Qualification, Validation, and Verification 3

Therefore, given the following from FDA's Guide to Inspections of Pharmaceutical Quality Control Laboratories: "Methods appearing in the USP are considered validated and they are considered validated if part of an approved ANDA" (8), the use of Method 3 would be valid if the conditions stated are met in testing the material of interest. The same FDA document states "For compendial methods, firms must demonstrate that the method works under the actual conditions of use," which, for the sake of this article, will be considered verification. Chapter ‹1047› provides several other procedures, all also validated, that could be considered given test material that does not satisfy the conditions for Method 3.
Remember the purpose. It is important to bear in mind the purpose of the method to be validated. If the method is intended to serve as an alternative to a pharmacopeial method, then one must establish its equivalence to the pharmacopeial method in terms of the end result. Remember that the purpose of a method in the pharmacopeia is to determine whether the pharmacopeial article (for which a monograph exists in the pharmacopeia) satisfies the requirements in the monograph. If instead the purpose behind the use of a pharmacopeial method is for a purpose other than demonstrating that the article complies with monograph requirements (for example, imagine that total organic carbon is to be determined using Chapter ‹643› "Total Organic Carbon"), it is not necessary to perform the validation relative to the pharmacopeial results. This means that the validation should be conducted relative to the specific purpose for which it is intended. Also implicit in this is the use of a nonpharmacopeial method to determine something for which a pharmacopeial method exists, but again for purposes unrelated to satisfying a monograph requirement. In such a case, it is unnecessary to consider validating the method relative to that in the pharmacopeia.
If the use of the term validation is restricted to mean the demonstration of suitability of a method or process for its intended purpose, and the term verification for the demonstration that the previously validated method is suitable for use given specific experimental conditions that may or may not be appropriate given the conditions present during the validation, the terminological situation may be clarified.

Figure 1
These actual conditions include specific ingredients or products, specific laboratory personnel, equipment, and reagents. There are, however, instances in the literature where this distinction is not maintained. Consider the dictionary definition given previously for validation and its use of verification as a synonym for validation. Further muddying of the waters occurs when phrases such as "system suitability tests" (see Figure 1 and the system-suitability section in Chapter ‹621› "Chromatography"). The phrase also appears in the "Suitability of the Counting Method in the Presence of Product" section of Chapter ‹61› "Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests", the "Suitability of the Test Method" section of Chapter ‹62› "Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms", and the "Validation Test" section of Chapter ‹71› "Sterility Tests." (1). In all cases, the intention is to ensure that the validated method will work under the specific conditions the analyst plans to use. This means that a chromatographic system can deliver resolution and reproducibility on par with the system used during validation. For the two microbiology test chapters for nonsterile products, one must show that microbial growth in the presence of the article to be tested is not hindered. This is because the method depends on unencumbered microbial growth for it to work. In other words, a condition established in validating the method initially was unhindered microbial growth. The use of "validation test" in Chapter ‹71› is unfortunate because the intention was again to demonstrate that microbial growth is not hindered, as indicated in the following text:

No comments: