02497nas a2200253   4500000000100000008004100001260001500042653005100057653002100108653003800129653002400167653003100191653003100222653001100253100001600264700001300280700002000293245016300313856007200476300001100548490000800559520166200567022001402229       2026                            d  c2026-12-0110aCenter for drug evaluation and research (CDER)10aDrug development10aNew Approach Methodologies (NAMs)10aNonclinical studies10aNonclinical study category10aRegulatory decision making10amodels1 aYanning Hao1 aTyna Dao1 aNakissa Sadrieh00aApplications of in vitro new approach methodologies (NAMs) in drug development: A scoping analysis of titles of nonclinical study reports submitted to the FDA  uhttps://www.sciencedirect.com/science/article/pii/S0273230026002199  a1062460 v1723 aThe impact of New Approach Methodologies (NAMs) in drug development remains incompletely characterized. This scoping analysis used keyword searches of titles of nonclinical study reports submitted to the Center for Drug Evaluation and Research (CDER) from 2011 through 2025, followed by manual curation and classification by platform type and nonclinical study category. Among 574,963 nonclinical study reports submitted during the study period, 1381 in vitro NAM-related reports (0.24%) were identified across 981 applications. Despite this low representation, the annual number of identified in vitro NAM-related reports increased overall from 42 (0.14%) in 2014 to 186 (0.40%) in 2025, with 87.6% in Investigational New Drug applications (IND), 10.9% in New Drug Applications (NDA) and 1.5% in Biologics License Applications (BLA). Stem cell-derived models, co-culture systems, and sandwich culture systems accounted for most identified studies, whereas more complex systems, including 3D models, reconstructed tissue models, and microphysiological systems/organ-on-chip systems, were less frequent. Sandwich culture systems predominated in pharmacokinetic applications, stem cell-derived and co-culture systems were frequently used in pharmacology studies, and toxicology applications showed the greatest platform diversity. These findings suggest that in vitro NAMs serve as mechanistically informative, complementary tools rather than as direct replacements for traditional toxicology studies. Further integration among academia, regulators, and industry is will advance NAMs, inform regulatory guidance, and support fit-for-purpose use of the models.  a0273-2300