Method performance parameters

Method validation is defined in the international standard, ISO/IEC 17025 as, the confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use are fulfilled. This means that a validated method, if used correctly, will produce results that will be suitable for the person making decisions based on them. This requires a detailed understanding of why the results are required and the quality of the result needed, i.e. its uncertainty. This is what determines the values that have to be achieved for the performance parameters. Method validation is a planned set of experiments to determine these values. The method performance parameters that are typically studied during method validation are selectivity, precision, bias, linearity working range, limit of detection, limit of quantitation, calibration and ruggedness. The validation process is illustrated in Figure 4.2. 

Precision estimates are key method performance parameters and are also required in order to carry out other aspects of method validation, such as bias and ruggedness studies. Precision is also a component of measurement uncertainty, as detailed in Chapter 6. The statistics that are applied refer to random variation and therefore it is important that the measurements are made to comply with this requirement, e.g. if change of precision with concentration is being investigated, the samples should be measured in a random order. 

Method validation is carried out to provide objective evidence that a method is suitable for a given application. A formal assessment of the validation information against the measurement requirements specification and other important method performance parameters is therefore required. Although validation is described as a sequential process, in reality it can involve more than one iteration to optimize some performance parameters, e.g. if a performance parameter is outside the required limits, method improvement followed by revalidation is needed. 

Verification Confirmation that the method performance parameters established during method validation can be met. 

Method performance parameters are determined using equipment that is ... 

Many of the method performance parameters are usually evaluated as part of method development. It is for this reason that method validation is very closely related to method development. 

It is important to issue a common understanding on the topics of method validation, traceability, and uncertainty of measurements. Here, the interrelationships between method validation, traceability, and MU of results will be elucidated. Throughout the landscape of guidelines and standards, the most relevant information is selected, compiled, and summarized. Great importance is attached to the different method performance parameters and their definitions, ways of expression, and approaches for practical assessment. We discuss the role of method validation within QA as well as the topics of standardization, internal and external quality control (IQC and EQC, respectively), and accreditation and the links between these different aspects. 

Traceability and MU both form parts of the purpose of an analytical method. Validation plays an important role here, in the sense that it confirms the fitness-for-purpose of a particular analytical method [4]. The ISO definition of validation is confirmation by examination and provision of objective evidence that the particular requirements of a specified intended use are fulfilled [7]. Validation is the tool used to demonstrate that a specific analytical method actually measures what it is intended to measure and thus is suitable for its intended purpose [2,11]. In Section 8.2.3, the classical method validation approach is described based on the evaluation of a number of method performance parameters. Summarized, the cri-teria-based validation process consists of precision and bias studies, a check for... 

In practice, data from method validation and collaborative studies form the basis for but are only a part of MU estimation. MU is thus more than just a method performance parameter, as described extensively in Section 8.2.2. Over the years, the concept of MU has won attention in all analytical areas and this has led to two different approaches currently accepted and used for analytical method validation. 

Method Performance Parameter Identification Test Impurity Test Limit Impurity Quantitative Test Impurity Test Assay Test... 

Measure of capacity of analytical procedure to remain unaffected by small but deliberate variations in method performance parameters, which provides an indication of its reliability during normal usage (term used by USP/ICH only)... 

Precision plays a central role in collaborative studies. Wood [84] defines a collaborative trial as a procedure whereby the precision of a method of analysis may be assessed and quantified. Precision is the objective of interlaboratory validation studies, and not trueness or whichever other method performance parameter. Evalu-... 

Table 8.2. Method performance parameters assessed in a method validation study...

Measurement uncertainty and its implications for collaborative study method validation and method performance parameters 39... 

Table 6.5. Summary of Analytical Method Performance Parameters for Vitamin Analysis...

L for bisphosphonates. Method performance parameters such as calibration range, correlation coefficients, and detection limits are summarized in Table 8.10. Precision and accuracy were evaluated at 50 and 500pg/L, and the results are listed in Table 8.11. 

Table 8.12 Method performance parameters for the analysis of ethanolamines.

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