Validation by Type of Method
Regulatory guidelines recognize that is it not always necessary to evaluate every analytical performance parameter for every type of method or analytical procedure, or for both drug substances (active pharmaceutical ingredient [API]) and drug products, as discussed in Chapter 4 [1,2]. Several different types of methods are used to measure the API or impurities, degradants, excipients, and additional related substances either in the raw material or finished product during various stages of drug development. The methods discussed in this chapter are impurity (related substances) or stability indicating methods (SIMs), dissolution, bioanalytical methods, peptide mapping, and methods used in support of cleaning validation. The type of method and its intended use, as well as the phase of development, dictate which performance characteristics should be investigated, as summarized in Table 7.1. Both the USP and ICH divide analytical methods into four separate categories:
• Category I: Assays for the quantitation of major components or active ingredients
• Category II: Determination of impurities or degradation products • Category III: Determination of performance characteristics • Category IV: Identification tests
These methods and categories generally apply to drug substances and drug products, as opposed to bioanalytical samples, covered in Section 7.5.