This document discusses accuracy and precision in analytical procedure validation. It defines accuracy as closeness of agreement between a measured value and a standard or known value. Accuracy is expressed as percent recovery and is determined by analyzing samples of known concentrations. Precision refers to the degree of agreement among multiple measurements under similar testing conditions and is expressed as percent relative standard deviation. Methods are considered precise if repeated measurements show similar results. The document outlines ICH guidelines for determining accuracy and precision in method validation.

1. Accuracy and Precision in
analytical procedure
validation
Presented by:
Sampat Choudhary
Department of pharmaceutical
analysis
NIPER Hyderabad
Course code: GE-611

2. Flow of presentation
1. Introduction to validation
2. Validation Parameters
3. Accuracy
4. Precision
• Repeatability
• Intermediate precision
• Reproducibility
5. References

3. • A documented act of proving any procedure, process, equipment,
material, activity, or system actually leads to expected results.
Objectives:
• Important element of quality control
• Ensures that procedure is reliable and produce accurate results.
• Regulatory requirement.
Validation

4. As per ICH guideline Q2 R(1)
Validation parameters
1. Specificity
2. Linearity
3. Range
4. Accuracy
5. Precision
6. Detection
limit
7.
Quantitation
limit
8.
Robustness
9. System
suitability
testing

5. Types of analytical
procedure
Identification
test
Quantitation test Assay
- Dissolution
(measurement
only)
- Content/ potency
Quantitation Limit
Parameters
Accuracy - + - +
Precision
-Repeatability
-Intermediate
precision
-
-
+
+
-
-
+
+
Specificity + + + +
Detection limit - - + -
Quantitation limit - + - -
Linearity - + - +
Range - + - +
- signifies that this
characteristic is not
normally evaluated.
+ signifies that this
characteristic is
normally evaluated
Degree of validation depends on test:

6. • A closeness of agreement between the value which is
accepted either as a conventional true value or an
accepted reference value and the value found.
• Sometimes termed trueness.
• Expressed in percent (%) recovery.
• Estimated across the specified range of analytical
procedure.
Accuracy
100
90
80
70
60

7. Methods to determine accuracy
 Direct method:
• Analysing a sample of known concentration and comparing the measured value to
the true value.
 Spiked placebo (Product matrix) recovery method :
• A known amount of pure active constituent is added to formulation blank, Then assayed.
• A sample containing active pharmaceutical ingredient is assayed.
• A results obtained are compared with expected results.

8. 𝑃𝑒𝑟𝑐𝑒𝑛𝑡 𝑟𝑒𝑐𝑜𝑣𝑒𝑟𝑦 =
𝐴𝑛𝑎𝑙𝑦𝑡𝑖𝑐𝑎𝑙 𝑟𝑒𝑠𝑢𝑙𝑡
𝑇𝑟𝑢𝑒 𝑣𝑎𝑙𝑢𝑒
× 100
 Standard addition method:
• A sample containing API is assayed.
• A known amount of pure active constituent is added, and the sample is again assayed.
• The difference between the results of the two assays is compared.

9. As per ICH guideline Q2 (R1)
• Should be assessed using a minimum of nine determinations over a minimum of three
concentration levels (80%, 100%, 120%), covering the specified range.
Acceptance criteria:
Assay : Recovery should be between 98% to 102%
Dissolution : 95% to 105%
Impurities:
If, specification is ≤ 0.2 = 85% to 115%
If, specification is > 0.2 = 90% to 110%

10. 𝑅𝑆𝐷 % =
100
𝑥̅
𝑛=1
𝑛
𝑥̅𝑖 − 𝑥̅ 2
𝑛 − 1
𝑅𝑆𝐷 % = Percentage relative standard deviation
𝑥̅𝑖 = Individual measurement in set of n measurement
𝑥̅ = Arithmetic mean of set
𝑛 = Number of set
• A closeness of agreement between a series of measurements
obtained from multiple sampling of the same homogeneous sample
under the prescribed conditions.”
• Expressed as the variance, standard deviation or coefficient of
variation of a series of measurements.
Precision
100
90
80
70
60

11. Precision may be considered at
three levels;
• Repeatability
• Intermediate precision
• Reproducibility
System Precision
Repeatability
Intermediate precision
Reproducibility
Flow variability
integration Detection
Injection
Derivatization
Weighing
dilution
Extraction
Sample
preparation
Instrument
Collaboration
trial
Time (long-term)
Operator
Reagent
Reference
standard

12. Method:
• A minimum of 9 determinations covering the specified range for the procedure.
(e.g. 3 concentrations/ 3 replicates each)
or
• A minimum of 6 determinations at 100% of the test concentration
• Expresses the precision under the same operating conditions over a short interval of time.
• Also termed intra-assay precision.
Repeatability

13. Intermediate precision
• A precision expresses within-laboratories variations: different days, different analysts,
different equipment, etc.
Reproducibility
• A precision between different laboratories (collaborative studies, usually applied to
standardization of methodology).
Acceptance value:
• % RSD value should be below 2% for drug product.
• % RSD value should be below 1% for active drug substances.

14. 1. Guideline, ICH., Validation of analytical procedures: text and
methodology. Q2 (R1), 2005. 1(20): p. 05.
2. Gupta, et al., Method validation of analytical procedures.
PharmaTutor, 2015. 3(1): p. 32-39.
3. Ravichandran, V., et al., Validation of analytical methods–
strategies & importance. International Journal of Pharmacy and
Pharmaceutical Sciences, 2010. 2(3): p. 18-22.
4. Nash, R.A., et al., Pharmaceutical process validation. 2003: Marcel
Dekker New York.
References

15. Thank you
The astounding difference between accuracy and precision is,
consistency.
- Jaaziel Charishma Ragland