IVDR Performance Evaluation: Requirements, PEP and PER Guide

Executive Summary

IVDR performance evaluation is the continuous process of collecting, appraising, and analysing data to demonstrate the scientific validity, analytical performance, and clinical performance of an IVD for its intended purpose. Under Article 56 of the European Union’s In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (EU IVDR), it is a core requirement for showing that an in vitro diagnostic medical device is supported by sufficient clinical evidence and performs safely and effectively for CE marking and continued access to the European market.

Aimed at regulatory affairs, quality assurance, and clinical or medical writing teams at IVD manufacturers, especially small-to-mid sized companies, startups, CROs, and specialist freelancers, this guide explains the key IVDR performance evaluation requirements, the three pillars of performance evaluation, how the Performance Evaluation Plan (PEP) and Performance Evaluation Report (PER) are used, device classification considerations, literature review methodology, common challenges, and best practices for maintaining compliance across the full device lifecycle.

Key Takeaways

• IVDR performance evaluation is a continuous process of collecting, appraising, and analysing data to demonstrate scientific validity, analytical performance, and clinical performance
• Article 56 and Annex XIII Part A of the IVDR establish the primary requirements
• All four IVDR classes (A, B, C, and D) are subject to performance evaluation, with evidence proportionate to intended purpose and risk
• PERs for Class C and Class D devices must be updated as necessary and at least annually under Article 56(6); for Class A and B, updates follow the PMS plan
• Risk classification alone does not determine whether new clinical performance studies are required
• The PEP defines the evidence strategy; the PER documents and critically assesses the resulting evidence
• PMS and PMPF findings must feed back into the performance evaluation throughout the device lifecycle
• Where scientific literature supports the evaluation, literature review methodology must be clearly documented

Table of Contents

1. Direct Answer: What Is IVDR Performance Evaluation?
2. Why It Matters: Article 56 and Annex XIII
3. How It Works: Classes, Three Pillars, PEP, PER, and Evidence
4. Common Mistakes: Challenges in IVDR Performance Evaluation
5. Best Practices: Maintaining Performance Evaluation Across the Lifecycle
6. Comparison Table
7. Checklist
8. Definitions
9. Expert Perspective
10. FAQ
11. References
12. Related Resources
13. Call to Action

Direct Answer: What Is IVDR Performance Evaluation for an In Vitro Diagnostic Device?

IVDR performance evaluation is the continuous process of collecting, appraising and analysing data to demonstrate the scientific validity, analytical performance and clinical performance of an IVD for its intended purpose.

Manufacturers must assess the quality and relevance of available evidence, identify potential gaps and generate additional data where necessary to support the device’s intended clinical benefits, safety and performance claims.

The findings are documented in a Performance Evaluation Report (PER), which forms part of the device’s technical documentation.

Why It Matters: Article 56 and Annex XIII

The primary regulatory requirements for IVDR performance evaluation are established in Article 56 and Annex XIII, Part A, of Regulation (EU) 2017/746.

Article 56 requires manufacturers to plan, conduct and document a methodologically sound performance evaluation based on the three pillars of performance evaluation. The resulting clinical evidence must be sufficient to demonstrate conformity with the relevant General Safety and Performance Requirements (GSPRs) in Annex I, as performance evaluation requirements are specified in Annex I of IVDR and support conformity with the applicable Annex I general requirements. The level of clinical evidence required should be appropriate to the device’s characteristics and intended purpose, and manufacturers must justify the evidence considered necessary.

Annex XIII, Part A provides further requirements for planning, conducting and documenting performance evaluation. It addresses the Performance Evaluation Plan (PEP), the assessment of evidence supporting the three pillars, and the documentation of findings in the Performance Evaluation Report (PER).

Performance evaluation should also be aligned with the manufacturer’s risk management process. Evidence concerning analytical and clinical performance can help identify risks associated with incorrect or misleading test results, inform benefit-risk determinations and support conformity with the applicable GSPRs.

How It Works: Classes, Three Pillars, PEP, PER, and Evidence

How Performance Evaluation Differs Between IVDR Classes A, B, C and D

Under Annex VIII of Regulation (EU) 2017/746, each device is classified by risk class into four categories: A, B, C and D. All four classes are subject to the applicable performance evaluation requirements, including the assessment of scientific validity, analytical performance and clinical performance, with the supporting evidence proportionate to the device’s intended purpose and associated risks.

Class A represents the lowest risk class, and Class A IVDs can be self-certified under the IVDR, while Class D includes devices associated with the highest individual and public health risks. For lower-risk devices, established scientific knowledge and available performance data may provide sufficient evidence to support the intended purpose, provided that their relevance and adequacy are justified. Higher-risk devices may warrant more extensive performance data and closer scrutiny of the evidence supporting their clinical claims, particularly where incorrect results could have serious consequences for patients or public health.

Risk classification alone does not determine whether new clinical performance studies are required. Manufacturers must assess the available evidence and justify whether it is sufficient for the specific device and its intended purpose. Annex VIII sets out seven rules for classification.

The IVDR also establishes different conformity assessment and documentation requirements according to device classification. Under Article 56(6), Performance Evaluation Reports for Class C and Class D devices must be updated as necessary, but at least annually. For Class A and Class B devices, PERs must be updated as necessary and in accordance with the manufacturer’s post-market surveillance (PMS) plan. Many higher-risk devices also require oversight by independent notified bodies as part of conformity assessment.

Manufacturers should therefore consider both the device’s risk classification and its specific intended purpose when developing the Performance Evaluation Plan and determining the evidence needed to support the Performance Evaluation Report.

Examples are illustrative only. Classification depends on the precise intended purpose and Annex VIII rules, not the analyte or product name alone.

The Three Pillars of IVDR Performance Evaluation

Each of the three pillars addresses a distinct aspect of an IVD’s performance, with the supporting evidence considered collectively when assessing the device’s intended purpose.

Scientific Validity

Scientific validity establishes the association between an analyte or marker and a particular clinical condition or physiological state. It addresses whether the analyte being measured has an established scientific relationship with the condition or process that the IVD is intended to detect, diagnose, monitor or assess. For example, an HbA1c assay used in diabetes assessment relies on the scientifically established relationship between glycated haemoglobin and long-term glycaemic status.

Evidence supporting scientific validity may include peer-reviewed scientific literature, relevant scientific information concerning devices measuring the same analyte or marker, expert consensus statements or positions from professional associations, proof-of-concept studies, and clinical performance studies.

The manufacturer must assess the relevance and quality of the available evidence and document the findings and conclusions in a scientific validity report. Where the evidence comes from published literature, a structured and documented literature review methodology supports traceability.

Analytical Performance

Analytical performance demonstrates an IVD’s ability to reliably and consistently detect or measure a particular analyte under defined conditions. Depending on the device and its intended purpose, analytical performance characteristics may include analytical sensitivity and specificity, trueness and precision, repeatability and reproducibility, limits of detection and quantitation, measuring range and linearity, interference and cross-reactivity, and appropriate specimen collection and handling conditions.

Under Annex XIII, analytical performance is generally demonstrated through analytical performance studies. Any omission of an applicable performance parameter must be justified. The findings are documented in an analytical performance report.

Clinical Performance

Clinical performance demonstrates the ability of an IVD to yield results that are correlated with a particular clinical condition or physiological or pathological process, in accordance with its intended purpose and target population. While analytical performance establishes whether the test measures an analyte reliably, clinical performance considers whether the test’s results are appropriate for its claimed clinical application.

Relevant clinical performance characteristics may include diagnostic sensitivity and specificity, positive and negative predictive values, likelihood ratios, expected values in normal and affected populations, and other clinically relevant performance measures appropriate to the intended purpose.

Clinical performance may be demonstrated using clinical performance studies, peer-reviewed scientific literature or published experience gained through routine diagnostic testing. Under Article 56 and Annex XIII, clinical performance studies are required unless the manufacturer provides adequate justification for relying on other sources of clinical performance data. The evidence and conclusions are documented in a clinical performance report.

The evidence from all three components is critically assessed and brought together in the Performance Evaluation Report to demonstrate whether the device’s intended purpose and relevant IVDR requirements are adequately supported.

Performance Evaluation Plan (PEP): What to Include

Under Annex XIII, Part A of the IVDR, manufacturers must establish and update a Performance Evaluation Plan (PEP) outlining the strategy for demonstrating and maintaining an IVD’s scientific validity, analytical performance and clinical performance throughout its lifecycle.

The PEP should address the following elements, as applicable to the device:

• Intended purpose: A clear description of the device’s intended purpose, including the analyte or marker, target population, intended user and clinical application
• Device characteristics: Identification of the relevant device characteristics and applicable GSPRs requiring support from scientific validity and analytical and clinical performance data
• Scientific validity: Identification of the scientific evidence required to establish the association between the analyte or marker and the relevant clinical condition or physiological state
• Analytical performance: Identification of the analytical performance characteristics to be evaluated, including applicable parameters and acceptance criteria
• Clinical performance: Identification of the clinical performance characteristics to be assessed, taking into account the device’s intended purpose and target population
• Evidence sources: Description of the methods used to identify, collect and appraise relevant evidence, including scientific literature, existing performance data and performance studies
• Evidence gaps: Identification of limitations in the available evidence and the approach to addressing any gaps
• Performance evaluation methods: Description of the methods, tools and statistical approaches used to analyse the evidence and determine whether the available data are sufficient

The PEP should also address the benefit-risk determination, the device’s state of the art and any relevant development milestones. A state-of-the-art assessment provides the scientific and clinical context for evaluating the IVD, including current diagnostic practices, alternative testing methods and relevant performance expectations.

Where scientific literature is used to support the performance evaluation, the approach to identifying and appraising relevant publications should be clearly documented. This may include the literature search strategy, databases searched, inclusion and exclusion criteria, and methods used to assess the quality and relevance of the evidence. For a step-by-step approach to structured searching and screening see our guide on EU MDR literature review methodology and our article on PRISMA and EU MDR literature review.

The PEP provides the foundation for a consistent and traceable performance evaluation. By establishing the evidence requirements and evaluation methods in advance, manufacturers can more effectively identify gaps, plan appropriate studies and demonstrate how their performance claims are supported.

The PEP should be reviewed and updated as necessary when new evidence becomes available, when the intended purpose changes, or when the state of the art evolves.

Performance Evaluation Report (PER): Documenting the Evidence

The Performance Evaluation Report documents the results of the performance evaluation and provides a critical assessment of the evidence supporting an IVD’s intended purpose. A Performance Evaluation Report (PER) is necessary for demonstrating compliance with applicable EU regulation) requirements for the device, and it forms part of the technical documentation supporting conformity with the applicable IVDR requirements.

Under Annex XIII, Part A, Section 1.3, the PER must include the scientific validity report, analytical performance report and clinical performance report, together with an assessment of the clinical evidence.

A PER should bring together the following information:

• Device overview and intended purpose: Identification of the IVD, its intended clinical application and the performance claims being evaluated
• Scientific validity evidence: A summary and critical appraisal of the evidence supporting the relationship between the analyte or marker and the relevant clinical condition
• Analytical performance evidence: Results and conclusions from analytical performance studies, including the evaluation of applicable performance characteristics
• Clinical performance evidence: Results and conclusions from clinical performance studies, scientific literature or other relevant sources supporting the device’s clinical performance
• Evidence appraisal: An assessment of the quality, relevance, limitations and overall sufficiency of the available data
• Benefit-risk assessment: An evaluation of the clinical evidence in relation to the device’s intended clinical benefits and associated risks
• Evidence gaps and limitations: Identification of unresolved uncertainties and their implications for the overall performance evaluation
• Overall conclusions: A documented assessment of whether the available clinical evidence supports the intended purpose and relevant safety and performance requirements

Sources of Performance Evaluation Evidence

Depending on the device’s intended purpose and performance claims, relevant evidence may include peer-reviewed scientific literature and published clinical research, scientific validity data relating to the analyte or marker, analytical performance study results, clinical performance study results, published experience gained through routine diagnostic testing, relevant data from previously evaluated devices where scientifically justified, and post-market surveillance and PMPF data.

Manufacturers must assess the relevance, quality and sufficiency of the available evidence, recognising that not all sources will adequately support every aspect of a device’s performance evaluation.

Identifying and Addressing Evidence Gaps

Evidence gaps may arise when the available data do not adequately support a particular performance claim, intended population or clinical application. Examples include insufficient clinical performance data for a specific target population, limited analytical performance data for certain specimen types, inadequate evidence supporting a newly introduced biomarker, differences between the conditions evaluated in existing studies and the device’s intended use, and limited evidence supporting particular performance claims.

When gaps are identified, manufacturers should determine whether additional evidence can be obtained through literature review, existing datasets or appropriately designed performance studies. The evaluation should explain how identified limitations have been addressed or justify why the remaining evidence is sufficient.

When Are Performance Studies Required?

Under Annex XIII, analytical performance is generally demonstrated through analytical performance studies. Clinical performance studies are also required unless reliance on other sources of clinical performance data is adequately justified.

The need for additional studies depends on whether the available evidence sufficiently supports the device’s intended purpose and performance claims, rather than its risk classification alone. Where performance studies are required, manufacturers must ensure that the study design, target population, specimen selection, endpoints and statistical methods are appropriate to the device’s intended purpose.

Requirements for conducting performance studies are established in Articles 57 to 77 and Annex XIII of the IVDR, with additional provisions applying to certain types of studies.

Common Mistakes: Challenges in IVDR Performance Evaluation

Manufacturers may encounter several challenges when preparing and maintaining performance evaluation documentation under the IVDR.

Defining the intended purpose

Broad or unclear claims can make it difficult to determine the appropriate evidence requirements and performance characteristics. The intended purpose should remain consistent across the PEP, PER and technical documentation.

Demonstrating sufficient clinical evidence

Available evidence must support the specific device, target population and claimed clinical application. This can be particularly challenging for novel biomarkers or emerging technologies.

Assessing evidence quality and relevance

Differences in study design, patient populations, specimen types and reported outcomes may limit the applicability of published evidence.

Maintaining documentation consistency

Performance claims, supporting evidence and conclusions should remain aligned across the PEP, PER and associated technical documentation.

Keeping evaluations up to date

New scientific evidence, post-market findings, or changes in clinical practice may require manufacturers to review and update their performance evaluation documentation, and ongoing post-market surveillance is crucial for maintaining the safety and compliance of the diagnostic device. For the equivalent challenges under EU MDR see our article on reasons Clinical Evaluation Reports are rejected.

Best Practices: Maintaining Performance Evaluation and Quality Management System Across the Lifecycle

Performance evaluation extends beyond initial conformity assessment and CE marking. Manufacturers must continue to assess whether the available clinical evidence supports the IVD’s intended purpose, safety and performance throughout its lifecycle. Post-market surveillance and post-market performance follow-up (PMPF) contribute to this process by providing ongoing information about the device’s safety and performance.

PMPF activities can help manufacturers confirm the continued safety and performance of an IVD, identify previously unknown risks or limitations, monitor changes in clinical practice or the state of the art, evaluate whether existing clinical evidence remains sufficient, and identify the need for additional performance data or studies. Findings from PMS and PMPF activities should be considered when reviewing and updating the performance evaluation documentation. For the structure of the equivalent follow-up process under EU MDR see our article on what a PMCF plan must contain.

Preparing and maintaining IVDR performance evaluation documentation requires careful assessment of the available evidence and a clear understanding of the applicable regulatory requirements. CiteMed supports medical device and IVD manufacturers with evidence-based regulatory and scientific writing services, helping teams organise, evaluate and communicate the information needed for regulatory submissions and ongoing compliance. Support may include scientific literature reviews, evidence identification and appraisal, performance evaluation documentation, and the integration of relevant clinical and regulatory evidence into technical documentation. A systematic approach can help manufacturers identify evidence gaps, improve documentation consistency and maintain clear traceability between the device’s intended purpose, performance claims and supporting evidence.

Comparison Table: PEP vs PER

Checklist: IVDR Performance Evaluation Readiness

Planning:

• Intended purpose is clearly defined and consistent across the PEP, PER, and technical documentation
• Applicable GSPRs requiring clinical evidence support are identified
• Evidence requirements for each of the three pillars are defined in the PEP
• State-of-the-art assessment is included

Evidence:

• Scientific validity evidence is identified, appraised, and documented in a scientific validity report
• Analytical performance studies address applicable parameters, with any omissions justified
• Clinical performance evidence is documented, with reliance on non-study sources justified
• Literature search strategy, databases, and inclusion and exclusion criteria are documented
• Evidence gaps are identified and addressed or justified

Reporting and maintenance:

• PER includes the scientific validity, analytical performance, and clinical performance reports
• PER is updated at least annually for Class C and D devices
• PER for Class A and B follows the PMS plan update schedule
• PMS and PMPF findings are reflected in the performance evaluation
• Documentation remains aligned across the PEP, PER, and technical documentation

Definitions

IVDR performance evaluation
The continuous process of collecting, appraising, and analysing data to demonstrate the scientific validity, analytical performance, and clinical performance of an IVD for its intended purpose.

Performance Evaluation Plan (PEP)
The document, required under Annex XIII Part A, that outlines the strategy for demonstrating and maintaining an IVD’s scientific validity, analytical performance, and clinical performance throughout its lifecycle.

Performance Evaluation Report (PER)
The document that records the results of performance evaluation and provides a critical assessment of the evidence supporting the IVD’s intended purpose. It forms part of the technical documentation.

Scientific validity
The association between an analyte or marker and a particular clinical condition or physiological state.

Analytical performance
An IVD’s ability to reliably and consistently detect or measure a particular analyte under defined conditions.

Clinical performance
The ability of an IVD to yield results that are correlated with a particular clinical condition or physiological or pathological process, in accordance with its intended purpose and target population.

Post-Market Performance Follow-Up (PMPF)
An ongoing process used to collect and evaluate performance and scientific data after an IVD has been placed on the market.

General Safety and Performance Requirements (GSPRs)
The requirements in Annex I of the IVDR that an IVD must meet. Performance evaluation evidence supports conformity with the applicable GSPRs.

Expert Perspective

The IVDR performance evaluations that struggle in review are rarely missing a study. They are missing coherence. The intended purpose in the PEP says one thing, the performance claims in the PER say another, and the evidence supports a narrower claim than either. The three pillars are designed to be read together: a clinically meaningful analyte, measured reliably, with results that correlate with the claimed condition in the claimed population. When one pillar is thin, the claims built on top of it need to narrow to match. Manufacturers who define the intended purpose precisely at the start, and who treat the PER as a document that must be kept alive by post-market evidence, avoid most of the findings that others spend months remediating.

Frequently Asked Questions

What is performance evaluation under the IVDR?
Performance evaluation is the continuous process of assessing scientific validity, analytical performance and clinical performance data to demonstrate that an IVD performs as intended and is supported by sufficient clinical evidence. The requirements are established in Article 56 and Annex XIII Part A of Regulation (EU) 2017/746.

What are the three pillars of IVDR performance evaluation?
The three pillars are scientific validity, analytical performance and clinical performance. Together, they establish the scientific basis for the analyte or marker, the device’s ability to measure or detect it reliably, and its performance for the intended clinical application.

What is the difference between a PEP and a PER?
The Performance Evaluation Plan (PEP) outlines how the manufacturer intends to conduct the performance evaluation, including the evidence requirements and evaluation methods. The Performance Evaluation Report (PER) documents and critically assesses the resulting evidence and conclusions.

Are clinical performance studies mandatory under the IVDR?
Clinical performance studies are generally required unless the manufacturer can adequately justify reliance on other sources of clinical performance data. The need for additional studies depends on the device’s intended purpose and the sufficiency of the available evidence.

How often should an IVDR Performance Evaluation Report be updated?
Under Article 56(6), Performance Evaluation Reports for Class C and Class D devices must be updated as necessary, but at least annually. For Class A and Class B devices, updates are required as necessary and in accordance with the manufacturer’s post-market surveillance plan.

What is the relationship between PMPF and performance evaluation?
Post-market performance follow-up (PMPF) is an ongoing process used to collect and evaluate performance and scientific data after an IVD has been placed on the market. Its findings contribute to maintaining and updating the performance evaluation, and should be considered alongside post-market surveillance data when reviewing the PER.

How can literature review support IVDR performance evaluation?
Scientific literature is a key source of evidence for scientific validity and clinical performance, and it supports state-of-the-art assessment. Where literature is used, the search strategy, databases, inclusion and exclusion criteria, and appraisal methods should be clearly documented so the evidence pathway is traceable. See our guide to structured literature review methodology for more detail.

References

• Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR), particularly Article 56 and Annex XIII; adopted on April 5, 2017, and fully applicable on May 26, 2022. It repeals the previous vitro diagnostic directive from 1998, namely directive 98 79 ec, and amended transitional provisions were adopted on December 15, 2021.
• PRISMA 2020 Statement

Related Resources

• EU MDR Literature Review Services: Structured literature review supporting performance evaluation and clinical evaluation
• PRISMA and EU MDR Literature Review: Structured literature review methodology
• Post-Market Surveillance Under EU MDR: Building a proactive PMS system
• PMCF Surveys Solution: Structured post-market follow-up activities
• CER Checklist for EU MDR: The MDR counterpart to the IVDR PER
• Why Clinical Evaluation Reports Are Rejected: Common documentation gaps that also apply to PERs
• EU MDR Consulting Services: Expert regulatory support

Call to Action

If you are preparing a Performance Evaluation Plan or Report, or building a more structured approach to literature review and evidence management for IVDR compliance, CiteMed can help. Get in touch to discuss your requirements.