ISO 15194:2009

Overview

ISO 15194:2009 - "In vitro diagnostic medical devices - Measurement of quantities in samples of biological origin - Requirements for certified reference materials and the content of supporting documentation" - defines quality and documentation requirements for certified reference materials (CRMs) used in clinical and in vitro diagnostic (IVD) measurement systems. The standard specifies how CRMs can be considered of higher metrological order (per ISO 17511) and is applicable to CRMs classifiable as primary measurement standards, secondary measurement standards, and international conventional calibrators. It covers value assignment, presentation of assigned values and measurement uncertainty, and data collection for value determination. Annex A addresses nominal properties and ordinal quantities.

Key topics and technical requirements

• Scope and hierarchy: Defines hierarchical position of CRMs (primary, secondary, international conventional calibrators) in calibration systems.
• Properties and format: Requires systematic designation of the material system, components (analytes) and the stated kind-of-quantity (e.g., amount-of-substance concentration, mass).
• Production and characterization: Sets expectations for production processes, homogeneity, stability, and characterization activities that support assigned values.
• Value assignment and uncertainty: Specifies how to collect data for value determination and how to present the assigned value together with its measurement uncertainty.
• Supporting documentation: Details mandatory content for labels, certificates and certification reports - including sources of material, traceability, instructions for use, storage/stability data, and health/safety information.
• Commutability and matrix effects: Emphasizes consideration of commutability (behavior of CRMs relative to routine samples across methods) and potential matrix effects influencing measurement results.
• Applicability: Applies to CRMs with differential or rational quantity values; provides guidance on nominal/ordinal properties (informative Annex A).
• Exclusions: Does not apply to reference materials that are integrated parts of an IVD measuring system, though many elements can be useful.

Practical applications and users

ISO 15194:2009 is used by:

• Reference material producers to design, certify and document CRMs for clinical labs and IVD manufacturers.
• IVD manufacturers for calibrator selection and demonstrating metrological traceability.
• Clinical laboratories and external quality assessment providers for trueness control and calibration hierarchies.
• Metrologists, accreditation bodies and regulators to assess CRM quality, traceability and uncertainty statements.
  Benefits include improved comparability of measurement results, clearer traceability to higher-order standards, and reliable presentation of uncertainties.

Related standards

• ISO 17511 (metrological traceability for calibrators/control materials)
• ISO Guide 31, Guide 34, Guide 35 (reference materials and producer competence)
• ISO/IEC Guide 98-3 (GUM - measurement uncertainty)
• ISO/IEC Guide 99 (VIM - metrology vocabulary)
• ISO 18153 (enzymatic catalytic concentration traceability)

Keywords: ISO 15194:2009, certified reference materials, in vitro diagnostic, metrological traceability, measurement uncertainty, commutability, calibrators, reference material documentation.