Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Analytical Method Validation: Compilation of Relevant Legislation, Guidelines, and Literature

Dr. Michael Walser (Abschlußjahr: 2007)

This thesis presents a compilation of relevant legislation, guidelines, and publications on analytical method validation. The focus is set at the ICH regions. The presented documents are briefly summarised and supplemented by more detailed considerations from literature, when appropriate. The intention was, to prepare a paper which can be used to look-up quickly the most important facts and numbers in the field of analytical method validation and to trace back the provided information to the respective original document. Partly the form of a check-list was used to enable quick retrieval of the desired information. The content of the compilation is summarised below.

First of all, several definitions of the term “validation” are cited and briefly discussed. A well-known definition is for example included in ICH guideline Q2(R1): "The objective of validation of an analytical procedure is to demonstrate that it is suitable for its intended use". Document Q2(R1) entitled “Validation of Analytical Procedures: Text and Methodology” presents a discussion of the characteristics for consideration during the validation of the analytical procedures included as part of marketing authorisation applications submitted within the EU, USA and Japan. It can be regarded as a basic document for analytical method validation. In this guideline, several types of analytical procedures (e.g. identification, testing for impurities, assay) are listed and assigned to the respective recommended validation characteristics (accuracy, precision, specificity, detection limit, quantitation limit,  linearity, range). Furthermore, some guidance and recommendations are provided, on how to consider the various validation characteristics for each analytical procedure. Additional details on the practical evaluation of the validation  characteristics are presented in this thesis.

Application for a marketing authorisation is not the only reason for validating methods. Validation of analytical procedures is required by GMP as well. The "EU Guidelines to GMP" as published by the European Commission in 2005 include the statement "Analytical methods should be validated." EU Commission Directive 2003/94/EC on GMP which refers to these guidelines can be considered as a legal basis for analytical method validation. In the USA the corresponding legislation is laid down in 21 CFR 210/211 on cGMP. ICH document Q7A, entitled “GMP Guide for Active Pharmaceutical Ingredients”, also requires the validation of analytical procedures, unless the method is included in a relevant pharmacopoeia. However,  in this case the methods must at least be verified by demonstrating the generation of reliable results under actual conditions of use.

Prior to the start of the experimental validation activities, acceptance criteria have to be defined for the individual validation characteristics. The validation requirements depend for example on the intended use of the analytical method and the development stage of the drug product. Some typical acceptance criteria are presented in this thesis. Eventually, the requirements described in the European Pharmacopoeia (Technical Guide for the Elaboration of Monographs) and the USP (Validation of Compendial Methods), as for example system suitability testing, are briefly outlined and discussed.

Pages: 56,
Annexes: pages: 1