[Interpretation and analysis of the requirements of the standard EN ISO 15189: 2012]. / Analyse interprétative de la norme NF EN ISO 15189 : système de management de la qualité (chapitre 4).

The requirements related to quality management system of the standard EN ISO 15189 (2012) and the requirements of the French regulation as reported in the COFRAC document SH REF 02, are applied into actions to display, documents to write and to make available and traceability to ensure (records).

[Recommendations for the preparation of the quality manual]. / Recommandations pour la rédaction du manuel qualité d'un laboratoire de biologie médicale.

A quality manual includes the quality policy as established by the management of the medical laboratory, the objectives and indicators to control the quality management system. This manual describes the quality management system and the structure of the documentation used, with reference to supporting documents and technical procedures. It is also the responsibility of the management to establish, implement and monitor the proper functioning of all equipment, reagents and analytical systems. The management needs to ensure that preventive maintenance is done on a regular basis and all the manufacturers 'recommendations should be adopted and made available to laboratory staff. The development of a manual quality is one of the first steps of the management of quality in a medical laboratory. A model of quality manual for a fictive laboratory is given as well in annex to helping to prepare as a concrete basis.

[Evaluation of the quality management system according to the standard EN ISO 15 189: 2012. Proposition for a greed]. / Grille d'évaluation du système de management de la qualité en application de la norme NF EN ISO 15189 version 2012.

This article gives a greed for evaluation of the application in medical laboratory according to requirements of the standard EN ISO 15189 : 2012. This is to allow the responsible of the laboratory to check the requirements of this standard to be applied.

[Detection of Aspergillus antigen galactomannan using ELISA method: validation of the performances of the method for accreditation]. / Validation d'une méthode Elisa pour la recherche de l'antigène aspergillaire galactomannane en vue de l'accréditation.

Diagnosis of invasive aspergillosis for patients with high risk of infection is based on the monitoring of Aspergillus antigenemia assessed by the detection of galactomannan in serum by a sandwich-type ELISA (Biorad(®)). The validation of the method was displayed according to the guide COFRAC SH GTA 04. The internal quality control system settled, involves two quality control samples made of pools of sera (negative and positive). The repeatability of the measurements, as estimated by the coefficients of variation (CV), obtained by two different technicians was found from 9 to 13.7% for the positive control. The CV of the negative control, for which the provider indicates it is not useful in the analytical process, was found from 7.1 to 30%. In our experience it could be an indicator of environmental contamination. The evaluation of the intermediary fidelity was 15.7% for the positive control and 22.5% for the negative one. In the lack of reference material (International Standard) and recommendation from scientific societies, performances obtained will be discussed according to the results reported in the technical form of the supplier and those obtained by 39 laboratories participating in the only available external quality assessment program organized in France by ProBioQual(®) where the CV of reproducibility are 44.7% of unit (mean index 0.131) for the negative control and 18% (mean index 1.089) for the positive one in 2011.

[Post-examination phase: description and management control of the process]. / Description et maîtrise du processus post-analytique en biologie médicale.

This article defines the scope of the post-analytical process. This process transforms the results after quality control review into validated results, interpreted by authorized "medical biologists", reported and communicated to the clinicians and patients. This phase includes the treatment of the samples after analysis, their storage and disposal and records archiving. This phase is a key step of the examination involved often in dysfunctions that could hardly harm the patient. These errors are usually the consequence of failing in the control of organization, lack of communication with the clinicians and defect of adaptation to their needs. Examples of quality indicators are proposed, as well as a model of clinico-biological contract.

[Guidelines for validation of the results in laboratory medicine]. / Recommandations pour la validation des résultats d'examens de biologie médicale.

The validation of the results is defined as the review and verification of the coherency and likelihood of the whole results of the examination for a patient, taking into account needed clinical data, uncertainty of measurement and anteriority's as well. The signature of the authorized person certifies this validation according to the requirements of the French regulation and ISO standard as well. Recommendations are given for the organization of this step specially for duty periods and in case of utilization of an expert system software. Requirements about the content, the release and the signature of the reports are given. A quality indicator applied to the control of the validation process is proposed.

[Guidelines for results reports of biological examinations]. / Recommandations concernant la transmission des résultats d'examens de biologie médicale.

This article presents recommendations for results reports after release by authorized person to fulfill the French regulation and ISO 15189 requirements. This document points out who can be authorized to communicate the reports and to whom. The advantages and disadvantages of the different ways to use for results report are discussed, as traceability and confidentiality rules to apply. Particular situations as critical values to report and correction of transmitted erroneous results. A table summarizes the different modalities available to communicate the results of examinations performed by the laboratory.

[Guidelines for records control and documents retention]. / Recommandations concernant la gestion des enregistrements et l'archivage documentaire.

The quality management system is based on records to maintain, according to the requirements of ISO 15189 standard and those of the French regulation as well, to ensure traceability of data. This article provides the nature of information and documents to be stored by the laboratory and the time they have to be maintained according to the French regulation. Moreover, it provides recommendations for the management and the control of records. Auditing the traceability of activities being a part of the elements of verification by COFRAC evaluators, a frame form for audit is also provided for self-assessment and preparation of accreditation.

[Interpretative analysis of ISO 15189 standard: post-examination phase aspects]. / Analyse interprétative de la norme NF EN ISO 15189 : aspects post-analytiques.

The requirements related to post-examination phase (chapters 5.7 and 5.8) and to advisory services (4.7, 5.1.4 et 5.1.12) of the standard ISO 15 189 and requirements of the French regulation, as included in the COFRAC document SH REF 02, are applied into actions to display, documents to write and to make available and traceability to ensure.

[Guidelines for point-of-care testing quality management according to ISO 22870]. / Recommandations pour la mise en place d'un système de management de la qualité des examens de biologie médicale délocalisés.

In this paper, we focus on the additional requirements of EN ISO 22870 compared to those described in Chapter 4: Quality Management of EN ISO 15189. They concern the quality policy, the management reviews and the audits. Thus, we propose a template of quality policy statement, and specific requirements for conducting management review of POCT are given. Finally, a questionnaire for performing an audit of POCT activities is proposed. The composition and activities of the multidisciplinary group for the supervision of POCT activities, which is also a specific requirement of EN ISO 22870, is discussed in another article of this volume.

[Guidelines for the management of point-of care testing pre-examination, examination and post-examination phases according to the EN ISO 22870 standard]. / Recommandations pour la maîtrise des phases pré-analytique et analytique des examens de biologie médicale délocalisés.

Quality of point-of-care examinations depends on the quality assurance system settled. This paper describes the different tools used to control the pre-examination, examination and post-examination procedures taking part in the quality of patient care according to the requirements of the standard EN ISO 22870 and EN ISO 15189 as well. They include mainly: For the pre-examination phase, the sample traceability and for the analytical phase, the practice of internal quality control and the participation in external quality assessment programme.

[Guidelines for the management of point-of care testing nonconformities according to the EN ISO 22870]. / Recommandations pour la gestion des non-conformités des examens de biologie médicale délocalisés.

In this paper, guidelines are proposed to fulfill the requirements of EN ISO 22870 standard regarding the management of point-of-care testing (POCT) nonconformities. In the first part, the main nonconformities that may affect POCT are given, the means for resolution and the control of adverse events are proposed. In the second part, we propose recommendations in case of unavailability of a point-of-care testing device from the occurring of the adverse event, to the restarting of the device.

[Medium-chain acyl-CoA-dehydrogenase (MCAD) deficiency: French consensus for neonatal screening, diagnosis, and management]. / Déficit en acyl-CoA-déshydrogénase des acides gras à chaîne moyenne (MCAD): consensus français pour le dépistage, le diagnostic, et la prise en charge.

MCAD deficiency is the most common fatty acid oxidation disorder, with the prevalence varying from 1/10,000 to 1/27,000 in the countries adjacent to France. As the High Authority for Health has recently proposed including MCAD deficiency in the panel of diseases neonatally screened for in France, a consensus was written for the management of MCAD deficiency diagnosed either clinically or by neonatal screening. Patients may present acutely with hyperammonemia, hypoglycemia, encephalopathy, and hepatomegaly, mainly after a prolonged fast of intercurrent infection. Sudden death related to heartbeat disorders may also occur. The diagnosis of MCAD deficiency is suspected on the plasma acylcarnitine and/or the urinary organic acid profile. The diagnosis is confirmed by molecular biology and the enzymatic activity for patients who are not homozygous for the main mutation c.985A>G. However, some MCAD-deficient individuals may remain asymptomatic throughout life. The mainstay of treatment consists in avoiding prolonged fast and prescribing l-carnitine for patients who exhibit a deficiency in plasma carnitine. This management has radically modified the natural history of MCAD deficiency. This consensus will allow homogeneous management of these patients once the neonatal screening of MCAD deficiency has been introduced in France.

Long-term follow-up of bezafibrate treatment in patients with the myopathic form of carnitine palmitoyltransferase 2 deficiency.

Carnitine palmitoyltransferase 2 (CPT2) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder characterized by myalgia, exercise intolerance, and rhabdomyolysis. We evaluate the efficacy of bezafibrate (BZ), a hypolipidemic drug, as a treatment for this form of CPT2 deficiency. A pilot trial was conducted with BZ in six patients for 6 months. There was a follow-up period of 3 years. The oxidation rates of the long-chain fatty acid derivative palmitoyl-CoA, measured in the mitochondria of the patients' muscles, were markedly lower than normal before treatment and increased significantly (+39 to +206%; P = 0.028) in all patients after BZ treatment. The evaluation of the therapeutic effects by the patients themselves (using the Short Form Health Survey (SF-36)), as well as by the physicians, indicated an improvement in the condition of the patients; there was an increase in physical activity and a decline in muscular pain. The results suggest that BZ has a therapeutic effect in the muscular form of CPT2 deficiency.

[Interlaboratory comparison/external quality assessment]. / Comparaisons inter-laboratoires/évaluation externe de la qualité.

External quality assessment is an important issue in the demonstration of the quality of analytical process. The aim of this document is to help the laboratory in the choice, implementation and interpretation of external quality assessment schemes.

[Examination procedures]. / La procédure analytique.

Examination procedures have to be written for each examination according to the standard requirements. Using CE marked devices, technical inserts can be used, but because of their lack of homogeneity, it could be easier to document their use as a standard procedure. Document control policy applies for those procedures, the content of which could be as provided in this document. Electronic manuals can be used as well.

[Internal quality control]. / Contrôle interne de qualité

The internal quality control is a key technical requirement through accreditation by the NF EN ISO 15189. This document presents recommendations to assist the medical laboratory to design, implement and operate daily and retrospectively an efficient system of internal control quality. It identifies the important issues attached to these different steps.

[The maintenance of automatic analysers and associated documentation]. / Maintenance des analyseurs et documentation associée.

The maintenance of automatic analysers and associated documentation taking part in the requirements of the ISO 15189 Standard and the French regulation as well have to be defined in the laboratory policy. The management of the periodic maintenance and documentation shall be implemented and fulfilled. The organisation of corrective maintenance has to be managed to avoid interruption of the task of the laboratory. The different recommendations concern the identification of materials including automatic analysers, the environmental conditions to take into account, the documentation provided by the manufacturer and documents prepared by the laboratory including procedures for maintenance.

[Analytical validation of the results]. / Validation analytique des résultats.

The results obtained using automatic analysers have to be reviewed before release to the laboratory information system (LIMS) for definitive validation by the authorised person. The objective of such a review is to ensure that quality indicators are in agreement with the defined requirements and that the procedures have been carefully fulfilled.

[Uncertainty of measurement]. / Incertitude de mesure.

The ISO 15189 standard requires the evaluation of measurement uncertainty where relevant and possible. This document presents recommendations for a simple evaluation of the uncertainty from data available in medical laboratory and illustrates the value of such a determination.