Preliminary validation experiments

Prior to beginning the validation activities, the following deliverables should be complete from the method development exercise and reports available (1) method robustness, (2) method optimization, (3) method specificity, (4) system suitability, (5) method procedure, and (6) preliminary validation experiments used to establish validation acceptance criteria. 

The suitability of a method for its intended use should be proven in initial experiments. These introductory studies should include the approximate precision, accuracy, detection limit, and working range. If these preliminary validation data appear to be inappropriate, either the method itself or the acceptance limits should be changed. The developer does not know whether the method conditions are acceptable until validation studies are performed. Results of validation studies may indicate that a change in the procedure is necessary, which may then require revalidation. In this way, method development and validation seems to be an iterative process during each developmental phase, key method parameters are determined and then used for all subsequent validation steps. 

If there is no or little information on the method s performance characteristics, it is recommended that the method s suitability for its intended use in initial experiments be proven. These studies should include the approximate precision, working range, and detection limits. If the preliminary validation data appear to be inappropriate, the method itself, the equipment, the analysis technique, or the acceptance limits should be changed. In this way method development and validation is an iterative process. For example, in liquid chromatography selectivity is achieved through selection of mobile-phase composition. For quantitative measurements the resolution factor between two peaks should be 2.5 or higher. If this value is not achieved, the mobile phase composition needs further optimization. 

Strawbridge K. B. and Hoff R. M. (1996) LITE validation experiment along California s coast preliminary results. Geophys. Res. Lett. 23, 73-76. 

A recent example is coupled T-H-M modelling of the Tunnel Sealing Experiment (TSX) in URL (Guo et al. 2002). To provide data for preliminary validation a surface laboratory experiment known as the Thermal Evaluation of Material Test (TEMT) was conducted. A steel vessel, 1.47 m long with an interior diameter of 0.74 m, was filled with a medium-grained sand and heated by circulating hot water. An array of thermistors monitored the evolution of temperature. Comparison between the physical test results and MOTIF simulation results. Figure 6, shows that MOTIF can be used to simulate convection dominated heat transfer in a porous medium. 

Another possibility is that the crossover between mean field and Ising critical behavior, which is spread out over many decades in 1 — TITc (68,69), also causes the exponents xi, X2, X3 in equation 10 to be effective exponents, which show a significant variation when one studies B N),cQ ), etc. over many decades in N. Usually experiments and simulations have only 1 to 2 decades in N at their disposal, and therefore all conclusions on the validity of equations 10 and 11 are still preliminary. However, experiments do allow a study of enough decades in 1 - T/Tcl to confirm the theoretical expectation that the critical exponents etc. take the values of the Ising universality class. 

Equation (2.28) shows that any plane of constant concentration propagates proportionally to the square root of time. Based on the above considerations, Eq. 2.28 may serve the dual function (a) it is useful for preliminary validation of the value of the experimentally obtained DC and (b) can be used for the preliminary estimation whether limited or semi-infinite diffusion model should be applied. These estimates are using the thickness of the sample and the experiment duration, as well as the predetermined possible range of DC values. Eor example, when experiment duration equals 1 h, a nonporous electrode with the thickness of few millimeters behaves as semi-infinite media when diffusion coefficients are greater than 10 cm s ... 

At sufficiently low strain, most polymer materials exhibit a linear viscoelastic response and, once the appropriate strain amplitude has been determined through a preliminary strain sweep test, valid frequency sweep tests can be performed. Filled mbber compounds however hardly exhibit a linear viscoelastic response when submitted to harmonic strains and the current practice consists in testing such materials at the lowest permitted strain for satisfactory reproducibility an approach that obviously provides apparent material properties, at best. From a fundamental point of view, for instance in terms of material sciences, such measurements have a limited meaning because theoretical relationships that relate material structure to properties have so far been established only in the linear viscoelastic domain. Nevertheless, experience proves that apparent test results can be well reproducible and related to a number of other viscoelastic effects, including certain processing phenomena. 

Two variables, the concentration of LSD-25 in the nebulizer and the inspiration time were varied. Experiments indicated that this technique of changing the response in this type of experiment has some validity. Table II summarizes the experiments. These preliminary experiments indicated to the writer tiiat the response of a well-tested subject was fairly regular since with a given dose of40,000 mcg-seconds (calculated administration of 56 meg) severe... 

Moreover, significant results may be obtained with very few cells. An experiment which may require 100 rats or 1000 humans in order to clarify some point may be statistically equally valid if 100 coverslip cultures or one microwell plate are used. If each cell is regarded as an independent experiment then one coverslip culture may yield more reliable results than a hospital full of people. This is obviously a major advantage as far as man is concerned but also overcomes the ethical problems which often arise when large numbers of animals are used for experimental purposes. However, in the final analysis, many experiments must be performed on whole animals, but this is no justification for not using cultured cells for the preliminary work. 

For the catalyst testing, several important points were taken into consideration. The catalyst was diluted in quartz sand in order to avoid hot spots and to allow a proper plug-flow of the gas through the reactor bed. The reaction conditions (amount of catalyst, feed gas composition, temperature) were chosen, such that the conversion of CH4 and O2 is limited. The so called kinetic regime is valid. Usually, several preliminary experiments or a lot of experience is necessary to determine the appropriate reaction conditions, but this is hardly mentioned in the final publication of the results. 

T wo questions immediately arise from these preliminary experiments 1. What is (are) the reason(s) for the different conversions and 2. in view of this difference, is the Kennedy-Gillham scheme valid for and can it be used in our intended investigation ... 

The availability, size, and surfaces or composition of the required equipment should be specifically identified so that the scale-up effort may be representative of a production run. A preliminary compatibility screen of contact surfaces should be completed before the selection of scale-up equipment. The location of the equipment in reference to other requirements, such as services or the packaging area, may be a factor in the selection of equipment. A cleaning-validation study should be conducted to ensure that no residues of active ingredient or cleaning agent remain after cleaning and that the equipment is suitable for production use again. Alternative equipment may be considered and used however, experience will dictate its suitability. 

A team of PwC professionals with experience in sustainability and the chemical industry reviewed the survey results and consulted with a panel of experts and practitioners from the industry for their perspective on what the raw numbers and responses indicated. We then developed our preliminary findings. We also identified additional issues where more structured discussion might elicit further insights and conducted two focus groups to better understand some of the findings and validate our overall conclusions. 

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