The Role of Prevalidation in the Development, Validation and Acceptance of Alternative Methods

Abstract

Experience has shown that the outcome of large and expensive validation studies on alternative methods can be compromised if their managers do not insist that optimised test protocols and proof of their performance are submitted before the start of the formal validation study. One way for the sponsors of validation studies to confirm both the likely relevance of a method for its stated purpose and its readiness for validation would be to require a prevalidation study before formal validation was contemplated. This process would involve the developers (or other proponents of the method) and selected independent laboratories in protocol refinement (Phase I) and protocol transfer (Phase II). The optimised protocol would then be assessed in a protocol performance phase (Phase III), which would involve the testing of a relevant set of coded test materials and an evaluation of a proposed prediction model. In certain circumstances, a successful outcome of Phase III might be sufficient for promotion of the regulatory acceptance of the method. Normally, however, the method would proceed to a formal validation study. The European Centre for the Validation of Alternative Methods, a recognised validation authority, now proposes to introduce this prevalidation scheme into its validation strategy.