Accuracy experiment

For a drug substance, the accuracy experiment should demonstrate that the method is free from the interference of process impurities and... 

The ICH recommends that repeatability be assessed using a minimum of nine determinations covering the specified range for the procedure (e.g., three concentrations/three replicates as in the accuracy experiment) or using a minimum of six determinations at 100% of the test concentration. Reporting of the standard deviation, relative standard deviation (coefficient of variation), and confidence interval is required. The assay values are independent analyses of samples that have been carried through the complete analytical procedure from sample preparation to final test result. Table 1 provides an example set of repeatability data. 

A minimum of nine determinations covering the specified range for the procedure (e.g., three concentrations/three replicates as in the accuracy experiment), or... 

Prepare the test and control solutions from the aforementioned sample according to the method of test solutions selected and the control solutions preparation procedure specified in the limit test method in the Specifications and Testing Methods. Use these solutions to determine the quantity of heavy metal by the same calibration curve from the accuracy experiment. This procedure is repeated for each test solution. 

The filter compatibility and accuracy experiments should provide analysis values within the precision of the DS method. The specificity experiment should also show no interference from placebo components or degradants. If these criteria are met, there is a high level of confidence that method validation will prove successful. Any values outside the expected range would necessitate method modification with a subsequent feasibility study. 

Whereas the selectivity experiments for the first approach can be performed during a pre-validation phase (no need for quantification), those for the second approach are usually performed together with the precision and accuracy experiments during the main validation phase. 

An accuracy experiment can often be considered as a practical test of the adequacy of the standard measurement method. One of the main... 

Meanwhile, these effects are in no way included in the usual measures of accuracy as they result from a method-performance study in accordance with the accepted protocols [24, 25]. The accuracy experiment defined by ISO 5725 (Ref. 24, Part 1, Section 4) does not presuppose any variable matrix-dependent contribution, being... 

DESIGN OE THE VALIDATION EXPERIMENTS Precision and Accuracy Experiment Robustness Experiment... 

In certain cases a difficulty occurs in the calculation of the results this consists in the formation of new and unknown endothermic compounds, an occurrence which, though very interesting, is difficult to take into account. It would therefore constitute a great advance if the maximum temperature of the explosion, in addition to the maximum pressure, could be measured with the necessary accuracy. Experiments with this object have, however, not yet led to any satisfactory results possibly it will be easier to make use of the temperature of freely burning flames to obtain supplementary assistance. 

The accuracy of the method is a measure of how close to the true value the results from the method are. Accuracy is usually checked by preparing samples spiked with known amounts of the component of interest. The accuracy should be examined over a range that extends beyond the range of samples the method is likely to analyse. If the method is designed to measure samples at 100% of expected strength then it would be useful to check the accuracy at that value and at 80% and 120% of the expected strength. Results from the accuracy experiments should normally agree to within 2% of the true value. 

The accuracy of our calculations is strongly dependent on the accuracy of the experimental data used to obtain the necessary parameters. While we cannot make any general quantitative statement about the accuracy of our calculations for multicomponent vapor-liquid equilibria, our experience leads us to believe that the calculated results for ternary or quarternary mixtures have an accuracy only slightly less than that of the binary data upon which the calculations are based. For multicomponent liquid-liquid equilibria, the accuracy of prediction is dependent not only upon the accuracy of the binary data, but also on the method used to obtain binary parameters. While there are always exceptions, in typical cases the technique used for binary-data reduction is of some, but not major, importance for vapor-liquid equilibria. However, for liquid-liquid equilibria, the method of data reduction plays a crucial role, as discussed in Chapters 4 and 6. 

Figure 1 compares data reduction using the modified UNIQUAC equation with that using the original UNIQUAC equation. The data are those of Boublikova and Lu (1969) for ethanol and n-octane. The dashed line indicates results obtained with the original equation (q = q for ethanol) and the continuous line shows results obtained with the modified equation. The original equation predicts a liquid-liquid miscibility gap, contrary to experiment. The modified UNIQUAC equation, however, represents the alcohol/n-octane system with good accuracy. 

While many methods for parameter estimation have been proposed, experience has shown some to be more effective than others. Since most phenomenological models are nonlinear in their adjustable parameters, the best estimates of these parameters can be obtained from a formalized method which properly treats the statistical behavior of the errors associated with all experimental observations. For reliable process-design calculations, we require not only estimates of the parameters but also a measure of the errors in the parameters and an indication of the accuracy of the data. 

Two different types of calibration marks are used in our experiments, planar circles and circular balls. The accuracy of the calibration procedure depends on the accuracy of the feature detection algorithms used to detect the calibration marks in the images. To take this in account, a special feature detection procedure based on accurate ellipses fitting has been developed. Detected calibration marks are rejected, if the feature detection procedure indicates a low reliability. 

In this section results will be presented using test samples to determine the accuracy of our approach. Further on an example is shown using the system to analyse casting defects. For the experiments moderate projective magnifications between 1.1 and 1.4 were chosen. The test samples used to determine the accuracy of calibration, 3D defect position and volume estimation consist of several holes representing internal defects of different but known size and shape. 

After having proved the principles a dynamic test facility has been constructed. In this facility it is possible to inject 3 tracers in a flownng liquid consisting of air, oil and water. By changing the relative amounts of the different components it is possible to explore the phase diagram and asses the limits for the measurement principle. Experiments have confirmed the accuracy in parameter estimation to be below 10%, which is considered quite satisfactorily for practical applications. The method will be tested on site at an offshore installation this summer. 

The accurate and absolute measurement of the distance, D, between the surfaces is central to the SFA teclmique. In a typical experiment, the SFA controls the base position, z, of the spring and simultaneously measures D, while the spring constant, k, is a known quantity. Ideally, the simple relationship A F(D) = IcA (D-z ) applies. Since surface forces are of limited range, one can set F(D = go) = 0 to obtain an absolute scale for the force. Furthennore, SF(D = cc)/8D 0 so that one can readily obtain a calibration of the distance control at large distances relying on an accurate measurement of D. Therefore, D and F are obtained at high accuracy to yield F(D), the so-called force versus distance cur >e. 

Accuracy, however, in biomolecular trajectories, must be defined somewhat subjectively. In the absence of exact reference data (from experiment or from an analytical solution), the convention has been to measure accuracy with respect to reference trajectories by a Verlet-like integrator [18, 19] at a timestep of 1 or 0.5 fs (about one tenth or one twentieth the period, respectively, of the fastest period an 0-H or N-H stretch). As pointed out by Deufihard et al. [20], these values are still larger than those needed to... 

The many approaches to the challenging timestep problem in biomolecular dynamics have achieved success with similar final schemes. However, the individual routes taken to produce these methods — via implicit integration, harmonic approximation, other separating frameworks, and/or force splitting into frequency classes — have been quite different. Each path has encountered different problems along the way which only increased our understanding of the numerical, computational, and accuracy issues involved. This contribution reported on our experiences in this quest. LN has its roots in LIN, which... 

These various techniques were recently applied to molecular simulations [11, 20]. Both of these articles used the rotation matrix formulation, together with either the explicit reduction-based integrator or the SHAKE method to preserve orthogonality directly. In numerical experiments with realistic model problems, both of these symplectic schemes were shown to exhibit vastly superior long term stability and accuracy (measured in terms of energy error) compared to quaternionic schemes. 

The preferable theoretical tools for the description of dynamical processes in systems of a few atoms are certainly quantum mechanical calculations. There is a large arsenal of powerful, well established methods for quantum mechanical computations of processes such as photoexcitation, photodissociation, inelastic scattering and reactive collisions for systems having, in the present state-of-the-art, up to three or four atoms, typically. " Both time-dependent and time-independent numerically exact algorithms are available for many of the processes, so in cases where potential surfaces of good accuracy are available, excellent quantitative agreement with experiment is generally obtained. In addition to the full quantum-mechanical methods, sophisticated semiclassical approximations have been developed that for many cases are essentially of near-quantitative accuracy and certainly at a level sufficient for the interpretation of most experiments.These methods also are com-... 

Though the results obtained were relatively few in number, they conformed fully to Graham s relation within the experimental accuracy. Sub sequently further evidence has been provided by the accurate experiments of... 

The number of ethylenic linkages In a given compound can be established with accuracy by quantitative titration with perbenzoic acid. A solution of the substance ajid excess of perbenzoic acid in chloroform is allowed to stand for several hours at a low temperature and the amount of unreacted perbenzoic acid in solution is determined a blank experiment is run simultaneously. 

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