Model development with validation

In addition to the somewhat empirical and difficult development of NIR applications, thorough documentation must be produced. NIR methods have to comply with the current good manufacturing practice (cGMP) requirements used in the pharmaceutical industry. Various regulatory aspects have to be carefully considered. For example, NIR applications in classification, identification, or quantification require extensive model development and validation, a study of the risk impact of possible errors, a definition of model variables and measurement parameters, and... 

Does the above described complexity allow one to reliably predict thermodynamic solubility for drug candidates While we think that this is impossible at present, we believe it is realistic to make compound rankings for solubility behavior, provided that the model used is trained appropriately. VolSurf offers a solubility model developed with controlled literature data and in-house solubility data. Although the solubility error in the prediction phase can be evaluated in 0.7 log units (not suitable to rank the solubility of very similar compounds), the model can still be valid to filter compounds with calculated solubility below a certain threshold. 

Step 4 POL test in an experimental model) The mechanistic models developed are validated with experimental data. The experiments are inevitably reductionist, but for most high-order behaviors, there will be strong systems interactions making reductionist analysis complicated. Therefore, there will be a tension between this tendency to oversimplify the model at the experimental level and the theoretical goodness of the model. In order to strengthen the convergence between the observational and mechanistic models, two principles are applied ... 

In snmmary, although improvements in model development and validation procedures would be beneficial, it is unlikely that a universal protocol will be adopted due to the diversity of PB/PK models. As with any modeling endeavor, the modeler should have a clear idea of which parameter estimation procedures will be employed so that experiments may be designed properly. Methods to estimate specific model parameters are given below. 

Deleebeeck, N.M., K.A. De Schamphelaere, and C.R. Janssen. 2009. Effects of Mg(2+) and H(+) on the toxicity of Ni(2+) to the unicellular green alga Pseudokirchneriella subcap itata Model development and validation with surface waters. Sci. Total Environ. 407 1901-1914. 

The PCA models developed with the training samples (calibration samples in PLS analysis) classify the validation samples with almost 100% certainty. This again illustrates the effectiveness of the PCA model in classifying the samples. The data profiles of the 75 oil mixtures (15 from each adulterant) that were set aside were classified by the PCA model developed above. 

Simpson, R., Almonacid, S., and Mitchell, M. Mathematical model development, experimental validation, and process optimization Retortable pouches packed with seafood in cone frustum shape. J. FoodEng., 63(2), pp. 153-162 (2004). 

In the first example of applications of the theory in this chapter, we made a point with respect to the polarizability of molecules and showed how the problem could have been handled by the RISM-SCF/MCSCF theory. However, the current level of our method has a serious limitation in this respect. The method can handle the polarizability of molecules in neat liquids or that of a single molecule in solution in a reasonable manner. But in order to be able to treat the polarizability of both solute and solvent molecules in solution, considerable generalization of the RISM side of the theory is required. When solvent molecules are situated within the influence of solute molecules, the solvent molecules are polarized differently depending on the distance from the solute molecules, and the solvent can no longer be neat. Therefore, the polarizable model developed for neat liquids is not valid. In such a case, solvent-solvent PCF should be treated under the solute... 

Ocean-Atmosphere Interactions. To determine how the ocean responds to a C02-induced climate forcing, it will be necessary to develop a combined ocean and atmospheric general circulation model. It will take 10-20 years to develop a model with appropriate chemistry and biology to the level of confidence necessary to make valid projections. In the interim, two approaches can be pursued in parallel with this model development. 

Modelling is a process of continuous development, in which it is generally advisable to start off with the simplest conceptual representation of the process and to build in more and more complexities, as the model develops. Starting off with the process in its most complex form, often leads to confusion. A process of continuous validation is necessary, in which the model theory, data, equation formulation and model predictions must all be examined repeatedly. In formulating any model, it is therefore important to... 

The temperature with large columns may not be homogenous. A mathematical model of the effect of a radial temperature gradient has been developed and validated on octadecyl-packed columns of 11-15 cm diameter... 

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