Accuracy and precision presentation

validation parameter

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)

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.   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) S hould 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. = Percentage relative standard deviation = Individual measurement in set of n measurement = Arithmetic mean of set = 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 p recision 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. Guideline, ICH., Validation of analytical procedures: text and methodology. Q2 (R1), 2005. 1 (20): p. 05.  Gupta, et al., Method validation of analytical procedures. PharmaTutor, 2015. 3 (1): p. 32-39. Ravichandran, V., et al., Validation of analytical methods–strategies & importance. International Journal of Pharmacy and Pharmaceutical Sciences, 2010. 2 (3): p. 18-22. 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