Validation of the analytical method

In chemical analysis the property of interest to be determined, e.g. trace elements or organic substances, is rarely directly measurable, as may be the case in physical 

Validation of a method consists in establishing a number of properties and quantifying performance criteria that will demonstrate that the method achieves the requested performances for a given purpose. These criteria are described below. 

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Validation of the analytical methods for food of animal origin has to be performed with milk, egg, meat, and fat. The latter is required only if log Pqav is >3 and metabolism studies indicate significant residues in fat, because in this case it is likely that an MRL will be set. Other tissues such as kidney or liver must be validated only if an MRL is set or proposed for these tissues. The issue of the general necessity of analytical methods for food of animal origin is not addressed in Directive 96/46/EC or SANCO/825/00. At this moment, the Working Group Pesticide Residues proposes an MRL on a case-by-case basis. However, a pragmatic approach is presented in SANCO/825/00. 

M. Careri, L. Elviri and A. Mangia, Liquid chromatography-electrospray mass spectrometry of /J-carotene and xanthophylls. Validation of the analytical method. J. Chromatogr.A 854 (1999) 233-244. 

Test methods used in the laboratory are generally derived from pharmacopoeias such as the US Pharmacopoeia, British Pharmacopoeia, or European Pharmacopoeia. For test methods that are not from recognized pharmacopoeias, validation of the analytical methods is required. The validation includes testing for accuracy, specificity, ruggedness, robustness, precision, detection limit, quantitation hmit, and range. A discussion of analytical methods vahda-tion is presented in Section 9.6.5. 

Fitness for purpose is the ultimate goal of the person doing the job in the laboratory, especially for the choice of method and instrumentation used to carry out an analysis. The validation of the analytical method is the important part to guarantee the fitness. 

In analytical chemistry, validation of the analytical methods is of utmost importance [4,5]. One of the aspects of this validation is the robustness of analytical methods against variations in experimental circumstances. The term experimental circumstances is very broad it might even include inter-laboratory variation. In this book, only intra-laboratory experimental conditions are considered. No explicit attention is given to inter-laboratory variations, although some of the presented methodology might be useful in that area. 

Validation of the analytical method running on that equipment... 

PQ should be performed on a daily basis or whenever the instrument is used. The test frequency not only depends on the stability of the equipment but on everything in the system that may contribute to the results. For a liquid chromatograph, this may be the chromatographic column or a detector s lamp. The test criteria and frequency should be determined during the development and validation of the analytical method. 

Some critical differences in risk assessment procedure lead to confusing situations on a worldwide basis. These differences are due to some very controversial areas of safety issues including the calculation of the acceptable daily intake (ADI), the assignment of the ADI to maximum residue limit (MRL)/tolerance, the validation of the analytical methods needed to regulate drug residues, and the fitness of legislation to toxicology. 

How much validation of the analytical methods used for stress-testing studies is appropriate ... 

When the analytical laboratory is not responsible for sampling, the quality management system often does not even take these weak links in the analytical process into account. Furthermore, if sample preparation (extraction, cleanup, etc.) has not been carried out carefully, even the most advanced, quality-controlled analytical instruments and sophisticated computer techniques cannot prevent the results of the analysis from being called into question. Finally, unless the interpretation and evaluation of results are underpinned by solid statistical data, the significance of these results is unclear, which in turn greatly undermines their merit. We therefore believe that quality control and quality assurance should involve all the steps of chemical analysis as an integral process, of which the validation of the analytical methods is merely one step, albeit an important one. In laboratory practice, quality criteria should address the rationality of the sampling plan, validation of methods, instruments and laboratory procedures, the reliability of identifications, the accuracy and precision of measured concentrations, and the comparability of laboratory results with relevant information produced earlier or elsewhere. 

Developing the validation protocol is a crucial step in the validation process. It is the culmination of the regulatory and technical accomplishments to this point in the development of the method. The protocol must define which validation parameters are needed and the specific experiments necessary to demonstrate the validity of the analytical method. The protocol must contain all of the acceptance criteria for each of the relevant validation parameters. Additionally, the protocol must define the number of replicates, the reporting format, and the number of significant figures. In short, the validation protocol instructs the analyst on how to validate the analytical method. 

Validation of the Analytical Method as a Precursor to Cleaning Validation... 

Data Elements Use this section to provide thorough and complete documentation of the validation of the analytical method. Include summaries of experimental data and calculations substantiating each of the applicable analytical performance parameters. These parameters are described in the following section. 

Validation of the analyticed methods and justification of the choice of routine tests and reference substances. 

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. 

The estimation of uncertainty replaces a full validation of the analytical method. It generates the necessary information at the right time. The statistical information received from the analysis can be used for the interpretation of the data and finally the analysis is designed to the customers needs. In this case measurement uncertainty is a good alternative to validation. 

The primary objective of the validation of the analytical method (see section 2.1.3.) is to establish the traceability of the result to the recognised reference (pure substance, characterised organism or CRM) in absolute terms or through a well established method. In practice traceability implies the existence of means to recover and verify the information. 

Figures 2.16 a and b summarise where RMs and CRMs can be used in the case of type III and type II methods. Two main categories exist materials certified or not for the calibration of the instruments and materials for the validation of the analytical method RMs for the precision and development and control of the method, CRMs for establishing the accuracy...

Method Validation. Validation of the analytical methods used to support the process validation, cleaning validation, in-process testing, and release testing of the product. 

Martin-Smith M and Rudd DR (1990) The importance of proper validation of the analytical methods employed in the quality control of pharmaceuticals. Acta Pharmaceu-tica Yugoslavia 40 7-19. 

The validation of the analytical method is carried out by comparing its results with that of the FEM finite elements model. The graph in the following figure shows the results of the two methods in the axes of coordinates H and L previously defined (figure 7). 

The method is also depi. ndent, of course, on the degree of quality assurance exercised to assure that the physical system matches the risk projection model being used. A final consideration is the validity of the analytical methods utilized to generate the consequence data. 

For products described in a pharmacopoeia, the official specifications can and should be used for the product file, with referral to the official source. The same applies to preparations from standard formulatimis, in which quality requirements are included. For in-house formulations, the quality requirements have to be set by an appropriately competent person internally. Useful information can be found in the formulatimi or validatimi studies. The results of stability studies may be useful when setting the quality requirements for the product, because the premise is that a preparation should comply to the quality requirements throughout the whole shelf life. An overview of the applicable quality requirements, including supporting information, has to be included in the product file. In addition it should be specified how the packaging and labelling are checked, and how and with what analytical method the product quality is controlled. Additionally the validation of the analytical methods is included in this section of the product file. 

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