QUALIFICATION CORE ABSTRACT The Qualification Core is the “trust but verify” part of the proposed Translational Center for Microphysiological Systems-Based Drug Development Tools for Pregnancy and Women's Health. The vision of the Center is to overcome existing limitations and challenges in pre-clinical and clinical testing of drug candidates for pregnant women. The goal of the Qualification Core is to facilitate commercialization and widespread use of the MPS for pregnancy and women’s health as drug development tools. The Core will be based at Texas A&M University; it is a direct extension of the TEX-VAL Tissue Chip Testing Center (funded by NCATS 2016-2020) that has since evolved into a self-sustained university-based private-public partnership – TEX-VAL Consortium. The latter is funded through annual fees by a diverse set of stakeholders (Sanofi, Merck Healthcare, Bristol Myers Squibb, Roche, Unilever, American Chemistry Council, US EPA and the National Toxicology Program). Since 2016, TEX- VAL tested over 30 MPS from both academia and companies. TEX-VAL experience with careful evaluation of diverse MPS and promoting their use by the industry and regulators is the foundation of the Qualification Core and a unique strength of the Center. The Core’s faculty and staff have experience in toxicology, regulatory science, validation of alternative methods, and all proposed assays and PBPK modeling. The Core’s work will be organized around three Specific Aims. First, the Core will establish functionality, reproducibility, robustness, and reliability of 5 MPS platforms as drug development tools for pregnancy and women's health. By focusing on key feto-maternal tissues supporting pregnancy (placenta, fetal membranes, decidua, and cervix), we will enable recapitulation of pregnancy-associated physiological barriers. We will be testing 4 compounds (3 small molecules to 1 biological) in one of the 5 MPS models each year. We selected Aspirin, Celecoxib, Sofosbuvir and exosome- encapsulated IL-10 as candidates for drug repurposing in pregnant women. The proposed qualification contexts of use are: (i) to characterize human-relevant pharmacokinetic profile of a drug during pregnancy, including information on drug amounts in different intra-uterine tissue compartments (both maternal and fetal), and inter- individual variability; and (ii) to evaluate potential human-relevant toxic (pharmacodynamic) effects of a drug on intra-uterine tissues during pregnancy. Each round of testing will be based on the scientific confidence framework as published in 2023 by the National Academies and will use a standardized workflow consisting of material transfer, testing of cell seeding and drug binding, replication of the data from the Resources Core, and deposition of data/protocols to the MPS Database and preparation of FDA ISTAND qualification packages. Second, the Core will manage and assure quality of the data that will be derived from testing reference compounds by follow...