Chemistry Reference
In-Depth Information
1
Introduction to Analytical
Method Validation
1.1 IntroductIon
The primary focus of this topic is analytical method validation (AMV); however,
it is important to have a perspective on where AMV fits into the overall process
of validation, in addition to how the process is governed and regulated, before
going into too much detail. Therefore, this chapter provides a brief overview of the
drug development process; the organization and hierarchy of the main regulatory
agency, the Food and Drug Administration (FDA); important contributions of the
International Conference on Harmonization (ICH); and pertinent AMV guidelines
and their purpose. It also discusses the basic concepts of how AMV fits into the
overall validation process, how AMV differs depending on the various phases of the
drug development process, and addresses the importance of trained personnel in a
regulated environment.
1.2 drug development process
The stages of drug discovery and development are well defined and can be divided
into several distinct phases as outlined in Figure 1.1 [1]. In the drug discovery phase,
laboratories are mostly concerned with drug characterization studies, structure
determinations, solubility, p
K
a, spectral data, stability, chromatographic content and
purity analysis, and related method development. The amount of method validation
that is required at this early stage is very limited. As the drug shows more promise
for a target in screens, or in cell and tissue assays, additional analytical method
development and validation work is pursued and performed. Just as analytical meth-
ods must evolve, so too must AMV. The ability to conduct “good science” at the right
time with the best use of resources must be balanced against the ability to quickly
implement change during drug development. Indeed, much of the work performed
this early on in drug development is performed outside of regulatory scrutiny, in a
non-Good Manufacturing Practice (GMP) setting or format.
In the preclinical phase, bioanalytical method development and validation from
serum, tissue, or other biological matrices often ensues, and Good Laboratory
Practice (GLP) regulations apply. The type of method development and validation
studies performed at the preclinical stage of drug development is also used in sup-
port of pharmacokinetic, toxicokinetic, and drug metabolism studies. Such methods
may also be used to support drug formulation and drug delivery (e.g., dissolution
studies); and similar to the bioanalytical studies, these studies are performed in a
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