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Data Elements Required For Assay Validation

Both the USP and the ICH recognize that is it not always necessary to evaluate every analytical performance parameter. The type of method and its intended use dictates which parameters need to be investigated, as illustrated in Table 1.

The USP divides analytical methods into three separate categories:

  • Quantitation of major components or active ingredients.
  • Determination of impurities or degradation products.
  • Determination of performance characteristics.

For assays in category 1, LOD and LOQ evaluations are not necessary because the major component or active ingredient to be measured is normally present at high levels. However, since quantitative information is desired, all of the remaining analytical performance parameters are pertinent. Assays in category 2 are divided into two sub-categories: Quantitative and Limit Tests. If quantitative information is desired, a determination of LOD is not necessary, but the remaining parameters are required. The situation reverses itself for a Limit Test. Since quantitation is not required, it is sufficient to measure the LOD and demonstrate specificity and ruggedness.


Table 1: USP Data Elements Required For Assay Validation

 

 
The parameters that must be documented for methods in USP assay category 3 are dependent upon the nature of the test. Dissolution testing, for example, falls into this category. The ICH treats analytical methods in much the same manner, as shown in Table 2.

USP categories 1 and 2 match the ICH categories of Assay and Impurity Testing, respectively, and the corresponding discussion above still applies.

 

Table 2: ICH Validation Characteristics Versus
Type of Analytical Procedure

The ICH has not yet chosen to specifically address methods for performance characteristics (USP category 3), however, but has instead addressed analytical methods for compound identification. In this ICH category, it is only necessary to prove that the method is specific for the compound being identified.