Vagueness in the ICH Q2A and Q2B guidelines necessitates effective protocol design and data analysis. For specificity (detection in the presence of interfering substances), the goal is statistical differences with meaningful implications on assay performance. Linearity (results directly proportional to concentration of analyte in the sample) is typically demonstrated via least squares regression. Accuracy (difference between measured and true values) usually is presented as a percent of nominal. Precision analysis is vital because it supports claims of accuracy and linearity. A well-designed experiment and statistically relevant methods will facilitate method validation in accordance with ICH guidelines.
Approaches other than those set forth in this guideline may be applicable and acceptable. It is the responsibility of the applicant to choose the validation procedure and protocol most suitable for their product. However, it is important to remember that the main objective of validating an analytical procedure is to demonstrate that the procedure is suitable for its intended purpose. Due to their complex nature, analytical procedures for biological and biotechnological products in some cases may be approached differently than in this document.3
The ICH guidelines suggest combining individual validation characteristics to minimize total testing. A statistical approach to validation of analytical methods can minimize the amount of testing while meeting the requirements of the guidelines. This assertion is based on the following comment from the ICH Q2B document:
In practice, it is usually possible to design the experimental work such that the appropriate validation characteristics can be considered simultaneously to provide a sound, overall knowledge of the capabilities of the analytical procedure, for instance: specificity, linearity, range, accuracy and precision.3
TYPES OF ANALYTICAL METHODS
The elements of the analytical method requiring proof through validation as contained in the ICH Q2A guideline are summarized here in Table 1.4