Quality control proficiency testing

It must be remarked that terminology is not consistent and there are many widely used synon)ms. Quality control in this Chapter refers to practices best described as internal quality control. Quahty assessment is often referred to as external quality control, proficiency testing, interlaboratory comparisons, round robins or other terms. Internal Quality Control and External Quality Assessment are preferred because they best describe the objectives for which the RMs are being used, i.e. the immediate and active control of the results being reported from an analytical run or event, and an objective, retrospective assessment of the quality of those results. 

An active program of surveillance of the quality of the immunostains produced must be defined. The primary elements of such a quality assurance (QA) program include procedures and policies for patient test management, quality control, proficiency testing, comparison of test results, relationship of clinical information to patient test results, personnel assessment, communications, complaint investigations, QA review with staff, and QA records. The documentation and review by the laboratory director of all QA procedures is imperative and cannot be overstressed. A brief explanation of each of the QA elements is as follows ... 

IUPAC, ISO, and AOAC International International Union of Pure and Applied Chemistry, International Organisation for Standardization, Association of Official Chemists Method validation, Standardization, internal quality control, proficiency testing, accreditation 4,8, 62-71... 

EN17 Daggett, S.G., Greenberg, N. and Peters, C. (1991). Examples of non-physio-logical interferences in external quality control (proficiency test) samples that affect accuracy assessment. Clin. Chem. 37, 959, Abstr. 234. 

False-positive results with bDNA have been observed with proficiency testing specimens for HTV-1 in the College of American Pathologists HIV-1 viral load survey and HCV in the viral quality control program administered by the Netherlands Red Cross. The reason for the false-positive results with these proficiency testing specimens is not known but may be sample matrix effects. The extent to which this problem occurs with clinical samples has not been determined. However, both the HIV-1 and HCV bDNA assays were designed to have a false-positive rate of 5%. 

Identify available information, including information from quality control charts, performance in proficiency testing rounds, literature and validation information on related methods and data concerning comparison with other methods. Use the available information and professional judgement to review each relevant validation issue and sign-off issues adequately addressed and documented. 

This chapter deals with handling the data generated by analytical methods. The first section describes the key statistical parameters used to summarize and describe data sets. These parameters are important, as they are essential for many of the quality assurance activities described in this book. It is impossible to carry out effective method validation, evaluate measurement uncertainty, construct and interpret control charts or evaluate the data from proficiency testing schemes without some knowledge of basic statistics. This chapter also describes the use of control charts in monitoring the performance of measurements over a period of time. Finally, the concept of measurement uncertainty is introduced. The importance of evaluating uncertainty is explained and a systematic approach to evaluating uncertainty is described. 

The previous chapters of this book have discussed the many activities which laboratories undertake to help ensure the quality of the analytical results that are produced. There are many aspects of quality assurance and quality control that analysts carry out on a day-to-day basis to help them produce reliable results. Control charts are used to monitor method performance and identify when problems have arisen, and Certified Reference Materials are used to evaluate any bias in the results produced. These activities are sometimes referred to as internal quality control (IQC). In addition to all of these activities, it is extremely useful for laboratories to obtain an independent check of their performance and to be able to compare their performance with that of other laboratories carrying out similar types of analyses. This is achieved by taking part in interlaboratory studies. There are two main types of interlaboratory studies, namely proficiency testing (PT) schemes and collaborative studies (also known as collaborative trials). 

There is no experimentally established optimum frequency for the distribution of samples. The minimum frequency is about four rounds per year. Tests that are less frequent than this are probably ineffective in reinforcing the need for maintaining quality standards or for following up marginally poor performance. A frequency of one round per month for any particular type of analysis is the maximum that is likely to be effective. Postal circulation of samples and results would usually impose a minimum of two weeks for a round to be completed and it is possible that over-frequent rounds have the effect of discouraging some laboratories from conducting their own routine quality control. The cost of proficiency testing schemes in terms of analysts time, cost of materials and interruptions to other work has also to be considered. 

Thus, as for the European Union, the requirements are based on accreditation, proficiency testing, the use of validated methods of analysis and, in addition, the formal requirement to use internal quality control procedures which comply with the Harmonised Guidelines. Although the EU and Codex Alimentarius Commission refer to different sets of accreditation standards, the ISO/IEC Guide 25 1990 and EN 45000 series of standards are similar in intent. It is only through these measures that international trade will be facilitated and the requirements to allow mutual recognition to be fulfilled will be achieved. 

As shown above, these include a laboratory to be third-party assessed to international accreditation standards, to demonstrate that it is in statistical control by using appropriate internal quality control procedures, to participate in proficiency testing schemes which provide an objective means of assessing and documenting the reliability of the data it is producing and to use methods of analysis that are fit-for-purpose . These requirements are summarised below and then described in greater detail later in this chapter. 

ISO, IUPAC and AOAC INTERNATIONAL have co-operated to produce agreed protocols on the Design, Conduct and Interpretation of Collaborative Studies 14 and on the Proficiency Testing of [Chemical] Analytical Laboratories .11 The Working Group that produced these protocols has prepared a further protocol on the internal quality control of data produced in analytical laboratories. The document was finalised in 1994 and published in 1995 as the Harmonised Guidelines For Internal Quality Control In Analytical Chemistry Laboratories .12 The use of the procedures outlined in the Protocol should aid compliance with the accreditation requirements specified above. 

The list has been constructed on the premise that contractors will use methods of analysis that are appropriate and accredited by a third party (normally UKAS), participate in and achieve satisfactory results in proficiency testing schemes and use formal internal quality control procedures. In addition, Parts B and C are made available to the potential contractors so that they are aware of what other demands will be made of them and can build the costs of providing the information into their bids. 

Traditionally, the education that chemists and chemistry laboratory technicians receive in colleges and universities does not prepare them adequately for some important aspects of the real world of work in their chosen field. Today s industrial laboratory analyst is deeply involved with such job issues as quality control, quality assurance, ISO 9000, standard operating procedures, calibration, standard reference materials, statistical control, control charts, proficiency testing, validation, system suitability, chain of custody, good laboratory practices, protocol, and audits. Yet, most of these terms are foreign to the college graduate and the new employee. 

Analytical method validation forms the first level of QA in the laboratory. Analytical quality assurance (AQA) is the complete set of measures a laboratory must undertake to ensure that it is able to achieve high-quality data continuously. Besides the use of validation and/or standardized methods, these measures are effective IQC procedures (use of reference materials, control charts, etc.), with participation in proficiency testing schemes and accreditation to an international standard, normally ISO/IEC 17025 [4]. Method validation and the different aspects of QA form the subject of Section 8.2.3. 

Thompson, M., and Lowthian, P. J. (1993), Effectiveness of analytical quality control is related to the subsequent performance of laboratories in proficiency tests, Analyst, 118, 1495-1500. 

Procedures carried out in the laboratory, as opposed to proficiency testing or other interlaboratory collaborations, are known as in-house or internal quality control procedures. When running batches of samples with calibration solutions and unknowns, there are a number of extra samples that can be analyzed that cover different aspects of quality control (QC samples). These QC samples should be documented in the quality manual and be part... 

Maier, E A., Quevauviller, Ph, and Griepink, (1993), Interlaboratory studies as a tool for many purposes proficiency testing, learning exercises, quality control and certification of matrix materials. Analytica Chimica Acta, 283 (1), 590-99. 

For external quality control, laboratories running the DMB assay should regularly exchange samples and discuss problematic cases. Currently, there is no official quality control scheme/proficiency testing available. 

There are proficiency testing programs that are geared toward clinical sensitivity or specificity by seeking to determine whether a disease can be detected versus other types of controls that are use to test sensitivity, selectivity, and most importantly, reproducibility and precision. With mass spectrometry, the controls are and should be no different than those used for other assays, with one interesting exception. Quality assurance materials prepared for MS/MS may not be useful in other assays that are less selective. The example is newborn screening where quality assurance/control QA/QC materials have a mixture of compounds present in the blood specimens. However, in less selective immunoassays, the mixture creates interferences. In addition, material is used to spike a blood sample is key and one should ensure there is no enzyme activity. We have encountered such a problem with a d/1 mixture of metabolites where one form was degraded in the prepared blood. 

Among the elements of quality control in mycotoxin analysis, proficiency tests, control materials (reference materials and certified reference materials), traceability in spiking, and recovery checks have been demonstrated to be particularly relevant. 

Quality control sample, often chosen randomly, from a batch of samples and undergoing separate, but identical sample preparation and analysis whose purpose is to monitor method precision and sample homogeneity. Duplicate testing also aids in the evaluation of analyst proficiency. Volume 1(10). 

Quality control of laboratories depends on the availability of CRMs, round-robin studies, intercomparisons and proficiency tests between methods and between laboratories. Of special importance is a full knowledge of the complex analytical process and the painstaking pursuit of the true value by defining all sources of errors and the application of an adequate error source budget. The application of Poisson and Bayesian statistics could have some advantage. 

Process in reasonable control the indirect proficiency test will be most economical of resources when the participating laboratories are consistently producing PT material lots having good quality. This condition facilitates use of the ratio methods mentioned in the previous section of this paper, and thus reduces the number of accurate, traceable measurements that are required. 

The ISO/IEC GUIDE 25 [1] stresses, in paragraphs 5.6 and 9.3, the importance of participation in proficiency testing programs or other interlaboratory comparisons, as appropriate and when suitable programs are available. This would imply that such activities are an important part of a laboratory s quality control procedures. 

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