Revalidation, test methods

For HPLC methods, significant changes could occur, and the recommended parameters for revalidation are summarized in Table 2. For bioanalytical methods, precision, accuracy, and limit of quantitation are considered to be the minimum revalidation tests. 

Table 2 Method changes and revalidation tests required...

According to the validation life cycle,test methods may reqnire additional validation or revalidation when regnlatory agencies issne new reqnirements or when changes are made to the methodology. Method changes and additional validation activities may be required when there are... 

Detailed evaluation of test method validation procedures containing all of the recommendations and precautions to be taken into consideration when the TLC method is being routinely used some recommendations should be given as to when and why revalidation might be necessary. 

Initially, robustness testing was performed to identify potentially important factors, which could affect the results of an interlaboratory study.Therefore, the robustness test was executed at the end of the method validation procedure, just before the interlaboratory study. Flowever, a method found to be non-robust should be redeveloped and revalidated, leading to a waste of time and money. For these economical reasons, nowadays, method robusmess is verified at an earlier stage in the lifetime of the method, i.e., at the end of method development or at the beginning of the validation procedure. ... 

A change in the excipient composition may change the product impurity profile. This change may make the method deficient in its specificity for the assay or impurity tests and may require redevelopment and revalidation. 

There are various situations during the life cycle of a dissolution test that will require revalidation of the method. These are similar to those described for the potency assay in Chapter 2. 

Method validation is the process to confirm that the analytical procedure employed for a specific test is suitable for its intended use. Methods need to be validated or revalidated as follows ... 

One way of detecting the kind of changes that should initiate revalidation is the use of tests and methods of analysis capable of measuring characteristics that may vary. Such tests and methods usually yield specific results going beyond the mere pass/fail basis, thereby detecting variations within product and process specifications and allowing determination of whether a process is slipping out of control. 

In order to have confidence that the chain of supply is not only operating properly, but to confirm that water quality is being maintained and achieved, verification is required. Verification is the use of methods, procedures or tests, in addition to those used in operational monitoring, to determine whether the water safety plan complies with the stated objectives outlined in the water quality targets, or whether it needs to be modified and revalidated. 

The other aspect of this mode of transfer is that it does not normally require comparison of data generated at the receiving lab with data previously reported by the originator lab. The receiving labs are certified to perform the tests once they complete revalidation of the methods. 

The proper functioning of analytical methods should be verified on the new system. This covers testing of significant method characteristics, for example, limit of detection, limit of quantification, selectivity, and linearity. If the method has not been validated or if its scope did not cover the new instrument, the method should either be newly validated or revalidated. 

Robustness tests examine the effect operational parameters have on the analysis results. For the determination of a method s robustness, a number of chromatographic parameters (e.g., flow rate, column temperature, injection volume, detection wavelength, or mobile phase composition) are varied within a realistic range and the quantitative influence of the variables is determined. If the influence of the parameter is within a previously specified tolerance, the parameter is said to be within the method s robustness range. Obtaining data on these effects will allow one to judge whether a method needs to be revalidated when one or more of parameters are changed, for example, to compensate for column performance over time. 

Once the method is vahdated, any modification requires revalidation to demonstrate that it still works as defined. If the new parameter is within the tolerance range of the method as specified during the ruggedness test of method validation, the method does not need to be revalidated. In other cases, it should go through revalidation. With the system suitability software frequently offered by analytical equipment vendors, methods can be automatically revalidated with little operator interaction. The validation can be performed overnight. 

Method transfer is loosely defined as a process that qualifies a laboratory to use a test procedure or analytical method. According to this definition, any and all means of having a laboratory qualified would meet the criteria for transfer. The most common variations of method transfer are comparative testing, covalidation between two laboratories or sites, complete or partial method validation or revalidation, and the omission of formal transfer processes, sometimes termed the transfer waiver. ... 

If the automated assay method is sufficiently different from the manual method, then the differences between the two methods must be carefully examined to determine the best testing approach. This may result in the need to partially revalidate each assay on the automated system. Once this is done, a decision must be made about whether both the methods can be used to generate data for the same subject/study/ project. This involves quite a lot of work and serves as an example of why standardizing the manual and automated methods is so important. 

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