IVDR Scientific Validity Report (SVR): Requirements and Preparation
We help IVD manufacturers demonstrate the link between their analyte and the clinical condition, from literature search to a notified-body-ready Scientific Validity Report.
Scientific Validity: The First Pillar of IVD Clinical Evidence
Article 2(38) of IVDR (EU) 2017/746 defines scientific validity of an analyte as the association of an analyte with a clinical condition or a physiological state. It sits alongside analytical and clinical performance in every performance evaluation.
A Scientific Validity Report (SVR) is the document that records how you identified, appraised and analysed the evidence for that association for your device’s intended purpose, and what you concluded. Under Annex XIII of the IVDR it is one of the three reports that the Performance Evaluation Report (PER) brings together, with the analytical performance and clinical performance reports.
The association between the analyte and the clinical condition or physiological state.
The ability of the device to give results that correlate with the clinical condition in the intended population.
Why Scientific Validity Matters for IVDR Compliance
If the analyte is not shown to be linked to the condition in your intended purpose, analytical and clinical data cannot support your claims. The Scientific Validity Report feeds directly into the Performance Evaluation Report reviewed by your notified body.
- Required for every IVD, not only novel tests
- Sets the clinical context for analytical and clinical performance
- Must stay current through the device lifecycle and PMPF
Well-known analytes still need a documented, reproducible literature review. "Well established" is never a reason to skip scientific validity.
Controls, calibrators and accessories
Products that do not perform the assay themselves still need to address scientific validity. Your Performance Evaluation Plan should justify how it applies, usually by documenting the scientific validity of the analyte measured by the assays they support.
For Class C and D devices, the Performance Evaluation Report, including scientific validity, must be updated at least annually with PMPF data.
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How to Prepare an IVDR Scientific Validity Report
Scientific validity is planned in the PEP and documented in a report that a reviewer can follow and repeat. These four steps follow Annex XIII of the IVDR and MDCG 2022-2.
State the analyte, clinical condition, target population, specimen type and test purpose.
Set sources, databases, search strings, inclusion criteria and the appraisal method.
Screen each source and score it for relevance to your intended purpose and for quality.
Confirm the association and align it with analytical and clinical performance.
Sources of evidence accepted under Annex XIII
Scientific validity can be based on one or more of the following, each appraised for relevance and quality:
- Information on CE-marked IVDs measuring the same analyte for the same intended purpose
- Peer-reviewed literature, regulatory guidance and conference proceedings
- Expert opinion, clinical guidelines and professional position statements
- Results of proof-of-concept studies
- Results of clinical performance studies meeting Annex XIII, Section 2
Document the literature search
Record databases (for example PubMed or Embase), search strings, date ranges and the reason each article was excluded. The protocol and results belong in the report and in your IVDR technical documentation.
What an IVDR Scientific Validity Report Should Contain
Notified bodies expect a structured, traceable report. These are the elements we include in every Scientific Validity Report.
Analyte, measurand, clinical condition, population and specimen type.
The condition, current clinical practice and the state of the art.
Databases, search strings, date limits and inclusion criteria.
Screening flow with the number of records found, excluded and included.
Relevance and quality score for every included source.
How the evidence supports the analyte–condition association.
Overall conclusion, any gaps and how PMPF will address them.
Links to the PEP, PER, references and related reports.
Common gaps notified bodies raise
- Search that cannot be repeated: no strings, dates or screening records
- Evidence for a different population, specimen or clinical use
- Reliance on another device's IFU without independent appraisal
- Conclusions that conflict with analytical or clinical performance data
- Search limited to one database or a short date range, with no justification
- No appraisal criteria, or every source rated as relevant without explanation
- Analyte, specimen type or population described differently from the IFU and PEP
- Gaps identified in the report but not addressed in the PMPF plan
- Text carried over from IVDD files that no longer reflects the state of the art
Keeping scientific validity current
Scientific validity is a lifecycle activity. New literature, changes in clinical guidelines and PMPF findings can all change your conclusions.
Plan periodic literature updates in the PEP and record the outcome in each PER update, including the Summary of Safety and Performance where it applies.
How much evidence do you need?
The type of evidence depends on how well the analyte is established, as described in MDCG 2022-2, section 6.4.
Guidelines, textbooks and peer-reviewed literature confirm the association for the same intended purpose.
Example: HbA1c for monitoring long-term glycaemic control in people with diabetes, supported by clinical guidelines and decades of published evidence.
Known analyte used in a new population, specimen type or clinical role.
Example: HbA1c moving from monitoring diabetes to diagnosing prediabetes. The analyte is the same, but the clinical role and decision limits are new, so the association must be shown again.
Limited published evidence, so proof-of-concept or clinical performance studies are expected.
Example: a new blood biomarker for early detection of Alzheimer’s disease, where published evidence is limited and still developing.
Whichever level applies, state in the SVR why the evidence you used is enough for your exact intended purpose, and carry any remaining gaps into your PMPF plan.
Scientific Validity Under the IVDR vs US FDA
Many IVD manufacturers prepare for both markets at once. Both regulators expect evidence that the analyte is clinically meaningful for the intended use, but they ask for it in different ways.
| Topic | EU IVDR | US FDA |
|---|---|---|
| Where the requirement sits | Article 2(38) and Annex XIII, Part A of Regulation (EU) 2017/746, with guidance in MDCG 2022-2 | Premarket submission requirements for 510(k), De Novo and PMA, with “valid scientific evidence” defined in 21 CFR 860.7 |
| Terminology | Scientific validity, analytical performance and clinical performance | Usually analytical validity and clinical validity (clinical performance) |
| Output document | A standalone Scientific Validity Report, summarised in the PER and kept in the technical documentation | No separate document called a Scientific Validity Report; the evidence is presented within the submission |
| Well-established analytes | Still need a systematic, documented and reproducible literature review | For a 510(k), clinical relevance is usually supported through the predicate device’s intended use |
| Novel analytes or new uses | Gap analysis, then proof-of-concept or clinical performance studies where evidence is insufficient | Typically a De Novo request or PMA with clinical data; early feedback through a Q-Submission (Pre-Sub) is recommended |
| Who reviews it | The notified body, for Class B, C and D devices and sterile Class A devices | FDA reviewers at the Center for Devices and Radiological Health (CDRH) |
| After market entry | Updated through PMPF and each PER update | A significant change to the intended use usually needs a new submission |
Using one evidence base for both markets
Search protocols, screening records and appraisal tables can serve both submissions. What differs is how the results are presented: under the IVDR they go into the Scientific Validity Report and the PER, while for the FDA they support the clinical performance section of the submission.
Keep the intended purpose wording consistent across both markets. A difference in population, specimen type or clinical role can make the same evidence acceptable in one market and not in the other. For US requirements, see our guide to FDA IVD clinical evidence.
How I3CGLOBAL Prepares Your Scientific Validity Report
We follow the same traceable method for every device, so a notified body reviewer can repeat the search and reach the same conclusion.
- Review intended purpose and existing data. We check your IFU, device description, PEP and any IVDD-era performance evaluation to confirm the analyte, clinical condition, population and specimen type.
- Agree the search protocol. Databases, search strings, date limits, inclusion and exclusion criteria and the appraisal method are fixed in the PEP before the search starts.
- Search, screen and appraise. We run the search, screen every record and score each included source for relevance and quality, keeping a full audit trail.
- Write the report and close gaps. We draft the SVR, align its conclusions with analytical and clinical performance, and propose PMPF activities for any remaining gaps.
- Support notified body review. We answer reviewer questions and update the report if the notified body asks for more evidence.
What we need from you
- Instructions for use and intended purpose statement
- Device description and labelling claims
- Existing PEP, PER or IVDD performance evaluation
- Any in-house or published studies on the analyte
- Similar CE-marked devices you are aware of
What you receive
- Search protocol ready to include in your PEP
- Scientific Validity Report with a screening flow diagram
- Appraisal tables and a full reference list
- Gap analysis with PMPF recommendations
- Responses to notified body questions on scientific validity
IVDR Scientific Validity Support from I3CGLOBAL
Our IVDR consultants support IVD manufacturers of every risk class worldwide with:
- Scientific validity planning within your Performance Evaluation Plan
- Systematic literature search, screening and appraisal
- Scientific Validity Reports aligned with your PER
- Gap assessment of existing reports before notified body review
Start your IVDR project
Share your device details and get a tailored proposal for your Scientific Validity Report.
IVDR Scientific Validity: Frequently Asked Questions
What is scientific validity under the IVDR?
Article 2(38) of the IVDR defines scientific validity of an analyte as the association of an analyte with a clinical condition or a physiological state. It is one of the three elements of clinical evidence, with analytical and clinical performance.
Is the Scientific Validity Report part of the Performance Evaluation Report?
Yes. Under Annex XIII, the Performance Evaluation Report brings together the scientific validity, analytical performance and clinical performance reports, and their conclusions must agree.
Is scientific validity required for every IVD?
Yes. For well-established analytes a systematic review of literature and guidelines is usually enough. For new analytes or new intended purposes, proof-of-concept or clinical performance studies may be needed.
Can scientific validity be based on literature alone?
Yes, for well-established analytes where peer-reviewed literature and clinical guidelines confirm the association for the same intended purpose. The search must be systematic, documented and reproducible.
Do controls and calibrators need scientific validity?
Their performance evaluation must still address it, usually by documenting the scientific validity of the analyte measured by the assays they support, with a justification in the Performance Evaluation Plan.
Where is the Scientific Validity Report kept in the technical documentation?
It forms part of the performance evaluation documentation in your IVDR technical documentation under Annex II of the IVDR, alongside the PEP and PER, and is reviewed by the notified body.
How often should scientific validity be updated?
Throughout the device lifecycle, using new literature, state-of-the-art changes and PMPF data. For Class C and D devices the PER must be updated at least annually.
Which guidance applies to IVDR scientific validity?
Article 56 and Annex XIII of Regulation (EU) 2017/746, and MDCG 2022-2 on general principles of clinical evidence for IVDs.
What is the difference between the Scientific Validity Report and the Performance Evaluation Report?
The Scientific Validity Report covers only the association between the analyte and the clinical condition or physiological state. The Performance Evaluation Report (PER) brings it together with the analytical performance and clinical performance reports and states the overall conclusion on the clinical evidence for the device.
Who prepares the Scientific Validity Report?
The manufacturer is responsible for it. It is usually prepared by regulatory or clinical affairs specialists with literature-search and subject-matter expertise, or by an external IVDR consultant, and it is assessed by the notified body as part of the technical documentation where a notified body is involved.
How long does a Scientific Validity Report take, and what does it cost?
It depends mainly on how well established the analyte is, how many intended purposes and claims the device has, and how much literature must be screened and appraised. A well-established analyte supported by literature needs less work than a novel analyte that needs proof-of-concept or clinical performance data. Request a quote for a proposal for your device, or see our IVDR CE certification cost guide.
Do legacy IVDD devices need a Scientific Validity Report under the IVDR?
Yes. Devices moving from the IVDD to the IVDR need a performance evaluation that meets Annex XIII, including scientific validity. Existing data can be reused where it is still relevant, but it must be searched, appraised and documented to IVDR requirements.
Which databases should the scientific validity literature search use?
Most searches combine at least two bibliographic databases, commonly PubMed/MEDLINE and Embase, with clinical guidelines, regulatory sources and information on CE-marked devices for the same analyte. MDCG 2022-2 expects the search protocol to be defined before the search starts, so record and justify the sources you chose for your analyte.
Can one Scientific Validity Report cover several devices?
Yes, when the devices measure the same analyte for the same intended purpose, population and specimen type. Where any of these differ, the report must address each one separately, because evidence for one intended purpose may not support another.
What happens if the notified body finds the scientific validity evidence insufficient?
The notified body will raise a question or nonconformity. You may need to widen or justify the literature search, add evidence from CE-marked devices, or generate new data through proof-of-concept or clinical performance studies, and then update the PEP and PER. Certification cannot be completed until the finding is closed.
Updated | Author: Sobha Augustine, Founder, I3CGLOBAL | Reviewed by: Swathi Tummala, Senior Regulatory Consultant, I3CGLOBAL