Method Validation in Pharmaceuticals

Standard Operating Procedure of Method Validation in Pharmaceuticals is describe in this post.

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1. Purpose:

1.1. To ensure the validity of the method for quantitative determination of active ingredients that applied for the products. 

2. Scope:

2.1. This procedure is applicable for validation of all methods performed of all products in Pharmaceuticals.

3. Responsibility:

3.1. Production Manager

3.2. QA Manager

3.3. QC Manager

3.4. QC Analyst

3.5. QA Officer

4. Procedure:

4.1. Pharmacopeial or any in-house testing method under which the material are imported for manufacturing at the premises, must be acquired from the manufacturer according to which the tests are reconfirmed

4.2. Quantitative Determination:

4.3. Contents:

Stated Quantity: as stated in the label of the specimen

4.4. Accuracy and Precision of the method:

4.4.1. Accuracy:

Definition: The accuracy of an analytical method is the closeness of the test results obtained by that method to the true value.


Inthe case of assay of a drug substance, accuracy may be determined by the application of the analytical method to an analysis of known purity (e.g Reference Standard) or by the comparison of the method with those of a second well-characterized analysis should be repeated 6 times of 6 samples.

4.5. Precision:   (Definition).

Then precision of an analytical method is the degree of agreement among individual test results when the method is applied repeatedly to multiple samplings of a homogenous sample. It is usually expressed as the standard deviation or relative standard deviation (coefficient of variation)Both accuracy and precision should be calculated by repeating the analysis 6 times and successfully applying the following formulae:

4.5.1. Precision (%) =
                        xi =     value resulting from each single trial 
n     number of trials (6)
x     average value out of n trials 
                    t 0.05 =   Students “t” (df = 5; 95%  probability)

4.5.2. Accuracy  

            Accuracy  (%)             = x  min    .    100
            Where:  x min =     value found out of n trials

                                x         =     average value of n trials

4.6. Results should be calculated as:

No. of trials Calculation of value found

             Results x  i in % age  / tab xi2

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                        n = 6 ∑ x i =                 ∑ x2 i = 

x                              =
xmin                 =
Precision (%)         =
Accuracy (%) =

4.7. Linearity:

The linearity of an analytical method is its ability to elicit test results that are directly proportional to the concentration of analysis in samples within a given range

4.7.1. Linearity should be established across the range of the analytical procedure. It should be established initially by visual examination of a plot of signals as a function of analyte concentration of content. If there appears to be linear relationship, test result should be established by appropriate statistical methods (e.g by calculation of a regression line by the method of least squares).  For the established of the linearity a minimum of 5 sample concentration normally be used. For measuring the linearity of assay of a drug substance the test concentration is used for a finished product from 80% to 120% of the tested specimen

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