Applications of In vitro New Approach Methodologies (NAMs) in Drug Development: A Scoping Analysis of Titles of Nonclinical Study Reports Submitted to the FDA.

The 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, 1,381 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.