Analytical laboratory results greatly influence medical diagnosis, about 70% of medical decisions are based on laboratory results. Quality assurance and quality control are designed to detect and correct errors in a laboratory’s analytical process to ensure both the reliability and accuracy of test results. Unreliable performance can result in misdiagnosis and delayed treatment. Furthermore, improved quality guarantees increased productivity at a lower cost. Quality assurance programmes include internal quality control, external quality assessment, proficiency surveillance and standardization. It is necessary to try to ensure compliance with the requirements of the standards at all levels of the process. The sources of these standards are the International Standards Organization (ISO), national standards bodies, guidelines from professional organisations, accreditation bodies and governmental regulations. Laboratory networks increase the performance of laboratories in support of diagnostic screening programme. It is essential that genetic laboratories of a network have procedures underpinned by a robust quality assurance system to minimize errors and to reassure the clinicians and the patients that international standards are being met. This article provides an overview of the bases of quality assurance and its importance in genetic tests and it reports the EBTNA quality assurance system which is a clear and simple system available for access to adequate standardization of a genetic laboratory’s network.
- Quality assurance
- EBTNA Quality System
- laboratory network
- genetic tests
Laboratory networks are an important component of disease genetic screening systems because they provide accurate and timely diagnosis, but they need a common and standardized quality system to guarantee safe and uniform results. Genetic laboratories use a wide variety of technologies and new tests are continuously being introduced (
Quality assurance (QA) is crucial to maintaining the highest quality standards in genetic testing laboratories. The QA is based on two tools: process control and quality statistical control (
The analytical quality management of a laboratory is carried out by adopting different types of QA programs, an internal quality assessment (IQA) and an external quality assessment (EQA) (13). The World Health Organization (WHO) defines IQC as “the set of procedures undertaken by the staff of a laboratory for continuously assessing laboratory work and the emergent results, in order to decide whether they are reliable enough to be released”. The IQA provide to maintain a high degree of confidence in test accuracy, but not necessarily of precision; its procedures include sample input, management, test, interpretation of results, and report output. IQA has a dual objective: controlling the analytical performance of the method and verifying the medium and long-term stability of the analytical method. Intra-laboratory quality control means checking genetic test results by using algorithms for measuring control materials, mainly to assess their reproducibility. An important component in the organization of the internal quality control is the selection of adequate control material. Multicentral management of an “extended” internal quality assessment to affiliated laboratories is very important and it can be facilitated by the use of software that allows a real-time update of its data management and of that other laboratories. This control system is the one that mainly consents for continuous monitoring because the widespread use of control materials and their daily use provide greater data availability, both as a number and as frequency distribution, which allows comparison of results between different labs that use the same control materials (13,14). EQA is defined by WHO as “a system of objectively checking laboratory results by means of an external agency. The checking is necessarily retrospective, and the comparison of a given laboratory’s performance on a certain day with that of other laboratories cannot be notified to the laboratory until some time later. The main objective of EQA is not to bring about day-to-day consistency, but to establish interlaboratory compatibility” (13,15). The EQA comparing test results with those obtained from different laboratories or recognized standards is a key element for measuring the reliability of test results (16). EQA programs allow a periodic and retrospective estimate of the total error. The laboratories participating in the program receive a report with information processed by the provider. EQA programs are not intended to improve the performance of a laboratory medicine service, but are an index to measure effectiveness (15). Grading report content is more important than scoring genotypes, and best practice guidelines provide an important framework for this process. The molecular genetic test reports must be accurate and complete with all the information to enable effective decision-making by doctors and patients (17). It is important to follow-up EQA results and discuss the reports in laboratory meetings and preventive and corrective actions should be documented. EQA provides continuous education and training for laboratories (18). The accreditation of the genetic laboratories by national or international accreditation bodies such as ILAC (International Laboratory Accreditation Cooperation) or EA (European Cooperation for Accreditation) against international standards, such as ISO (International Organization for Standardization) is important. In particular, adherence and “good conduct” to an EQA program are key and qualifying elements for all professional certification and accreditation programs (19).
The concept of quality as “total quality” and “quality management” finds its utmost expression with the ISO 9000, a set of standards defining a “quality system” model designed as a tool of character, organizational and managerial focused on monitoring and controlling processes that have a direct influence on the quality of the service provided (20). The ISO has developed an international standard for the accreditation of testing laboratories in general (ISO 17025) and one specifically for medical laboratories (ISO 15189) (21,22). The genetic laboratories make use of this accreditation system. The rational of the IS0 15189 is based on the following phases: Description of process and identification of critical phases; detection of the verification steps of the analysis process and development of a sample traceability system in the analysis process; development of a training plan, a calibration and maintenance plan, internal and external quality control systems, and analysis of results with possible implementation or corrective action plans, indication of procedures, protocols and modules. More precisely, the ISO 15189 accreditation standard covers two sections: management requirements and technical requirements of QA. Management elements include document control, identification of non-conformities, implementing of corrective and preventive actions, action plans, performance of internal audit and management review, resolution of complaints, evaluation of external services, suppliers, contracts and referral laboratories. Technical elements comprise personnel and training, accommodation, equipment, validation and assuring quality of examination procedures by IQC, EQA, maintenance and calibration. The fundamental principles of ISO 15189 are: The laboratory management has a responsibility to manage; the laboratory must know who are its users and meet their requirements and the physical laboratory should not interfere with laboratory workers or laboratory samples (22,23).
Genetic laboratories must have various elements of quality assurance to maintain a consistently high standard of performance in according to ISO 15189 (24). The principal key systems for implementation of quality management are:
IS0 15189 can be used by any authorized accreditation organizations and does not require re-accreditation if the laboratory changes its method of analysis. ISO 15189 allows other accreditation bodies to adapt ISO 15189 to local circumstance.
The ISO publishes the documents in multiple languages and copies of ISO standards can be obtained through the website of ISO (
ISO is the main reference source for quality control of genetic laboratories, but subsequently other establishments for genetic laboratories have been developed, always referring to the ISO system and numerous guidelines have been published. For instance, OECD has published specific guidelines for quality assurance in molecular genetic testing, which might be used in combination with the existing accreditation standards for improvement of the system. These guidelines can be download from the OECD website (
In 2008, the Maputo Declaration on strengthening of laboratory systems recognized the following as areas requiring strengthening in resource-limited settings: leadership, human resources, career path structures, retention of staff, national laboratory policies, strategic planning, physical infrastructure, supply-chain management and quality management systems (39). Following the Maputo statement, the World Health Organization (WHO) denoted the relevance of laboratory quality management systems (40). In 2012, in line with the Health 2020 European policy for health and well-being, the WHO Regional Office for Europe (OMS) started the “Better Labs for Better Health” initiative (41). The “Better Labs for Better Health” approach indicate the minimum quality standards for laboratory as a requirement to provide accurate and reliable results in a timely manner for disease prevention and management (
Main characteristics of European Biotechnology Thematic Network Association (EBTNA) is the presence of symbiotic relationship between science, education and biotechnological industry (47). The EBTNA has proposed a simple and efficient certification system according to IS0 15189 and to the model established by WHO which promoted the initiative “Better Labs for Better Health” dictating the minimum quality standards for laboratories as a requirement to provide reliable results in a timely manner for disease prevention and management. The EBTNA certification follows the EMQN model (
Each laboratory within the network must perform selected genetic tests for all the members, so that the network as a whole could offer a vast majority of genetic tests with highest quality and lowest price. The network must cover all parts of Europe including regions that do not provide a wide range of diagnostic genetic test list. The network has to offer a good service to patients and ensure that each partner has economic gains. The EBTNA main laboratory has to be based in an area of Europe that has low rental cost and low taxes. Strengthening laboratory services includes several goals:
Provide quality laboratory support for illnesses;
Improve the quality of laboratory services in Europe for routine surveillance;
Provide guidance on the most appropriate laboratory technologies and best practices;
Effective transfer technology and sharing of knowledge;
Promote the integration and / or coordination of specific laboratories for diseases with other laboratory activities;
Attract, map resources and coordinate their mobilization to strengthen the network.
To implement the quality management system, activities must be divided into four stages of implementation:
I) Ensure that the primary process of the lab works properly and safely;
II) Check and ensure quality and create traceability;
III) Ensure proper management leadership and organization;
IV) Create a continuous improvement and prepare for accreditation.
If there is stringent application to standards, this has to be certified. It is indispensable to demonstrate that the genetic test satisfies the requirements by clinical and molecular guidelines. The conformity assessment process is advantageous for patients and clinicians, also it gives a competitive edge and helps regulators to ensure that safety conditions are met.
Key points of the quality control system implementation are:
A trained and certified personnel;
A set of documentations (procedures, manuals and protocols);
A working system and a reporting system for management, when choosing an appropriate service based on effectiveness indicators, statistical accounting systems and monitoring of molecular genetic tests.
The products of a genetic laboratory are authorized reports containing laboratory testing results, as well as data on the patient (name, age, sex, and diagnosis), type of biological sample, time of taking it and delivering it to the laboratory, actual interpretation on of the results and other related information.
EBTNA quality assurance system is a simple application that can easily be accessible as a source of utility for those genetic laboratories willing to join the network. To ensure proper coherence to quality standards for genetic laboratories it is crucial that the set of documents including manuals, procedures, and protocols are prepared systematically and they are basic enough to provide homogeneity, clarity and completeness of the quality assurance process.
The manuals provide operational guidance on how to perform specific tasks such that the document illustrates what exactly the operator must do in order to ensure the quality of the system. The procedures describe the organizational and management modes so as to identify roles and responsibilities and to pursue the goals of effectiveness, efficiency and process control. The protocols are complex of rules and procedures to be followed for carrying out technical-professional activities. The EBTNA quality system organization is described in
EBTNA standards are given in the supplemental materials under the quality folder. Files with “PO” include planning and provision of molecular biology service (S1) and instructions for sending samples (S2) ; “admission” (S3); “working instructions” which includes extraction of DNA from blood Mini Kit, Gel electrophoresis, DNA quantification, PCR amplification of DNA and purification of PCR products (S4: a,b,c,d); “ forms” which include informed consent, PCR amplification worksheet, report, worksheet restriction enzyme digestion, clinical record of patients, single sample sequencing request, genetic test request and sample receipt form (S5:a,b,c,d,e,f,g,h) and some other examples of protocols “protocols”(S6:a,b,c). Further information and details can be found on EBTNA’s website (
Clinical laboratory tests are mainly required for two reasons; one is to confirm diagnosis and the other is to monitor disease activity. Laboratory quality management covers diverse aspects of genetic testing including parameters such as internal and external quality assessments, control materials, training, document controls, maintenance of equipment, internal auditing and laboratory accreditation. The improvement in appropriate use of laboratory testing is required as it is an essential part of many health care systems (24). This concept has been described and the inter-relations are gathered in a pyramidal form in which the major phases of the evaluation are technical quality of the test, diagnostic accuracy, change in diagnostic thinking, change in patient management, change in patient outcomes and societal costs and benefits (48). At the heart of diagnostic effort is the foundation of a laboratory network, which can foster sharing of skills and knowledge to improve the diagnosis. Genetic laboratory networks must encompass many aspects, such as quality management, information databases, new technologies, public health and education. On this basis, EBTNA has developed a quality system based on international standards that can guarantee equal results by all laboratories affiliated by the network with the same efficiency and safety.