Literature Review Report(LRR) under IVDR

Cracking the Code: IVDR Literature Review Made Simple
Under the IVDR (EU Regulation 2017/746), manufacturers of in vitro diagnostic (IVD) medical devices must prove that their devices are safe, reliable, and perform as intended. One of the key components of this process is the Literature Review Report (LRR), which gathers and evaluates published scientific studies related to the device. This report helps show that the device has a valid scientific basis, can accurately measure what it is designed to detect, and performs well in real-world clinical settings. The IVDR splits performance evaluation into three main parts: Scientific Validity (is there a clear link between the biomarker and the disease?), Analytical Performance (does the device correctly detect or measure the biomarker?), and Clinical Performance (are the test results useful and reliable for patients?). A well-done literature review supports all three of these pillars by summarizing peer-reviewed research, reducing the need for new studiesespecially for low-risk or established devices. Manufacturers must follow a structured process when performing the literature review. This includes deciding where to search (e.g., PubMed, Cochrane), which studies to include or exclude, and clearly explaining their search methods and results. The findings are then included in the Performance Evaluation Report (PER) a core document that Notified Bodies review to determine if the device meets safety and performance requirements. Lastly, the literature review isn’t just a one-time task. It must be updated regularly, especially after the device is launched, to reflect new information from scientific studies, user feedback, and market experience. These updates are crucial for Post-Market Surveillance (PMS) and Periodic Safety Update Reports (PSUR), helping manufacturers continuously ensure the safety and effectiveness of their IVD devices.

Cracking the Code: IVDR Literature Review Made Simple

Under the IVDR (EU Regulation 2017/746), manufacturers of in vitro diagnostic (IVD) medical devices must prove that their devices are safe, reliable, and perform as intended. One of the key components of this process is the Literature Review Report (LRR), which gathers and evaluates published scientific studies related to the device. This report helps show that the device has a valid scientific basis, can accurately measure what it is designed to detect, and performs well in real-world clinical settings.

The IVDR splits performance evaluation into three main parts: Scientific Validity (is there a clear link between the biomarker and the disease?), Analytical Performance (does the device correctly detect or measure the biomarker?), and Clinical Performance (are the test results useful and reliable for patients?). A well-done literature review supports all three of these pillars by summarizing peer-reviewed research, reducing the need for new studiesespecially for low-risk or established devices.

Manufacturers must follow a structured process when performing the literature review. This includes deciding where to search (e.g., PubMed, Cochrane), which studies to include or exclude, and clearly explaining their search methods and results. The findings are then included in the Performance Evaluation Report (PER) a core document that Notified Bodies review to determine if the device meets safety and performance requirements.

Lastly, the literature review isn’t just a one-time task. It must be updated regularly, especially after the device is launched, to reflect new information from scientific studies, user feedback, and market experience. These updates are crucial for Post-Market Surveillance (PMS) and Periodic Safety Update Reports (PSUR), helping manufacturers continuously ensure the safety and effectiveness of their IVD devices.

INTRODUCTION

Under the In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (IVDR), a literature review report is a mandatory component of the clinical evidence package submitted within the Performance Evaluation Report (PER). Its role is to provide comprehensive, systematic insight into existing published data relevant to the IVD device. The review should demonstrate how peer-reviewed evidence supports the device’s scientific validity, analytical performance, and clinical performance. The literature review is not just a one-time activity but part of a continuous performance evaluation process that informs regulatory submissions, post-market updates, and notified body audits.

MAPPING EVIDENCE TO SCIENTIFIC VALIDITY, ANALYTICAL & CLINICAL PERFORMANCE

IVDR (2017/746): For in vitro diagnostic medical devices, manufacturers are required to conduct a performance evaluation based on three pillars as part of the clinical evaluation :

Scientific Validity
Analytical Performance
Clinical Performance

Scientific validity – “‘scientific validity of an analyte’ means the association of an analyte with a clinical condition or a physiological state.” (IVDR Article 2(38))

Analytical performance – “‘analytical performance’ means the ability of a device to correctly detect or measure a particular analyte.” (IVDR Article 2(40))

Clinical performance – “‘clinical performance’ means the ability of a device to yield results that are correlated with a particular clinical condition or a physiological or pathological process or state in accordance with the target population and intended user.” (IVDR Article 2(41))

Performance evaluation – “‘performance evaluation’ means an assessment and analysis of data to establish or verify the scientific validity, the analytical and, where applicable, the clinical performance of a device.” (IVDR Article 2(44))

Cross-links to Annex XIII and Article 56:

Annex XIII, Part A requires that your PER demonstrates scientific validity, analytical performance, and clinical performance and contains the literature search methodology, protocol, and search report.
Article 56(3) requires a defined and methodologically sound procedure to demonstrate (a) scientific validity, (b) analytical performance, and (c) clinical performance, with the conclusions forming the device’s clinical evidence.

REGULATORY FRAMEWORK : LITERATURE REVIEW REPORT

The In Vitro Diagnostic Regulation (IVDR) 2017/746, manufacturers must establish and maintain evidence for their devices through a structured Performance Evaluation. This evaluation is required to demonstrate that the device consistently achieves its intended performance and is safe for its intended purpose. The IVDR clearly outlines that performance evaluation must be based on three interlinked pillars:

Scientific Validity
Demonstrating the association of the analyte or biomarker with the clinical condition or physiological state of interest. This ensures that the scientific principles underlying the device are sound and justifiable.

Annex XIII, Part A, Section 1.2.1: Requires manufacturers to collect and assess all available scientific data including peer-reviewed literature to support the analyte/marker–condition relationship.
Literature review here helps build a robust scientific foundation for the claims.

Analytical Performance
Demonstrating how well the device measures the analyte it claims to measure (e.g., precision, accuracy, limit of detection). This pillar focuses on laboratory-based evidence rather than clinical studies.

Though primarily based on internal testing, the literature review can support or supplement analytical performance claims, especially when similar devices or methods are described in peer-reviewed publications.
Annex XIII, Part A Section 1.2.2

Clinical Performance
Demonstrating the ability of the device to yield results that correlate with a defined clinical condition or physiological state, thus proving clinical utility.

Annex XIII, Part A, Section 1.2.3: Explicitly states that clinical performance data can be derived from clinical performance studies, literature reviews, or a combination of both.
Here, the literature review can often substitute for new studies, especially for lower-risk devices or well-established tests, as long as the data are robust, relevant, and systematic.

Integration into the Performance Evaluation Report (PER)

The IVDR mandates that findings from the literature review covering scientific validity, analytical performance, and clinical performance must be consolidated into the Performance Evaluation Report (PER):

Annex XIII, Part A, Section 2.3.2: Specifies that the PER must provide a comprehensive, critical evaluation of the evidence collected, including literature. This report demonstrates the device’s conformity with the General Safety and Performance Requirements (GSPRs) under Annex I.
The PER acts as the document summarizing all evidence, including literature findings, and is part of the technical documentation submitted to the Notified Body for review.

Why This Matters

Traceability: Literature findings must be transparently linked to specific performance claims.
Systematic Approach: Search methods, inclusion/exclusion criteria, and critical appraisal must be documented to withstand Notified Body scrutiny.
Continuous Updating: Annex XIII also requires that the literature review be updated regularly as part of the Post-Market Performance Follow-Up (PMPF) process, ensuring ongoing compliance.

The Literature Review Report (LRR) under IVDR is an integral component of the Performance Evaluation Plan (PEP) and Performance Evaluation Report (PER). It directly supports the three pillars mandated by IVDR and provides the documentary evidence needed to demonstrate conformity with EU requirements.

WHERE THE LITERATURE REVIEW FITS IN THE PERFORMANCE EVALUATION

The literature review is an essential part of the performance evaluation process as defined in IVDR Article 56 and Annex XIII. It directly supports the three core evidence pillars that must be addressed in the Performance Evaluation Report (PER).

Scientific Validity Report (SVR): Demonstrates that the analyte or marker targeted by the device is scientifically linked to the clinical condition or physiological state it is intended to detect or monitor.

Analytical Performance Report (APR): Presents evidence—through studies and supporting literature that the device can accurately and reliably measure the intended analyte.

Clinical Performance Report (CPR): Provides data showing the clinical effectiveness of the device, supported by clinical studies, real-world data, or published peer-reviewed literature.

According to Annex XIII, the literature review must be pre-defined in the Performance Evaluation Plan (PEP). This plan should specify the objective of the review, search methodology, selection criteria, and how the literature will be assessed and used. If the manufacturer does not perform a clinical performance study, the literature review becomes even more critical to justify clinical claims or equivalence to other devices.

The PER itself must include:

A clearly described literature search methodology: what databases were used, search terms, filters, inclusion/exclusion criteria.
The search protocol: defining parameters such as timeframes, language limits, and peer-reviewed-only restrictions.
The search report: including, summary tables of identified literature, critical appraisals, and links to performance claims.

Reference: Regulation (EU) 2017/746, Annex XIII Part A, Sections 1.2 and 1.3

HOW TO DESIGN A COMPLIANT LITERATURE REVIEW

Search Protocol

Databases: Use primary scientific repositories such as PubMed, Embase, Scopus, and Cochrane Library, NIH Clinical Trials, NICE, and Zmed (Livivo), MAUDE (FDA’s adverse event reporting system), MHRA (UK), HPRA (Ireland), and TGA (Australia) to ensure high-quality peer-reviewed data.
Filters: Set clear language and publication date limits aligned with device development and regulatory needs.
Boolean strategies: Combine keywords using Boolean logic (AND, OR, NOT) to fine-tune search results for sensitivity and specificity.
Selection criteria: Define inclusion/exclusion rules based on study design (e.g., clinical trials, reviews), population relevance, device technology, and context of use.

UPDATES, PMS/PSUR, AND PMPF LINKAGES

Literature reviews under IVDR are part of an ongoing, dynamic performance evaluation process. They must be routinely updated to reflect new data obtained after the device is placed on the market. This is particularly important for Class C and D devices, where Article 56(6) and Annex XIII Part A, Section 1.3.2 require that the Performance Evaluation Report (PER) be updated at least annually.

Post-Market Surveillance (PMS) Integration

Your PMS Plan, in line with Articles 78–80, must define how you continuously collect and evaluate relevant clinical and performance data. This includes:

User feedback, customer complaints, and vigilance reports
Market experience and technical failures
Newly published scientific literature on the device or similar devices

All of these data sources must be reviewed for their impact on existing performance claims. If they suggest potential issues or new benefits, the literature review must be revised accordingly.

Periodic Safety Update Report (PSUR)

For Class C and D devices, the PSUR (per Article 81) must be generated at least annually and include:

A summary of PMS findings
Key outcomes from the Post-Market Performance Follow-up (PMPF) activities
An updated benefit-risk conclusion

The PSUR draws directly from the updated PER and literature review. If the literature review identifies emerging risks or loss of effectiveness, this must be reflected in the PSUR.

PMPF and Literature Review Link

PMPF activities (outlined in Annex XIII Part B) gather real-world clinical and performance data post-market. This may include follow-up studies, registries, or surveys. Insights from PMPF:

Help confirm ongoing scientific validity and clinical relevance
Identify areas needing further investigation or evidence
Feed back into the literature review and PER

The Feedback Loop

Notified Bodies expect a well-documented feedback loop:

PMS captures new data
Data is screened for relevance to performance claims
The literature review is updated accordingly
Updates feed into the PER, SSP, and PSUR

References: Regulation (EU) 2017/746 — Articles 56(6), 78 to 81; Annex XIII Part A Section 1.3.2; Annex XIII Part B

CONCLUSION

The Literature Review Report is a cornerstone document in demonstrating compliance with the IVDR. It provides a scientifically sound and resource-efficient means of gathering performance evidence, especially when clinical trials are impractical or unnecessary. To ensure continued compliance, manufacturers should treat LRRs as living documents, updating them as part of PMS/PMPF activities. When executed thoroughly, an LRR strengthens the credibility of the device’s performance claims and facilitates smoother regulatory approval.

REFERENCES

Article 56 – Performance evaluation & clinical evidence (scope, methodology, update cadence).

Annex XIII Part A – What must be in the PER, including the literature search methodology/protocol/report and component reports.

Article 29 – Summary of Safety & Performance (C/D), alignment with PER.

Articles 78 to 81 – PMS system, PMS report (A/B), PSUR (C/D) and use of literature in PMS.

Article 2 – Definitions of scientific validity, analytical performance, clinical performance, performance evaluation.

MDCG 2022-2 – Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs)

HOW WE CAN HELP

At Morulaa, supports IVD manufacturers with IVDR compliance by conducting structured literature reviews, drafting complete Performance Evaluation Reports (SVR, APR, CPR), and aligning documentation with Article 56 and Annex XIII. We help implement PMS plans, prepare PSURs for Class C/D devices, and design PMPF strategies. Our team ensures traceability of claims, resolves technical gaps, and prepares you for notified body reviews with up-to-date, audit-ready documentation.