In July 2015, the FDA released new comprehensive guidance for validation of analytical methods. The guidance applies the modern integrated lifecycle approach with related new requirements for using quality-by-design components, risk assessment, design space, and continuous improvement. The guidance will significantly change the way FDA regulated methods will be developed, validated, and used. In addition to changes to method scopes and lengths, the guidance also includes new sections, and revisions to essential information, reference standards, re-validation, and method development.
Scope and content of the guidance
Unlike the 2000 version, the revision extends its scope to include biologics. That means that the guideline’s requirements apply to new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and related variation applications, as well as to Type II Drug Master Files. Investigational new drug applications (INDs) are not included in the scope of the document.
Lifecycle management of analytical procedures
According to the new guidance, analytical methods should be reviewed during the lifecycle of a product as revalidation may be indicated should a process parameter drift or be redefined. Further, the guidance recommends that the method be studied over time; specifically “Trend analysis on method performance should be performed at regular intervals to evaluate the need to optimize the analytical procedure or to revalidate all or a part of the analytical procedure.”
Related Article: The Analytical Lifecycle Approach
Analytical method transfer studies
A final key point concerns the transfer of methods between laboratories. In these situations, to evaluate accuracy and precision, the guidance suggests that a sufficient number of representative samples are used by both the originating and receiving laboratories to perform comparative studies. Further, any inter-laboratory variability should be noted
Essential to establishing the suitability of the method is to demonstrate that the method can detect changes in a quality attribute. One common approach is to challenge the method by using samples spiked with target analytes and various interferences. Further, you may add samples that have undergone various laboratory stress conditions; and product samples that are either aged naturally of which have been stored under accelerated temperature and humidity conditions.
LABCAST: Be sure to attend Ludwig Huber’s Lab Manager Academy webinar, “Understanding the Final FDA Guidance for Validation of Analytical Methods” on June 8, or afterward at www.labmanager.com/FDA-guidance to watch the archived video.
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