Ruggedness test definition

A ruggedness test is a part of method validation (Table 3.1) and can be considered as a part of the precision evaluation [2,4,5]. Ruggedness is related to repeatability and reproducibility. Some definitions for ruggedness come very close to those for reproducibility. Certain interpretation methods to identify the significant factors in a ruggedness test use criteria based on results for repeatability or reproducibility. These two items will be considered in Section 3.4.7. 

Agencies or authorities such as ISO or lUPAC still do not provide any definition of ruggedness. In the chemical literature however, a ruggedness test was defined as [4,12] An intralaboratory experimental study in which the influence of small changes in the operating or environmental conditions on measured or calculated responses is evaluated. The changes introduced reflect the changes that can occur when a method is transferred between different laboratories, different experimentators, different devices, etc. . 

From the definitions given above it can be seen that there are two approaches to ruggedness testing (also equal to levels 1 and 2 given in the Acceptable Methods document [14]). In the first approach factors to be examined are selected from the set of operating and environmental conditions that are or could be stipulated in the analytical procedure. This kind of factors can be called procedure related factors. 

Other results obtained from the ruggedness test are the definition of optimized method conditions for the factors and of system suitability criteria for a number of responses. System suitability parameters [6,17] are defined as an interval in which a response can vary for a rugged method. The system suitability criteria are the range of values between which a response (e.g. retention time, capacity factor, number of theoretical plates, resolution) can vary without affecting the quantitative results of the analysis. For instance, a design is performed and the retention time of the main substance varies between 200 s and 320 s without affecting the quantitative determination of the substances. The system suitability criteria for the retention time is then defined as the interval 200 s - 320 s. 

The nested designs can be used to perform a ruggedness test following the definition of the US Pharmacopeia [7] or the second level requirements of the Canadian Acceptable Methods [14]. However, to our knowledge this methodology has not been applied yet for this purpose. 

Other results from a ruggedness test described by some authors are the definition of rugged intervals and of system suitability parameters and the selection of optimal values for the factors. Rugged intervals are defined as the interval between the levels of a factor for which no significant effect is seen on a response [19]. 

Some other sources have definitions that are different from the one given above [7,14]. The US Pharmacopeia [7] defines ruggedness as The ruggedness of an analytical method is the degree of reproducibility of test results obtained by the analysis of the same sample under a variety of normal test conditions, such as different laboratories, different analysts, different instruments, different lots of reagents, different elapsed assay times, different assay temperatures, different days, etc. Ruggedness is normally expressed as the lack of influence on test results of operational and environmental variables of the analytical method. Ruggedness is a measure of reproducibility of test results under normal, expected operational conditions from laboratory to laboratory and from analyst to analyst . In fact this is nearly the definition of reproducibility. This definition is also followed by other authors [15]. 

The Canadian Acceptable Methods document [14] gives more or less a combination of the two definitions described above and considers 3 levels in the testing of the ruggedness of a method, with the third level being performed only rarely. Level one requires verification of the basic insensitivity of the method to minor changes in environmental and operational conditions and should include verification of reproducibility by a second analyst . The first part of this definition resembles the French Guide s definition. The second part is a check on the adequacy of the method description and should be done without input from the original analyst. 

The robustness of an analytical method can be described as the ability to reproduce the method in different laboratories or under different circumstances without the occurrence of unexpected differences in the obtained results. The term ruggedness is considered here as a synonym for robustness. The robustness of a method is tested in a robustness test. The most frequently u.sed definition for robustness in this area is due to the International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) [79,80. It defines robustness as follows. The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage."... 

In fact, the definition of ruggedness by Youden and Steiner equals the USP and ICH definitions of robustness. It is also the most widely applied definition. Further in this chapter, only consequences related to this definition are considered, and only the term robustness is used. In such type of robustness testing, usually screening designs are applied. 

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