Laboratoriemedicin

This international standard specifies technical requirements and documentation necessary to establish metrological traceability of values assigned to calibrators, trueness control materials and human samples for quantities measured by IVD MDs. The human samples are those intended to be measured, as specified for each IVD MD. Metrological traceability of values for quantities in human samples extends to the highest available reference system component, ideally to RMPs and certified reference materials (CRMs).

All parties having a role in any of the steps described in a calibration hierarchy for an IVD MD are subject to the requirements described. These parties include but are not limited to manufacturers (of IVD MDs), RMP developers (see ISO 15193), RM producers (see ISO 15194), and reference/calibration laboratories (see ISO 15195) supporting calibration hierarchies for IVD MDs.

NOTE Producers of RMs intended for use in standardization or calibration of IVD MDs include commercial and non-commercial organizations producing RMs for use by many end-users of IVD MDs and/or calibration laboratories, or for use by a single end-user medical laboratory, as in the case of a measurement standard (calibrator) intended to be used exclusively for calibration of a laboratory-developed MP.

This international standard is applicable to:

a) all IVD MDs that provide measurement results in the form of numeric values, i.e. rational (ratio) and/or differential (interval) scales, and counting scales

b) IVD MDs where the measurement result is reported as a qualitative value established with a ratio of two measurements (i.e. the signal from a specimen being tested and the signal from a RM with a specified concentration or activity at the cut-off), or a counting scale, with corresponding decision threshold(s). This also includes IVD MDs where results are categorized among ordinal categories based on pre-established quantitative intervals for a quantity.

c) RMs intended for use as trueness control materials for verification or assessment of calibration of IVD MDs, i.e. some commutable CRMs and some external quality assessment (EQA) materials (if so indicated in the RM’s intended use statement)

d) IVD MD-specific calibrators and trueness control materials with assigned values, intended to be used together with a specified IVD MD.

e) IVD MDs as described in a) and b), where no end-user performed calibration is required (i.e. when the manufacturer performs a factory calibration of the IVD MD).

This international standard is not applicable to:

a) calibrators and trueness control materials for IVD MDs which, due to their formulation, are known to have zero amount of measurand.

b) control materials that are used only for internal quality control purposes in medical laboratories to assess the imprecision of an IVD MD, either its repeatability or reproducibility, and/or for assessing changes in IVD MD results compared to a previously established calibration condition;

c) control materials that are used only for internal quality control purposes in medical laboratories and which are supplied with intervals of suggested acceptable values that are not metrologically traceable to higher order reference system components;

d) properties reported as nominal scales and ordinal scales, where no magnitude is involved

NOTE 1 Nominal scales are typically used to report e.g. identity of blood cell types, microorganism types, identity of nucleic acid sequences, identity of urine particles.

NOTE 2 Ordinal scales are often applied to results differentiated into dichotomous groupings (e.g. ‘sick’ vs. ‘healthy’), and may also be applied to results differentiated into non-dichotomous categories where the result categories are rank-ordered but the rank-ordered categories cannot be differentiated in terms of relative degree of difference, e.g. negative, +1, +2, +3 for grading of presence of haemoglobin in urine specimens by visual observation.

This document specifies requirements and gives guidance on the procedures to be followed in the preparation of samples and the selection of reference materials for medical device testing in biological test systems onlyin accordance with one or more parts of ISO 10993. Specifically, this document addresses the following:

— test sample selection;

— selection of representative portions from a medical device;

— test sample preparation;

— experimental controls;

— selection of, and requirements, for reference materials;

— preparation of extracts.

This document is not applicable to live cells, but can be relevant to the material or medical device components of combination products containing live cells.

This document specifies the procedure for the assessment of medical devices and their constituent materials with regard to their potential to produce irritation. The tests are designed to predict and classify the irritation potential of medical devices, materials or their extracts according to ISO 10993-1 and ISO 10993-12.

This document includes:

— pre-test considerations for irritation, including in silico and in vitro methods for dermal exposure;

— details of in vitro and in vivo irritation test procedures;

— key factors for the interpretation of the results.

Instructions are given in Annex A for the preparation of materials specifically in relation to the above tests. In Annex D several special in vivo irritation tests are described for application of medical devices in areas other than skin. In addition, Annex E provides information for conducting human skin irritation testing.