Beyond accuracy, precision and TAE: Direct assay validation against product specification aligned with USP

Abstract

Current validation methodologies - whether based on accuracy and precision or total analytical error (TAE) and risk - fall short when the analytical target profile (ATP) is defined in terms of product and process specifications, as is the case in the USP guideline for biological assay validation. In this paper, we critically examine the limitations of these existing methodologies and introduce a statistically correct methodology tailored to the ATP formulation. While this novel methodology is demonstrated in the context of potency assay validation in line with the USP guideline, it is broadly applicable to other analytical procedures governed by ICH Q2(R2), with only minor adaptations. A freely accessible online application has also been developed to facilitate discussion and adoption of the novel methodology in practice.