Beyond Accuracy, Precision and TAE: Direct assay Validation Against Product Specification Aligned with USP  

Traditional validation methodologies - whether based on accuracy and precision or total analytical error (TAE) and risk - focus primarily on the intrinsic performance of an analytical procedure, largely disregarding its intended use environment. In contrast, this paper introduces a novel validation methodology that evaluates whether a procedure performs sufficiently well when integrated into its actual context of use. This approach aligns more closely with the intent of USP <1033> , where the Analytical Target Profile (ATP) is stated in terms of product and process requirements, rather than abstract analytical procedure requirements. By shifting the focus from theoretical performance to practical applicability, the proposed methodology ensures that analytical procedures meet quality requirements in practice - not just in principle. Although demonstrated here for potency assay validation in accordance with the USP <1033> guideline, the methodology is broadly applicable to other analytical procedures governed by ICH Q2(R2), with only minor adaptation. A freely accessible online application is provided to facilitate discussion and adoption of the novel methodology in practice.