Introduction

The EU In Vitro Diagnostic Medical Devices Regulation (IVDR) 2017/746 establishes a robust regulatory framework for ensuring the safety and performance of in vitro diagnostic devices (IVDs) before they are placed on the EU market. One of the key pillars of this framework is the demonstration of performance, which consists of:

• Scientific Validity

• Analytical Performance

• Clinical Performance

Under Article 2(40), analytical performance is defined as:

“The ability of a device to correctly detect or measure a particular analyte.”

Under the IVDR, performance evaluation is the continuous process that brings together scientific validity, analytical performance, and (where applicable) clinical performance to demonstrate conformity with the General Safety and Performance Requirements (GSPRs). Analytical performance must be demonstrated and documented as part of the Performance Evaluation (Article 56 and Annex XIII).

Scope of Analytical Performance: Where IVDR Requires Evidence

 Relevant Sections in IVDR

• Annex I, Chapter II, Section 9.1: Lists the characteristics that must be addressed.

• Annex II, Section 6.1: Specifies what evidence must be documented.

• Annex XIII: Describes the requirements for the Performance Evaluation Report (PER), which must integrate analytical data.

Defining Analytical Performance: Key Parameters

GSPR 9.1(a) lists the key analytical parameters: analytical sensitivity, analytical specificity, trueness (bias), precision (repeatability/reproducibility), accuracy (from trueness + precision), LoD, LoQ, measuring range, linearity, cut-off; plus criteria for specimen collection/handling and control of interferences/cross-reactions.

Accuracy: Trueness and Precision

• Trueness (bias): Provide data establishing closeness to a reference (where certified reference materials/methods exist).

• Precision: Describe repeatability and reproducibility studies (design, replicates, factors like operators/instruments/lots).

Analytical Sensitivity and Analytical Specificity

• Analytical sensitivity: Study design, specimen/matrix, analyte levels, number of replicates, and calculation approach.

• Analytical specificity: Interference and cross-reactivity studies covering endogenous/exogenous substances; include substance/concentration, specimen type, analyte level, and results.

Linearity and Measuring Range

Provide linearity evaluation (or alternative fit) and measuring range (including LoD). Document specimen type, replicates, matrix, analyte levels, how levels were set; note any high-dose hook effect and mitigation.

 limit of blank (LoB), Limit of Detection, (LoD) and Limit of Quantitation (LoQ)

• LoB: Highest background signal (no analyte) → defines threshold over which detection may occur needed to set detection threshold; step before LoD.

• LoD: Include in measuring-range section with a method for establishing detection capability.

• LoQ: Required characteristic per GSPR 9.1(a); show the lowest concentration that can be quantitated with acceptable precision/accuracy (methodology justified).

Cut-off Determination

Summarize the analytical data and study design used to set the assay cut-off: population(s) studied, specimen characterization method, and statistical methods (e.g., ROC) including any grey/equivocal zone.

Robustness and Stability

Robustness: While not named explicitly as a standalone subsection, IVDR expects performance under intended conditions and control of interferences; design/manufacture must ensure characteristics and performance remain suitable throughout use (see GSPR 9.1 and related design provisions). Consider small deliberate variations (e.g., time, temperature, operators) in your analytical studies to show resilience.

Stability (excluding specimen): Provide shelf-life, in-use, and shipping stability:

• Shelf-life: at least three lots; accelerated allowed initially but must be followed by real-time data; include protocol, acceptance criteria, intervals, and conclusions.

• In-use: open-vial/on-board (one lot reflecting routine use); include calibration stability if claimed.

• Shipping: real and/or simulated conditions; include protocol, method for simulation, and recommended conditions

Structure of an Analytical Performance Report

Per Annex XIII Part A, analytical performance must be demonstrated and documented in an Analytical Performance Report (APR), which is one of the required components (along with SVR and CPR) that feed into the Performance Evaluation Report (PER) included in the technical documentation (Annex II/Section 6). 

Study Designs to Demonstrate Compliance

Design analytical studies according to intended purpose and device risks. The Clinical Performance Study Plan (CPSP) requirements list core design elements (intended purpose, user, calibration/control, statistical design, bias minimization). While CPSP targets clinical performance, Annex XIII also requires analytical performance to be generated via analytical performance studies by default, with justified exceptions for novel markers.

Integrating Analytical and Clinical Performance

Manufacturers must appraise scientific validity, analytical performance, and clinical performance together to generate clinical evidence; conclusions are compiled in the PER and updated via PMPF/PMS throughout the lifecycle.

Documentation and Submission Strategy

Include in technical documentation (Annex II):

• Analytical performance characteristics and detailed substantiation (Section 6.1.2), metrological traceability (9.3), interferences, measuring range/LoD, and assay cut-off; include the APR and PER.

• Stability packages (Section 6.3).

• Ensure instructions for use (IFU) include key analytical characteristics (Annex I/20.4(w)).

• The PER, containing SVR/APR/CPR, is part of technical documentation and must be kept up to date via PMS/PMPF.

Best Practices for Manufacturers

• Map each GSPR 9.1(a) characteristic to study evidence; justify any omission.

• Ensure metrological traceability of calibrators/controls to higher-order references where available

• Use MDCG guidance to frame evidence expectations, aggregation in the PER, and lifecycle updates (MDCG 2022-2 general principles; MDCG 2025-5 on analytical studies scope and linkage to GSPRs).

Conclusion 

Analytical performance is central to IVDR compliance: it’s explicitly listed in GSPR 9.1(a), must be proven through analytical studies, and must be documented in the APR and rolled up into the PER. Analytical performance is a cornerstone of IVDR compliance. It provides objective proof that an IVD can detect or measure an analyte with the required degree of confidence. Each analytical parameter must be evaluated through validated methods and integrated into the device’s technical file and performance evaluation.

• By aligning with Annex I and Annex II requirements, manufacturers can ensure their IVD devices are safe, effective, and eligible for CE marking under IVDR 2017/746.

• The PER is living documentation, updated with PMPF/PMS data to maintain conformity over the device lifecycle.
  
  

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). 

References

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

2. . REGULATION (EU) 2017/746