Chemistry Reference
In-Depth Information
7
Validation by Type
of Method
7.1 IntroductIon
Regulatory guidelines recognize that is it not always necessary to evaluate every
analytical performance parameter for every type of method or analytical proce-
dure, 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 sub-
stances) 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 per-
formance 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: Identiication tests
These methods and categories generally apply to drug substances and drug products,
as opposed to bioanalytical samples, covered in Section 7.5.
In this chapter, the level of validation required corresponding to the type of
method and the category, along with some method-type and phase-specific valida-
tion criteria are discussed. Some specific methods are addressed, including impurity
(related substances) or stability indicating methods (SIMs), dissolution, bioanalytical
methods, peptide mapping, and methods used in support of cleaning validation.
7.1.1 c
Ategory
I m
ethodS
Category I tests target the analysis of major components, and include methods such
as content-uniformity and potency-assay analyses. A method used for
assay
is one
that measures the active ingredient concentration in a drug product or substance.
A
content uniformity
method is similar to an assay method, but specifically tar-
gets the measurement of the variability in drug concentration within a batch of
119
