Method Validation

ISO 17025:2005 defnition

Validation is the confrmation by examination and the provision of efective
evidence that the particular requirements for a specifc intended use are fulflled.
ICH Q2(R1) defnitions
Specifcit
Specifcity is the ability to assess unequivocally the analyte in the presence of
components which may be expected to be present. Typically these might include
impurities, degradants, matrix, etc. ac! of specifcity of an individual analytical
procedure may be compensated by other supporting analytical procedure"s#.
$%Validation &.'( $xample of a Selectivity determination by )omparison of
)alibration ines
!cc"#ac
The accuracy of an analytical procedure expresses the closeness of agreement
between the value which is accepted either as a conventional true value or an
accepted reference value and the value found. This is sometimes termed trueness.
$%Validation &.'( $xample of the *ccuracy determination by a t+test
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$#ecision
The precision of an analytical procedure expresses the closeness of agreement
"degree of scatter# between a series of measurements obtained from multiple
sampling of the same homogeneous sample under the prescribed conditions.
,recision may be considered at three levels( repeatability, intermediate precision
and reproducibility. ,recision should be investigated using homogeneous, authentic
samples. -owever, if it is not possible to obtain a homogeneous sample it may be
investigated using artifcially prepared samples or a sample solution. The precision
of an analytical procedure is usually expressed as the variance, standard deviation
or coe%cient of variation of a series of measurements.
"i# .epeatability
.epeatability expresses the precision under the same operating conditions over a
short interval of time. .epeatability is also termed intra+assay precision.
$%Validation &.'( $xample of the .epeatability determination evel by evel from
/ultiple /easurements
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"ii# 0ntermediate precision
0ntermediate precision expresses within+laboratories variations( diferent days,
diferent analysts, diferent equipment, etc.
"iii# .eproducibility
.eproducibility expresses the precision between laboratories "collaborative studies,
usually applied to standardi1ation of methodology#.
%etection &i'it
The detection limit of an individual analytical procedure is the lowest amount of
analyte in a sample which can be detected but not necessarily quantitated as an
exact value.
Q"antitation &i'it
The quantitation limit of an individual analytical procedure is the lowest amount of
analyte in a sample which can be quantitatively determined with suitable precision
and accuracy. The quantitation limit is a parameter of quantitative assays for low
levels of compounds in sample matrices, and is used particularly for the
determination of impurities and2or degradation products.
$%Validation &.'( $xample of the 3etection and 4uantitation imit determination
from a calibration curve
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&inea#it
The linearity of an analytical procedure is its ability "within a given range# to obtain
test results which are directly proportional to the concentration "amount# of analyte
in the sample.
$%Validation &.'( $xample of the inearity determination
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Ran(e
The range of an analytical procedure is the interval between the upper and lower
concentration "amounts# of analyte in the sample "including these concentrations#
for which it has been demonstrated that the analytical procedure has a suitable
level of precision, accuracy and linearity.
Ro)"stness
The robustness of an analytical procedure is a measure of its capacity to remain
unafected by small, but deliberate variations in method parameters and provides
an indication of its reliability during normal usage.
$%Validation &.'( $xample of the .obustness determination
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*nce#taint
5ncertainty is a parameter associated with the result of a measurement, that
characterises the dispersion of the values that could reasonably be attributed to the
measurand. The parameter may be, for example, a standard deviation, or the width
of a confdence interval.
5ncertainty of measurement comprises, in general, many components. Some of
these components may be evaluated from the statistical distribution of the results
of series of measurements and can be characterised by standard deviations. The
other components, which also can be characterised by standard deviations, are
evaluated from assumed probability distributions based on experience or other
information. The 0S6 7uide refers to these diferent cases as Type * and Type 8
estimations respectively.
$%Validation &.'( $xample of the 5ncertainty determination from ,artial
5ncertainties
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Cont#ol Cha#t
* chart on which observations are plotted as ordinates in the order in which they
are obtained and on which control lines are constructed to indicate whether the
population from which the observations are being drawn is remaining the same.
)ontrol charts are used especially in industrial quality control.
ISO 17025:2005+ chapte# 5,-,1 states:
The laboratory shall have quality control procedures for monitoring the validity of
tests and calibrations underta!en. The resulting data shall be recorded in such a
way that trends are detectable and, where practicable, statistical techniques shall
be applied to the reviewing of the results. This monitoring shall be planned and
reviewed and may include, but not be limited to, the following(
a. regular use of certifed reference materials and2or internal quality control
using secondary reference materials9
b. participation in interlaboratory comparison or profciency+testing
programmes9
c. replicate tests or calibrations using the same or diferent methods9
d. retesting or recalibration of retained items9
e. correlation of results for diferent characteristics of an item.
$%Validation &.'( $xample of a )ontrol )hart : example from the 0S6 ;<=; standard
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Cali)#ation
)alibration is a basic tool needed in quantitative analysis to construct the
relationship between the measured analytical signal and sample concentration.
)alibration process typically consists of "i# 3efning the purpose and range of
calibration, "ii# ,reparation and execution of calibration experiments, "iii#
)onstruction of the model, "iv# 5se of the model in routine practice
$%Validation &.'( $xample of )alibration
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Inte#la)o#ato# Co'pa#ison
0nterlaboratory studies2comparisons are performed with the aim of evaluating the
extend of similarity in the results obtained by diferent laboratories using the same
method. The study typically consists of "i# ,lanning, "ii# Selection2recruitment of
laboratories, "iii# $xecution according the plan and "iv# statistical evaluation of
results
$%Validation &.'( $xample of 0nterlaboratory Study according the 0S6
;<=; standard
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.eat"#es
Software compliance
/odules
o /ethod Validation
o 5ncertainties
o )ontrol )harts
o )alibration
o 0nterlaboratory )omparison
o $lectronic aboratory oogboo!s
o Software Validation
,roduct Tour
/lect#onic &a)o#ato# &oo()oo0s
Traceability of test results, samples, documents, equipment calibrations, reference
standards, etc., is a basic requirement in both the 0S6 >?'<= accrediated and 7x,
laboratories.
Software $%Validation enables to maintain and control the following specifc
laboratory loogboo!s(
a. Samples9
b. Specifcations9
c. $quipment,
d. 3ocuments,
e. 3eviations,
f. .eference standards9
g. )hemicals9
h. Volumetric solutions9
i. )ontacts.
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$%Validation &.'( $xample of an electronic laboratory loogboo!
.eat"#es
Software compliance
/odules
o /ethod Validation
o 5ncertainties
o )ontrol )harts
o )alibration
o 0nterlaboratory )omparison
o $lectronic aboratory oogboo!s
o Software Validation
,roduct Tour
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