DATA QUALITY Flashcards
defined as a deviation from the
absolute value or from the true
average of a large number of results.
Error
can be classified as systematic
error or indeterminate error
Error
Systematic Errors
- also known as the
determinate errors.
errors that are reproducible and can be
discovered and corrected.
Systematic Errors
Systematic Errors Can be further classified into:
Instrumental Error
- Method Error
- Personal Error
failure to calibrate, degradation of
parts in the instrument, power fluctuations, variation in
temperature.
Instrumental Error
rrors due to no ideal physical or
chemical behaviour, completeness and speed of
reaction,
interfering side reactions, sampling problems.
method Errors
occur where measurements require
judgment, result from prejudice, color acuity problems,
negligence to follow proper procedures
Personal errors
are observed by the same
analyst when the successive measurements are
made with the same identical conditions.
Random Errors
Random Errors also known as the
indeterminate errors .
appear as slight variations in successive
measurements due to causes that the analyst
can not control.
Random Errors
A plot of indeterminate error would show a
normal frequency curve
Minimization of Errors
Proper calibration of the glass ware, pipettes,
burettes, weights, balances, instruments, etc.
* By running the blank with the sample. The blank
solution is defined as the solution by omitting
the sample addition. The blank and the sample
solutions are carried simultaneously to obtain
the accurate results.
* By running the parallel determinations.
* Correctly recording and computing data results
is establishing documented
evidence which provides a high degree of
assurance that a specific process, method, system,
activity or equipment consistently produce a
product meeting its predetermined specifications
Validation
pertains to agreement of an
experimental results with true value
Accuracy
is the measure of reproducibility of
data within a series of results.
Precision
In a normal distribution,
__% of the values should
fall within one standard
deviation in either side of
the mean
68%
In a normal distribution,
68% of the values should
fall within ____ standard
deviation in either side of
the mean
ONE
And __% should fall within
two standard deviations of
the mean
95
And 95% should fall within
___ standard deviations of
the mean
2
So, standard deviation
should be a ____
percentage of the mean.
SMALL
measure of central tendency
Mean
difference between largest/smallest
observations in a set of data
Range
measures the difference of the
actual values with the mean value
Average Deviation
determined by
dividing the average deviation by the mean
Relative average deviation
sum of squares difference of the actual
values with the mean value/total number of
samples
Variance
Square root of variance
Standard Deviation
Is used to measure precision of a data
set.
Relative Standard Deviation (%RSD)
is a
measure of the accuracy of the
method.
Percentage Relative Error (E)
is the process by
which it is established, by laboratory studies, that the
performance characteristics of the procedure meet
the requirements for the intended analytical
applications.
Validation
provides an assurance of reliability
during normal use, and is sometime referred to as
“the process for providing documented evidence that
the method does what it is intended to do.
validation
Purpose of Validation
For identification of sources and
quantitation of potential error
* To determine if method is acceptable
for intended use.
* To satisfy FDA requirements
* To ensure the consistency of the
output
TYPES OF ANALYTICAL
PROCEDURES TO BE VALIDATED
- Identification tests
- Quantitative tests for impurities content.
- Limit tests for the control of impurities .
- Quantitative tests of the active moiety in
samples of drug substance.
VALIDATION PARAMETERS
- Accuracy
- Precision
- Range
- Specificity
- Linearity
- Ruggedness
is the
closeness of test results obtained by that
procedure to the true value.
ACCURACY
Determined by application of the analytical
procedure to an analyte of known purity
ACCURACY
Accuracy should be assessed using a minimum
of ____ determinations over a minimum of
three concentration levels, covering the
specified range.
9
Accuracy should be assessed using a minimum
of nine determinations over a minimum of
____ concentration levels, covering the
specified range.
3
It is the degree of agreement among individual
test results when the procedure is applied
repeatedly to multiple samplings of a
homogeneous sample.
PRECISION
Precision may be a measure of either the
degree of ______ OR _____ of
the analytical procedure under normal operating
conditions .
reproducibility or of repeatability
3 Levels of Precision
1, Repeatability
2. Intermediate Precision
3. Reproducibility
expresses the precision under the
same operating conditions over a short interval of
time.
Repeatability
Repeatability is also termed
intra-assay
precision.
expresses variations within
laboratories, such as different days, different
analysts, different equipment, and so forth.
- to verify that in the same laboratory the method will
provide the same results once the development phase
is over.
Intermediate precision
expresses the precision
between laboratories. The objective of
reproducibility is to verify that the method will
provide the same results in different
laboratories
Reproducibility
the ability to measure accurately and
specifically the analyte of interest in the
presence of other components that may be
expected to be present in the sample matrix
SPECIFICITY
In case of identification tests, the method
should be able to discriminate between
compounds of closely related structures which
are likely to be present.
SPECIFICITY
It is the lowest amount of analyte in a
sample that can be detected, but not
necessarily quantitated, under the stated
experimental conditions.
DETECTION LIMIT
Its usually expressed as the concentration of
analyte (e.g., percentage, parts per billion)
in the sample
DETECTION LIMIT
The detection limit is a characteristic of
limit
tests
It is the lowest amount of analyte in a sample
that can be determined with acceptable
precision and accuracy under the stated
experimental conditions
QUANTITATION LIMIT
is a characteristic of
quantitative assays for low levels of compounds
in sample matrices, such as impurities in bulk
drug substances and degradation products in
finished pharmaceuticals
QUANTITATION LIMIT
Its ability to elicit test results that are directly,
or by a well-defined mathematical
transformation, proportional to the
concentration of analyte in samples within a
given range
LINEARITY
refers to the linearity of the
relationship of concentration and assay
measurement.
LINEARITY
it is the interval from the upper to the lower
concentration (amounts) of analyte in the sample
for which it has been demonstrated that the
analytical procedure has a suitable level of
precision, accuracy and linearity
RANGE
It’s the measure of its capacity to remain
unaffected by small but deliberate variations in
procedural parameters listed in the procedure
documentation and provides an indication of its
suitability during normal usage
ROBUSTNESS
Refers to the degree of reproducibility of
test results under a variety of conditions
such as
q Different laboratories
q Different Analysts
q Different Instruments
q Different Days
RUGGEDNESS
Analytical methods for quantitation of major
components of bulk drug substances
Category I:
Analytical methods for determination of impurities
in bulk drug substances
Category II:
Analytical methods for determination of
performance characteristics
Category III:
Identification tests.
Category IV:
