Quality assurance and quality control in the routine molecular diagnostic laboratory for infectious diseases

Abstract

Molecular diagnostics has become one of the dominant platforms in clinical laboratory medicine. Technological improvements, from automated sample preparation to real time amplifi cation technology, provide the possibility to develop and run assays for a growing number of clinical questions. However, quality assurance and quality control issues have often remained underdeveloped but are still critical. To relate patient results to prior results or to absolute values in clinical practice guidelines, those results need to be comparable across time and methods. This may be achieved either by producing the identical value across methods and test versions or by using reliable and stable conversions. The establishment of international standards and reference materials is thus of paramount importance. This review focuses on general and specifi c issues relevant for quality assurance and quality control in the routine molecular diagnostics laboratory.Keywords: molecular diagnostics; quality assurance; quality control. Accreditation issuesThe framework of common standards including the international standards ISO 9001:2008 and ISO 15189 has been established allowing laboratories to plan and operate a medical testing with an effective quality management system that has strong elements of quality assurance, quality control, and quality improvement. When medical testing laboratories effectively implement this quality management system, they have continuous assurance that they are meeting their customers ' needs and expectations for consistent, accurate, and timely test results.Among several issues, these standards contain certain validation and verifi cation procedures because the suitability of a laboratory technique does not necessarily prove that it would be performed correctly and provide valid results. To prove this, quality management systems have been implemented in the majority of routine diagnostic laboratories. For laboratories in the European Union, the European Union ' s Directive on In Vitro Diagnostic (IVD) Medical Devices (98/79/EC) requires data demonstrating that an IVD achieves the stated performance and will continue to perform properly after it has been shipped, stored, and put to use at its fi nal destination (1) . Additionally, common technical specifi cations enforced for tests or test systems are outlined in the Commission Decision of 7 May 2002 on common technical specifi cations for IVD medical devices (2) . For laboratories in the US, the Food and Drug Administration (FDA) has established regulations based on current ISO standards (3) . In addition to supervision, description, and conformity of processes by the use of standard operating procedures, the validation procedure focuses on the competence of the laboratory providing reliable test results and their correct interpretation. Validation and verifi cation workAs for all medical testing, laboratories performing molecular assays must adhere to established validation practices to ensure confi dence and reliability in test results produced....

Contributions of CCLM to advances in quality control

“…Some have maintained that quality assurance and quality control is relatively underdeveloped in this rapidly growing area. A review published last year with an emphasis on issues relevant to quality assurance and quality control in the routine molecular diagnostics laboratory was timely and informative [ 34 ].…”

Detection of mycobacterial DNA by a specific and simple lateral flow assay incorporating cadmium selenide quantum dots

“…The smallest concentration that produced a clearly detectable positive result in all five repeats was 25 fmole of PCR product diluted in a sample volume of 4µl corresponding to 6.25 fmole/µl (Fig. 3), which was defined as the method's LOD [10], [11].…”

“…Research and most significantly reliable diagnostic application of PCR, requires confirmation of the specificity of the amplification product [10], [12]. While PCR is a very demanding process in terms of quality control [10], [11], [12], [13] it is already widely practiced, the methodologies that implement it within the context of the assessment mentioned above are usually "within reach" in most of the laboratories involved in this type of research or routine diagnostics.…”

“…While PCR is a very demanding process in terms of quality control [10], [11], [12], [13] it is already widely practiced, the methodologies that implement it within the context of the assessment mentioned above are usually "within reach" in most of the laboratories involved in this type of research or routine diagnostics. However the additional requirements of the respective assessment, which is usually performed by various DNA hybridization assays, sequence analysis or in connection to real time PCR, by TaqMan or dual labelled probes, are considerable in terms mainly of time, cost and complexity.…”

Standardization of Diagnostics in Blood Safety

“…Moreover, participation in external quality assurance programs is necessary. Several programs for proficiency testing for infectious diseases have been established in molecular diagnostics in Europe, including EQUALqual, a project proposed under the auspices of the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) and funded by the European Commission, and several commercially available programs provided by, for example, Quality Control for Molecular Diagnostics (QCMD, UK), the United Kingdom National External Quality Assessment Service (NEQAS, UK), the Reference Institute for Bioanalytics (RfB, Germany), and the Institute for Standardization and Documentation in Medical Laboratory (INSTAND, Germany) [5]. Recently, a novel format for a personalized external quality assurance program (EQAP) was described that provides a collaborative trial for genomic detection of eight viruses simultaneously: HAV, HBV, HCV, HIV-1, HIV-2, parvovirus B19 (B19V), WNV and human cytomegalovirus (HCMV) [6].…”