Validation, component case studies

The thermodynamic treatment of systems in which at least one component is an electrolyte needs special comment. Such systems present the first case where we must choose between treating the system in terms of components or in terms of species. No decision can be based on thermodynamics alone. If we choose to work in terms of components, any effect of the presence of new species that are different from the components, would appear in the excess chemical potentials. No error would be involved, and the thermodynamic properties of the system expressed in terms of the excess chemical potentials and based on the components would be valid. It is only when we wish to explain the observed behavior of a system, to treat the system on the basis of some theoretical concept or, possibly, to obtain additional information concerning the molecular properties of the system, that we turn to the concept of species. For example, we can study the equilibrium between a dilute aqueous solution of sodium chloride and ice in terms of the components water and sodium chloride. However, we know that the observed effect of the lowering of the freezing point of water is approximately twice that expected for a nondissociable solute. This effect is explained in terms of the ionization. In any given case the choice of the species is dictated largely by our knowledge of the system obtained outside of the field of thermodynamics and, indeed, may be quite arbitrary. 

The chapter ends with a case study. Four different reduced kinetic models are derived from the detailed kinetic model of the phenol-formaldehyde reaction presented in the previous chapter, by lumping the components and the reactions. The best estimates of the relevant kinetic parameters (preexponential factors, activation energies, and heats of reaction) are computed by comparing those models with a wide set of simulated isothermal experimental data, obtained via the detailed model. Finally, the reduced models are validated and compared by using a different set of simulated nonisothermal data. 

Typically, a BMS is a mixture of software categories it is important, therefore, that the Validation Plan identihes what are the categories of software which make up the system, as well as incorporates the results of the system and component risk assessment into the overall validation strategy. Another important element that feeds into the validation plan is the result of the supplier audit. The validation life cycle presented here is consistent with GAMP Guidance and related case study material. - ... 

Table 111-4, modified and updated from similar tables presented by Chortyk and Schlotzhauer (722) and by Baker (171a), summarizes the major precursor relationships proposed and/ or demonstrated to date between tobacco leaf components and tobacco smoke components. These proposals are based in part on the results of a great variety of pyrolysis studies. In some cases, the validation of the proposals is based on the results obtained by addition of leaf components to tobacco and assessing the effect on the levels of specihc MSS components when the spiked tobacco is actually smoked in a... 

Kvalheim, O.M. Karstang, T.V. (1992). SIMCA-Classification by means of disjoint cross validated principal component models. In Multivariate Pattern Recognition in Chemometrics, illustrated by case studies, R.G. Brereton (Ed.), 209-245, Elsevier, ISBN 0444897844, Amsterdam, Netherland... 

Finally, a case study describing the application of the hybrid interference fitted-adhesive bonded joint technique on the automotive steel wheel system is presented. The study was carried out in collaboration with the MW company, a division of the CLN group. The business of MW concerns the steel wheel market for passenger cars, light and heavy commercial vehicles and motorcycles. Bonded wheel prototypes were submitted to static and dynamic mechanical tests adopted for components validation. The results obtained on bonded wheel prototypes were compared with the traditional welded wheels and with the samples tested at laboratory level. 

Table 1. The reasons for the apparent breakdown of the original principle have included chemical interaction between one couple and an intermediate species of the other, changes produced in the structure of the electrode surface and, most common of all, adsorption on the surface of a component of one couple that affected the electrode kinetics of the other. The underlying problem in these cases has been the untenable premise that each couple acts quite independently of the other and is not affected by the other s presence. However, as many of these studies have shown, the premise of additivity still applies whenever the interactions have been allowed for by carrying out the electrochemical experiments in an appropriate fashion. The validity of adding or superimposing electrochemical curves can therefore be considerably extended by restating the principle as follows ...

As we shall see, all relaxation rates are expressed as linear combinations of spectral densities. We shall retain the two relaxation mechanisms which are involved in the present study the dipolar interaction and the so-called chemical shift anisotropy (csa) which can be important for carbon-13 relaxation. We shall disregard all other mechanisms because it is very likely that they will not affect carbon-13 relaxation. Let us denote by 1 the inverse of Tt. Rt governs the recovery of the longitudinal component of polarization, Iz, and, of course, the usual nuclear magnetization which is simply the nuclear polarization times the gyromagnetic constant A. The relevant evolution equation is one of the famous Bloch equations,1 valid, in principle, for a single spin but which, in many cases, can be used as a first approximation. 

Methods which can be used to determine the size and shape of polysaccharides have been reviewed.107 (A critical survey of these has recently been given by Sadron108 and by Ogston.109) Special problems exist in the case of the undegraded starch components. In view of the branched nature of amylopectin and the large size of the amylose molecule, chemical methods of estimating size are inadequate, and it is questionable whether results are valid.38 The free components may also aggregate in aqueous solution. Study of derivatives is therefore more convenient, and the preparation of these is an essential preliminary to estimations of molecular size. 

If a secondary method is required during early phase development, a level 3 method is developed and validated to support phase 2b or early phase 3 clinical studies. This method should be capable of separating all components of interest identified up to this stage of pharmaceutical development. In cases where the initial primary method is still viable, the level 1-level 2 method may be maintained. As in early development, the use of an orthogonal method to evaluate DS generated via new synthetic schemes and to evaluate new formulations remains an important means of assuring that the primary method is sufficient for characterizing DS and DP. 

Although theoretical considerations are helpful to an understanding of the principles involved and may be useful for studying and predicting simple extractions of pure substances, an empirical approach ultimately must be resorted to for cases involving such complex and undefinable mixtures as kerosenes and lubricating oils. The ideal distribution law which states that the ratio of concentrations of a component distributed between two mutually insoluble phases is a constant dependent only on the temperature (K = C1/C2), is analogous to Henry s law for absorption and is rarely valid for commercial extraction problems. 

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