Chemistry Reference
In-Depth Information
4
Method Validation Basics
4.1 IntroductIon
Method validation is one part of the overall validation process that encompasses
at least four distinct steps: (1) software validation, (2) hardware (instrumentation)
validation/qualification, (3) method validation, and (4) system suitability, and each
step is critical to the overall success of the process. Method validation establishes
through laboratory testing that the performance characteristics of the method meet
the requirements of the intended analytical application. It provides an assurance
of reliability of laboratory studies during normal use, and is sometimes referred
to as the process of providing documented evidence that the method does what it
is intended to do. In addition to being good science, regulated laboratories must
carry out method validation in order to be in compliance with governmental or other
regulatory agencies. In addition to providing proof that acceptable scientific prac-
tices are used, method validation is therefore a critical part of the overall validation
process. A well-defined and documented method validation process not only satisfies
regulatory compliance requirements, but also provides evidence that the system and
method are suitable for their intended use, and aids in method transfer [1-4].
Many regulated industries have well-defined processes in place for method vali-
dation, for example, environmental monitoring laboratories under the oversight of
the US Environmental Protection Agency (EPA) [5] and organizations that rely on
the International Organization for Standardization (ISO) [6]. This chapter's primary
focus is on the validation of analytical procedures employed by the pharmaceutical
industry; in addition to the general process of method validation, terms and defini-
tions, protocol, and reporting are discussed. Because HPLC is the predominant tech-
nology used in the regulated pharmaceutical laboratory, where possible the examples
here will highlight its use, and the information presented here can be applied to other
analytical procedures and techniques. Practitioners should also bear in mind, how-
ever, that any analytical technique used in a regulated laboratory must be validated
for its intended use using the guidelines cited here. In nonregulated industries (e.g.,
academic laboratories), there is also a need for high-quality methods that provide
reliable data. In these instances, method validation is also strongly recommended
even when it is not required by regulation, and many peer-reviewed journals these
days also require data supporting method validation.
4.2 metHod vAlIdAtIon guIdelInes
In the late 1980s, the US Food and Drug Association (FDA) first designated the
specifications listed in the current edition of the
United States Pharmacopeia
(USP) as those legally recognized to determine compliance with the Federal Food,
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