scope:

EP32-R provides guidance on establishing traceability of the chemical calibration step in clinical laboratory measurements, based on the traceability requirements for in vitro diagnostic (IVD) medical devices as given in ISO 175111 and ISO 18153,2 and in accordance with the requirements for traceability as stated in the IVD Directive (i.e., Directive of the European Parliament on In Vitro Diagnostic Medical Devices Directive 98/79/EC3). Though this report is aimed principally at manufacturers of IVD medical devices, the concepts and approaches recommended may be extended to apply to routine analysis conducted in the clinical laboratory either with commercially available or "home-brew" IVDs.

This report specifically addresses traceability of the chemical calibration of a routine measurement procedure to the highest order reference that is available for a measurand. A traceable result requires that traceability be established for all quantities that have significant influence on the magnitude of the results. Traceability is discussed in more complete scope in other references, most notably, the Eurachem/CITACa Guide: Traceability in Chemical Measurements4 (available at http://www.measurementuncertainty.org/), the principles of which are applied for laboratory medicine in this report.

The primary area of activity to which this report can be applied is the determination of "assigned" values for calibrators and trueness controls for IVD measurement devices that are intended for use in the quantitative measurement of defined substances in human body fluids. While the focus of this report is on establishing traceability of manufacturers' product calibrators, this is likely to be the key element in the traceability of results at the patient bedside performed on bodily fluids from patients.

This report discusses measurement uncertainty and method validation in relation to their respective roles in achieving traceability. Detailed descriptions of these processes are not provided, and may be found elsewhere (see the References section).

Throughout this report, it is assumed that laboratories or manufacturing facilities following the present guidance have in place effective quality assurance and control measures to ensure that all applicable measurement processes are stable and in control. These measures include, but are not limited to, appropriately qualified staff, continuous documented training of the technical staff, proper maintenance of equipment, correctly prepared reagents, and use of documented measurement procedures and control charts. ISO 170255 provides a detailed description of the expectations of a competent laboratory responsible for chemical calibration and testing in general. ISO 151896 builds on ISO 170255 and provides recommendations specific to medical laboratories. Also of interest is ISO 151957 which identifies specific aspects of calibration laboratories in the field of laboratory medicine.