Validation test establishment calibration

NARL test methods include details of how traceability was established at the time the method was validated. Provided that the documented test method is followed, and all critical control points are addressed, measurements made using the test method will correctly identify and selectively and accurately measure the analyte of interest. Such measurements are traceable to the standards used in method validation and the calibration processes. For the test methods used in homogeneity testing of study samples, traceability of chemical measurements is maintained by ... 

Anklam et al. [7] as well as Ahmed [8] recently published a comprehensive overview of different PCR assays that have been published in the literature. The authors tried to include performance data adding to the value of the review articles. The validation of PCR methods and thus the establishment of such performance criteria is still the subject of much debate. H bner et al. [9] suggested an approach for the validation of PCR assays. In general, it is currently the view of most researchers that validation of a PCR assay should not differ essentially from the validation of other analytical methods. Thus, all principles outlined in the ISO standard 17025 General requirements for the competence of testing and calibration laboratories, ISO standard 5725 Accuracy (trueness and precision) of measurement methods and results as well as the principles as laid down by Codex Alimentarius (http //www.co-dexalimentarius.net), are applicable to PCR. 

Calibration of medical instruments, as a set of operations establishing the relationship between the values indicated by the instrument and the values realized by standards, is accomplished by INM laboratories, area organized calibration laboratories of BRML, or by recognized calibration laboratories for medical instruments, as shown in Fig. 2. Validation of such instruments includes instrument testing and calibration specify the intend use, a test to determine if the specifications are met and documentation. More details on out-... 

Thus, if quality is established in terms of precision and reproducibility of the results obtained in the studies (i.e. in the respective sets of measurements or experiments), the need to provide for each of the studies a study plan, approved by the head of the laboratory before the experiments or measurements can be started, will not be an important consideration. Certainly, Standard Operating Procedures will have to be observed, and the acknowledged methods will have to be followed, with any deviations to be described and justified. Since it is the quality of the result which counts for the determination of the test facility s quality , and not the way on which it has been obtained, there is no need for a single point of study control in the person of the Study Director. Certainly, a laboratory head will have to be appointed, who has to ensure that the quality of the data obtained in the laboratory remains high, and who has to provide the necessary education and training for the technical personnel in order to enhance and update their technical expertise. If precision and reproducibility are the primary purpose of the test facility s quality concerns, then apparatus, instruments, equipment and computerised systems have to comply to the highest technical standards in terms of validation, maintenance and calibration. 

With cross-validation [28], the same objects are used both for model estimation and testing. A few objects are left out from the calibration data set and the model is calibrated on the remaining objects. Then the values for the left-out objects are predicted and the prediction residuals are computed. The process is repeated with another subset of the calibration set, and so on until every object has been left out once then all prediction residuals are combined to compute the validation residual variance and root mean square error in prediction (RMSEP). It is of utmost importance that the user is aware of which level of cross-validation one wants to validate. For example, if one physical sample is measured three times, and the objective is to establish a model across samples, the three replicates must be held out in the same cross-validation segment. If the objective is to validate the repeated measurement, keep out one replicate for all samples and generate three cross-validation segments. The calibration variance is always the same it is the validation... 

For a new process plant, calculations can be carried out using the heat release and plume flow rate equations outlined in Table 13.16 from a paper by Bender. For the theory to he valid, the hood must he more than two source diameters (or widths for line sources) above the source, and the temperature difference must be less than 110 °C. Experimental results have also been obtained for the case of hood plume eccentricity. These results account for cross drafts which occur within most industrial buildings. The physical and chemical characteristics of the fume and the fume loadings are obtained from published or available data of similar installations or established through laboratory or pilot-plant scale tests. - If exhaust volume requirements must he established accurately, small scale modeling can he used to augment and calibrate the analytical approach. 

Once the appropriate dissolution conditions have been established, the method should be validated for linearity, accuracy, precision, specificity, and robustness/ruggedness. This section will discuss these parameters only in relation to issues unique to dissolution testing. All dissolution testing must be performed on a calibrated dissolution apparatus meeting the mechanical and system suitability standards specified in the appropriate compendia. 

All measuring and test equipment having an effect on the accuracy or validity of calibrations or tests shall be calibrated and / or verified before being put into service. The laboratory shall have an established program for calibration and verification of its measuring and test equipment."... 

Ensures that the inspection, measuring, and test equipment is capable of the accuracy and precision necessary Establishes, documents, and maintains calibration procedures, including details of equipment type, identification number, location, frequency of checks, check method, acceptance criteria, and the action to be taken when results are unsatisfactory Identifies, calibrates, and adjusts all inspection, measuring, and test equipment and devices that can affect product quality at prescribed intervals or, prior to use, against certified equipment having a known valid relationship to nationally recognized standards. Where no such standards exist, the basis used for calibration is documented. 

Once a valid calibration has been established, the calibration curve is stored in computer memory for ongoing usage. Modern NIR instmments are highly stable with respect to sensitivity drift, and extensive calibration and diagnostic test procedures have been developed which may be routinely applied to ensure this... 

Method validation makes use of a series of tests to determine its performance characteristics and to establish the method s acceptance for general use. The following are a list of criteria associated with the validation of a method selectivity and specificity, linearity and calibration, accuracy or trueness, range, precision, limit of detection, limit of quantification, ruggedness and application. 

The validation has the objective to identify, during the method development process, all sources of error and eliminate them or to quantify their contribution to the total uncertainty of the determination. For trace organic determinations particular attention must be given to the quantitative extraction and clean-up of all PCBs. Several types of adapted materials must be prepared to test all steps of the process (from simple calibrant solutions or mixtures, spiked extracts, to spiked soil material). CRMs should be used for validating trueness. Laboratory RMs must be prepared for the establishment of control charts when the method is under statistical control. 

The revised version of this guide gives an approach for the use of CRMs. After having validated his method (see Chapter 2) with intralaboratory tools, the analyst analyses the CRM. He calculates the mean value X of at least five determinations, possibly ten. These determinations have to be fully independent. This means that he starts five or more times from a fresh test sample and does a new calibration of the instrument. If the same operator does the job, in a short period of time, it can be considered as having being done under repeatability conditions (r). Otherwise a reproducibility value is established (R). Having calculated the mean X and the standard deviation... 

Instrumental and technical factors equipment within specification, working correctly, properly calibrated, procedures established for operational control and calibration, traceability of measurement to the criteria for test validity. 

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