on the EU market, or even device withdrawal. As IVDR demands thorough, methodologically sound performance evaluations backed by up-to-date clinical evidence, it’s essential for manufacturers to proactively assess potential gaps and act accordingly. This is not only a regulatory necessity but also an opportunity to reinforce patient safety and product reliability in a changing landscape.
In this blog post, we describe how to document and keep performance evaluation and related data up to date and how to avoid the most common pitfalls in the performance evaluation process. Previously, we described the overall performance evaluation process and the different elements of clinical evidence as well as performance study requirements. Through a clear breakdown of expectations, this blog aims to help manufacturers understand IVDR requirements, prepare robust clinical evidence, and navigate the transition period to maintain market access and uphold patient safety.
How is clinical evidence documented?
All relevant scientific validity, analytical and clinical performance data must be assessed to verify the conformity of the device with the relevant General Safety and Performance Requirements (GSPRs) described in IVDR annex I that have been identified in the performance evaluation plan (PEP) to require support from this data. The amount and quality of that data must allow the manufacturer to make a qualified assessment whether the device will achieve the intended clinical benefits and safety, when used as intended by the manufacturer. The data and conclusions drawn from this assessment constitutes the clinical evidence for the device. The clinical evidence must scientifically demonstrate that the intended clinical benefits and safety are achieved according to the state of the art in medicine, i.e., that the benefit-risk ratio is acceptable and comparable to the state of the art. Concerning the comparison to state of the art, the following aspects should be addressed as applicable:
- the device is compatible with current clinical practices,
- the performance and safety have been compared to similar devices available on the market, and
- the device has been designed, manufactured and tested according to current regulations and industry standards.
The clinical evidence is documented in a performance evaluation report (PER). The PER must include the scientific validity report, the analytical performance report, the clinical performance report and an assessment of those reports allowing demonstration of the clinical evidence. Additionally, usability and stability data and any other relevant verification or validation data should be included. The PER is intended to be a stand-alone document; thus, it shall contain all the essential information without needing to read the original reports.
The PER is part of the device’s technical documentation. Both favourable and unfavourable data considered in the performance evaluation need to be included in the technical documentation. The clinical performance study documents also need to be included and/or fully referenced in the technical documentation.
What needs to be included in the performance evaluation report?
According to the IVDR, the PER must include:
- the justification for the approach taken to gather the clinical evidence,
- the literature search methodology and the literature search protocol and literature search report of a literature review,
- the technology on which the device is based, the intended purpose of the device and any claims made about the device’s performance or safety,
- the nature and extent of the scientific validity and the analytical and clinical performance data that has been evaluated,
- the clinical evidence as the acceptable performances against the state of the art in medicine, and
- any new conclusions derived from post-market performance follow-up (PMPF) reports.
How is the performance evaluation updated?
The clinical evidence and its assessment in the PER must be updated throughout the life cycle of the device with data obtained from the implementation of the PMPF plan as part of the performance evaluation and the post-market surveillance (PMS) system. For class C and D devices, the PER must be updated at least annually. The summary of safety and performance needs to be updated simultaneously with the PER where necessary.
The performance evaluation is updated through continuous PMPF. When conducting PMPF, performance and relevant scientific data from the use of the device within its intended purpose needs to be proactively collected and evaluated with the following aims:
- confirming the safety, performance and scientific validity throughout the expected lifetime of the device,
- identifying previously unknown risks or limits to performance and contra-indications,
- identifying and analysing emerging risks based on factual evidence,
- identifying possible systematic misuse, and
- ensuring the continued acceptability of the clinical evidence and of the benefit-risk ratio.
PMPF is performed with a documented method described in a PMPF plan. The PMS plan must include or refer the PMPF plan. According to the IVDR, the PMPF plan must include at least:
- the general methods and procedures of the PMPF to be applied, such as gathering of clinical experience gained, feedback from users, screening of scientific literature and of other sources of performance or scientific data,
- the specific methods and procedures of PMPF to be applied, such as ring trials and other quality assurance activities, epidemiological studies, evaluation of suitable patient or disease registers, genetic databanks or post-market clinical performance studies,
- a rationale for the appropriateness of these methods and procedures,
- a reference to the relevant parts of the PER and to the risk management,
- the specific objectives to be addressed by the PMPF,
- an evaluation of the performance data relating to equivalent or similar devices, and the current state of the art,
- reference to any relevant common specifications, harmonised standards when used by the manufacturer, and relevant guidance on PMPF, and
- a detailed and adequately justified time schedule for PMPF activities, such as analysis of PMPF data and reporting, to be undertaken by the manufacturer.
The manufacturer needs to analyse the findings of the PMPF and document the results in a PMPF evaluation report that updates the PER and is part of the technical documentation.
The conclusions of the PMPF evaluation report need to be taken into account in the PER and in the risk management. If, through the PMPF, the need for preventive and/or corrective measures has been identified, the manufacturer must implement them.
If PMPF is not deemed appropriate for a specific device then a justification must be provided and documented within the PER.
What are the most common pitfalls of IVD performance evaluations and how to avoid them?
| PITFALL | SOLUTION |
| Scientific validity is mixed up with the concept of ‘state of the art’. | Remember that scientific validity and state of the art are separate concepts although they are connected. ‘Scientific validity’ means the association of an analyte with a clinical condition or a physiological state. ‘State of the art’ is the developed stage of technical capability at a given time as regards products, processes and services, based on the relevant consolidated findings of science, technology and experience. The state of the art embodies what is currently and generally accepted as good practice in technology and medicine but does not necessarily imply the most technologically advanced solution. |
| Individual publications selected are not analysed on how they contribute to the evidence of scientific validity. | Include analysis of each included publication to the scientific validity report. |
| Not knowing which analytical performance parameters are applicable. | Go through all parameters listed in IVDR Annex I section 6.1. Refer to applicable CLSI guidelines. Commission Implementing Regulation (EU) 2022/1107 lays down common specifications for certain class D IVDs. These can be used as guidance even if not applicable to the subject device. |
| Samples used in analytical performance studies have not been detailed and justified or all intended sample types have not been addressed. | Investigate all intended sample types to show performance differences or equivalence. Literature evidence can also be utilised in the demonstration of equivalence/performance differences. Evidence of equivalence extends to e.g., different anticoagulants and other stabilizing agents. Fresh-frozen equivalence is expected to be demonstrated if performance studies employ frozen samples. |
| There is no justification for the samples tested in clinical performance studies, or the samples used to demonstrate clinical performance do not represent the intended patient population (age, gender, geographical representation). | Provide a rationale for the selected samples that are based on representativeness. |
| Performance/equivalence concerning employed sample types in clinical performance studies has not been shown (e.g., other sample types or frozen samples have been utilized but the impact of this has not been demonstrated, or the tested samples have gone through a different preanalytical workflow than intended for the subject device). | Utilize samples in clinical performance studies that are as close to real clinical situation as possible. Demonstrate performance differences/equivalence between all intended sample types and fresh/frozen samples or other different preanalytical sample handling methods in analytical performance data. |
| Performance evaluation has not been integrated properly with PMS/PMPF or risk management, or state-of-the-art updates are neglected. | Ensure alignment between performance evaluation, risk management, and PMS/PMPF. The execution of performance evaluation must reflect identified risks and evolving scientific expectations. Establish a connection between all aspects of clinical evidence (scientific validity, analytical performance, and clinical performance) as well as additional performance aspects (e.g., stability and usability) and risk management and prepare to upkeep them through PMS activities. |
| Incomplete or inconsistent performance evaluation documentation. | Refer to Team-NB Position Paper-BPG-IVDR-V2-20250903 Best Practice Guidance for the Submission of Technical Documentation under Annex II and III of In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 and MDCG 2022-2. |
| Poor performance evaluation planning for high-risk devices. | Especially for Class C and D devices, ensure the Performance Evaluation Plan remains achievable and reflects current clinical expectations and regulatory guidance. Set up internal review checkpoints to validate performance claims. |
| Insufficient cross-functional collaboration. | Foster strong communication between regulatory, quality assurance, clinical, and R&D teams. |
Where can I get more information or help with documentation and upkeep of IVD performance evaluations?
The performance evaluation documentation and upkeep requirements are demonstrated in detail in IVDR Article 56 and Annex XIII. Additionally, the following documents give additional guidance on these requirements:
- MDCG 2022-2 Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs)
- Team-NB Position Paper-BPG-IVDR-V2-20250903 Best Practice Guidance for the Submission of Technical Documentation under Annex II and III of In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746
Medfiles offers support for IVD performance evaluations, covering everything from writing performance evaluation plans to planning, monitoring, and documenting clinical performance studies, as well as writing comprehensive performance evaluation reports. Working with Medfiles ensures that your performance evaluation process is well-structured from the outset and seamlessly integrated with post-market surveillance and risk management activities. Medfiles also provides ongoing support in monitoring regulatory updates and best practice guidance, ensuring your performance evaluation documents are continuously revised and remain current with evolving requirements.
If you lack the time or internal resources/expertise to gather clinical evidence, conduct performance studies, or compile documentation, 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 5 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 exited about contributing to the development of innovative, high-quality devices that meet both regulatory requirements and user needs.
Free webinar: Medical device clinical evaluation
In this webinar you will learn if your medical device is in a need of clinical investigations. You will also learn about properly documenting a clinical evaluation, including how to compile a clinical evaluation plan and a clinical evaluation report according to the requirements in the MDR. In the webinar we will also give practical tips for ensuring that your clinical investigation meets the needed GCP requirements and none of the essential elements are forgotten.
See also:
- How to conduct IVD performance studies 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
