Analytical method validation as per ich and usp

Analytical method validation is a process of documenting/ proving that an analytical method provides analytical data acceptable for the intended use.After the development of an analytical procedure, it is must important to assure that the procedure will consistently produce the intended a precise result with high degree of accuracy. The method should give a specific result that may not be affected by external matters. This creates a requirement to validate the analytical procedures. The validation procedures consists of some characteristics parameters that makes the method acceptable with addition of statistical tools.

1. Analytical method validation as per ICH and USP SHREYAS B.R 1 ST MPHARM QA

2. CONTENTS Introduction Objective Types of analytical procedures to be validated Validation parameters as per ICH and USP Conclusion Reference

3. INTRODUCTION Validation is the documented act of proving that any procedure, process, equipment, material, activity or system actually leads to the expected result. Analytical method validation is a process of documenting/proving that an analytical method provides analytical data acceptable for the intended use. A pharmaceutical drug product must meet all its specifications through out its shelf-life. The method of analysis used must be validated. This is required to ensure the product’s safety and efficacy through out all phases of its shelf-life.

4. Objective The main objective of analytical validation is to ensure that a selected analytical procedure will give reproducible and reliable results that are adequate for the intended purpose. This is applicable to all the procedure either pharmacopoeial or non pharmacopoeial.

5. Types of analytical procedures to be validated The required validation parameters also termed “ analytical performance characteristics”, depends upon the type of analytical method. Pharmaceutical analytical methods are characterized into 5 general types Identification tests Potency assays Limit tests for the control of impurities Impurity tests- quantitative Specific tests

6. Validation parameters as per ICH/USP USP Specificity Linearity or range Accuracy Precision Limit of detection Limit of quantitation Ruggedness Robustness ICH Specificity Linearity Range Accuracy Precision Limit of detection Limit of quantitation Robustness

7. Accuracy Definition : “The accuracy of an analytical procedure is the closeness of agreement between the values that are accepted either as conventional true values or an accepted reference value and the value found”. Determination Assay Drug substance Drug product Impurities (quantitation)

8. Recommended data: Assessed by 9 determinations over a minimum of 3 concentration levels covering a specified range. Limit Typical accuracy of the recovery of the drug substance is expected to be about 99 – 101%. Typical accuracy of the recovery of the drug product is expected to be about 98 – 102%.

9. 2. Precision Definition : “The closeness of agreement (degree of scatter) between a series of measurements obtained from multiple samplings of the same homogeneous sample”. Precision includes: Repeatability Intermediate Precision Reproducibility

10. Repeatability Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability should be assessed using a minimum of 9 determinations covering the specified range. Intermediate precision Intermediate precision expresses variations within laboratories, such as different days, different analysts, different equipment etc. Reproducibility Reproducibility expresses the precision between laboratories.

11. Following parameters should be reported Standard deviation. Relative standard deviation. Concentration µg/ml Absorbance SD and %RSD 8 0.337 0.00041, 1.223% 0.348 0.341 12 0.575 0.0106, 1.815% 0.583 0.596 20 0.967 0.0091, 0.933% 0.985 0.978

12. 3. Limit of detection It is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated. 4. Limit of quantitation It is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy.

13. Determination of LOD and LOQ Limit of detection Method Based on visual examination. Based on standard deviation of response and slope. Signal to noise ratio 2:1 or 3:1 Limit of quantitation Method Based on visual examination. Based on standard deviation of response and slope. Signal to noise ratio 10:1

14. 5. Specificity Definition : Specificity is the ability to assess unequivocally the analyte in presence of components which may be expected to be present. Determination Identification tests Assay and impurity test(s) Impurities are available Impurities are not available

15. 6. Linearity Definition : The Ability of the method to obtain test results that are directly proportional to concentration within a given range. Method : dilution of stock solution/separate weightings Minimum 5 concentrations are used.

16. 7. Range Definition : The interval between the upper and lower concentrations of analyte in the sample that have been demonstrate to have a suitable level of precision, accuracy, and linearity. Established by confirming that the method provides acceptable degree of linearity, accuracy, and precision. Specific range dependent upon intended application of the procedure.

17. Assay : 80 to 120% of test concentration. Content uniformity : 70 to 130% of test concentration. Dissolution : 20% to 120% Impurities reporting level : 120% of specification limit (with respect to test concentration of API)

18. 8. Ruggedness Definition : The ruggedness of an analytical method is the degree of reproducibility of test results obtained by the analysis of the same samples under a variety of conditions, such as different laboratories, different analysts, different instruments, different days, etc. Certain may include- Source Concentration and stability of solution Heating rate Column temperature Humidity

19. 9. Robustness Definition : “The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage”. Determination: The evaluation of robustness should be considered during the development phase and depends on the type of procedure under study.

20. Variations may include: stability of analytical solution variation of pH in a mobile phase different column (lot/supplier) temperature flow rate

21. 10. System suitability System suitability testing is an integral part of many analytical procedures. The tests are based on the concept that the equipment, electronics, analytical operations and samples to be analyzed constitute an integral system that can be evaluated as such. System suitability testing has been recommended by USP in HPLC procedures.

22. Conclusion When the method is properly validated consistent, reliable and accurate results are obtained. Analytical method validation is an important analytical tool to ensure the accuracy and specificity of the analytical procedures with a precise agreement. Validation of analytical methods is also required by regulations. Hence it is very important to validate any analytical method that has been developed.

23. References Gupta P. C method validation of analytical procedures. pharmatutor. 2015;3(1):32-39. Lopez P, Buffoni E, Pereira F, Vilchez Quero J. Analytical Method Validation. Wide Spectra of Quality Control. 2011;:1-19. [Internet]. Who.int. 2016 [cited 2 March 2019]. https:// www.who.int/medicines/areas/quality_safety/quality_assurance/Guideline_Validation_AnalyticalMethodValidationQAS16-671.pdf Daksh S. VALIDATION OF ANALYTICAL METHODS – STRATEGIES & SINGFICANCE. International Journal of Research and Development in Pharmacy and Life Sciences. 2015;4(3):1489-1497 . [Internet]. Ich.org. [cited 2 March 2019]. https://www.ich.org/fileadmin/PublicWebSite/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1Guideline.pdf Sharma P. validation in pharmaceutical industry. 2nd ed. Delhi: Vandana publications; 2007. P: 425-448

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