Validation of analytical procedures

Validation of an analytical procedure is the process by which the performance characteristics of the procedure are shown to meet the requirements for the intended application. Validation is very important to meet the requirements of regulatory agencies, such as, the FDA (Food and Drug Administration). It is also necessary to ensure that the method can work reproducibly and reliably in QC (Quality Control) laboratories for support of manufacturing. 

The major steps in the evaluation process are listed below, although some may be changed or eliminated based on the particular situation. 

Accuracy. The accuracy of an analytical procedure is the closeness of test results to the true value, as determined by analysis of a Reference Standard or by comparison with the results obtained by a second, well-characterized procedure. 

In the assay of a drug in a formulated product, a reference standard may be prepared in the form of a synthetic mixture of the drug product components to which known amounts of the analyte have been added. In the quantitative analysis of impurities accuracy can be assessed on samples of the drug spiked with known amounts of impurities. 

Accuracy is calculated as the difference between the mean and the accepted true value, together with confidence intervals. It is recommended that accuracy should be assessed 

---

International Conference on Harmonization (Step 5, 1996), Q24A Validation of Analytical Procedures, Definitions and Terms. 

The second guideline, ICH Topic Q2B, Validation of analytical procedures Methodology, reached Step 4 in November 1996, was approved by the CPMP in Europe in December 1996 (CPMP/ICH/281/95) and came into operation in June 1997. It is complementary to the first guideline and provides some guidance and rec-... 

Q2(R1) Validation of Analytical Procedures Text and Methodology Impurities... 

GLl Validation definitions Validation of analytical procedures definition and terminology... 

GL2 Validation methodology Validation of analytical procedures methodology... 

A pharmacopoeial reference substance is intended for the determination of the main component of a substance or for the active ingredient of a pharmaceutical formulation which is usually present at a high proportion of the total. The reference substance is to be used as a primary standard in a specific method validated as prescribed in the ICH Guideline Validation of Analytical Procedure Methodology" (Technical Guide for the Elaboration of Monographs 1996 ICH Guideline 1997). the reproducibility of which is known. This is taken into account when the limits of acceptance (tolerance) for the substance or product are fixed (Daas and Miller 1997,1998). 

ICH Guideline (1997) Validation of analytical procedure methodology. IFPMA, Geneva, (ref. 31)... 

ICH Expert Working Group, Q2B Validation of Analytical Procedures Methodology, International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use, 1996. 

International Conference on Harmonization, Guideline on validation of analytical procedures definition and terminology, Fed. Reg., 60(40), 11260 (1995). 

International Conference on Harmonization, Validation of analytical procedures methodology, step 2. The Third International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Yokohama, Japan. Nov. 29-Dec. 1, (1995). 

Comparison of test values with a conventional true value ( reference value ) of a (certified) reference material (RM, CRM). In method development and validation of analytical procedures, the comparison of experimental results with standards of diverse kind (laboratory standards, certified reference materials, primary standards) plays an essential role. The decision as to whether an experimental result hits the reference value depends not only from the result itself but also from its uncertainty interval. 

J. Ermer and J. S. Landy, Validation of analytical procedures, Encyclopedia of Pharmaceutical Technology, Marcel-Dekker, Inc., 2002, pp. 1-22. 

Guidance for Industry, Q2B Validation of Analytical Procedures Methodology, US Department of Health Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine. 

Validation of analytical procedures methodology Guideline on Impurities in New Drug Substances Guideline on Impurities in New Drug Products Availability Notice... 

ICH Q2B. Validation of Analytical Procedures Methodology. ICH Harmonised Tripartite Guideline, November 1996. http //www.fda. gov/ downloads/Regulator%20yInformation/Guidances/UCM128049.pdf. Accessed on 04th September 2012. 

Laboratory Controls General Controls Testing of Intermediates and APIs Validation of Analytical Procedures Certificate of Analysis Stability Monitoring of APIs Expiry and Retest Dating Reserve/Retention Samples Validation... 

Source International Conference for Harmonization. Validation of Analytical Procedures ... 

International Conference on Harmonisation (ICH) Q2A, Text on validation of analytical procedures March 1995. 

Analytical procedures used as part of a registration dossier in Europe, Japan, or the United States of America should be validated according ICH guideline Q2(R1) Validation of Analytical Procedures Text and Methodology. The objective of analytical method validation is to demonstrate that the analytical procedure is suitable for its intended purpose. Depending on the type of analytical procedure, evaluation of different validation parameters is required. The four most common types of analytical procedures described in this ICH guideline are... 

International Conference of Harmonization Q2B, Validation of Analytical Procedures Methodology, Geneva, Switzerland, 1996. 

---