From application-first to science-first: A two-phase validation framework for complex in vitro NAMs

Validation of new approach methodologies increasingly requires developers to define a context of use (CoU) before establishing scientific credibility, constraining complex in vitro models. This CoU first strategy can impose a structural limitation on validation. We propose a two-phase framework that separates scientific validation from context-specific qualification, bridged by a shared data repository. Under this structure, the model's scientific capabilities and limitations inform the range of potential applications, rather than being constricted to the first CoU selected.