When developing a new method for a new biopharmaceutical product, optimizing an existing method for an existing product, or when changing a release method for a licensed product, many development and validation elements should be considered.1–4 Analytical method validation (AMV) follows analytical method development (AMD).5
Portions of the AMD data that are summarized in the AMV protocol may not need to be repeated during validation as long as the AMD data were generated under GMP conditions. Therefore, AMV should not be used to modify or change critical assay elements (for example, statistical data reduction). We must be careful not to invalidate the AMD data that was used to establish robustness, system suitability, and possibly other performance characteristics.6 The formal AMV process should ideally only be a confirmation of test method performance that can be considered the least significant overall task from an operational perspective because we are usually only confirming but not improving anything in this process. The AMV process is often the most important task from a compliance perspective (inspections and submissions) and needs to be executed well mostly for this reason.6Table 1 lists all International Conference on Harmonization (ICH) characteristics that may apply to a particular test procedure, including the corresponding minimum requirements, reported results, and acceptance criteria. Some AMD and AMV elements were added to the required ICH characteristics. In practice, more data may need to be generated. For example, three spike levels may not be sufficient to evaluate accuracy and repeatability precision over the valid assay range. Several critical elements of the AMV protocol are discussed in more detail below.