Qualification, Validation, and Verification 1

By: David A. Porter
The terms qualification, validation, and verification occur numerous times in US Pharmacopeia 29 (1). Qualification is found in Chapters ‹1035› "Biological Indicators for Sterilization," ‹1043› "Ancillary Materials Cell, Gene, and Tissue-Engineered Products," ‹1046› "Cell and Gene Therapy Products," and ‹1119› "Near-Infrared Spectrophotometry," among others. Validation appears in ‹1225› "Validation of Compendial Procedures," ‹1223› "Validation of Alternative Microbiological Methods," ‹1010› "Analytical Data—Interpretation and Treatment," ‹1043› "Ancillary Materials for Cell-, Gene-, and Tissue-Engineered Products," ‹1117› "Microbiological Best Laboratory Practices," ‹1120› "Raman Spectrophotometry," and many others. Verification appears in ‹1010› "Analytical Data—Interpretation and Treatment," ‹1035› "Biological Indicators for Sterilization," ‹1035› "Biological Indicators for Sterilization," ‹85› "Bacterial Endotoxins Test," and others. The terms also are present in documents from the US Food and Drug Administration, the Environmental Protection Agency (EPA), and the International Conference on Harmonization (ICH). Given the numerous definitions for the three terms, this article in part is intended to provide an approach to fostering more consistency in the usage of the terms. A recent issue of the Pharmacopeial Forum (2) had a diagram from a proposed General Chapter ‹1058› "Analytical Instrument Qualification" that was intended to show "...four critical components involved in the generation of reliable and consistent data (quality data)." From most to least critical, the components were quality-control check samples, system suitability tests, analytical methods validation, and analytical instrument qualification. In this article, consider system-suitability tests to be the same as verification. Why this usage should be acceptable will be explained. This article will consider validation and verification in detail. Reference to analytical instrument qualification is made. For further discussion of the top tier, "Quality Control Check Samples," refer to Chapter ‹1058› "Analytical Instrument Qualification" (1).
Qualification
Qualification of analytical instrumentation is essential for accurate and precise measurement of analytical data. If the instrumentation is not qualified, ensuring that the results indicated are trustworthy, all other work based upon the use of that instrumentation is suspect. For the purposes of this article, the assumption will be made that the foundation of validation and verification work to follow is based solidly upon well-qualified instrumentation. Validation
Definitions. Numerous documents provide definitions of validation. A dictionary definition (3) of validation includes "...the process of determining the degree of validity of a measuring device," and for validate: "to make legally valid," with synonyms "verify, substantiate." Clearly, the synonyms do not distinguish between validation and verification, so let us now turn to definitions provided by other sources. USP chapter ‹1225› "Validation of Compendial Procedures" provides the following:
"Validation of an analytical procedure is the process by which it is established, by laboratory studies, that the performance characteristics of the procedure meet the requirements for the intended analytical applications."
From the ICH document Validation of Analytical Procedures: Text and Methodology:
However, it is important to remember that the main objective of validation of an analytical procedure is to demonstrate that the procedure is suitable for its intended purpose