Performance Evaluation Plan (PEP)

IVDR Performance Evaluation: What Notified Bodies Expect
Performance evaluation under IVDR is simply how you prove your IVD test really works for what you claim it does not only in the lab, but also in the intended users and setting. IVDR expects evidence for three linked “pillars”: scientific validity (the marker/analyte is truly connected to a clinical condition), analytical performance (the test measures correctly and consistently), and clinical performance (the test result matches the patient’s real clinical status in the intended population). This is required under Article 56 and Annex XIII (Part A). To organize this evidence, manufacturers create a Performance Evaluation Plan (PEP) think of it as a roadmap. The PEP clearly states the intended purpose, what performance characteristics must be shown (Annex I, Section 9), what studies or literature will be used, the acceptance criteria (pass/fail targets), and who will do what and when. A notified body reviews this plan as part of the technical documentation, so if it’s vague or missing acceptance criteria, you’ll usually get questions and delays. After you execute the plan, you write the Performance Evaluation Report (PER) this is the “results and conclusion” document that shows whether the device met the planned criteria, what limitations exist, and why the benefit–risk remains acceptable. Under IVDR, performance evaluation is not a one-time activity: you must keep it updated across the device lifecycle using new information from PMS and PMPF (real-world performance trends, complaints, new literature, etc.). In short: PEP = plan how you’ll prove performance; PER = prove it with data; PMS/PMPF = keep proving it after launch. This lifecycle approach is what supports CE marking and keeps the device compliant over time, especially for higher-risk IVDs.

IVDR Performance Evaluation: What Notified Bodies Expect

Performance evaluation under IVDR is simply how you prove your IVD test really works for what you claim it does not only in the lab, but also in the intended users and setting. IVDR expects evidence for three linked “pillars”: scientific validity (the marker/analyte is truly connected to a clinical condition), analytical performance (the test measures correctly and consistently), and clinical performance (the test result matches the patient’s real clinical status in the intended population). This is required under Article 56 and Annex XIII (Part A).

To organize this evidence, manufacturers create a Performance Evaluation Plan (PEP) think of it as a roadmap. The PEP clearly states the intended purpose, what performance characteristics must be shown (Annex I, Section 9), what studies or literature will be used, the acceptance criteria (pass/fail targets), and who will do what and when. A notified body reviews this plan as part of the technical documentation, so if it’s vague or missing acceptance criteria, you’ll usually get questions and delays.

After you execute the plan, you write the Performance Evaluation Report (PER) this is the “results and conclusion” document that shows whether the device met the planned criteria, what limitations exist, and why the benefit–risk remains acceptable. Under IVDR, performance evaluation is not a one-time activity: you must keep it updated across the device lifecycle using new information from PMS and PMPF (real-world performance trends, complaints, new literature, etc.).

In short: PEP = plan how you’ll prove performance; PER = prove it with data; PMS/PMPF = keep proving it after launch. This lifecycle approach is what supports CE marking and keeps the device compliant over time, especially for higher-risk IVDs.

Introduction

Performance evaluation is a mandatory part of ensuring that an in vitro diagnostic (IVD) device fulfills the safety and performance expectations laid out in the regulation. Under IVDR, manufacturers must show that their device achieves its claimed purpose under normal conditions of use and that it answers relevant safety, accuracy, reliability issues. This involves demonstrating three pillars: scientific validity, analytical performance, and clinical performance. (Ref: IVDR Article 56, Annex XIII Part A)

Legal Basis: Articles and Annex References

Some of the key legal provisions are:

Article 56 of IVDR: Specifies that performance evaluation must be planned, conducted, and documented so that clinical evidence supports the intended purpose. It also mandates continuous updating throughout device life.
Annex I, especially Section 9: Details the general safety and performance requirements (GSPR) related to performance characteristics (analytical & clinical) that must be satisfied.
Annex XIII, Part A: Lays down what must be in the PEP (Performance Evaluation Plan), including the criteria, methods, characteristics, analytes, etc.
MDCG-2022-2: Provides guidance on the general principles of clinical evidence—how to interpret scientific validity, how to plan performance evaluation, how to handle post-market performance follow-up.

Importance in IVD Lifecycle and CE Marking

The PEP is essential before placing the device on the market: it forms part of the technical documentation that a Notified Body will assess. If the PEP is weak or missing elements, CE marking may be delayed.
After market entry, the plan supports ongoing collection and review of data (PMPF / PMS) to ensure continued compliance and safety. Under IVDR, especially for higher-risk devices (Class C & D), the evidence must be updated regularly.
Helps in risk management: by mapping what could fail (analytical or clinical performance) and preparing for monitoring, mitigations, or improvements.

What is a Performance Evaluation Plan (PEP)?

A Performance Evaluation Plan is a documented plan which:

Defines the intended purpose of the device (what it claims to detect or measure, in what population, setting, etc.).
Identifies which performance characteristics (per Annex I Section 9) need demonstration.
Specifies methods, statistical tools, acceptance criteria, reference materials, etc., that will be used to generate evidence.
Sets out timelines, responsibilities, and how updates will be made.

In short, it’s the roadmap for how you will build up the evidence (analytical, clinical, scientific) required under IVDR.

When and Why It Is Required

When: Before market launch, as part of the pre-market technical documentation. Also, regularly updated during the lifecycle of the device, especially for Class C & D devices.
Why: To ensure conformity with IVDR, particularly GSPR. Also to ensure that the performance claims are scientifically valid, reliable, safe, and useful. Without a proper PEP, risk that device fails to meet regulatory expectations, or the Notified Body requests more data.

Relationship with the Performance Evaluation Report (PER)

The PEP lays the foundation: what you plan to do, how, when, with what criteria.
The PER is the deliverable: after doing the work, gathering data, you report what you found, whether the device meets those criteria, and any limitations. It includes documentation of literature, data, study design, statistical methods, results, etc.
Regulatory requirement: IVDR mandates that the PER be part of the technical documentation. Also, PER must be updated based on the PEP, as post-market data come in.

Regulatory Requirements for PEP

Here are the main Articles / Annexes relevant, and what they require of the PEP:

Legal Provision	Key Requirements Related to PEP
Article 56	Must plan, conduct, document performance evaluation; clinical evidence must support intended purpose; evidence must be continuous; must justify level of clinical evidence appropriate to device characteristics and intended purpose; must update throughout lifecycle.
Article 57	Governs clinical performance studies: when required, design, safety, conduct, ethics. PEP may include whether such studies are needed or justified.
Annex I Section 9	Identifies which performance characteristics are relevant: analytic sensitivity/specificity, limit of detection, measurement range, etc. PEP must map which of these characteristics apply, and how to test them.
Annex XIII Part A	Contains explicit details about what a PEP must include: device intended use, analytes, reference materials, patient group definitions, methods & statistical tools, state of the art, benefit-risk acceptability, milestones, acceptance criteria, etc.

Scientific Validity: Planning and Documentation

Scientific Validity is defined under IVDR as demonstrating that the analyte or marker is associated with a clinical condition or physiological state. This is foundational.
When planning validity assessment:
1. Literature Review / Systematic Review. Identify existing peer-reviewed studies, expert consensus, meta-analysis. Document method: which databases (e.g. PubMed, Embase), search strategy, inclusion/exclusion, critical appraisal.
2. Gap Identification. What is not known: specificity, populations not covered, conflicting evidence. Plan new studies if needed.
3. Proof-of-Concept / Pilot Data. If the analyte is novel or claims ambitious, small studies may establish association.
For documentation, include in PER a scientific validity report covering all these, with transparent methodology. IVDR Annex XIII demands that this be documented.

Analytical Performance: Parameters and Methods

Analytical performance refers to how well the device measures what it claims to measure, under normal (and sometimes stressed) use conditions. Components include:
- Precision: repeatability (same operator, same instrument), reproducibility (different conditions).
- Accuracy / Trueness: comparing with reference methods.
- Limit of Detection (LOD) and Limit of Quantitation (LOQ).
- Linearity / Measurement Range.
- Specificity / Analytical Specificity: ability to avoid false positives from similar substances (cross-reactivity).
- Interferences.
- Stability: of reagents, sample handling, etc.
Methods:
- Identify certified reference materials / validated measurement procedures if available.
- Use appropriate sample size; define statistical analysis (e.g. confidence intervals, acceptable error margins).
- Predefine acceptance criteria: what error tolerances are acceptable, what performance thresholds to meet.

Clinical Performance: Study Design and Objectives

Purpose: to show that the diagnostic result produced by the device correlates with the clinical condition in the intended population.
Key design elements:
- Comparators: gold standard tests or other diagnostics.
- Population and setting: demographic, disease prevalence, specimen types.
- Endpoints: sensitivity, specificity, predictive values where relevant.
- Prospective vs retrospective: which is feasible and acceptable.
Use of real-world evidence / literature: when justifiable (e.g. for low risk devices or where clinical studies are difficult). Must be well documented.
Ethical & safety aspects: Sample collection, handling patient consent, ensuring minimal risk.

Performance Evaluation Strategy

Ensure that scientific validity, analytical and clinical performance are not treated in isolation but are integrated. For example, a clinical performance study may also provide analytical performance data under field conditions.
The plan should have versioning and triggers for review. For example, if new literature emerges, or if user complaints suggest performance issues, or after a certain period (especially for Class C & D devices, IVDR mandates annual updates).
The strategy should be risk-based: higher risk = more rigorous evidence; lower risk or simpler devices may justify fewer or literature-based clinical performance studies.

Relationship Between PEP, PER, and PMS / PMPF

PMS (Post Market Surveillance) is the set of activities after market entry to collect information about device performance, safety, complaints, etc.
PMPF (Post Market Performance Follow-Up) is more specific: planned studies, data collection to follow up performance claims, monitor long-term performance, detect performance drift.
Data from PMS / PMPF feed back into updating the PEP (if new risks or evidence emerge), and revisions to the PER (to reflect current evidence).
For Class C & D devices, IVDR requires the PER be updated at least annually when needed.

Common Pitfalls and Best Practices in Creating a PEP

Common Pitfalls

Omitting negative or contradictory data – Excluding unfavorable literature or study results introduces bias and weakens the scientific validity required by Annex XIII, Part A.
Unclear acceptance criteria – Using terms like “good sensitivity” without defined numerical thresholds fails to meet the analytical requirements of Annex I, Section 9.1(a).
Poorly defined intended purpose or population – An incomplete or vague description can misalign study data with real use and may lead to non-conformity (Ref: Article 56(1) and Annex I, Section 20).
No structured post-market plan – Lack of a Post-Market Performance Follow-up (PMPF) and surveillance strategy breaches Annex XIII, Part B and Articles 78 to 81.
Failure to update documents – Not revising the PEP or Performance Evaluation Report (PER) when new data, device changes, or updated standards emerge violates Article 56(6).

Best Practices

Include all relevant evidence, positive or negative, with transparent justification.
Define measurable, risk-based acceptance criteria for all analytical and clinical parameters.
Align the PEP with the risk management file and assign clear responsibilities for PMS/PMPF activities.
Maintain version control and update the PEP and PER promptly to reflect new evidence or regulatory changes.

Templates and Checklists for PEP Preparation

Device Description and Intended Purpose

Provide a detailed description of the in vitro diagnostic device, including its trade name, model or catalogue number, and a precise statement of the intended purpose.
This section must also specify the medical condition, clinical indications, and user profile (professional, point-of-care, or self-testing). Include claimed performance characteristics, limitations, and contraindications as required by Annex I, Section 20.

Target Population and Use Environment

Define the target population (e.g., age range, disease status, and relevant demographic factors) and the intended use environment (e.g., laboratory, clinical setting, home).
Identify the specimen types to be used and describe any specific conditions for specimen collection, transport, and storage.

Definition of Analytes or Markers

Provide a clear and scientifically sound description of each analyte or marker that the device is intended to detect or measure.
Demonstrate the clinical relevance of these analytes or markers in accordance with Article 2(38) and Annex XIII, Part A.

Reference Materials and Measurement Traceability

List reference materials, reference measurement procedures, and standards that will be used to ensure metrological traceability.
Establish how traceability to appropriate reference standards will be maintained, as required by Annex I, Section 9.1(a).

State of the Art and Relevant Standards

Summarize the current state of the art for the intended diagnostic purpose, including recognised scientific and clinical guidelines, harmonised standards, and common specifications.
Identify benchmark devices or technologies to be used for comparative purposes in analytical and clinical performance assessments.

Analytical Performance Plan

Identify all analytical performance parameters relevant to the device and provide detailed protocols for their evaluation, including:

Accuracy and trueness
Precision (repeatability and reproducibility)
Analytical sensitivity and specificity
Limit of detection (LOD) and limit of quantitation (LOQ)
Linearity and measuring range
Potential interferences and cross-reactivity
For each parameter, specify study design, statistical methods, acceptance criteria, and reference measurement procedures. This section should align with Annex I, Section 9 and Annex XIII, Part A.

Clinical Performance Plan

Describe the methodology for demonstrating clinical performance, which may include clinical performance studies, literature reviews, or real-world evidence.
Provide detailed information on study design, intended clinical endpoints, comparator methods, sample size justification, inclusion and exclusion criteria, and ethical considerations in accordance with Article 57 and Annex XIII, Part A.

Benefit–Risk Evaluation and Risk Management Alignment

Summarise the benefit–risk assessment for the device, integrating the risk management process defined in ISO 14971 and required by Annex I, Section 3.
Document how the risk management file interacts with and supports the PEP.

Timelines, Milestones, and Responsibilities

Provide a schedule of planned activities, including start and completion dates for each phase of the performance evaluation.
Assign responsibilities to designated individuals or functions to ensure accountability and traceability throughout the process.

Post-Market Surveillance (PMS) and Post-Market Performance Follow-up (PMPF)

Define the strategy for collecting and evaluating post-market data to confirm the ongoing safety and performance of the device.
Describe how PMS and PMPF findings will be integrated into periodic updates of the PEP and the Performance Evaluation Report (PER), as required by Annex XIII, Part B and Articles 56 and 78–81.

Version Control and Document Change Management

- Establish a version control system to track updates to the PEP.
- Include a change log documenting the reason for each revision, the date of implementation, and the responsible person or department.

FAQs on Performance Evaluation Plan under IVDR

Does every IVD device require a PEP?
Yes. IVDR mandates that all IVDs, except where very specifically exempted (if ever), must have a performance evaluation. The manufacturer must establish a PEP as part of the technical documentation.

How often should the PEP / PER be updated?

For Class C & D IVDs: PER must be updated at least annually, and whenever new data (post-market, PMPF) emerge that affect performance or safety.
For lower risk: updates when triggered (new evidence, changes in state of art, changes in intended use or observed performance issues).

Is PER always mandatory?

Yes. The Performance Evaluation Report is required and is part of the technical documentation. Even if relying on literature or other indirect data, the PER must include justification, methods, findings, limitations.

Conclusion

The PEP is central to IVDR compliance: it is how the manufacturer shows that they understand what performance is needed, how to measure it, and how to maintain performance over time. A robust PEP, followed by a well-conducted PER and strong PMS / PMPF, makes the regulatory review smoother and reduces risk of non-conformity. Trends to watch: greater reliance on real-world evidence, more detailed guidance from notified bodies / standardized common specifications, evolving standards (analytical & clinical), more emphasis on traceability and reproducibility of results.

Key References

IVDR (EU) 2017/746, especially:

Article 56: Performance evaluation and clinical evidence
Article 57: General requirements regarding performance studies
Annex I: General Safety and Performance Requirements (GSPR), e.g. Section 9 on performance characteristics
• Annex XIII, Part A: Performance Evaluation and Performance Studies; Part B: Post‑Market Performance Follow‑Up (PMPF)

MDCG‑2022‑2: Guidance document published 27 January 2022, setting out general principles of clinical evidence, the performance evaluation process, the role of risk management, PEP, PER, continuous updating, etc.

How Morulaa Supports IVDR Compliance

Morulaa HealthTech we support IVD manufacturers in meeting EU IVDR requirements by developing clear, compliant, and structured Performance Evaluation Plans (PEP). Our team assists in drafting, reviewing, and updating PEPs to align with Annex XIII and Article 56, ensuring robust evidence of scientific validity, analytical, and clinical performance. We perform gap assessments to identify missing or weak areas and define strategies to strengthen your technical documentation. From literature reviews to study planning and statistical methods, we guide you through each step. We also support post-market activities including PMS and PMPF to maintain performance evidence throughout the device lifecycle. Every solution is tailored to your device risk class and target market, ensuring a smooth and effective regulatory pathway.