Information about Validation04

Published on August 9, 2014

Author: saidadheeravath



PowerPoint Presentation: Validation Part 4: QC-related validation Supplementary Training Modules on Good Manufacturing Practice Validation: Validation Introduction Why is analytical monitoring necessary? What is the purpose of analytical validation? Validation: Validation Objectives To introduce the concepts of : Protocol development Instrument qualification Analytical procedure Extent of validation Method transfer Chemical and physical, biological, and microbiological test validation PowerPoint Presentation: Validation of analytical procedures requires: Qualified and calibrated instrument s Documented methods Reliable reference standards Qualified analysts Sample integrity Validation PowerPoint Presentation: Validation protocol for analytical method Statement of purpose and scope Responsibilities Documented test method List of materials and equipment Procedure for the experiments for each parameter Statistical analysis Acceptance criteria for each performance parameter Validation PowerPoint Presentation: Qualification of the instrument Make, model and maker’s manual Modifications Installation and operational qualification Calibration programs Maintenance schedules Validation Validation: Characteristics of analytical procedures (1) Accuracy Precision Repeatability Reproducibility Validation Validation: Validation Relationship between accuracy and precision Accurate AND Precise Validation: Characteristics of analytical procedures (2) Ruggedness Robustness Variability caused by: Day-to-day variations Analyst-to-analyst Laboratory-to-laboratory Instrument-to-instrument Chromatographic column-to-column Reagent kit-to-kit Instability of analytical reagents Validation Validation: Characteristics of analytical procedures (3) Linearity and range Specificity Sensitivity Limit of detection Limit of quantitation Validation Validation: Table of values (x,y) x y  # Reference material mg/ml Calculated mg/ml 1 0.0100 0.0101 2 0.0150 0.0145 3 0.0200 0.0210 4 0.0250 0.0260 5 0.0300 0.0294 6 0.0400 0.0410 Validation Validation: Linearity Statistics Intercept -0.0002 Limit of Linearity and Range 0.005 – 0.040 mg/mL Slope 1.0237 Correlation coefficient Pearson 0.9978 Olkin and Pratt 0.9985 Relative procedure standard deviation 3.4% Validation Validation: LOQ, LOD and SNR Limit of Quantitation Limit of Detection Signal to Noise Ratio noise Peak A LOD Peak B LOQ Baseline Validation Validation: Different classes of analytical tests Class A: To establish identity Class B: To detect and quantitate impurities Class C: To determine quantitatively the concentration Class D: To assess the characteristics Validation Validation:     * A degree of bias may be allowed Characteristic A B quant . B Limit test C D Accuracy     X   X X* Precision   X   X X Robustness X X X X X Linearity and range   X   X X Specificity X X X X X Limit of detection   X     Limit of quantitation   X       Validation Validation: Extent of validation New methods require complete validation Pharmacopoeial methods require partial validation (or verification) Significant changes mean partial revalidation equipment changes formula changed changed suppliers of critical reagents Validation Validation: Analytical method transfer Method transfer protocol and procedure precision accuracy ruggedness Written and approved specific test method Proficiency check Formal acceptance by new laboratory Validation Validation: Chemical laboratory validation requirements (1) Balances Chromatography HPLC, HPTLC, GC, TLC Dissolution or disintegration apparatus Karl Fischer moisture determination Melting, softening or freezing point apparatus Ovens, refrigerators, incubators Validation Validation: Chemical laboratory validation requirements (2) pH meter Polarimeter - optical rotation Refractometer Spectrophotometer UV/Vis, IR, FTIR, Raman, AA Timers Viscometer Volumetric equipment Validation Validation: Validation Typical validation of HPCL assay (1) System suitability (performance check) system precision column efficiency symmetry factor capacity factor Validation: Validation Typical validation of HPLC assay (2) Method validation specificity accuracy precision linearity robustness Validation: Biological assays Can be difficult to "validate" "Validity" on a case by case basis Strictly adhere to the Biological Testing monographs in pharmacopoeias Validation Validation: Microbiological testing requiring validation Microbial limit testing Microbial count Sterility testing Preservative effectiveness testing Environmental monitoring program Biological testing Validation Validation: Validation of microbial test procedures (1) Virtually impossible to completely validate test procedures for every microorganism Neutralize /inactivate inhibitory substances, or dilute Periodic media challenge Media QC Reliable methods Validation Validation: Validation of microbial test procedures (2) Incubation temperature and time Media may not grow all microorganisms Variations in media may affect recovery Inhibitory disinfectants or preservatives Sample procedures handling, storage, transport Validation Validation: Microbiological viable count method validation (1) Methods pour plate / spread plate membrane filtration Most Probable Number S ample size Test dilution Inoculation size Validation Validation: Microbiological viable count method validation (2) Membrane filtration conditions Incubation conditions Acceptance criteria Validation Validation: Sterility testing validation requirements Media growth promotion, sterility, pH Product validation Stasis testing Environmental monitoring Negative controls Challenge organisms Validation

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