Purpose

The purpose of this Notice is to invite applications focused on Tobacco Product Pharmacokinetic Research to support biomedical and behavioral research that will provide scientific data to inform the regulation of tobacco products to protect public health.

Background

The Family Smoking Prevention and Tobacco Control Act (FSPTCA), signed by the President in June 2009, created the FDA Center for Tobacco Products and granted it authority to regulate the manufacture, marketing, and distribution of tobacco products in order to protect public health. Under the law, FDA regulates cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco products. The law also gave FDA the ability to regulate additional tobacco products, commonly referred to as "deeming" them through rulemaking. A full description of the FSPTCA can be found at: http://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/ucm298595.htm.

FDA finalized the "deeming" rule, effective August 8, 2016 "to regulate all tobacco products that were not under its jurisdiction that meets the statutory definition of "tobacco product", including Electronic Nicotine Delivery Systems or ENDS (e.g., e-cigarettes, vape pens), cigars, pipe tobacco, gels, hookah (waterpipe) tobacco, and future tobacco products, but not including accessories of newly deemed products." Products deemed under this rule are subject to the same FD&C Act provisions that cigarettes, roll-your-own tobacco, and smokeless tobacco are subject to, including but not limited to: (1) required submission of ingredient listing and reporting of harmful and potentially harmful constituents (HPHCs) for all tobacco products; (2) prohibition against use of modified risk descriptors (e.g., "light," "low," and "mild" descriptors) and claims unless FDA issues an order permitting their use; and (3) premarket review requirements. These actions will improve the public health by affording FDA information regarding the health risks of such products, evaluating whether marketing of new products would be appropriate for the protection of public health or are substantially equivalent to an identified predicate product, and preventing misleading claims about the relative risk of tobacco products. In addition, FDA has the authority to develop product standards, when appropriate for the protection of public health.

The awards under this Notice will be administered by NIH using funds that have been made available through FDA CTP and the Family Smoking Prevention and Tobacco Control Act (P.L. 111-31). Research results from this FOA are expected to generate findings and data that are directly relevant in informing the FDA's regulation of the manufacture, distribution, and marketing of tobacco products to protect public health.

Research Objectives

Topics to be addressed by this NOSI include areas where knowledge gaps exist, and research is needed - in particular, the following questions regarding the pharmacokinetics of tobacco products. The Institutes listed above are issuing this Notice to highlight interest in receiving grant applications addressing the following questions:

1. Investigate the impact of various ENDS product characteristics on nicotine pharmacokinetics (PK) and exposure, subjective effects, use behaviors, abuse liability, and health effects. Consider use during prescribed (i.e., directed) and ad libitum puffing protocols for the following:

• Nicotine salt (of varying types) vs. free-base nicotine e-liquids

• E-liquid nicotine and menthol concentrations (i.e., dose-dependent effects)

• Product power, temperature, double coils

• Flavored e-liquids

• Product types [i.e., disposable, non-refillable cartridge; open system (refillable cartridge or tank system]

2. How do the nicotine PK profile and subjective effects differ between heated tobacco products and ENDS during prescribed (i.e., directed) and ad libitum puffing protocols?

3. What is the nicotine PK profile for menthol and non-menthol SPECTRUM VLNCs (all nicotine levels, including newly marketed VLN products) among adults and youth/young adults? Consider use under prescribed (i.e., directed) and ad libitum puffing protocols.

Application and Submission Information

This notice applies to due dates on or after July 17, 2020 and subsequent receipt dates through February 13, 2021.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice

• RFA-OD-19-028 - Tobacco Regulatory Science (R01 Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include "NOT-OD-20-081" (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

• Applications non responsive to terms of this NOSI will be not be considered for the NOSI initiative. Applications proposing work outside of FDA-CTP's regulatory authority or outside of the scope of RFA-OD-19-028 will not be reviewed.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.