Method transfer testing laboratory selection

When identifying suitable testing labs, the main emphasis should be on the method application requirements, for example, sample analysis for preclinical or clinical studies, testing in conformance with GLP guidelines and, last but not least, the extent and philosophy of method validation between the laboratories. The selection of a compatible laboratory as the receiving laboratory is pivotal to the success of the method transfer process. 

Method transfer between instruments and laboratories may require some revalidation in CE due to differences in the construction of the instruments, especially the detector and injection systems. Therefore, it is preferable to specify an injection volume that is independent of a specific instrument. To assess the performance of a method in routine analysis system suitability tests comparable to HPLC such as selectivity, resolution, or system precision are recommended. Peak symmetry is not considered as the injection of high concentration often leads to peak distortion in CE. 

The transfer protocol must include suitable acceptance criteria relevant to the tests and specific dosage forms. Selection of the acceptance criteria is a critical element of the method transfer. Criteria that are too tight could lead to rejection of acceptable results, thereby causing delays in the transfer process. On the other hand, if criteria are too loose, the receiving laboratory may pass the transfer but be unable to appropriately test the actual product s), leading to poor decision making with respect to approval of marketed product. Of the two risks, the latter is more critical since, approving a laboratory that is truly not qualified could affect marketed product safety and/or efficacy and ultimately patient safety. This could lead to recalls and severe quality and compliance issues. 

Snow, especially its water-soluble fraction, is one of the most sensitive and informative indicators of mass-transfer in the chain air - soil - drinking water. Therefore analytical data on snow-melt samples were selected for inter-laboratory quality control. Inter-laboratory verification of analytical results estimated in all the groups have shown that relative standard errors for the concentrations of all the determined elements do not exceed (5-15)% in the concentration range 0.01 - 10000 microg/1, which is consistent with the metrological characteristics of the methods employed. All analytical data collected by different groups of analysts were tested for reliability and... 

Defining and selecting the factors to be examined should be carefully thought through before starting a robustness test. Usually, the factors in a robusmess test are operational or environmental factors. The former are selected from the operating procedure of the method, while the latter are not necessarily specified in this procedure. Those factors, which are most likely to vary when a method is transferred between different laboratories, analysts or instruments, are selected. 

As a first step one selects a number of factors to examine. The selected factors should be chosen from the description of the analytical procedure or from environmental parameters which are not necessarily specified explicitly in the analytical method. The factors can be quantitative (continuous, numerical) or qualitative (discrete). The factors to be tested should represent those that are most likely to be changed when a method is transferred, for instance, between different laboratories, different devices, or over time, and that potentially could influence the response of the method. However it is not always obvious which factors will influence a response and which will not. This is one of the reasons why screening designs are used (see Section 3.4.4). They allow to screen a large number of factors in a relatively small number of experiments. 

Acceptance criteria should take into account method performance attributes and the intended use of the methods. For example, in some instances it may be critical that the method precision and sensitivity (i.e., for impurities) are similar to that obtained by the method development laboratory. In such cases, the samples selected for transfer purposes, the statistical tools applied to demonstrate equivalence and the acceptance criteria should be selected carefully to ensure that the method performance is properly evaluated. On the other hand, in some instances the capabilities (e.g., sensitivity) of the development method may exceed the method performance requirements for commercial release testing. For example, while a gas chromatographic (GC) method may be validated to have sensitivity down to 0.002% for a number of residual solvents monitored during development and, if the specifications are set only on total residual solvents with a limit of 0.5%, it may not be necessary to demonstrate sensitivity for individual solvents to 0.002% to qualify the QC laboratory for routine use. The acceptance criteria should be considered on a case-by-case basis for each method for each product and must be established in advance of the formal testing. 

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