Holistic testing

Detector linearity would normally be tested as part of an overall holistic test that examines the linearity of the complete instrument, the injector, as well as the detector. The test would normally be designed to cover the range up to 2 absorbance units (AU). 

Performance Qualification Performance qualification is the process that provides documented evidence to demonstrate that the instrument has fulfilled the user requirements. Holistic testing which involves all the functional components in the system is required for the PQ testing. Performance qualification can be demonstrated by running a typical application that requires all the modules to function together as a whole system to deliver the intended application and the expected results. 

The performance of an HPLC system can be evaluated by examining the key functions of the various modules that comprise the system, followed by holistic testing that challenges the performance of the HPLC components as an integrated system. The holistic testing is commonly referred to as the performance qualification (PQ). The holistic test can be as simple as running a frequently used HPLC method in the laboratory. Modular testing of various components, which is... 

If a system comprises several modules, it is recommended that system tests be performed for parameters that are affected by multiple modules (holistic testing) rather than performing tests module by module (modular testing). Individual module tests should be performed if the parameter is affected by that module only (e.g., the wavelength accuracy of an HPLC variable-wavelength detector or the temperature accuracy of a column compartment). 

Most laboratory systems require maintenance and inclusion preventative maintenance programmes. Therefore any holistic testing should form part of Performance Qualification to ensure on-going compliance. 

The type and degree of validation of a computerized analytical system depends on its complexity. For example, the functions of a simple, computer-controlled system, with little or no flexibility regarding data input or evaluation, can be verified by execnting holistic tests and by comparing the test results with anticipated results. On the other hand, a more complicated compnterized system with on-line databases and extensive flexible data evalnation requires complex validation. 

When the intended aim is to change a formula, reduce costs or duplicate a formula, an evaluation is sought. Holistic tests (with same-different or triangular tests) can be used in the context of a similarity-based approach (beta risk). In practice, these tests can certainly be implemented, but at project team level they are impossible to manage because of insufficient participants. Rework of products is also difficult, because these tests do not provide any information on how products differ. We have therefore formalized an approach that can evaluate proximity between tests and a reference product. 

The holistic thermodynamic approach based on material (charge, concentration and electron) balances is a firm and valuable tool for a choice of the best a priori conditions of chemical analyses performed in electrolytic systems. Such an approach has been already presented in a series of papers issued in recent years, see [1-4] and references cited therein. In this communication, the approach will be exemplified with electrolytic systems, with special emphasis put on the complex systems where all particular types (acid-base, redox, complexation and precipitation) of chemical equilibria occur in parallel and/or sequentially. All attainable physicochemical knowledge can be involved in calculations and none simplifying assumptions are needed. All analytical prescriptions can be followed. The approach enables all possible (from thermodynamic viewpoint) reactions to be included and all effects resulting from activation barrier(s) and incomplete set of equilibrium data presumed can be tested. The problems involved are presented on some examples of analytical systems considered lately, concerning potentiometric titrations in complex titrand + titrant systems. All calculations were done with use of iterative computer programs MATLAB and DELPHI. 

Because of their wide-ranging and holistic character, assays of behavioral effects have been used as screening procedures when testing for neurotoxicity (see, for example, Iversen 1991, Tilson 1993). They can provide sensitive indications of neurotoxic disturbances, which can then be traced back to their ultimate cause by using mechanistic biomarker assays. 

Regarding OQ validation, if one has only an isocratic pump available, it is recommended that one does not perform a detector linearity test at this time. However, this test can be subsequently performed as part of either the PQ validation or individual method validation, both of which typically test the performance of the system as a whole (holistically). 

As stated earlier, these tests should be designed to test that the HPLC system, in its entirety, is performing in accordance with the pre-approved user requirements (URS) for routine operation. Ultimately, the best way to do this is to test the system as holistically as possible. 

It would be quite difficult to incorporate this test holistically. One would need to perform the test by using a very consistent... 

This test could conceivably be performed holistically, as part of the injection reproducibility test (defined later). Using retention time as an indicator, such an approach would work provided the retention time for a test component was very stable from week to week. However, this is often not that easy to control consistently, since one often encounters column/mobile phase variations and other variables. Therefore, flow accuracy is typically not tested in this manner. 

Following pre-installation qualification and the actual installation of an HPLC system, both the IQ and the OQ protocols should be implemented, back to back, soon after the installation. Again, the IQ is used to verify that the installation of the system was successful, with all instrument components powering-up properly. The OQ follows, verifying that the system components perform as they were functionally specified by the vendor. Finally, the PQ protocol serves to verify that the system as a whole performs to the URS established by the user and within the functional limitations of the system as a whole. As part of the PQ, it is recommended to test the system as a whole, called holistic validation. This... 

When it comes to performance qualification, a holistic approach must be taken to test the analytical system with all the necessary modules working together to deliver the intended applications as specified in the user requirement (Figure 3). The proper functioning of each individual module of the analytical system does not... 

There are some existing texts that cover the material in this book, but I have tried to take a holistic view of quality assurance at a level that interested and competent laboratory scientists might learn from. I am continually surprised that methods to achieve quality, whether they consist of calculating a measurement uncertainty, documenting metrological traceability, or the proper use of a certified reference material, are still the subject of intense academic debate. As such, this book runs the risk of being quickly out of date. To avoid this, I have flagged areas that are in a state of flux, and I believe the principles behind the material presented in this book will stand the test of time. 

A recently developed technology takes a different approach to solving the stress problem (14). Rather than chemically plasticizing the sulphur, non-reactive additives are used to holistically plasticize the sulphur concrete mix. In essence these additives are lubricants which operate at the sulphur/aggregate interface to allow slippage and stress relief without disruption and cracking. The apparent permanency of this plasticization approach has been demonstrated by extensive testing over a four year period. 

The development of green Foodomics runs parallel to the improvement and design of techniques able to assess the environmental impact of the different protocols/processes/operations involved. At present several techniques can be found in the literature to test, for instance, the impact of analytical chemistry methods (such as the Greeness profile, the HPLC-EAT, or the Analytical Eco-Scale) and the environmental impacts associated with a product or process, over its entire life cycle (such as Life Cycle Assessment). Nevertheless, techniques able to provide a more holistic view of the different aspects... 

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