Validation evidence

There is no scientifically valid evidence that anti aging drugs presently on the market can increase longevity (Turnheim 2004), hence aging is still an inevitable process. 

A chemical for which there is scientifically valid evidence that it is a combustible liquid, a compressed gas, explosive, flammable, an organic peroxide, an oxidizer, pyrophoric, unstable (reactive) or water-reactive. 

Since 1974, evidence has accumulated in the literature which indicates that chromatin itself may be considered as an assembly system. It is true that chromatin is more complex than assembly systems analyzed to date, both with respect to the size of the nucleic acid involved and therefore the amount (and variety) of protein complexed with it and with respect to the dynamic aspect of the multilevel higher order structure. Nevertheless, at least at the lower levels of organization, the interpretation of chromatin as an assembly system may be valid. Evidence for this derives from three basic lines of research described in previous sections (1) the reconstitution of the nucleosome, (2) the self-assembly of the octamer, and (3) the putative self-organization of nucleosomes into higher order structures. 

Each event or condition should be based upon valid evidence or, if presumptive, shown by dotted rectangles or ovals. 

The documentation of procedures to be followed, including training outlines and manuals, are an important part of the validation evidence. Accompanying that documentation should be an expert review for appropriateness and a confirmatory observation to determine the degree to which those documented procedures reflect the reahties of the laboratory. 

Since the most significant portion of validation evidence rests upon ethos proof, the credentials of the validators are of utmost importance. The credibility of their collective testimony relies upon both their expertise and the objectivity of their conclusions. That expertise is a matter of education and training, experience, and access to appropriate tools and... 

Guyatt, G.H., Sackett, D.L., and Cook, D.J. (1993) Users guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid Evidence-Based Medicine Working Group./AMA 270 2598-2601. 

Ellis and Honeyman80 have raised strong doubts as to the validity of the structural determinations that have been applied to glycosylamines these doubts are based on the fact that such compounds are readily isomerized, as evidenced by their mutarotation. The formation of a trityl ether cannot be considered valid evidence for the presence of a primary hydroxyl group in the compound tritylated, and periodate oxidation, which is often excessive, may lead to faulty conclusions. 

Since 1990, most firms have found the predistribution three-lot requirement practical and useful. Some have made the mistake of believing that critical parameters should be varied during the three runs in order to develop new validation evidence, usually of the kind that can be developed in the laboratory or pilot plant more economically and with less risk of failure. 

The outlier result should only be used along with a preponderance of other scientifically valid evidence to provide additional support to invalidate an OOS result. It alone cannot identify the source of an extreme result and thus should not be used as the exclusive reason to invalidate. 

In 1983 the FDA issued what became known as the Blue Book (because of the color of its cover). This publication gave guidance to inspectors on what was reasonable to accept as validation evidence for computer systems. The Blue Book formally introduced the expectation of a documented life-cycle approach to validation. The aim was to build quality into software from the earliest stages of the life cycle (quality assurance) rather than vainly trying to test quahty in at the end (quality control). 

During regulatory inspections, the Validation Plan can be presented with a Validation Report or Validation Summary Report to demonstrate that a particular computer system has been validated. These documents provide a regulator with additional detail to the Validation Determination document and Validation Certificate but without digressing into the supporting validation evidence. 

The FDA will consider the lack of computer validation as a significant inspection finding and log it as a 483 noncompliance citation. The MHRA may take a more lenient view depending on the criticality of the system on GxP operations. The lack of a detailed written description of an individual computer system (kept up to date with controls over changes), its functions, security and interactions (EU GMP Annex 11.4) a lack of evidence for the quality assurance of the software-developed process (EU GMP Annex 11.5), coupled with a lack of adequate validation evidence to support the use of GxP-related computer systems may very well be either a critical or major deficiency. Ranking will depend on the inspector s risk assessment. 

Typically, the validation evidence for a SCADA system is created and approved through system development. Large systems are often formed of smaller subsystems and integrated during development and start-up efforts. Care should be taken to avoid using checklists as a substimte for validation deliverables or quality assurance reviews checklists simply indicate the presence or absence of required validation products. 

Documents should include written statements by responsible personnel regarding the acceptability of validation evidence. These conclusions may be documented at various stages. When reviewing validation documents, look for evidence that data are available and consistent these should have a stated conclusion. Validation checklists, punch lists, and the final summary report are considered historical documents. 

Some years later a strong rebuttal was made by these groups to the criticism by Kronman and Bratcher (1983). Permyakov et al. (1987) stated that there is no valid evidence of artifact in their determinations and... 

By contrast, there was no valid evidence of a genotoxic effect on somatic cells of cats chronically exposed to methylmercury orally (Miller et al. 1979). However, only minimal toxicity was observed at the high dose (0.046 mg Hg/kg/day) in this study. Doses of 0.86, 1.7, or 3.4 mg Hg/kg as methylmercury hydroxide administered once by intraperitoneal injection to groups of 2 male CBA mice did not cause an... 

Smith s placement model, which is based upon multiple types of validation evidence.) This study was singularly focused on strengthening the curriculum-assessment connection between placement readers evaluations and the writing program s curricular values. 

Exactly what kind of evidence of validation is required How much evidence is sufficient to establish clear control These questions can be answered through an examination of two dimensions. Validation evidence falls into six broad issue categories further defined by two cross-matrices of risk and application. Before defining these two cross-matrix dimensions, though, a detailed description of the issue categories will be helpful. 

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