Chemistry Reference
In-Depth Information
5
Robustness and
System Suitability
5.1 IntroductIon
The robustness of an analytical procedure is defined as a measure of its capacity to
obtain comparable and acceptable results when perturbed by small but deliberate
variations in procedural parameters listed in the documentation [1,2]. Robustness
provides an indication of the method's suitability and reliability during normal use
and is the cornerstone of any good method validation process. One consequence of
the evaluation of robustness is the establishment of system suitability parameters to
ensure that the validity of the analytical procedure is maintained whenever used.
Although not formally a part of method validation according to the USP, system
suitability tests are an integral part of chromatographic methods [3]. System suit-
ability tests are used to verify that the resolution and precision of the system are
adequate for the analysis to be performed. System suitability tests are based on the
concept that the equipment, electronics, analytical operations, and samples consti-
tute an integral system that can be evaluated as a whole, and in this way system suit-
ability can be thought of as the test that pulls together the entire validation process.
This chapter discusses both topics from an experimental design and specification-
setting standpoint. Both USP Chapter 1225: Validation of Compendial Methods,
and the International Conference on Harmonization (ICH) Guideline: Validation of
Analytical Procedures: Text and Methodology Q2 (R1), address robustness [1,2].
While the USP is the sole legal document in the eyes of the FDA, this chapter draws
from both guidelines as appropriate for definitions and methodology.
5.2 robustness studIes For metHod vAlIdAtIon
The ICH and the USP guidelines define the robustness of an analytical procedure
as a measure of its capacity to remain unaffected by small but deliberate variations
in procedural parameters listed in the documentation, providing an indication of the
method's or procedure's suitability and reliability during normal use. Traditionally,
robustness has not been considered a validation parameter in the strictest sense
because it is usually investigated during method development, once the method is
at least partially optimized. When thought of in this context, evaluation of robust-
ness during development makes sense, as parameters that affect the method can be
easily identified when manipulating selectivity for method optimization purposes.
Evaluating robustness either prior to or at the beginning of the formal method valida-
tion process also fits into the category of “you can pay me now, or you can pay me
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