FDA issues final Nicotine Replacement Therapy Drug Products guidance

[4/28/2023] Today, the U.S. Food and Drug Administration issued a final guidance for industry titled Smoking Cessation and Related Indications: Developing Nicotine Replacement Therapy Drug Products, which replaces the draft guidance of the same name published in February 2019.

FDA intends for this guidance to assist sponsors in the clinical development of nicotine replacement therapy (NRT) drug products intended to help cigarette smokers stop smoking.

“Through this guidance, we are encouraging innovation in NRT development by providing detail and clarity on product development strategies,” said Theresa Michele, M.D., director of the Center for Drug Evaluation and Research’s Office of Nonprescription Drug Products. “It demonstrates our commitment to enabling the development of safe and effective product innovations that may help smokers quit combustible cigarettes and improve their health.”

This guidance includes several innovations in the regulatory pathway for NRT drug products. For example, the guidance discusses “reduction in risk of relapse” as a potential indication to assist smokers in remaining smoke-free. The guidance outlines the development program for two new potential treatment regimens: 1) pretreatment before quit day, and 2) quitting by gradual reduction (“reduce to quit”). It also considers the combination and use of more than one NRT drug product. In addition, it discusses additional efficacy endpoints that may be used in NRT drug products that have already demonstrated effectiveness in smoking cessation or reduction of risk of relapse: reduction in urge to smoke, relief of cue-induced craving in former smokers, and relief of withdrawal symptoms not associated with a cessation attempt.

The guidance describes abbreviated pathways and strategies for NRT products, including a bracketing approach based on previous findings of safety and efficacy. Bracketing allows sponsors to rely in part on the agency’s previous finding of safety for the higher nicotine exposure drug product and the agency’s previous finding of effectiveness for the lower nicotine exposure drug product.

Further, the guidance states that NRT drug products that have demonstrated effectiveness for cessation or reduction in risk of relapse may include information in the labeling regarding how quitting smoking can lower a person’s chances of having lung disease, heart disease, and the risk of getting certain types of cancer that are related to smoking, without providing additional data. The guidance outlines nonprescription drug development considerations specific to NRT drug products and makes recommendations for nonprescription label development, efficacy studies, and consumer behavior studies. It also discusses pediatric population study considerations and reinforces FDA’s commitment to development of alternative products and treatment modalities for smoking cessation and vaping cessation in youth.

The Center for Drug Evaluation and Research (CDER) performs an essential public health task by making sure that safe and effective drugs are available to improve the health of people in the United States. As part of the FDA, CDER regulates nonprescription (over-the-counter) and prescription drugs, including biological therapeutics and generic drugs.