Analytical methods about manufacturing process

These two examples demonstrate how analytical methods provide useful information about the manufacturing processes. Analytical methods are developed to provide information about a particular process. Accordingly they are developed concurrently with the manufacturing process and reflect that process. If they are to be used to provide information about drug... 

If you are in charge of quality control laboratories in manufacturing companies, it is important to distinguish between the variability of a product and the variability of the analysis. When analyzing tablets on a pharmaceutical production line, variability in the results of an analysis has two contributions from the product itself and from the analytical procedure. Your bosses are interested in the former, and you, the analyst, must understand and control the latter. It is usually desired to use methods of analysis for which the repeatability is much less than the variability of the product, in which case the measured standard deviation can be ascribed entirely to the product. Otherwise, analysis of variance can be used to split the total variance of duplicate results into its components (chapter 2). In the discussion that follows, the emphasis is on measurement variability, but the principle is the same, and the equations and methods can be used directly to obtain information about the product or manufacturing process. 

During the last forty years a great deal has been learned, both by model studies and by the application of sophisticated analytical methods to foods, about the chemistry which accounts for these flavors. To date, however, there is little or no evidence that the in-depth chemical information has had any impact on the processes by which authentic, "natural" foods are manufactured. 

There are no comprehensive data files for CD spectra for SRM s that compare with the many exhaustive files for absorbance data, either electronic or vibrational. Nor is there a plan in place to compile such a compendium. Analysts are required therefore to prepare their own reference files using whatever SRM s might be available from the usual manufacturers of fine chemicals. An obvious difficulty associated with this endeavor is the fact that although these materials are certified to be chemically pure few are ever certified to be 100% enantiomerically pure. More likely than not, these few materials have natural, rather than synthetic, origins. In actuality such materials probably do not exist. If they do, proof of their absolute enantiomeric purity is beyond the capabilities of currently available analytical methods [31]. Tn addition enantiomeric purity can be a time dependent transient state for materials that are prone to racemization, a process that is most likely for chiral liquids and chiral solutes in solution. It is not possible therefore to speak with conviction about exact molar ellipticity values. 

The original manufacturing formula (HV) and five variations are performed in the first step of the synthesis. Six samples are analysed. The results of these six analyses are used to assess the validation of this process step. In this case validation of the analytical method is a prerequisite for any decision that is made about the validity of the process. This information is needed before the process research chemist can start variations of the process otherwise it is possible that the data received cannot be assessed. The difficulty of assessing the data of the process validation results from the fact that the data is influenced by the analytical method and the uncertainty of the chemical process. If the uncertainty of the analytical method is larger or in the same range as the variations of the chemical process, assessment of the data is not possible. 

Let s discuss now some possible statistical approaches for evaluating the data obtained from development or scale-up activities, to learn all there is about the process prior to transfer to manufacturing. In addition, let s see how this data can be used to establish practical and reasonable in-process requirements and acceptance criteria for the process and product as we enter the process validation phase. The examples used in the following sections are of solid dosage forms, although the techniques are certainly applicable to other dosage forms and also analytical method development. 

ELISA tests are used widely for the detection of contaminants both in analytical laboratories and in the food industry. Commercial kits are generally used, as they have the advantage of containing all the materials necessary to run the tests (in some cases the preparation of solutions is required). They meet performance specifications set by the manufacturer, which are evaluated by the end user to see if the method is suitable for his or her application (processed food, type of matrix, etc.). Quantitative tests require the use of a microplate or strip reader. Some commercial ELISA kits are available on the market for the detection of soy allergens [12,13] (see Table 17.1 for performance parameters). The column raw and processed food relates to information provided by the manufacturer about the applicability to raw and processed food. 

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