CEN/TC 140 - In vitro diagnostic systems

This document defines concepts, establishes general principles, and specifies essential requirements for information supplied by the manufacturer of IVD medical devices.
This document does not address language requirements since that is the domain of national laws and regulations.
This document does not apply to:
a) IVD medical devices for performance evaluation (e.g. for investigational use only);
b) shipping documents;
c) material safety data sheets / Safety Data Sheets;
d) marketing information (consistent with applicable legal requirements).
.

This document specifies requirements for information supplied by the manufacturer of in vitro diagnostic (IVD) reagents, calibrators and controls intended for professional use.
This document can also be applicable to accessories.
This document is applicable to the labels for outer and immediate containers and to the instructions for use.
This document does not apply to:
a) IVD instruments or equipment;
b) IVD reagents for self-testing.

This document specifies requirements for information supplied by the manufacturer of in vitro diagnostic (IVD) instruments intended for professional use.
This document also applies to apparatus and equipment intended to be used with IVD instruments for professional use.
This document can also be applicable to accessories.
This document does not apply to:
a) instructions for instrument servicing or repair;
b) IVD reagents, including calibrators and control materials for use in control of the reagent;
c) IVD instruments for self-testing.

This document specifies requirements for information supplied by the manufacturer of in vitro diagnostic (IVD) instruments intended for self-testing.
This document is also applicable to apparatus and equipment intended to be used with IVD instruments for self-testing.
This document can also be applicable to accessories.
This document does not apply to:
a) instructions for instrument servicing or repair;
b) IVD reagents, including calibrators and control materials for use in control of the reagent;
c) IVD instruments for professional use.

This document specifies requirements for information supplied by the manufacturer of in vitro diagnostic (IVD) reagents, calibrators, and controls intended for self-testing.
This document can also be applicable to accessories.
This document is applicable to the labels for outer and immediate containers and to the instructions for use.
This document does not apply to:
a) IVD instruments or equipment;
b) IVD reagents for professional use.

This document defines good study practice for the planning, design, conduct, recording and reporting of clinical performance studies carried out to assess the clinical performance and safety of in vitro diagnostic (IVD) medical devices for regulatory purposes.
NOTE 1    The purpose of these studies is to assess the ability of an IVD medical device in the hands of the intended user, to yield results pertaining to a particular medical condition or physiological/pathological state, in the intended population.
The document is not intended to describe whether the technical specifications of the IVD medical device in question are adequately addressed by the clinical performance study.
This document identifies the principles that underpin clinical performance studies and specifies general requirements intended to
—          ensure the conduct of the clinical performance study will lead to reliable and robust study results,
—          define the responsibilities of the sponsor and principal investigator,
—          assist sponsors, clinical research organization, investigators, ethics committees, regulatory authorities and other bodies involved in the conformity assessment of IVD medical devices, and
—          protect the rights, safety, dignity and well-being of the subjects providing specimens for use in clinical performance studies.
Analytical performance studies are out of the scope of this document.
NOTE 2    When the collection of specimens specifically for the analytical performance study creates an additional collection risk for subjects, some of the elements of this document (particularly the annexes) can be useful for ensuring subject safety.
Clinical performance studies that are performed for reasons other than pre- and post-market regulatory purposes, such as for re-imbursement purposes, are out of the scope of this document.
NOTE 3    Some of the elements of this document can be useful for the design of such studies, including subject safety and data integrity.
This document does not include safety information for laboratory workers or other personnel collecting the study specimens.
NOTE 4    Such information is included in other publications[1][12][13].
NOTE 5    Users of this document can consider whether other standards and/or requirements also apply to the IVD medical device which is the subject of the clinical performance study, for instance, in the situation for which there is an IVD medical device and a medical device used in an integrated system (e.g. a lancet, an IVD test strip, and a glucose meter), aspects of both this document and ISO 14155 can be considered.

This document specifies requirements and gives recommendations for next generation sequencing (NGS) workflows for in vitro diagnostics and biomedical research. This document covers the pre-examination processes, human DNA (somatic and germline) isolation, sequencing library preparation, sequencing, sequence analysis and reporting of the examination of sequences for diagnostic purposes from isolated DNA from, e.g. formalin-fixed and paraffin embedded tissues, fresh frozen tissues, fine needle aspirates (FNA), whole blood, circulating tumour cells (CTCs), exosomes and other extracellular vesicles, circulating cell free DNA from plasma, and DNA from saliva.
NOTE 1   Typical applications include, but are not limited to, NGS for oncology, pharmacogenomics and clinical genetics; approaches include panels (e.g. disease panels, exome panels, target gene panels and in silico panels), exome and whole genome sequencing, as well as certain epigenetics and certain single-cell analyses.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories, molecular pathology laboratories and molecular genetic laboratories. This document is also applicable to laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions, and organizations performing biomedical research.
This document is not applicable for in situ sequencing, DNA-mediated protein sequencing, forensic sequencing, sequencing of pathogens or microorganisms and microbiome analysis.
NOTE 2   International, national or regional regulations or requirements or multiples of them can also apply to specific topics covered in this document.

This document specifies requirements and gives recommendations for next generation sequencing (NGS) workflows for in vitro diagnostics and biomedical research. This document covers the pre-examination processes, human RNA isolation, sequencing library preparation, sequencing, sequence analysis and reporting of the examination of sequences for diagnostic purposes from isolated RNA from, e.g. formalin-fixed and paraffin embedded tissues, fresh frozen tissues, fine needle aspirates (FNA), whole blood, circulating tumour cells (CTCs), exosomes and other extracellular vesicles, and circulating cell free RNA from plasma.
NOTE 1   Typical applications include, but are not limited to, NGS for oncology and clinical genetics, certain single-cell analyses.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories, molecular pathology laboratories and molecular genetic laboratories. This document is also applicable to laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions, and organisations performing biomedical research.
This document is not applicable for in situ sequencing, forensic sequencing, sequencing of pathogens or microorganisms and microbiome analysis.
NOTE 2   International, national or regional regulations or requirements or multiples of them can also apply to specific topics covered in this document.

This document specifies requirements for quality and competence in medical laboratories.
This document is applicable to medical laboratories in developing their management systems and assessing their competence. It is also applicable for confirming or recognizing the competence of medical laboratories by laboratory users, regulatory authorities and accreditation bodies.
This document is also applicable to point-of-care testing (POCT).
NOTE            International, national, or regional regulations or requirements can also apply to specific topics covered in this document.

This document provides requirements and recommendations for the design, development, verification, validation and implementation of analytical tests for detecting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using nucleic acid amplification. It addresses pre-examination, examination and post-examination process steps for human specimens.
This document is applicable to medical laboratories. It is also intended to be used by in vitro diagnostic developers and manufacturers, as well as by institutions and organizations supporting SARS-CoV-2 research and diagnostics.
This document does not apply to environmental samples.

This document provides recommendations and requirements on the handling, storage, processing and documentation of venous whole blood specimens intended for circulating cell free DNA (ccfDNA) examination during the pre-examination phase before an analytical test is performed. This document covers specimens collected in venous whole blood collection tubes.
This document is applicable to any molecular in vitro diagnostic examination performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for stabilizing blood genomic DNA, which are not described in this document. Blood genomic DNA is covered in ISO 20186-2.
Different dedicated measures are taken for preserving DNA in circulating exosomes, which are not described in this document.
NOTE    ccfDNA obtained from blood by the procedures cited in this document can contain DNA originally present in exosomes[8][9].
DNA in pathogens present in blood is not covered by this document.

This document specifies requirements and gives recommendations on the handling, storage, processing and documentation of body fluids specimens intended for human cfDNA examination during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examinations performed by medical laboratories. It is also intended to be used by health institutions including facilities collecting and handling specimen, laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Dedicated measures that need to be taken for cytohistological analysis of body fluid derived nucleated cells are not described in this technical specification. Neither are measures for preserving and handling of pathogens, and other bacterial or whole microbiome DNA in body fluids described.
Different dedicated measures need to be taken for preserving ccfDNA from other body fluids such as blood, lymph and others. These are not described in this document. ccfDNA from blood is covered in EN ISO 20186-3.
NOTE   International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, storage, processing and documentation of venous whole blood specimens intended for DNA, RNA and protein examination from exosomes and other extracellular vesicles during the pre-examination phase before a molecular examination is performed. This document covers specimens collected in venous whole blood collection tubes.
The pre-examination process described in this document results in isolated DNA, RNA and proteins from enriched exosomes and other extracellular vesicles.
This document is applicable to molecular in vitro diagnostic examinations performed by medical laboratories. It is also intended to be used by health care institutions including facilities collecting and handling specimen, laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken during the pre-examination phase for venous whole blood circulating cell-free RNA (ccfRNA) examination and for venous whole blood circulating cell-free DNA (ccfDNA) examination, both without prior enrichment of exosomes and other extracellular vesicles. These are not described in this document but are covered in EN ISO 20186 3, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 3: Isolated circulating cell free DNA from plasma and CEN/TS 17742, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Isolated circulating cell free RNA from plasma.
NOTE   International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, storage, processing and documentation of venous whole blood specimens intended for genomic DNA examination during the pre-examination phase before a molecular examination is performed. This document covers specimens collected in venous whole blood collection tubes.
This document is applicable to any molecular in vitro diagnostic examination performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for stabilizing blood cell free circulating DNA, which are not described in this document.
NOTE       Circulating cell free DNA in blood is covered in ISO 20186-3.
Different dedicated measures are taken for collecting, stabilizing, transporting and storing capillary blood as well as for collecting and storing blood by paper based technologies or other technologies generating dried blood. These are not described in this document.
This document does not cover the isolation of specific blood cells and subsequent isolation of genomic DNA therefrom.
DNA in pathogens present in blood is not covered by this document.

This document gives guidelines on the handling, storage, processing and documentation of venous whole blood specimens intended for cellular RNA examination during the pre-examination phase before a molecular examination is performed. This document covers specimens collected in venous whole blood collection tubes.
This document is applicable to any molecular in vitro diagnostic examination performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for stabilizing blood cell free circulating RNA and RNA in exosomes circulating in blood. These are not described in this document.
Different dedicated measures are taken for collecting, stabilizing, transporting and storing capillary blood as well as for collecting and storing blood by paper based technologies or other technologies generating dried blood. These are not described in this document.
This document does not cover the isolation of specific blood cells and subsequent isolation of cellular RNA therefrom.
RNA in pathogens present in blood is not covered by this document.

This document specifies requirements and recommendations for the pre-examination phase of circulating cell free RNA (ccfRNA) from venous whole blood specimens, including but not limited to the collection, handling, storage, processing and documentation of venous whole blood specimens intended for ccfRNA examination. This document covers specimens collected in venous whole blood collection tubes.
The pre-examination process described in this document results in circulating cell free RNA isolated from blood plasma without prior enrichment of exosomes and other extracellular vesicles.
This document is applicable to molecular in vitro diagnostic examinations performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Different dedicated measures need to be taken during the pre-examination phase for isolated RNA from enriched exosomes and other extracellular vesicles enriched from venous whole blood and for cellular RNA isolated from venous whole blood. These are not described in this document but are covered in CEN/TS 17747,  Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for exosomes and other extracellular vesicles in venous whole blood - Isolated DNA, RNA and proteins, and in EN ISO 20186 1, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for venous whole blood - Part 1: Isolated cellular RNA.
NOTE   International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document specifies the requirements for competence to carry out reference measurement procedures in laboratory medicine, using the requirements of ISO/IEC 17025:2017 as a normative reference and listing additional requirements for calibration laboratories to perform their tasks adequately.
The relationship between clauses in this document and ISO/IEC 17025:2017 are summarized in Annex A.
Examinations of properties with results reported on a nominal or ordinal scale are not included.
This document is not applicable to medical laboratories.
NOTE       Requirements for medical laboratories are specified in ISO 15189[1].

This document gives guidelines on the handling, documentation, storage and processing of formalin-fixed and paraffin-embedded (FFPE) tissue specimens intended for DNA examination during the pre-examination phase before a molecular assay is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories and molecular pathology laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
NOTE       International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document establishes acceptable performance criteria for antimicrobial susceptibility test (AST) devices that are used to determine minimum inhibitory concentrations (MIC) of bacteria to antimicrobial agents in medical laboratories.
This document specifies requirements for AST devices and procedures for assessing performance of such devices. It defines how a performance evaluation of an AST device is to be conducted.
This document has been developed to guide manufacturers in the conduct of performance evaluation studies.

This document gives guidelines on the handling, documentation, storage and processing of formalin-fixed and paraffin-embedded (FFPE) tissue specimens intended for the examination of isolated proteins during the pre-examination phase before a molecular assay is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories and molecular pathology laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
This document is not applicable for protein examination by immunohistochemistry.
NOTE       International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, documentation, storage and processing of formalin-fixed and paraffin-embedded (FFPE) tissue specimens intended for RNA examination during the pre-examination phase before a molecular assay is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories and molecular pathology laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
NOTE       International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, documentation, storage and processing of frozen tissue specimens intended for the examination of isolated proteins during the pre-examination phase before a molecular assay is performed.
This document is applicable to any molecular in vitro diagnostic examination performed by medical laboratories and molecular pathology laboratories that evaluate proteins isolated from frozen tissue. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organisations performing biomedical research, and regulatory authorities.
NOTE       International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, documentation, storage and processing of fine needle aspirates (FNAs) intended for gDNA examination during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories and molecular pathology laboratories that examine gDNA isolated from FNAs. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organisations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for collecting, stabilizing, transporting and storing of core needle biopsies (FNA Biopsy or FNA B) and are not covered in this document, but EN ISO 20184-3, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for frozen tissue - Part 3: Isolated DNA and EN ISO 20166-3, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for formalin-fixed and paraffin-embedded (FFPE) tissue - Part 3: Isolated DNA.
This document is not applicable for pathogen DNA examination and gDNA examination by in situ detection.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, documentation, storage and processing of fine needle aspirates (FNAs) intended for protein examination during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories and molecular pathology laboratories that examine proteins isolated from FNAs. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organisations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for collecting, stabilizing, transporting and storing of core needle biopsies (FNA Biopsy or FNA B) and are not covered in this document, but in EN ISO 20184-2, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for frozen tissue - Part 2: Isolated proteins and EN ISO 20166-2, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for formalin fixed and paraffin-embedded (FFPE) tissue - Part 2: Isolated proteins.
This document is not applicable for protein examination by immunohistochemistry.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, documentation, storage and processing of fine needle aspirates (FNAs) intended for RNA examination during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examination including laboratory developed tests performed by medical laboratories and molecular pathology laboratories that examine RNA isolated from FNAs. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organisations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for collecting, stabilizing, transporting and storing of core needle biopsies (FNA Biopsy or FNA B) and are not covered in this document, but in EN ISO 20184-1, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for frozen tissue - Part 1: Isolated RNA and EN ISO 20166-1, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for formalin fixed and paraffin-embedded (FFPE) tissue - Part 1: Isolated RNA.
This document is not applicable for RNA examination by in situ detection.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document specifies requirements and recommendations on the handling, storage, processing and documentation of saliva specimens intended for human DNA examination during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examination including laboratory developed tests performed by medical laboratories. It can also be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Dedicated measures that need to be taken for saliva collected on absorbing material or by mouth washes are not described in this document. Neither are measures for preserving and handling of native saliva cell-free DNA, pathogens, and other bacterial or whole microbiome DNA in saliva described.
NOTE       International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document describes a method for testing the susceptibility to antifungal agents of yeasts, including Candida spp. and Cryptococcus neoformans, that cause infections. The reference method described here has not been used in studies of the yeast forms of dimorphic fungi, such as Blastomyces dermatitidis and/or Histoplasma capsulatum variety capsulatum. Moreover, testing filamentous fungi (moulds) introduces several additional problems in standardization not addressed by the current procedure. Those methods are beyond the scope of this document.
This document describes the broth micro-dilution reference method, which can be implemented by either of two pathways. One pathway involves visual determination of MICs (CLSI method)[1][5]; the second pathway involves spectrophotometric determination of MICs (EUCAST method)[2][10]. The MIC reflects the activity of the drug under the described test conditions and can be interpreted for clinical management purposes by taking into account other factors, such as drug pharmacology or antifungal resistance mechanisms. In addition, MIC distributions can be used to define wild type or non-wild type fungal populations. Clinical interpretation of the MIC value is beyond the scope of this document; interpretive category breakpoints specific to the CLSI- and EUCAST-derived methods can be found by consulting the latest interpretive tables provided by the organizations[5][15]. Routine susceptibility testing methods or diagnostic test devices can be compared with this reference method in order to ensure comparable and reliable results for validation or registration purposes.

This document specifies requirements and test methods for specialized single-use evacuated and non-evacuated containers, intended by their manufacturers, for the primary containment and preservation of specimens, other than blood specimens, derived from the human body, for the purposes of in vitro diagnostic examination. It is not intended to cover specimen containers for forensic investigations.
Examples of such specimens include, but are not limited to, cerebral spinal fluid (CSF), faeces, infected bodily fluids, saliva, ejaculate, sputum, urine, tissue samples.
Specimens and types of devices specifically excluded are specialized containers for cryo-preservation, samples for nucleic acid testing and swabs.
NOTE       Requirements and test methods for evacuated and non-evacuated single-use human venous blood specimen collection containers are specified in ISO 6710.
This document does not specify requirements for auxiliary devices used in conjunction with specimen containers.

This document specifies requirements and gives recommendations for the collection, handling, documentation, transport, storage and processing during the pre-examination phase of formalin-fixed and paraffin-embedded (FFPE) tissue specimens intended for qualitative and/or (semi-)quantitative in situ examination of the morphology and of biomolecules, such as metabolites, proteins, DNA and/or RNA, on FFPE tissue sections by using different in situ detection techniques.
This document is applicable to in vitro diagnostic examinations using in situ detection techniques. These include laboratory developed tests performed by pathology laboratories (histopathology laboratories) as well as by molecular pathology laboratories and other medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, as well as institutions and commercial organizations performing biomedical research, and regulatory authorities.
This document is not applicable to the pre-examination phase of RNA, proteins and DNA isolated from FFPE tissue for examination. These are covered in ISO 20166-1, ISO 20166-2 and ISO 20166-3, Molecular in vitro diagnostic examinations — Specifications for pre-examination processes for isolated RNA, proteins and DNA, respectively.
Different dedicated measures are taken for pre-examination processes for fine needle aspirates (FNAs). These are covered in CEN WI 00140128, CEN WI 00140126, and CEN WI 00140129, Molecular in vitro diagnostic examinations — Specifications for pre-examination processes for Fine Needle Aspirates (FNAs) isolated cellular RNA, isolated proteins, and isolated genomic DNA, respectively.
NOTE     International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document specifies the minimum requirements for equipment and critical aspects of the test methods for best practice in laboratories performing basic examination of human semen collected by ejaculation.
This document is applicable to the entire process of basic manual semen examination and also to sample preparation for Computer-Aided Sperm Analysis (CASA).
This document does not apply to the post-vasectomy assessments.
NOTE       Given the medico-legal ramifications surrounding the evaluation of post-vasectomy ejaculates, the methodology in this document is in all likelihood inadequate to establish an ejaculate as being completely “clear” (i.e. no spermatozoa in the ejaculate).

This document specifies requirements and gives recommendations for the handling, documentation and processing of urine, venous blood plasma and serum intended for metabolomics analysis in the pre-examination processes. This document is applicable to metabolomics examinations and can be used by biomedical laboratories, customers of laboratories, in vitro diagnostics developers and manufacturers, institutions and companies performing biomedical research, biobanks, and regulatory authorities.

This document 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 1      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 document 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 document 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 2  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 3

This document specifies requirements and gives recommendations for the handling, storage, processing, and documentation of frozen tissue specimens intended for DNA examination during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories and molecular pathology laboratories that evaluate DNA isolated from frozen tissue. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Tissues that have undergone chemical stabilization pre-treatment before freezing are not covered in this document.
NOTE      International, national, or regional regulations or requirements can also apply to specific topics covered in this document.

This document specifies requirements and gives recommendations for the pre-examination phase of human specimens, such as stool, saliva, skin and urogenital specimens, intended for microbiome DNA examination. The pre-examination phase includes but is not limited to specimen collection, handling, transport, storage, processing, isolation of DNA, and documentation.
This document is applicable to molecular in vitro diagnostic examinations performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
Different dedicated measures are taken for pre-examination processes for infectious disease examination (e.g. targeted pathogen identification) and for microbiome DNA examination from tissue (e.g. biopsies). These are outside of the scope of this document.
Different dedicated measures are taken for pre-examination processes for saliva for human genomic DNA examination. These are not described in this document but are covered in CEN/TS 17305, Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for saliva - Isolated DNA.
NOTE    International, national or regional regulations or requirements can also apply to specific topics covered in this document.

ISO 6710:2017 specifies requirements and test methods for evacuated and non-evacuated single-use venous blood specimen containers.
It does not specify requirements for blood collection needles, needle holders, blood culture receptacles or "arterial" blood gas collection devices that can be used for venous blood.

This document describes one reference method, broth micro-dilution, for determination of MICs. The MIC can be a guide for the clinician, and reflects the activity of the drug under the described test conditions, by taking into account other factors, such as drug pharmacology, pharmacokinetics, or bacterial resistance mechanisms. This allows categorisation of bacteria as "susceptible" (S), "intermediate" (I), or "resistant" (R). In addition, MIC distributions can be used to define wild type or non-wild type bacterial populations. Although clinical interpretation of the MIC value is beyond the scope of this document, modifications of the basic method are required for certain antimicrobial agent - bacteria combinations to facilitate clinical interpretation. These modifications are included in a separate annex of this document. It is necessary to compare other susceptibility testing methods (e.g. disc diffusion or diagnostic test devices) with this reference method for validation, in order to ensure comparable and reliable results.

This document specifies a process for a medical laboratory to identify and manage the risks to patients, laboratory workers and service providers that are associated with medical laboratory examinations. The process includes identifying, estimating, evaluating, controlling and monitoring the risks.
The requirements of this document are applicable to all aspects of the examinations and services of a medical laboratory, including the pre-examination and post-examination aspects, examinations, accurate transmission of test results into the electronic medical record and other technical and management processes described in ISO 15189.
This document does not specify acceptable levels of risk.
This document does not apply to risks from post-examination clinical decisions made by healthcare providers.
This document does not apply to the management of risks affecting medical laboratory enterprises that are addressed by ISO 31000, such as business, economic, legal, and regulatory risks.

This document gives guidelines on the handling, storage, processing and documentation of venous blood
specimens intended for the examination of human genomic DNA isolated from Circulating Tumor Cells (CTCs) during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
This document does not cover the isolation of specific blood cells and subsequent isolation of genomic DNA therefrom.
DNA in pathogens present in blood is not covered by this document.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, storage, processing and documentation of venous whole blood specimens intended for the examination of human cellular RNA isolated from Circulating Tumor Cells (CTCs) during the pre-examination phase before a molecular examination is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
This document does not cover the isolation of cellular RNA directly from venous whole blood containing CTCs. This is covered in EN ISO 20186-1.
This document does not cover the isolation of specific blood cells and subsequent isolation of cellular RNA therefrom.
RNA in pathogens present in blood is not covered by this document.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, storage, processing and documentation of venous whole blood and the CTC (Circulating Tumor Cell) enrichment, CTC isolation and other preparations for analytical staining (i.e., conventional cytochemical and immunocytochemical staining) of CTCs during the pre-examination Phase before the cytopathological evaluation is performed.
This document is applicable to molecular in vitro diagnostic examinations including laboratory developed tests performed by medical laboratories. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organizations performing biomedical research, and regulatory authorities.
This document does not cover specific staining procedures.
NOTE International, national or regional regulations or requirements can also apply to specific topics covered in this document.

This document gives guidelines on the handling, documentation, storage and processing of frozen tissue specimens intended for RNA examination during the pre-examination phase before a molecular assay is performed.
This document is applicable to any molecular in vitro diagnostic examination performed by medical laboratories and molecular pathology laboratories that evaluate RNA extracted from frozen tissue. It is also intended to be used by laboratory customers, in vitro diagnostics developers and manufacturers, biobanks, institutions and commercial organisations performing biomedical research, and regulatory authorities.
Tissues that have undergone chemical stabilization pre-treatment before freezing are not covered in this document.
NOTE       International, national or regional regulations or requirements can also apply to specific topics covered in this document.

ISO 15197:2013 specifies requirements for in vitro glucose monitoring systems that measure glucose concentrations in capillary blood samples, for specific design verification procedures and for the validation of performance by the intended users. These systems are intended for self-measurement by lay persons for management of diabetes mellitus.
ISO 15197:2013 is applicable to manufacturers of such systems and those other organizations (e.g. regulatory authorities and conformity assessment bodies) having the responsibility for assessing the performance of these systems.

ISO 23640:2011 is applicable to the stability evaluation of in vitro diagnostic medical devices, including reagents, calibrators, control materials, diluents, buffers and reagent kits, hereinafter called IVD reagents. ISO 23640:2011 can also be applied to specimen collection devices that contain substances used  to preserve samples or to initiate reactions for further processing of the sample in the collection device.  
ISO 23640:2011 specifies general requirements for stability evaluation and gives specific requirements for real time and accelerated stability evaluation when generating data in:
       the establishment of IVD reagent shelf life, including transport conditions suitable to ensure that product specifications are maintained;
       the establishment of stability of the IVD reagent in use after the first opening of the primary container;
       the monitoring of stability of IVD reagents already placed on the market;
       the verification of stability specifications after modifications of the IVD reagent that might affect stability.

ISO 19001:2013 specifies requirements for information supplied by the manufacturer with reagents used in staining in biology. It applies to producers, suppliers and vendors of dyes, stains, chromogenic reagents and other reagents used for staining in histology and cytology including bacteriology, haematology, histochemistry, as performed in medical laboratories, both routine and research bacteriology. The requirements for information supplied by the manufacturer specified in ISO 19001:2013 are a prerequisite for achieving comparable and reproducible results in all fields of staining in biology.

ISO 15193:2009 specifies requirements for the content of a reference measurement procedure for in vitro diagnostic medical devices and medical laboratories.
ISO 15193:2009 applies to reference measurement procedures providing values of differential or rational quantities. Annex A provides information on nominal properties and ordinal quantities.
ISO 15193:2009 is valid for any person, body or institution involved in one of the various branches of laboratory medicine whose intention is to write a document to serve as a reference measurement procedure.

ISO 15194:2009 specifies requirements for certified reference materials and the content of their supporting documentation, in order for them to be considered of higher metrological order in accordance with ISO 17511. It is applicable to certified reference materials classifiable as primary measurement standards, secondary measurement standards and international conventional calibrators that function either as calibrators or trueness control materials. ISO 15194:2009 also provides requirements on how to collect data for value determination and how to present the assigned value and its measurement uncertainty.
ISO 15194:2009 applies to certified reference materials with assigned values of differential or rational quantities. Annex A provides information on nominal properties and ordinal quantities.
ISO 15194:2009 does not apply to reference materials that are parts of an in vitro diagnostic measuring system, although it is possible that many elements are helpful.

This European Standard applies to external quality assessment schemes, hereafter called EQAS, that include in their functions the assessment and evaluation of the performance of specified in vitro diagnostic procedures (including in vitro diagnostic medical devices, hereafter called IVD MDs). It sets out the requirements that are necessary to enable EQAS to fulfil this function relating to:
- scheme design and organisation;
- identification of procedures (IVD MDs) used by the participant;
- classification and evaluation of data.
NOTE   External quality assessment data generated according to these criteria will help manufacturers, users or competent authorities to monitor independently the post-marketing performance of IVD MDs.
This European Standard does not specify ways in which EQAS themselves are organised, nor how the individual or collective performance of clinical laboratories is evaluated.

ISO 18153:2003 specifies how to assure the metrological traceability of values assigned to calibrators and control materials intended to establish or verify trueness of measurement of the catalytic concentration of enzymes.
The calibrators and control materials are those provided by the manufacturers as part of, or to be used together with, in vitro diagnostic medical devices.
The following subjects are outside the scope of ISO 18153:2003: requirements for the design or selection of a reference measurement procedure; quantities involving mass of enzyme or immunoreactivity of enzymes; control materials that do not have an assigned value and are used only for assessing the precision of a measurement procedure, either its repeatability or reproducibility (precision control materials); control materials intended for intralaboratory quality control purposes and supplied with intervals of suggested acceptable values, each interval obtained by interlaboratory consensus with respect to one specified measurement procedure, and with limiting values that are not metrologically traceable; metrological traceability of routine results to the product calibrator and their relations to any medical discrimination limit; properties involving nominal and ordinal scales.

This European Standard specifies sampling procedure requirements for acceptance testing of finished in vitro diagnostic medical devices, which require EU verification by a notified body.
Two different provisions are addressed:
a) verification by testing attributes and/or variables on a statistical basis;
b) verification by testing a homogeneous batch which has been defined by appropriate means of process validation and in-process control.
This standard specifies requirements and criteria for testing procedures to establish and verify the homogeneity of processes and products. This standard is also applicable for drawing up sampling plans for finished products according to the requirements laid down for manufacturers' product certification and production quality systems.