Quality control uncertainty

The approaches to analytical procedures uncertainty prognosis are developed. The correctness of these approaches is confirmed in 3rd and 4th rounds of pharmaceutical laboratories inter-laboratory testing ( Phamia-Test program of State Inspection for Quality Control of Medicines, Ministry of Health of Ukraine). 

A quality control laboratory had a certain model of HPLC in operation. One of the products that was routinely run on the instrument contained two compounds, A and B, that were quantitated in one run at the same detector wavelength setting. At an injection volume of 20 /tL, both compounds showed linear response. The relatively low absorption for compound B resulted in an uncertainty that was just tolerable, but an improvement was sought. 

By now, it should be clear what role RMs play in measurement science. This puts great responsibility on the producers of RMs, as they must see how to satisfy the requirements set impHcitly or explicitly by the users regarding matrix, parameters, uncertainty, and traceability. Laboratories use RMs often as a quality control measure, but it this obviously only vahd if the RM is produced under proper conditions. 

In addition to the requirements regarding traceability of measurement results, the measurement methods employed should represent "state-of-the-art in the particular field. Failing to do so would lead to a reference material with an uncertainty that has become too large to serve as a quality control. The better the methods perform in terms of uncertainty and traceability, the better the reference material will serve the interests of the (potential) users. 

Of the four strategies given above, the best condition for obtaining independent data for quality control (QC) are satisfied when INAA and RNAA results are compared, because the use of RNAA dramatically improves the selectivity of signal measurement and eliminates or greafiy reduces the measurement uncertainty sotuces, such as spectral interferences. A variety of radiochemical separations and... 

Some of the intended categories of use of radioisotopic reference material have been reviewed recently by Fajgelj et al. (1999). They include assignment of property values, establishing the traceability of a measurement result, determining the uncertainty of a measurement result, calibration of an apparatus, assessment of a measurement method, use for recovery studies and use for quality control purposes. It should be noted however that, in general, natural matrix reference materials are not recommended for calibration purposes. This should preferably be done with pure chemical forms of the element labelled with the isotope of interest. Calibrated isotopic sources of this kind are available from a number of commercial suppliers and are not the subject of this review. 

Ingamells CO, PiTARD FF (1986) Applied Geochemical Analysis, pp L-84.Wiley, New York. International Federation of Clinical Chemistry (IFCC) (1978) Expert Panel on Nomenclature and Principles of Quality Control in Clinical Chemistry. Clin Chim Acta 83 L89F-202F. International Organization for Standardization (ISO) (1993) Guide to the expression of uncertainty. Geneva. 

On most occasions CRMs are used as Quality Control materials, rather than as calibrations . As outlined above, this common application adds significantly to the user s uncertainty budget, since at a minimum it is necessary to consider at least two independent measurement events (Um). so increasing the combined uncertainty of the results. Again this process rapidly increases the combined uncertainty with increasing complexity of the analytical system and so the usefulness of a control analysis may be downgraded when a correct uncertainty budget is formulated. 

The principles of quality assurance are commonly related to product and process control in manufacturing. Today the field of application greatly expanded to include environmental protection and quality control within analytical chemistry itself, i.e., the quality assurance of analytical measurements. In any field, features of quality cannot be reproduced with any absolute degree of precision but only within certain limits of tolerance. These depend on the uncertainties of both the process under control and the test procedure and additionally from the expense of testing and controlling that may be economically justifiable. 

Internal quality control (IQC) is one of a number of concerted measures that analytical chemists can take to ensure that the data produced in the laboratory are of known quality and uncertainty. In practice this is determined by comparing the results achieved in the laboratory at a given time with a standard. IQC therefore comprises the routine practical procedures that enable the analyst to accept a result or group of results or reject the results and repeat the analysis. IQC is undertaken by the inclusion of particular reference materials, control materials , into the analytical sequence and by duplicate analysis. 

Significant differences can easily be calculated, when precision data for repeatability and reproducibility are used. Quality controls based on the validation data can be used to confirm that the method is in control and producing meaningful results. Estimation of the measurement uncertainty enables expression of the result as a range of values in which the tme value for the measurement can be said to lie within a stated level of confidence. 

To provide a practical, understandable and common way of measurement uncertainty calculations, mainly based on already existing quality control and validation data covering all uncertainty sources in a integral way... 

An important consideration for quality control in industry and commerce relates to the trend of developing faster analytical methods than those described in official sfandards the question in such cases is whether a proposed method is acceptable as replacement for the standard. This problem relates to the concepts fitness for purpose and measurement uncertainty, the latter serving for the estimation of the LOD and LOQ parameters of analytical quality. An example of this dilemma relating to the peroxide value is discussed in Section IV.B.5. 

It is important to issue a common understanding on the topics of method validation, traceability, and uncertainty of measurements. Here, the interrelationships between method validation, traceability, and MU of results will be elucidated. Throughout the landscape of guidelines and standards, the most relevant information is selected, compiled, and summarized. Great importance is attached to the different method performance parameters and their definitions, ways of expression, and approaches for practical assessment. We discuss the role of method validation within QA as well as the topics of standardization, internal and external quality control (IQC and EQC, respectively), and accreditation and the links between these different aspects. 

The repeatability (sr) can be used to check duplicate repeats during normal operation of a method (see chapter 1). On its own, repeatability is not a complete basis for estimation of measurement uncertainty because it omits many effects that contribute to the bias of measurements made within a single laboratory. However, combined with a good estimate of the run bias, the intralaboratory precision, obtained from quality control data, can be used to give an estimate of measurement uncertainty. See section 6.6.3.2 for details on correction for bias and recovery. 

The uncertainty applicable to a measurement contains components for repeatability and reproducibility [9,19, 20], caused in part by variability of measurement-relevant parameters. The uncertainty also depends on the individual making the measurement, the laboratory facilities used, and the environment during the measurement. Without some quality control over measurements, statements on relevant traceability can have little meaning. Such controls provide a laboratory with confidence in its operators and credibility to the outside. 

All uncertainty estimates start with that associated with the repeatability of a measured value obtained on the unknown. It is neither required for the sake of quality control, nor could it always be economically justified, to make redundant determinations of each measured value, such as would be needed for complete statistical control. Repeat measurements of a similar kind under the laboratory s typical working conditions may have given satisfactory experience regarding the range of values obtained under normal operational variations of measurement conditions such as time intervals, stability of measurement equipment, laboratory temperature and humidity, small disparities associated with different operators, etc. Repeatability of routine measurements of the same or similar types is established by the use of RMs on which repeat measurements are made periodically and monitored by use of control charts, in order to establish the laboratory s ability to repeat measurements (see sect, entitled The responsible laboratory above). For this purpose, it is particularly important not to reject any outlier, unless cause for its deviation has been unequivocally established as an abnormal blunder. Rejection of other outliers leads a laboratory to assess its capabilities too optimistically. The repeatability in the field of a certified RM value represents the low limit of uncertainty for any similar value measured there. 

At the conclusion of the study, surplus test materials are offered for sale as reference materials for quality control and method development purposes. These materials have been studied for homogeneity and stability and have been assigned values for specific analytes. The more recently produced materials (since July 1999) have traceable assigned values with rigorously evaluated uncertainties. Older materials have consensus-based assigned values. 

It is now internationally recognized that for any laboratory to produce reliable data, an appropriate scheme of QA must be implemented. As a minimum, this must ensure that the laboratory is using methods that have been validated as fit for the purpose before their application to a specific task. These methods should be fully documented, staff should be trained, the laboratory infrastructure should be appropriate to the measurements to be made, and mechanisms ensuring that the procedure is under statistical control should be present. Implementation of appropriate QC measures ensures that the data produced and reported are of known quality and uncertainty. Last but not least, the laboratory should participate in PT schemes in order to demonstrate its competence.6... 

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