Quality assurance in biological monitoring of environmental exposure to pollutants: from reference materials to external quality assessment schemes

The presence of chemicals in the environment is a matter of concern in that it poses potential health risks. At present, exposure to toxic chemicals and their biological and biochemical effects can be better estimated by biological monitoring, through the systematic collection of specimens from potentially exposed humans. Biological monitoring of human exposure to environmental pollutants is hampered by the difficulty to assess data reliability. As a consequence, the validity of biological monitoring should depend on the strict implementation of a quality assurance (QA) program, which includes a series of procedures aiming to ensure that laboratory results meet defined standards of quality and are reliable. For the validation and monitoring of methods’ performance, to ensure the trueness of measurements and to warrant the traceability to international standards, reference materials (RMs) and certified reference materials should be used. Internal quality control and external quality assessment (EQA) are part of overall QA and are carried out to verify that analytical errors are compatible with the specific requirements or needs of the user. In particular EQA schemes (EQAS) allow to test independently the analytical performance of participating laboratories. In the last decades, increasing concern has been raised by urban air pollution; lead and benzene, two gasoline components released by motor vehicle exhausts, are known to be toxic to humans. For biological monitoring of lead exposure of the general population, screening campaigns, utilizing lead in blood as a biomarker, have been carried out since the 1970s. Strict strategies were adopted to ensure data comparability, including the preparation of RMs, the organization of EQAS and the cross-exchange and analysis of blood samples between laboratories. Biological monitoring of benzene exposure could be carried out by means of various biomarkers such as benzene in blood and benzene, trans,trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA) in urine. At present, few RMs and EQAS are available for these biomarkers. A pilot EQAS for t,t-MA in urine, adopted to assess the reliability of data regarding benzene exposure, has been organized and carried out between 1996 and 1997 in Italy. From the accrued experience, it clearly emerges the importance of strategies designed to guarantee the quality of biological monitoring data. The use of RMs and the participation in EQAS are highly recommended in order to improve the global performance of methods and laboratories involved in biological monitoring.     

A survey of workload, facilities and awareness of uncertainty of measurement among Italian laboratories performing analyses in occupational and environmental medicine

Biological monitoring is essential for risk assessment in the presence of exposure of workers or the general population to harmful chemical agents. Besides the choice of analytical methods which are fit for purpose and the skills of the analysts, the performance of laboratories, including those working in the field of environmental and occupational medicine, also depends on other technical factors such as frequency of testing, the use of well maintained and properly functioning equipment and the implementation of quality control procedures including the participation in External Quality Assessment Schemes (EQAS). Surveys of laboratory workload have been organized periodically since 1997 within the MeTos Project, an Italian national EQAS for biomarkers of environmental and occupational exposure to chemical agents. In 2001, a more extensive survey, including specific technical issues, was organized as part of the activities of the Thematic Network of European Organizers of External Quality Assessment/Proficiency Testing Schemes Related to Occupational and Environmental Medicine (Network survey). In addition, information on the awareness and implementation of the new requirement for laboratories to estimate the uncertainty of their measurements was collected since 2000. The results of these surveys are reported and compared here. In all surveys, Pb in blood was the biomarker most frequently determined. As for biomarkers of exposure to organic compounds, the data collected in the Network survey indicate that methylhippuric acid, hippuric acid and mandelic acid in urine were the assays most commonly performed. About a third of the participants stated that they estimate the uncertainty of at least some of their measurements. Preliminary analysis of data, limited to Pb in blood, showed that analytical performance improved with continuous participation in EQAS and was positively influenced by a high workload.     

Comprehensive quality control programme for serology and nucleic acid testing using an Internet-based application

The National Serology Reference Laboratory, Australia (NRL) has quality assured the serology for high risk blood-borne infections since 1985, commencing with anti-Human Immunodeficiency Virus (HIV) enzyme immunoassays and later extending the programmes to other blood-borne virus testing and to nucleic acid testing. A quality control (QC) programme was considered the most appropriate manner in which to achieve real-time monitoring. An Internet-based application, EDCNet, facilitates the entry of results of QC sample testing and returns the analysed results instantaneously. Results can be displayed in a variety of tables and charts, so that QC results from blood service and diagnostic laboratories can be monitored. Comparison of results between laboratories using the same system offers monitoring of accuracy, while within-laboratory comparisons offer monitoring of the assay precision. More than 200,000 data points were submitted to EDCNet in 2002 from blood service laboratories as well as from diagnostic laboratories. Analysis of reagent batch variability was determined, e.g. the coefficient of variation between batches of seven assays used to detect anti-hepatitis C virus (HCV) antibodies ranged from 4.9% to 21.6%. Using EDCNet, laboratories can monitor both precision and accuracy of results by comparison with the results of other laboratories. The system may be a highly cost-effective method for maintaining quality.

Estimates of uncertainty of measurement from proficiency testing data: a case study

The results obtained by a laboratory over a number of proficiency testing/external quality assessment schemes (PT/EQAS) rounds can give information on the uncertainty of its measurements for a given test, provided that conditions such as full coverage of the routine analytical range, traceability, and small uncertainty of the assigned values (compared to the spread of the results) are met and provided that systematic deviations and any other sources of uncertainty are considered. As organisers of the Italian EQAS (ITEQAS) in occupational and environmental laboratory medicine, we tested this hypothesis using as model data from well-performing laboratories taking part in ITEQAS for lead in blood over the last 2 years. We also investigated how different PT/EQAS features (frequency of trials and number of samples) would affect a laboratory estimate of its uncertainty. Such information can be helpful in improving PT/EQAS organisation and define, for a given test: (a) the state of the art of the uncertainty of current measurement procedures, (b) identify needs for improvement of analytical methodologies and (c) set targets for acceptable uncertainty values.Presented at the Eurachem PT Workshop September 2005, Portorož, Slovenia.Papers published in this section do not necessarily reflect the opinion of the Editors, the Editorial Board and the Publisher.     

Unification of the quality assurance systems of public health laboratories conformed to ISO 17025, ISO 15189, and ISO 9000: a major organizational change

The Department of Public Health Laboratories consists of five major laboratories located across the country of Israel: four environmental laboratories performing microbiological and chemical testing of food and water products [accredited according to International Organization for Standardization (ISO) 17025 since 1999) and a fifth laboratory that is dedicated to virology testing (certified according to ISO 9000 since 2003). Historically, each laboratory operated independently and developed its own quality assurance (QA). On November 2004, an important strategic decision was made: to unify all five laboratories’ QA systems conformed to ISO 17025, ISO 15189, and ISO 9000—a transition from five laboratories operating independently in the field of QA toward establishing a multisite laboratory. This process was considered and visualized as a major organizational change and therefore raised some resistance among both QA managers and the professional laboratories’ management. Thus, it was necessary to overcome the resistance and at the same time induce thoughts of ways of reshaping and formatting the new and uniform quality manual and uniform standard operating procedures (SOPs). In September 2005, the first phase of the process was completed, and all four environmental public health laboratories successfully passed a reaccreditation audit using a uniform QA manual guide and partially uniform SOPs. We shall share our experience and discuss the major contributions of this process to overall laboratory management. Presented at the 3rd International Conference on Metrology, November 2006, Tel Aviv, Israel.     

Quality assurance systems in research and routine analytical laboratories

In our article we explain the connections between the implementation of quality assurance (QA) in research and routine analytical laboratories. J. K. Taylor claims that QA in an analytical laboratory consists of two independent but closely related terms, quality control and quality assessment. If we construct the QA system according to his ideas, problems concerning quality can be solved with only one concept regardless of the type of analytical laboratory. Therefore there is no need to introduce new QA standards for research laboratories as suggested in some papers. In the routine laboratory quality control is more important, while in the research laboratory quality assessment is dominant.     

Quality assurance systems in research and routine analytical laboratories

 In our article we explain the connections between the implementation of quality assurance (QA) in research and routine analytical laboratories. J. K. Taylor claims that QA in an analytical laboratory consists of two independent but closely related terms, quality control and quality assessment. If we construct the QA system according to his ideas, problems concerning quality can be solved with only one concept regardless of the type of analytical laboratory. Therefore there is no need to introduce new QA standards for research laboratories as suggested in some papers. In the routine laboratory quality control is more important, while in the research laboratory quality assessment is dominant.

     

ISO 17025: practical benefits of implementing a quality system

As a laboratory certified to ISO 9001:2000 and accredited to ISO 17025, rtech laboratories has incorporated an overall system for technical and quality management, which results in benefits observed in daily laboratory practices. Technical requirements were updated to include the addition of formal personnel training plans and detailed records, method development and validation procedures, measurement of method uncertainty, and a defined equipment calibration and maintenance program. In addition, a stronger definition of the sample preparation process was documented to maintain consistency in sampling, and a more rigorous quality control monitoring program was implemented for chemistry and microbiology. Management quality improvements focused on document control to maintain consistent analytical processes, improved monitoring of supplier performance, a contract review process for documenting customer requirements, and a system for handling customer comments and complaints, with continuous improvement through corrective and preventive action procedures and audits. Quarterly management review of corrective actions, nonconforming testing, and proficiency testing aid in determining long-term trending. The practical benefits of these technical and management quality improvements are seen on a daily basis in the laboratory. Faster identification and resolution of issues regarding methods, personnel or equipment, improved customer satisfaction, meeting quality requirements of specialized customers, and overall increased laboratory business are all the result of implementing an effective quality system.     

The establishment of quality systems in veterinary diagnostic testing laboratories in developing countries: experiences with the FAO/IAEA External Quality Assurance Programme

Quality systems, established to internationally accepted standards, are one mechanism that can assist in evaluations of the sustainability of technology transfer, the proficiency of the user, and the reliability and comparability of data generated, resulting in potential enhancement of laboratory credibility. The means of interpreting existing standards and implementing quality systems in developing country veterinary diagnostic laboratories has become a significant adjunct to the technology transfer element within the Food and Agriculture/ International Atomic Energy Agency, FAO/IAEA programme. The FAO/IAEA External Quality Assurance Programme (EQAP) is given as an example for an initial step towards enhancing the “quality” culture in developing country veterinary laboratories. In 1995 the EQAP began as an effort to assure that test results emanating from laboratories using FAO/IAEA ELISA kits for animal disease diagnosis are valid. For this purpose 15 international external quality-assurance rounds have been performed to date for a variety of animal diseases e.g. Rinderpest, brucellosis, trypanosomosis, and foot-and-mouth disease (FMD). Results indicate that the EQAP is a valuable tool in the assessment of both the results provided by, and use of the ELISA kits provided through, the joint FAO/IAEA programme. Furthermore EQAP can assist laboratory diagnosticians to enhance quality control/quality assurance (QC/QA) procedures for conducting FAO/IAEA ELISAs and to advise on the implementation of similar QC/QA procedures in other laboratory activities. Based on the experiences made during the implementation of the EQAP a proposal for establishing a quality system standard was ratified through the World Organization for Animal Health (OIE) general conference in May 2000. The OIE Standard On Management And Technical Requirements For Laboratories Conducting Tests For Infectious Animal Diseases is based on ISO 17025 and provides a clear formula for establishing quality systems in veterinary diagnostic laboratories world-wide.     

Establishing a quality assurance plan for nucleic acid-based diagnostic laboratories: from planning to implementation

Nucleic acid-based technologies have opened new perspectives in diagnosis, prognosis, and treatment in clinical medicine. To maintain patient confidence in this rapidly expanding field and to provide the highest standard of analysis, strict laboratory quality assurance procedures must be followed. While impressive break-through are taking place in this field, the need for an appropriate and suitable quality assurance (QA) plan for nucleic acid-based diagnostic laboratories must be a top priority. In this study, we developed a systematic QA plan for this kind of diagnostic laboratories that would enable us to assure the highest quality standards of their services. We focus on those labs that would like to start introducing a quality system for the first time and discuss the most appropriate ways to pave the way to implement a QA plan from the beginning. This QA plan is suitable for any nucleic acid-based techniques laboratory regardless of the field or services provided.     

Blood lead monitoring in Italy: Assessment of the quality of results obtained between 1992 and 1994

Between 1992 and 1994, a new screening campaign for blood Pb monitoring in the Italian general population was carried out. Since the first campaign (started in 1978, in accomplishment of the European Community Directive 77/312/EEC) a working group of the Laboratory of Clinical Biochemistry at the Italian National Institute of Health (Istituto Superiore di Sanità), as the Reference Centre (RC), has coordinated the activity of various laboratories spread over the national territory. Appropriate quality assurance procedures, including an external quality assessment scheme (EQAS), were elaborated. Within the EQAS, three or four trials were carried out every year. Each laboratory participating in the trial analyzed eight control samples prepared from cow blood at different Pb concentrations. The results obtained by each peripheral laboratory and the RC between 1992 and 1994 have been compared by regression analysis. The same statistical method was adopted to compare the results obtained by each peripheral laboratory and the RC in the duplicate analysis of about 10 per cent of the human samples collected during the 1992–1994 monitoring campaign. There was no evidence of systematic differences between the regression lines obtained on control and human samples. In spite of the lower Pb concentration in the control samples analyzed during the 1992–1994 campaign, the analytical performance of the laboratories was better than that obtained in the previous screening campaign (1985–1986). Blood Pb levels observed in human samples collected between 1992 and 1994, confirm the downward time trend observed in the campaigns carried out in 1978–1979, 1980–1981 and 1985–1986. This study confirms that the results obtained in an EQAS are representative of the actual performance in the analysis of real (human) samples.     

Developing external quality assessment programmes for primary health: care level in resource limited countries

Laboratory services are an essential component of health care delivery in tropical countries and play a vital role in improving the accuracy of clinical diagnosis and the investigation of disease outbreaks. In developing countries, laboratories face numerous constraints to providing quality services, including poor selection of techniques, difficulties in equipment availability and maintenance, and shortages of supplies, staffing and supervision. Currently in the eastern African countries (Kenya, Tanzania and Uganda), internal quality control procedures are inconsistently carried out in most laboratories. National External Quality Assessment Schemes (EQAS) have been established in all countries addressing a limited number of tests, but are constrained by difficulties of sustainability and poor coverage. The Laboratory Programme of the African Medical and Research Foundation (AMREF) has been operating a simple EQAS for primary heath care laboratories since 1993. Tests addressed are those carried out in primary health care laboratories in eastern Africa. A total of 81 laboratories from 5 countries in the eastern African region have participated in the scheme since 1993 and 9 distributions were submitted since the start of the scheme. No laboratory participated in all distributions; 24 (30%) laboratories participated in 4 or more distributions. Of these, the hospital laboratories in Kenya and Tanzania showed improved average mean scores between the first two and subsequent distributions. The educational benefit of participation in the scheme is emphasised. There was an overall low rate of participation of laboratories (35%) once the scheme was expanded to include laboratories outside direct AMREF project activities. Contributing factors include shortages of staff and lack of time in busy rural laboratories, together with difficulties in communication; however, the voluntary nature and lack of appreciation of the benefits of participation may also play a role. To increase participation in the scheme and to address the quality of laboratory services throughout the region, AMREF is currently developing a Regional EQAS in collaboration with the Ministries of Health of Kenya, Tanzania and Uganda, in affiliation with the World Health Organisation (WHO). The approaches used to establish reference values for haemoglobin samples are discussed. The scheme has also been utilised to examine the performance of different techniques for haemoglobin estimation, demonstrating the inaccuracy of the visual comparator methods. Received: 13 April 2002 Accepted: 5 July 2002     

Sense and nonsense of quality assurance in an R&D environment

Quality has always been one of the key issues in laboratories in general and formal quality assurance (QA) in testing laboratories has gained popularity over the last decade. However, the implementation QA in research and development (R&;D) laboratories is still the domain of a few pioneers. We can even ask whether a QA system in research makes sense at all and if such a system really provides any added value? Difficulties with respect to the implementation of such a system are mainly associated with the nature of the research process itself. However, it is obvious that QA offers clear advantages in R&;D, if some critical success factors have been taken into account. An important issue is the selection of a good QA standard for R&;D. This is certainly not an easy task, since there are no specific standards. Fortunately, some useful international guides have been published recently.     

Quality assurance in analytical chemical laboratories: Towards harmonization and integration of current standards

This article presents the results of a comparative study of the main quality assurance (QA) and good laboratory practice (GLP) regulation systems and standards for analytical chemical laboratories currently being applied in Europe. A growing number of laboratories are being confronted with the need to cope with two or more of these systems, which involves separate audits and inspections for certification and accreditation. As these regulatory systems have essentially the same aims, there is an increasing interest in harmonization of QA and GLP guidelines. As a first step in exploring the possibilities of harmonization, similarities and differences of the current systems, compiled in the form of cross reference tables, have been analyzed (from a laboratory practice point of view) by a study group of EURACHEM, The Netherlands. The conclusions of this study have recently been endorsed by the Committee of EURACHEM Europe.     

Comparison of evaluation procedures used by European external quality assessment scheme organizers for haemoglobin concentration and leukocyte concentration

This study aimed to assess currently used evaluation procedures for haemoglobin concentration and leukocyte concentration in European external quality assessment schemes (EQAS). Participating EQAS organizers were asked to complete a questionnaire gathering information on the statistical procedures used to assess the performance of participants, and to analyse an Excel file with 262 results for haemoglobin concentration and leukocyte concentration. Responses were received from the New York State Proficiency Testing programme in the US and from 11 European EQAS: Belgium, Croatia, Finland, France, Germany, Hungary, Russia, Slovenia, Spain (two organizers), and Switzerland. Five of the 11 European EQAS use fixed limits based upon experience, biological variation, state of the art, or professional consensus. The other EQAS use variable limits based upon statistical analysis of the performance attained. With the exception of the German, Hungarian, and Slovenian schemes, all European EQAS use consensus target values. The percentage of unsatisfactory results obtained by the European EQAS organizers for the given set of data varied between 0.4 and 15.6% for haemoglobin concentration and between 0 and 19.8% for leukocyte concentration.     

Quality specifications for evaluation and comparison of performance among external quality assessment schemes in occupational and environmental laboratory medicine

Quality specifications (QS) are proposed for lead in blood and for aluminium, copper, selenium and zinc in serum as part of the aim to set standards of performance for laboratories so that results can be demonstrated to be fit for the purpose to which they are applied. The QS were established taking account of the analytical state-of-the-art, physiological variations in the concentrations of the analyte and the clinical purpose for which the assay is to be used. A procedure was devised that uses these QS to give equivalence of assessment among external quality assessment schemes (EQAS), thus avoiding conflicting information which has been demonstrated in the past. Advantages of this procedure are: to provide direct comparison of performance of laboratories taking part in different schemes, to provide equivalence of assessment of laboratory performance necessary to establish mutual recognition agreements, and to demonstrate the fitness for purpose of results from participants.Presented at the Eurachem PT Workshop September 2005, Portorož, Slovenia     

Accreditation of reference material producers: an Australian perspective

The National Association of Testing Authorities, Australia has operated an accreditation program for reference material producers since 1997 with accreditation now being offered to ISO Guide 34 (2000). This paper discusses the benefits and disadvantages to both the producers and the users of reference materials (testing laboratories) and their clients of a formal system of third-party accreditation of reference material producers. The merits of using ISO Guide 34 (2000) rather than ISO/IEC 17025 as the core standard in the accreditation process are discussed.     

NATA: 50 years experience with accreditation

 Laboratory accreditation is becoming increasingly accepted around the world as a means of identifying technically competent laboratories. It is also being used as a mechanism for the acceptance of test data both nationally and internationally. The concept and mechanisms of accreditation have been developed over the past 50 years. The first national laboratory accreditation system appeared in Australia in 1947. This organisation, known as the National Association of Testing Authorities (NATA), has since taken a leading role in developing accreditation practices that are now used world-wide in evaluating testing, measurement and calibration laboratories. This paper examines the development of the world's first and largest laboratory accreditation system, and looks at the difficulties and triumphs in gaining acceptance and recognition by government and industry of the benefits of laboratory accreditation. Received: 24 June 1996 Accepted: 25 June 1996     

The correlation of laboratory performance in proficiency testing with other QA characteristics

Although it seems self-evident that proficiency testing (PT) and accreditation can be expected to improve quality, their relative benefits remain uncertain as does their efficacy. The study reported here examines the following issues: (a) Why do laboratories take part in PT schemes? (b) How does participation in PT fit in with a laboratory's overall quality assurance (QA) system? (c) Is there a link between a laboratory's performance in specific PT and it's QA system? (d) How does PT performance change with time and how do laboratories respond to poor performance? The overall conclusion is that there is no evidence from the present study that laboratories with third-party assessment (accreditation and certification) perform any better in PT than laboratories without. The validity of this conclusion and its significance for the future design and operation of such schemes requires further investigation. In particular, study is required of the degree to which good performance in open PT correlates with blind PT performance, where laboratories are not aware that the samples being analysed are part of a quality assessment exercise.     

NIST reference materials to support accuracy in drug testing

Substance abuse is a major problem worldwide. There is considerable emphasis placed upon testing individuals for evidence of use of controlled substances. Because the consequences of a positive test can be quite severe, laboratories conducting such tests must rigorously follow a carefully designed quality assurance program. Such a QA program should include use of reference materials to assure that the methods used to detect and quantify drugs are providing accurate results. The National Institute of Standards and Technology (NIST) supports accuracy in drugs of abuse testing by providing Standard Reference Materials (SRMs) with certified concentrations of drugs of abuse in urine- and hair-based reference materials. NIST, working in collaboration with the College of American Pathologists (CAP), has developed urine-based SRMs for marijuana metabolite, cocaine metabolite, morphine and codeine, and morphine glucuronide and CAP Reference Materials for amphetamines and phencyclidine. Certification measurements performed at NIST involve two independent methods for each analyte, one of which always uses GC/MS with the other usually being an LC method with either MS or UV detection. Work has recently been completed on a seven component drug in urine SRM. In addition NIST conducts research in the analysis of hair for drugs of abuse. To assist laboratories testing hair for that purpose, NIST has developed two drugs in hair reference materials.College of American Pathologists Research Associate at NIST