MedTech Europe IVDR Clinical Evidence Requirements: Key Updates in the 3rd Edition

March 4, 2023

MedTech Europe IVDR Clinical Evidence Requirements have evolved again with the release of the third edition of the MedTech Europe eBook. This updated 129‑page resource provides deeper clarity on how manufacturers and regulatory teams can navigate clinical evidence expectations under the EU In Vitro Diagnostic Regulation (IVDR).

The new edition includes expanded examples, refined explanations, updated diagrams, and improved flow—making it an essential tool for all IVD stakeholders.

Below is a clear summary of the most important updates and what they mean for IVD and CDx manufacturers.

What’s New in the MedTech Europe IVDR Clinical Evidence Requirements eBook (Version 3)

Stronger Guidance for Companion Diagnostics (CDx)

CDx receives significant attention in the new edition, appearing in 20 out of 129 pages. The guidance helps CDx developers:

Define analytical and clinical performance endpoints
Establish cut‑off values and clinical benefit claims
Understand clinical data sources and scientific validity
Plan and conduct clinical performance studies for CE marking

The eBook also includes flowcharts showing how CDx developers should engage with EU Competent Authorities, and clarifies comparator selection and follow‑on CDx requirements.

Use of Non‑EU Clinical Data

A major clarification covers how to use clinical data generated outside the EU to support performance evaluation claims. This guidance helps manufacturers:

Determine when non‑EU data is acceptable
Ensure alignment with IVDR expectations
Strengthen global clinical evidence strategies

Updated Intended Purpose/Intended Use Guidance

The eBook expands its section on intended purpose by:

Adding updated examples aligned with IVDR definitions
Introducing a new COVID‑19 example
Emphasizing the need for a specific medical purpose

These updates help manufacturers ensure their intended purpose statements are precise, defensible, and MDR‑compliant.

Refined Guidance on Scientific Validity and Clinical Evidence

Improved Layout and Clarity

Chapters on scientific validity and clinical evidence have been reorganized to improve flow. Manufacturers now benefit from:

Clearer definitions
Step‑by‑step expectations
Better alignment with IVDR Annex XIII

This helps teams understand the level of evidence required for high‑risk IVDs.

Updated Use of Published Testing Data

The chapter on published experience now includes:

More rigorous scientific expectations
Additional requirements for evaluating routine testing data

This supports more robust scientific validity assessments for high‑risk IVD claims.

Equivalence and Similarity: New Clarifications

The updated chapter on equivalence focuses on performance evaluation concepts, not clinical equivalence as used in the MDR for medical devices. The new edition:

Refines the tool used to demonstrate equivalence
Clarifies similarities versus equivalence thresholds
Includes clearer examples and decision tools

This is especially relevant for Class C and D devices.

New Chapter on Benefit‑Risk Determination

A major addition is a new chapter dedicated to benefit‑risk determination, including:

How to assess benefit‑risk for IVDs that guide clinical decisions
When benefit‑risk claims align devices closer to CDx requirements
How to structure benefit‑risk information within Technical Documentation

This chapter strengthens alignment with IVDR Annex I, GSPRs, and clinical evaluation requirements.

Additional Technical Documentation Updates

The eBook also updates its chapter on documentation to reinforce:

Consistency across the product lifecycle
Alignment with the cyclical nature of clinical evidence generation
Traceability between clinical performance, scientific validity, and intended purpose

These updates support stronger conformity assessment submissions.

Why These Updates Matter for IVD Manufacturers

The third edition of MedTech Europe IVDR Clinical Evidence Requirements helps manufacturers:

Strengthen clinical evidence packages
Build more defensible performance evaluations
Understand how to design compliant CDx strategies
Prepare for Notified Body scrutiny
Navigate global clinical data integration

The eBook remains free to download on the MedTech Europe website and is considered one of the most practical, industry‑aligned resources available today.

How MDx CRO Supports IVDR Clinical Evidence Requirements

MDx CRO specializes in regulatory, clinical, and quality support for IVD and CDx manufacturers. With IVDR requirements expanding sharply, manufacturers increasingly rely on expert partners to navigate:

Intended purpose analysis
CDx development strategy
Clinical performance study design
Scientific validity assessments
GSPR checklists and technical documentation
QMS alignment (ISO 13485, ISO 14971, ISO 15189)
Notified Body interactions
AEMPS and Competent Authority submissions

Whether you need end‑to‑end support or targeted expertise, our MedTech regulatory team helps ensure your IVD meets all MedTech Europe IVDR Clinical Evidence Requirements.

MedTech Europe is making the Third Version available to be downloaded free of charge from its website, making it an essential resource for anyone involved in the IVD industry.

Written by:

Carlos Galamba

CEO

Senior regulatory leader and former BSI IVDR reviewer with deep experience in CE marking high-risk IVDs, companion diagnostics, and IVDR implementation.

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In a landmark announcement, Roche has revealed that its Ventana PD-L1 (SP263) Assay has received CE IVD approval, setting a new standard in the personalized treatment of non-small cell lung cancer (NSCLC). This cutting-edge diagnostic test now stands as a beacon of hope for patients with locally advanced and metastatic NSCLC, identifying those who are eligible for treatment with the groundbreaking immunotherapy, Libtayo (cemiplimab).

Bridging the Gap in Lung Cancer Treatment

Lung cancer remains the most prevalent and lethal cancer worldwide, with NSCLC accounting for up to 85% of all cases. The challenge of treating this disease lies in its late diagnosis, often at a stage where traditional therapies have limited efficacy. However, the advent of immunotherapy has introduced a new horizon of treatment options, necessitating precise diagnostic tools to identify suitable candidates.

The Role of Ventana PD-L1 (SP263) Assay

The Ventana PD-L1 (SP263) Assay is at the forefront of this medical evolution, designed to detect the expression of the PD-L1 protein on tumor and immune cells. The expression level of PD-L1 has been closely linked to the efficacy of PD-1/PD-L1 immunotherapy drugs, making it a critical factor in tailoring treatment plans for individual patients. The assay’s approval is based on the results of the Phase III EMPOWER-Lung 1 study, which underscored the potential of Libtayo monotherapy in improving patient outcomes.

Expanding Treatment Options with “Roche PD-L1”

With this CE mark approval, the Ventana PD-L1 SP263 Assay (Roche PD-L1) is the only CE IVD product in the market with NSCLC indications for four different immunotherapy drugs, thereby broadening the spectrum of treatment options available to oncologists and their patients. This development is a testament to Roche’s commitment to advancing personalized medicine and improving access to life-saving treatments.

Jill German, Head of Pathology Lab at Roche Diagnostics, highlighted the significance of this breakthrough: “With our companion diagnostics, we can ensure each patient receives the most appropriate targeted treatment. This approval not only broadens the treatment landscape for advanced lung cancer patients but also marks a pivotal step in our journey towards personalizing healthcare.”

A Step Towards Personalized Healthcare

The CE mark for the Ventana PD-L1 (SP263) Assay represents more than just a regulatory milestone; it signifies a shift towards a future where cancer treatment is tailored to the individual, maximizing efficacy while minimizing unnecessary exposure to potentially ineffective therapies. As the global medical community continues to make strides in the fight against lung cancer, the role of precise, reliable diagnostics will only become more crucial.

In embracing these advancements, we inch closer to a world where lung cancer, once a formidable foe, becomes a manageable condition, with patients receiving treatments designed for their specific biological makeup. The journey towards personalized healthcare is long and fraught with challenges, but with innovations like the Ventana PD-L1 (SP263) Assay, the path becomes clearer, offering new hope to those battling lung cancer.

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Multiplex IVD Devices under IVDR: Team-NB’s Common Assessment Approach

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Multiplex in vitro diagnostic (IVD) devices detect two or more targets or markers within a single procedure and are marketed as one device with a single intended purpose. Typical examples include large allergy panels or respiratory pathogen panels with dozens—sometimes hundreds—of analytes. The regulatory challenge under the IVDR (EU) 2017/746 is demonstrating sufficient evidence for each claimed target while keeping the review of the Technical Documentation (TD) efficient and traceable. Team-NB, the European association of Notified Bodies, has published a common approach that clarifies how NBs assess multiplex devices and when risk-based sampling is appropriate.

What “multiplex” means for evidence and classification

Under IVDR, the device is assessed against its intended purpose and the sum of claimed targets/markers. Because multiplex devices may include analytes with different IVDR classes (for example, a respiratory panel combining Class D markers like SARS-CoV-2 with Class C/B markers such as Influenza A/B or Adenovirus), the highest-risk elements drive scrutiny. Team-NB notes that reviewing the core detection technology, its analytical controls, and cross-reactivity/interference management is central to demonstrating performance across the panel.

Risk-based sampling: when and how NBs apply it

Because reviewing full clinical and analytical data for every single target may be impractical for very large panels, Team-NB supports a risk-based sampling approach—with clear guardrails.

All Class D marker documentation is reviewed in full. Given their public health impact and the IVDR’s enhanced controls for Class D, NBs expect complete evidence per analyte at this class.
Class C and B markers may be sampled using a documented, risk-based rationale. Sampling starts with highest-risk analytes and extends if deficiencies are found.
The focus remains on the detection technology (e.g., chemistry/primer-probe design, signal generation, software algorithms, cut-off establishment, cross-talk controls), supported by representative per-analyte evidence that shows claims are justified and transferable across the panel.

NBs may expand the sample or update the sampling plan during the certification cycle if multiple deficiencies appear in the initial review. The NB’s conformity-assessment report should describe the sampling approach and rationale, including how representative analytes were chosen and how conclusions extend to the remaining targets.

What your Technical Documentation must make easy

Team-NB repeatedly finds delays when evidence is missing or hard to locate. Manufacturers of multiplex IVDs should ensure that the TD:

Maps every claimed analyte to traceable evidence (analytical performance, clinical performance or clinical evidence strategy) and clearly distinguishes sampled vs. fully reviewed targets.
Explains transferability of evidence across the panel (e.g., shared technology, common reagent design, shared validation strategy) and justifies cut-offs and decision rules for each analyte category.
Aligns the intended purpose with labelling/IFU and Performance Evaluation Report (PER) conclusions; discrepancies trigger NB questions.
Includes a PMPF plan proportionate to residual uncertainty, with triggers to widen surveillance to additional analytes if signals appear.

For structure and completeness across Annex II/III items (including GSPR mapping, verification/validation reports, and PMS/PMPF files), Team-NB’s broader best-practice guidance for technical documentation is a useful companion.

Class D special considerations

Where the panel includes Class D analytes (e.g., certain blood-screening or high-consequence infectious markers), plan for EURL involvement where applicable and for full analyte-specific review—no sampling. Batch/lot verification or independent performance checks may be required once EU Reference Laboratories (EURLs) are designated for the relevant scope.

Bottom line for manufacturers

Multiplex panels can win on clinical utility and workflow efficiency, but under IVDR they succeed only when the technology narrative, per-analyte evidence, and a defensible sampling rationale fit together. Build your dossier so an NB reviewer can follow the logic for each claim, see how representative analytes anchor the panel, and understand how PMPF will continue to de-risk performance across all targets after certification.

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