Regulatory Science Policy Memoranda about FDA Review of Tobacco Product Applications

FDA’s science policy memoranda were developed to assist FDA reviewers with the evaluation of new tobacco product applications. FDA has put these documents on this site in response to public interest. 

These memos provide a snapshot of CTP’s internal thinking on certain aspects of tobacco regulatory science. The information in them is subject to change, such as based on changes in policy, the regulatory framework, or regulatory science Some of the memos may have been withdrawn or may not be current practice, and if so, we intend to label them accordingly. FDA’s review of tobacco product applications is based on the specific facts presented in each application, and is documented in reviews particular to each application.

Importantly, these documents should not be used as a tool, guide, or manual for the preparation of applications or submissions to FDA. Instead, all interested persons should refer to the Federal Food, Drug, and Cosmetic Act (FD&C Act), and its implementing regulations, as well as guidance documents prepared by FDA, for information on FDA’s tobacco authorities and regulatory framework. FDA also regularly posts additional resources for applicants, such as webinars and application tips, on its website and social media.

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Chemistry 

• Nov. 06, 2023: Considerations for Tobacco Specific Nitrosamines (TSNAs) In Cigar Filler, Wrapper and Binder, and Mainstream Smoke During Premarket Application Product Review
• Jan. 10, 2022: E-liquid Manufacturing Evaluation Responsibilities of Chemistry in the PMTA and MRTPA Review Program 
• Sept. 01, 2021: Recommended Approaches for Reviewing Nicotine Dissolution Profile Differences for Smokeless Tobacco Products and Other Orally Placed Tobacco Products in Pre-Market Tobacco Applications
• Oct. 02, 2020: Approaches to the Evaluation of Extractables and Leachables in Tobacco Product Application Review

Toxicology 

• Sept. 09, 2020: Normalization of HPHC Yields Between New and Comparison Products in ENDS PMTAs
• March 11, 2019: Use of Reference Values in the Toxicological Evaluation of Inhaled Tobacco Products

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View Reviewer Guides and Scientific Policy Memoranda about FDA Review of Tobacco Product Applications posted in 2019.

General

1. Unique Identification of Portioned Moist Snuff and Snus Products
2. Unique Identification of Tobacco Products

Chemistry/Toxicology

1. SE Review: Toxicological Implications of Fire Standards Compliant (FSC) Paper
2. SE Review: Evaluation of Estimated HPHC Impact of Single Ingredient (saccharides) Pyrolysis
3. SE Review: Evaluation of Multiple Ingredient Changes
4. Use of Surrogate Tobacco Products in SE Reports*
5. SE Review: Evaluating Carcinogenic HPHC Increases and Assumption of Linearity for Low Dose Extrapolation
6. Use of Cigarette Designer and Other Models to Predict HPHC Yields in SE Reports*
7. Effects of Increases of Ammonia and Other Basic Compounds on the Transfer of Free-Base Nicotine to Tobacco Smoke 
8. Equivalence Testing for SE Evaluations
9. Distribution of Menthol in Cigarettes and Smoke Transfer 
10. Use of Reverse Engineering to Reproduce Tobacco Products that are No Longer Manufactured or For Which Characteristics are Not Available
11. Review of Saccharides as Tobacco Ingredients: Effects on Smoke Chemistry 
12. Dissolution as a Critical Comparison of Smokeless Product Performance: SE Requirements and Recommendations for the Review of Dissolution Studies 
13. Harmful and Potentially Harmful Constituent (HPHC) Comparison and Evaluation Procedure for Comparing Two Tobacco Products in the Substantial Equivalence Reports
14. Use of Reference Values in the Toxicological Evaluation of Inhaled Tobacco Products

Engineering

1. Engineering Review of Substantial Equivalence (SE) Reports for Originally Regulated Products

Social Science

1. Product Quantity Changes in Substantial Equivalence Reports (SE Reports) for Statutorily Regulated Tobacco Products
2. Effects of Tobacco Product Package Shape on Consumer Perceptions, Initiation, and Cessation

Behavioral and Clinical Pharmacology

1. BCP Reviews of Characteristic Changes in SE Reports
2. BCP Reviews of SE Reports Involving Changes in the Ventilation of Combusted Filtered Cigarettes

Microbiology

1. Substantial Equivalence Reports: Recommended requirements for stability testing of smokeless tobacco products

Reviewer Guides

1. Behavioral and Clinical Pharmacology Guide for SE Reports
2. Social Science Reviewer Guide for SE Reports

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FDA recommends the following tools serve as resources for the preparation of SE Reports, requests for Exemption from SE, or Premarket Tobacco Product Applications:

• View Published Rules and Regulations
• Search for FDA Guidance Documents 
• Watch FDA Tobacco Compliance Webinars and Videos on Federal Tobacco Regulations 
• Avoid common deficiencies that may result in an unfavorable decision on an application by reviewing Common Issues Found in Substantial Equivalence Reports 

FDA oversees all pathways to legally market and distribute tobacco products in the U.S. Learn more about the various pathways to legally market and distribute a tobacco product.

Note: Documents include the outdated CTP terminology "grandfathered tobacco product." In August 2022, FDA updated the term "grandfathered tobacco product" to "pre-existing tobacco product."