02650nas a2200301   4500000000100000000000100001008004100002260001500043653001700058653002600075653003200101653003800133653002100171653002800192100001200220700001800232700001800250700001400268700001900282700001100301700001900312700001500331700002200346245006700368300002200435520187700457022001402334       2025                            d  c2025-11-1310aFDA/CDER/OND10ain vivo nonhuman test10ainnovative drug development10aNew Approach Methodologies (NAMs)10anonclinical test10aPharmacology/Toxicology1 aJia Yao1 aJackye Peretz1 aIlona Bebenek1 aAmy Avila1 aTessie Alapatt1 aBo Lee1 aDakshesh Patel1 aPaul Brown1 aKaren Davis-Bruno00aFDA/CDER/OND Experience With New Approach Methodologies (NAMs)  a109158182513842703 aThe U.S. Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), and Office of New Drugs (OND) has continuously encouraged the submission of nonclinical tests utilizing new approach methodologies (NAMs) and sponsor engagement with regulators to optimize NAM utility in supporting the safety and efficacy of new drugs. Previously, we published an FDA/CDER perspective on nonclinical testing strategies, discussed the opportunities and challenges of using NAMs to replace, reduce, and refine animal testing in drug development, and reported gaps and challenges underserved by existing nonclinical testing approaches that CDER Pharmacology/Toxicology reviewers face. Here, we demonstrate how FDA/CDER has historically incorporated NAMs into standard nonclinical assessments, describing how specific tests became validated and internationally accepted alternatives to animal testing for regulatory decision-making. We also provide a CDER/OND Pharmacology/Toxicology reviewer perspective on NAMs submitted to support new drug development, in an effort to provide insight into our experience with NAMs submitted for CDER-regulated products. Furthermore, we provide a CDER/OND Pharmacology/Toxicology reviewer perspective on the future of NAM incorporation into nonclinical development programs for new drugs as scientific technology continues to evolve. Ultimately, we hope that by sharing the FDA/CDER/OND experience with NAMs thus far and providing considerations for refining NAM submissions, we will (1) illustrate our scientific approach to evaluating NAM submissions, (2) reiterate FDA/CDER's steadfast commitment to the 3Rs, and (3) foster confidence in our continued efforts to encourage nonclinical test NAM submissions for regulatory decision-making, while maintaining our mission to protect public health and patients from unintended harm.  a1092-874X