European Union analytical methods

Assessment of residue analytical methods for crops, food, feed, and environmental samples the approach of the European Union... 

Validation of analytical methods for post-registration control and monitoring purposes in the European Union... 

Until 1991, manufacturers seeking authorizations for pesticides had to fulfil country-specific requirements of validation of enforcement methods. The term enforcement method means analytical methods which are developed for post-registration control and monitoring purposes. The harmonization of these requirements was initiated with the European Economic Community (EEC) Council Directive 91/414/EEC and temporarily finalized with the Guidance Document on Residue Analytical Methods SANCO/825/00 rev. 6, dated 20 June 2000 [Santd et Protection des Consommateurs (SANCO)]. The evaluation of validation studies by the competent authority is conducted by comparison of these European Union (EU) requirements with the study results and most often without any practical experience of the method. Some details of this evaluation are discussed below. 

Water for injection (WFI) is the most widely used solvent for parenteral preparations. The USP requirements for WFI and purified water have been recently updated to replace the traditional wet and colorimetric analytical methods with the more modern and cost-effective methods of conductivity and total organic carbon. Water for injection must be prepared and stored in a manner to ensure purity and freedom from pyrogens. The most common means of obtaining WFI is by the distillation of deionized water. This is the only method of preparation permitted by the European Pharmacopoeia (EP). In contrast, the USP and the Japanese Pharmacopeias also permit reverse osmosis to be used. The USP has also recently broadened its definition of source water to include not only the U.S. Environmental Protection Agency National Primary Drinking Water Standards, but also comparable regulations of the European Union or Japan. 

Seven laboratories participated in the interlaboratory evaluation within the framework of the PRISTINE, SANDRINE and INEXsPORT European Union Projects [6]. The results obtained for the analysis of diverse classes of surfactants by different analytical methods are listed in Table 4.5.1. The analytical strategies were based on LC coupled to either MS or FL detection in all cases with the exception of one laboratory using a test tube ELISA kit. Samples were spiked with the surfactants NPEO, CDEA, LAS, AEO, NPEO-SO4 and SAS. 

Consideration of the above requirements confirms that in future all methods must be fully validated if at all possible, i.e. have been subjected to a collaborative trial conforming to an internationally recognised protocol. In addition this, as described above, is now a legislative requirement in the food sector of the European Union. The concept of the valid analytical method in the food sector, and its requirements, is described below. 

Table 26.1 Classification of Analytical Methods in the European Union According to their Validation Status...

Quality criteria for quantitative analytical methods, in general, have been proposed or arc lo be proposed by several international organizations including the Association of Official Analytical Chemists, the Food and Drug Administration, the Codex Committee for Residues of Veterinary Drugs in Food, the International Dairy Federation, and the European Union. The European Union, in particular, has laid down minimum quality criteria for quantitative drug residue methods,... 

Apart from the European Union quality criteria, uncertainty factors may be used for defining the reliability of a qualitative method. The European Union criteria lay down standards that have to be fulfilled only in the detection step of the method (18). However, every method is a combination of many analytical steps, including sample extraction, sample cleanup, and detection. Uncertainty factors simply represent qualitative values for the remaining uncertainty after use of a well-defined analytical method (25). 

Even using uncertainty factors, the problem of determining the reliability of qualitative methods has not be solved because the usual statistical approaches are often not applicable. In residue analysis, this problem is often amplified because concenftations frequently are in the low or even sub-ppb range. Most promising appears to be a model that helps in estimating, in arbitrary units, the overall selectivity of an analytical method on the basis of partial selectivity indices. Selectivity indices are nothing more than a combination of the above-mentioned tools with the experience obtained within the European Union from recognized laboratory experts (26). 

In 1996 and 1997 the International Conference on Harmonization (ICH) published guidelines for analytical method validation [8]. These documents present a discussion of the characteristics for consideration during the validation of the analytical procedures included as part of registration applications submitted within the European Union, Japan, and the United States. 

This article deals with legal requirements in the European Union on basic principles of laboratory quality assurance for official notification to the EC Commission and on method validation concerning official laboratories. Widespread discussions and activities on measurement uncertainty are in progress, and the European validation standards for official purposes may serve as a basis for world-wide efforts on quality harmonization of analytical results. Although much time has already been spent, definitions and require-... 

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