%0 Journal Article
%T Human-Relevant Models Need Pharmacological Qualification Before They Can Replace Conventional Translation Pathways
%A Andrei Popescu
%A Mihai Ionescu
%A Elena Stan
%A Cristina Radu
%J International Journal of Pharmaceutical Research and Allied Sciences
%@ 2277-3657
%D 2026
%V 15
%N 2
%R 10.51847/x07yIx7SHv
%P 114-125
%X Human-relevant organoids, tissue models, and microphysiological systems increasingly reproduce biological features that conventional cultures or animal models represent incompletely. Yet biological resemblance is not equivalent to pharmacological qualification. A model can preserve human genetics, architecture, mechanical cues, or disease phenotypes while failing to reproduce clinically relevant exposure, target engagement, response kinetics, toxicity, interindividual variability, or interlaboratory performance. This Translational Perspective argues that replacement decisions should therefore be based on context-specific pharmacological qualification rather than on human origin or physiological complexity alone. Evidence from patient-derived organoids, organ-on-chip systems, quantitative pharmacokinetic models, mechanistic toxicity platforms, and multicentre reproducibility studies shows that strong predictive performance is achievable, but generally within defined diseases, compounds, endpoints, exposure conditions, and experimental architectures. We distinguish biological fidelity, exposure fidelity, mechanistic-readout validity, reproducibility, and human-pharmacology benchmarking as analytically separate requirements. This evidence supports a qualification approach in which the permissible translational claim is constrained by the least-resolved requirement that is necessary for the intended decision. Human-relevant models may consequently replace conventional pathways for narrowly qualified questions while remaining complementary for broader or insufficiently benchmarked decisions.
%U https://ijpras.com/article/human-relevant-models-need-pharmacological-qualification-before-they-can-replace-conventional-transl-gclovwhv2hykxhx