{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:42:29Z","timestamp":1792208549816,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:p>\n                    New Approach Methodologies (NAMs) represent a paradigm shift in drug development and regulatory science, offering human\u2010relevant alternatives to traditional preclinical models. This mini\u2010review highlights recent advances in NAM development, validation, and regulatory application from FDA's Division of Applied Regulatory Science (DARS). We describe\n                    <jats:italic>in silico<\/jats:italic>\n                    NAMs including quantitative systems pharmacology (QSP) modeling for opioid overdose scenarios, (quantitative) structure\u2013activity relationship ((Q)SAR) modeling for toxicity prediction and drug\u2013drug interaction assessment, and multi\u2010omics approaches for pharmacodynamic biomarker discovery. Additionally, we present\n                    <jats:italic>in vitro<\/jats:italic>\n                    NAMs including human\u2010induced pluripotent stem cell (hiPSC)\u2010derived neural networks for opioid pharmacology assessment, microphysiological systems (MPS) for pulmonary drug permeability, gastrointestinal models for intestinal transport, and standardized cardiac ion channel and hiPSC\u2010CM MEA assays for proarrhythmia risk prediction. These case studies demonstrate how NAMs can reduce reliance on animal studies while improving translation to clinical outcomes. The NAMs described here range from exploratory research tools to approaches actively informing regulatory submissions review. The integration of\n                    <jats:italic>in silico<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    NAMs into regulatory decision\u2010making frameworks represents a critical step toward more efficient, human\u2010relevant drug development and safety assessments.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70472","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:19:06Z","timestamp":1788419946000},"page":"1250-1254","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in New Approach Methodologies at\n                    <scp>FDA<\/scp>\n                    's Division of Applied Regulatory Science"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1123-3152","authenticated-orcid":false,"given":"Ksenia","family":"Blinova","sequence":"first","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7544-0666","authenticated-orcid":false,"given":"Kimberly","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-5820","authenticated-orcid":false,"given":"Anik","family":"Chaturbedi","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4895-2782","authenticated-orcid":false,"given":"Jahan","family":"Cooper","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-8742","authenticated-orcid":false,"given":"Tromondae K.","family":"Feaster","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-3389","authenticated-orcid":false,"given":"Paula L.","family":"Hyland","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6307-2314","authenticated-orcid":false,"given":"Lidiya","family":"Stavitskaya","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-4840","authenticated-orcid":false,"given":"Wendy W.","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1984-8026","authenticated-orcid":false,"given":"Jeffry","family":"Florian","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0463-9699","authenticated-orcid":false,"given":"Rodney","family":"Rouse","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"Division of Applied Regulatory Science.US Food and Drug Administration<https:\/\/www.fda.gov\/about\u2010fda\/cder\u2010offices\u2010and\u2010divisions\/division\u2010applied\u2010regulatory\u2010science>. 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