Validation test establishment fundamentals

Operational checks are normally presenting process control computer systems. These systems may contain code that is part of the master production record. At the system level, the purpose of operational checks is to execute algorithms, sequencing of operations, and safety-related functions as required in the applicable customer specification. Inspections and testing are fundamental processes to be performed during the validation of critical system sequences. In addition, an ongoing program must be established to frequently verify that critical operations occur in the proper sequence. 

The RNA world hypothesis provides a convenient focus for new experiments that will not only test its validity but will fundamentally advance our knowledge of nucleotide chemistry and RNA catalysis. Several critical experiments should more fully establish (or eliminate) the idea that the forebears of modem life were replicating RNA molecules. 

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. 

It is generally recognized and accepted that analytical methods must be suitable for the intended use. Furthermore, EU Directives 85/591/EEC, 89/397/EEC and 93/99/ EEC state that analytical procedures for compliance testing with food laws are to be carried out on the basis of validated methods. Method validation is known as the process used to confirm that a procedure is fit for a particular analytical purpose. This process, an essential part of analytical quality assurance, can be described as the set of tests used to establish and document performance characteristics of a method. The performance characteristics of a method are experimentally derived values for the fundamental parameters of importance in assessing the suitability of the method (Horwitz 1988, 1995 Thompson and Wood 1993, 1995 Eurachem 1996 FAO 1998 US EPA 1995 US FDA 1993a). These parameters include ... 

The primary objective of method validation is to provide a high degree of assurance that the specified method consistently provides accurate test results that evaluate a product against its defined specification and quality attributes (Chapter 12). The regulations require that validation data be available to establish that the analytical procedures used in testing meet proper standards of accuracy and reliability. All analytical procedures require some form of validation, regardless of whether the method is used for stability, in-process analysis, release, or acceptance. Most of the discussions focus on the validation of HPLC methods using assay and purity determinations nevertheless, fundamentals of the approach can be applied to most method validation activities. 

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