International Conference on
Harmonization
Validation of Analytical Procedure
Q2(R1)
Part 1
Text on Validation of Analytical
Procedures.
objective
To demonstrate that the analytical
procedure is suitable for its intended
use.
Types of analytical
procedures to be validated
1.
2.
3.
4.

Identification tests
Quantitative tests for impurities
content...
.

The objective of the analytical procedure
should be clearly understood since this will
govern the validation characteri...
.
• Specificity
• Detection limit
• Quantitation limit
• Linearity
• Range
• robustness
This should be typical for analyti...
Furthermore revalidation for:
• Changes in the synthesis of the drug
substance
• Changes in the composition of the
finishe...
glossary
Analytical procedure:
it is the way of performing the analysis
And should be described in detail the
steps necess...
specificity
The ability to assess unequivocally the
analyte in the presence of components
Which may be expected to be pres...
accuracy
Closeness of agreement between the
value which is accepted and the value
found.
precision
Closeness of agreement between a
series of measurements obtained from
multiple sampling of the same
homogeneouse...
Detection limit
It is the lowest amount of analyte in a
sample which can be detected but not
necessarily quantitated as an...
Quantitation limit
It is the lowest amount of analyte in a
sample which can be quantitatively
determined with suitable pre...
linearity
it is the procedure's ability to obtain
test results which are directly
proportional to the concentration of
ana...
range
It is the interval between the upper
and lower concentration of analyte in
the sample for which it has been
demonstr...
robustness
It is a measure of procedures capacity
to remain unaffected by small , but
deliberate variations in method
para...
Part 2
Validation of Analytical Procedures:
Methodology
specificity
An investigation of specificity should be
conducted during the validation of
identification test , the determi...
.

2. Assay and impurity tests
For chromatographic procedure ,
representative chromatograms should
be used to demonstrate ...
.2.1.impurities are available
This can be done by spiking pure
substance with appropriate levels of
impurities or/and exci...
2.2. impurities are not available
In this case specificity may be
demonstrated by comparing the test
results of samples co...
linearity
Should be evaluated by visual
inspection of a plot of signals as a
function of analyte concentration. If
there i...
range
The specified range is normally derived from
linearity studies and depends on the intended
application of the proced...
accuracy
1.Assay for drug substance and drug
product : there are several methods of
determining accuracy.
2.Impurities (qu...
precision
1.Repeatability : using a min. of 9
determination covering the specified range
for the procedure , or min. of 6
...
Detection limit
1. Based on visual evaluation:
Visual evaluation may be used for noninstrumental methods. The detection li...
Quantitation limit
1. Based on visual evaluation:
For non-instrumental methods and
determined by analysis of samples with
...
robustness
One consequence of the evaluation of
robustness should be that a series of
system suitability parameters is
est...
Thank you
Noushin Javidvand
2013
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International conference on harmonisation validation of analytical procedures

  1. 1. International Conference on Harmonization
  2. 2. Validation of Analytical Procedure Q2(R1)
  3. 3. Part 1 Text on Validation of Analytical Procedures.
  4. 4. objective To demonstrate that the analytical procedure is suitable for its intended use.
  5. 5. Types of analytical procedures to be validated 1. 2. 3. 4. Identification tests Quantitative tests for impurities content Limit tests for the control of impurities Quantitative tests of the active in samples of drug substance or drug product or the selected components in the drug product
  6. 6. . The objective of the analytical procedure should be clearly understood since this will govern the validation characteristics which need to be evaluated .typical validation characteristics which should be considered are listed below: • Accuracy • Precision • Repeatability • Intermediate precision
  7. 7. . • Specificity • Detection limit • Quantitation limit • Linearity • Range • robustness This should be typical for analytical procedures but occasional exceptions should be dealt with on a case-by-case basis.
  8. 8. Furthermore revalidation for: • Changes in the synthesis of the drug substance • Changes in the composition of the finished product • Changes in the analytical procedure
  9. 9. glossary Analytical procedure: it is the way of performing the analysis And should be described in detail the steps necessary to perform each test for sample, reference standard and reagents preparations , use of apparatus , generation of calibration curve ,etc.
  10. 10. specificity The ability to assess unequivocally the analyte in the presence of components Which may be expected to be present. Like: impurities , degradants , matrix . • To ensure the identity of an analyte • As a purity test • Assay (content or potency)
  11. 11. accuracy Closeness of agreement between the value which is accepted and the value found.
  12. 12. precision Closeness of agreement between a series of measurements obtained from multiple sampling of the same homogeneouse sample under the prescribed conditions.
  13. 13. Detection limit It is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value
  14. 14. Quantitation limit It is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. It is used for the determination of impurities and/or degradation products
  15. 15. linearity it is the procedure's ability to obtain test results which are directly proportional to the concentration of analyte in the sample
  16. 16. range It is the interval between the upper and lower concentration of analyte in the sample for which it has been demonstrated that the analytical procedure has a suitable level of precision , accuracy and linearity
  17. 17. robustness It is a measure of procedures capacity to remain unaffected by small , but deliberate variations in method parameters and provides an indication of its reliability during normal usage.
  18. 18. Part 2 Validation of Analytical Procedures: Methodology
  19. 19. specificity An investigation of specificity should be conducted during the validation of identification test , the determination of impurities and the assay. 1. Identification Suitable identification tests should be able to discriminate compounds of closely related structures which are likely to be present.
  20. 20. . 2. Assay and impurity tests For chromatographic procedure , representative chromatograms should be used to demonstrate specificity and individual components should be appropriately labelled. To provide evidence that there is no interference from other components
  21. 21. .2.1.impurities are available This can be done by spiking pure substance with appropriate levels of impurities or/and excipients and demonstrate that the assay results is unaffected by the presence of these materials by comparison with the assay result obtained on unspiked samples.
  22. 22. 2.2. impurities are not available In this case specificity may be demonstrated by comparing the test results of samples containing impurities to a second well-characterized .procedure , like pharmacopoeial method. This should include samples stored under relevant stress conditions, like light , heat , humidity, acid/base hydrolysis and oxidation
  23. 23. linearity Should be evaluated by visual inspection of a plot of signals as a function of analyte concentration. If there is a linear relationship , test results should be evaluated by appropriate statistical method. For thee stablishment of linearity , a minimum of 5 concentrations is recommended.
  24. 24. range The specified range is normally derived from linearity studies and depends on the intended application of the procedure Some of the minimum specified ranges that should be considered are : • For assay of a drug substance or drug product ;80%-120% of test concentration • For content uniformity;70%-130% of test concentration • For dissolution testing ; +/-20% over the specified range
  25. 25. accuracy 1.Assay for drug substance and drug product : there are several methods of determining accuracy. 2.Impurities (quantitation) : Accuracy should be assessed n samples spiked with known amount of impurities 3.Recommended data : Accuracy should be assessed using a minimum of 9 determinations over a minimum of 3 concentration levels covering the specified range
  26. 26. precision 1.Repeatability : using a min. of 9 determination covering the specified range for the procedure , or min. of 6 determination at 100% of the test concentration 2.reproducibility: is assessed by means of an inter-lab trial and reproducibility should be considered in case of the standardization of an analytical procedure
  27. 27. Detection limit 1. Based on visual evaluation: Visual evaluation may be used for noninstrumental methods. The detection limit is by analyzing a sample with a known concentration with minimum level in which can be detected 2. Based on the standard deviation of the response and the slope: DL=3.3 * std deviation of response/slope of the calibration curve
  28. 28. Quantitation limit 1. Based on visual evaluation: For non-instrumental methods and determined by analysis of samples with known concentrations of analyte and minimum level at which the analyte can be quantified with acceptable accuracy and precision 2.Based on signal-to-noise approach: It is performed by comparing measured signals from samples with known low concentration that the analyte can be quantified ; signal –to-noise ratio is 10:1.
  29. 29. robustness One consequence of the evaluation of robustness should be that a series of system suitability parameters is established to ensure that the validity of the analytical procedure is maintained whenever used. For example : different columns and ,flowrate.
  30. 30. Thank you Noushin Javidvand 2013

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