IVDR Analytical Performance Requirements: A Practical Guide for IVD Manufacturers
Analytical Performance Report Under EU IVDR Guide
The EU In Vitro Diagnostic Medical Devices Regulation (IVDR) 2017/746 provides an efficient regulatory framework that ensures safety and performance of IVDs before their marketing in the EU. The four pillars of such regulatory framework include the demonstration of performance, which includes the following elements:
Scientific Validity
Analytical Performance
Clinical Performance
According to Article 2(40), analytical performance means:
“The ability of a device to correctly detect or measure a particular analyte.”
Performance evaluation under the IVDR is a continuous activity of putting scientific validity and analytical performance, as well as clinical performance where relevant, into an integrated whole in order to prove conformity with GSPRs. Analytical performance has to be proven and documented as part of performance evaluation (Article 56 and Annex XIII).
Analytical Performance Scope: Where Evidence Is Required by IVDR
Relevant Articles in IVDR:
IVDR Annex I, Chapter II, Section 9.1: Details characteristics that need to be covered.
IVDR Annex II, Section 6.1: Outlines what evidence is needed.
IVDR Annex XIII: Outlines the PER requirements.
Definition of Analytical Performance Characteristics: Important Parameters
Parameters described in GSPR 9.1(a) include analytical sensitivity, analytical specificity, trueness (bias), precision (repeatability/reproducibility), accuracy (a combination of trueness and precision), limit of detection (LoD), limit of quantification (LoQ), measurement range, linearity, cut off
Accuracy: Trueness and Precision
Trueness (bias): Provide data demonstrating proximity to the reference (where certified reference materials/methods are available).
Precision: Describe the repeat and reproducibility experiments (design, replicates, influences such as operators/instruments/lots).
Analytical Sensitivity and Analytical Specificity
Analytical Sensitivity
Study design, specimen matrix, analyte concentrations, number of replicates, and method of analysis.
Analytical Specificity
Interferences and cross reactions for endogenous and exogenous substances. Substance, concentration, specimen type, analyte concentration, and findings.
Linearity and Measuring Range
Describe linearity assessment (or alternative model fit) and measuring range (including Limit of Detection). Include specimen type, number of replicates, matrix, analyte concentrations, method of setting analyte concentrations; high dose hook effect if present.
Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ)
LoB: Maximum background response (absence of analyte) → sets limit beyond which detection is possible, essential to establish detection limit, prior to LoD.
LoD: Add to measuring range description along with methodology to determine detection ability.
LoQ: Mandatory attribute according to GSPR 9.1(a); give the lowest concentration capable of being quantified with adequate precision/accuracy (support with methodology).
Determining Cut Off
Summarize the data analysis and design of studies used for establishing the assay cut off: population(s) studied, specimen characterization approach, and statistics (e.g., ROC) involved, including grey/equivocal zones, if applicable.
Robustness and Stability
Robustness: Though not formally labeled as a separate section, IVDR demands robustness of performance in intended conditions and management of interferences; design/production should ensure that the properties and performance are adequate throughout the life cycle (refer to GSPR 9.1 and design criteria associated) Make sure to consider the small controlled differences (e.g., time, temperature, and operators) in your analysis.
Stability (excluding specimen):Provide shelf life, in use, and shipping stability:
Shelf life: at least three lots; accelerated, acceptable initially but must be followed up with actual data; include test protocol, acceptance criteria, time points, and conclusions.
In use: open vial and/or on board (one lot); include calibration stability if indicated.
Shipping: actual and/or simulated conditions; include test protocol and simulated conditions.
Structure of the Analytical Performance Report
As specified in Annex XIII, part A, the performance of analysis needs to be shown and evidenced by means of an Analytical Performance Report (APR), which is one of the necessary documents (in addition to SVR and CPR) that constitute the Performance Evaluation Report (PER).
Study Designs to Demonstrate Compliance
Design analysis studies based on the intended use and risks of the medical device. The CPSP design criteria outline all the essential components of the design (intended use, user, calibration/control, statistical design, minimization of biases). Although CPSP focuses on clinical performance, the Analytical Performance Studies are also a requirement for the generation of analytical performance as per Annex XIII.
Integration of Analytical Performance and Clinical Performance
Analytical performance and clinical performance need to be assessed by the producers in order to obtain clinical evidence; all of this is done through PER and refined through PMPF/PMS.
Documentation and Approach for Submission
To be included in technical documentation (Annex II):
Analytical performance characteristics together with the evidence (Section 6.1.2), metrological traceability (9.3), interferences, measuring range/LoD and assay cut off; inclusion of APR and PER.
Stability studies (Section 6.3).
Instructions for use (IFU) to include important analytical performance characteristics (Annex I/20.4(w)).
PER, which includes SVR/APR/CPR, is part of the technical documentation and should be maintained current through PMS/PMPF.
Best practices for manufacturers
Match the characteristics of GSPR 9.1(a) to evidence from the study; explain any non inclusions.
Ensure that calibrators and controls have metrological traceability to higher order standards where possible
Follow MDCG guidance in order to define the documentation needs, consolidation in the PER and lifecycle updating (MDCG 2022-2 general principles; MDCG 2025-5 scope of analytical studies and relationship with GSP
Conclusion
The importance of the performance of the IVD cannot be overstated. This is because it is included under GSPR 9.1(a) and needs to be proven by evidence from the analytical studies and documented in the APR and PER. The performance of the IVD is crucial in proving compliance with IVDR regulations. The performance will prove objectively that the IVD has the capability of detecting or quantifying the analyte at the expected levels of performance.
By conforming to the provisions of Annex I and Annex II, the IVD devices will be safe and effective as well as able to carry the CE mark through IVDR 2017/746.
The PER is living documentation that is continually updated using the PMPF/PMS information.
Quick reference: where to look in IVDR
Article 56 (Performance evaluation & clinical evidence).
Annex I, Chapter II, 9.1(a) (Analytical performance parameters).
Annex II, Section 6.1.2 (Analytical performance detail incl. trueness, precision, sensitivity/specificity, measuring range/linearity, LoD, cut off).
Annex II, Section 6.3 (Stability studies).
Annex XIII, Part A (APR/CPR/SVR and PER structure; demonstration requirements). Annex I, 9.3 (Metrological traceability).
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