Chemistry Reference
In-Depth Information
A.4.2 S
yStem
S
uItAbIlIty
Describe how system suitability will be evaluated. For example, system suitability
parameters will be evaluated per the test method (Attachment) prior to performing
each of the discrete components of the validation described in the following sections.
When multiple validation components are analyzed in the same sample sequence, a
single system suitability evaluation may be performed, and for robustness studies
system suitability can be performed at each condition. System suitability criteria
should also be listed in this section, as well as in the draft method.
A.4.3 S
PecIfIcIty
Describe in this section how specificity will be evaluated. For example, specificity
will be evaluated by comparing the chromatographic results of individual solu-
tions (at concentrations described) of all available standards and related substances
(listed in the table) and a diluent blank. If different from above, sample and standard
solution preparation should be described. If utilized, mass spectrometry and pho-
todiode array methods used to evaluate peak purity (lack of coelutions) should be
described, particularly if validating a stability indicating method. Any forced degra-
dation/chemical stress studies performed within the scope of the study should also
be described in this section, along with specific conditions and sample treatments.
A.4.4 l
IneArIty
And
r
Ange
This section should describe the concentrations and range (e.g., 80% to 120% of nomi-
nal concentration) of the samples to be evaluated for linearity, and how they should be
prepared (e.g., according to the test method). The number of sample preparations (min-
imum of five levels), injections, and data treatment (averaged?) should be specified.
A.4.5 A
ccurAcy
This section should describe specific conditions used (numbers of samples, levels/
concentrations) to determine the accuracy of the procedure. Accuracy is typically
evaluated by preparing three sets of samples at three levels (e.g., 80%, 100%, and
120% of nominal), and is often combined with linearity determinations. Accuracy
is routinely performed at both the assay (100% of nominal) and at the impurity level
(0.1% of nominal), depending on the method's intended use.
A.4.6 P
recISIon
(r
ePeAtAbIlIty
And
I
ntermedIAte
)
Repeatability is performed by one analyst preparing and analyzing six separate sam-
ple solutions according to the method. Intermediate precision is demonstrated by a
second analyst preparing six separate additional sample solutions according to the
method using the same lot of standard as the first analyst and analyzing the samples
on a second column lot and a second instrument on a second day (relative to the first
analyst).
