Correspondence should be addressed to: Tong (Jenny) Liu, PhD, Excipients, USP Rockville, US Pharmacopeia, 12601 Twinbrook Parkway, Rockville, MD 20852-1790; email: jyl@usp.org.
This Stimuli article presents a revised framework for evaluating the safety of novel excipients by updating Excipient Biological Safety Evaluation Guidelines 〈1074〉. The USP Novel Excipients Expert Panel (NEEP) advocates a weight of evidence (WoE) approach that integrates in silico, in vitro, and in vivo data—aligning with the 3Rs of ethical animal use (reduce, refine, replace) and new approach methodologies (NAMs)—to reduce reliance on animal testing. Key considerations include regulatory compliance, existing safety data, species selection, and human experience from food or cosmetic use. The article highlights FDA’s Inactive Ingredient Database (IID) and read-across methods as tools to support safety evaluations and fill data gaps. As the article notes, although NAMs are encouraged, their regulatory acceptance is evolving. Stakeholders are encouraged to engage early with health authorities to optimize strategies for toxicity assessment. USP’s iterative approach, including emerging standards, supports a modern, ethical, and scientifically rigorous evaluation of excipient safety.