Swedish Match MR0000020 Modified Risk Tobacco Instruction Manual

Swedish Match MR0000020 Modified Risk Tobacco

Product Information

Specifications

• Manufacturer: Swedish Match USA, Inc.
• Product Type: General Snus
• Model Numbers: MR0000020-MR0000022, MR0000024-MR0000025, MR0000027-MR0000029
• Date of Initial Posting: June 24, 2024

Product Usage Instructions

1. Executive Summary

Provide a brief overview of the product and its key features.

2. Products in Scope of Renewal

Detail the specific products covered under the renewal.

3. Summary of Prior Authorizations

Summarize any previous authorizations related to the product.

4. Summary of Postmarket Surveillance and Studies

Provide insights into surveillance conducted by Swedish Match and relevant health risks.

5. Surveillance of New Research Study Findings

Discuss recent research findings related to health risks, consumer perceptions, and tobacco use behavior.

6. Responsible Marketing and Controls

Explain the marketing practices and controls implemented for the product.

7. Conclusions

Present the overall conclusions drawn from the briefing materials.

Frequently Asked Questions

• Q: How can I contact the Center for Tobacco Products?
  • A: You can reach the Center for Tobacco Products at 1-877-287-1373 or via email at CTPOutreach@fda.hhs.gov.
• Q: When will the fully accessible version of the PDFs be available?
  • A: The fully accessible version is currently in preparation and will be posted as soon as it is ready.

FDA is committed to ensuring digital accessibility for people with disabilities. We are continually improving the user experience for everyone and applying the relevant accessibility standards. At the time of initial posting on June 24, 2024, the attached PDFs may not be fully accessible to users using assistive technology. A fully accessible version of the PDFs is in preparation and will be posted as soon as it is ready. We regret any inconvenience that this may cause our readers.
Please let us know if you encounter accessibility barriers by contacting the Center for Tobacco Products at 1-877-287-1373 or CTPOutreach@fda.hhs.gov.

U.S. FOOD AND DRUG ADMINISTRATION Tobacco Products Scientific Advisory Committee
BRIEFING MATERIALS
Swedish Match USA, Inc.
General Snus Products
MR0000020-MR0000022 MR0000024-MR0000025 MR0000027-MR0000029
June 26, 2024

MRTP Renewal of MR0000020-MR0000022, MR0000024-MR0000025, MR0000027-MR0000029 Applicant: Swedish Match USA, Inc.

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MRTP Renewal of MR0000020-MR0000022, MR0000024-MR0000025, MR0000027-MR0000029 Applicant: Swedish Match USA, Inc.

Tables
Table 1. Table 2.

Product Name and FDA Authorization Information ………………………………………………….. 5 Demographics of General Snus Users Completing All Four Waves ……………………………. 13

Figures
Figure 1. Figure 2.
Figure 3. Figure 4.
Figure 5.
Figure 6. Figure 7.
Figure 8. Figure 9. Figure 10. Figure 11. Figure 12. Figure 13.

Sample General Snus Products ………………………………………………………………………………. 6
Annual Measured Values for General Snus TSNA and B[a]P Levels (GOTHIATEK Monitoring) …………………………………………………………………………………………………………. 7
General Snus Patterns of Use Study Experimental Design ……………………………………….. 10
Respondents Overwhelmingly Comprehend Relative Risk of Using General Snus Instead of Smoking Cigarettes ……………………………………………………………………………… 11
Respondents Overwhelmingly Understand Necessity of Eliminating or Significantly Limiting Cigarette Smoking in Addition to Using General Snus to Maintain a Lower Risk of Disease …………………………………………………………………………. 11
Established General Snus Users Report Prior Fairly Regular Use of TNPs …………………… 14
Five Most Reported TNP Use Categories (Past-30-Day) Among Established General Snus Users at Wave 1 (Everyday and Some Day) ………………………………………… 15
Switching and Reduction in Smoking Among Everyday Smokers at Wave 1……………….. 16
Reduction in Cigarettes per Day Among Everyday Smokers at Wave 1 ……………………… 16
Use of Flavored and Unflavored Snus Products by Adults in the PATH Survey……………. 17
Past-30-Day Use of Flavored Snus Products by Adults in the PATH Survey ………………… 17
NYTS P30D Use of Traditional Tobacco Products, Including Snus ……………………………… 19
Steps Required to Access the Modified Risk Claim………………………………………………….. 27

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Acronyms

g ACM AE APPH ATPs B[a]P CDC CHD CPD CTP CVD DWB ENDS FDA FD&C Act FTC g HPHCs MGO MRGO MRTP MRTPA MST ng NIH NNK NNN NRT NYTS OSH P30D PAD PATH PMSS PMTA POU SLT STN TNP TPL TPSAC TSNAs U.S. WHO

Microgram All-Cause Mortality Adverse Experience Appropriate for the Protection of Public Health Alternative Tobacco Products Benzo[a]pyrene Centers for Disease Control and Prevention Coronary Heart Disease Cigarettes per Day Center for Tobacco Products Cardiovascular Disease Dry Weight Basis Electronic Nicotine Delivery Systems Food and Drug Administration Food, Drug, and Cosmetic Act Federal Trade Commission Gram Harmful and Potentially Harmful Constituents Marketing Granted Order Modified Risk Granted Order Modified Risk Tobacco Product Modified Risk Tobacco Product Application Moist Smokeless Tobacco Nanogram National Institutes of Health 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone N-Nitrosonornicotine Nicotine Replacement Therapy National Youth Tobacco Survey Office on Smoking and Health Past-30-Day Peripheral Artery Disease Population Assessment of Tobacco and Health Postmarket Surveillance and Studies Premarket Tobacco Product Application Patterns of Use Smokeless Tobacco Submission Tracking Number Tobacco and Nicotine Product Technical Project Lead Tobacco Products Scientific Advisory Committee Tobacco-Specific Nitrosamines United States World Health Organization

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MRTP Renewal of MR0000020-MR0000022, MR0000024-MR0000025, MR0000027-MR0000029 Applicant: Swedish Match USA, Inc.

EXECUTIVE SUMMARY

We, Swedish Match USA, Inc. (Swedish Match)1, submitted applications on July 17, 2023, under section 911(g)(1) of the FD&C Act to request renewal of the MRGO issued on October 22, 2019, for eight General Snus products. These MRGOs authorized us to market these products with the following modified risk information:
“Using General Snus instead of cigarettes puts you at a lower risk of mouth cancer, heart disease, lung cancer, stroke, emphysema, and chronic bronchitis.”
When authorizing the products, FDA (or “the Agency”) concluded:
“The FDA’s review determined that the claim proposed by the company in its application is supported by scientific evidence, that consumers understand the claim and appropriately perceive the relative risk of these products compared to cigarettes, and that the modified risk products, as actually used by consumers, will significantly reduce harm and the risk of tobacco- related disease to individual tobacco users and benefit the health of the population as a whole.”2
As a function of receiving authorizations for the General Snus products, FDA required us to conduct certain PMSS and submit data in Annual Reports. FDA reviewed and approved all study designs before PMSS were conducted. The submitted PMSS data required by FDA includes the following:
· Serious and unexpected adverse experience (AE) monitoring · General Snus patterns of use (POU) study · Secondary analysis of nationally representative survey data on tobacco product use · Surveillance of new research study findings
We also collected additional postmarket evidence not specifically requested by the FDA, including product monitoring against the GOTHIATEK® standard.
Throughout the postmarket period, we continually monitor marketing and sales data to understand the consumer reach for General Snus. In the 2023 calendar year, we sold approximately 3.3 million cans of General Snus in about 13,000 retail locations in the U.S. We do not sell General Snus via e-commerce and employ extensive responsible marketing practices and controls within these confines. General Snus currently makes up around 7% of the overall U.S. snus market.
We submitted Annual Reports with PMSS data and all other new data generated, monitoring the impact of the authorized products and the respective reduced risk modification information on public health, including the impact on individual health risks, consumer understanding and perceptions, and tobacco use behavior and impact to the population on the whole.

1 Swedish Match USA, Inc. was previously known as Swedish Match North America, Inc. 2 Scientific Review of MRTPA under Section 911(d) of the FD&C Act ­ Technical Project Lead, available at: https://www.fda.gov/media/131923/download
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FDA’s original determination that the General Snus products, as actually used by consumers, will significantly reduce harm and the risk of tobacco-related disease continues to hold true today. Based on our PMSS:

· The authorized products continue to be appropriate for the protection of public health (APPH). FDA has not exercised their authority to withdraw any of the General Snus authorizations, indicating that FDA does not believe the currently available data raises any public health concerns.
· The available data demonstrates General Snus promotes consumer’s complete switching from and reduction of combusted products.
· Surveillance of the U.S. market shows General Snus does not appeal to nonusers of tobacco and nicotine products, including youth.
· We have complied with all aspects of the PMSS requirements since authorization. FDA has not communicated concerns to us regarding any of the new data and information submitted.
Finally, we employ effective and responsible marketing controls to ensure the products are not taken up by unintended user populations (e.g., youth), and these measures have helped to ensure that there is no significant youth use of snus, as confirmed by nationally representative, government funded surveys. Therefore, the TPSAC should recommend FDA authorize the MRGO renewal for the General Snus products.

PRODUCTS IN SCOPE OF RENEWAL

The MRTPA renewal encompasses eight authorized General Snus products (Table 1), which are smokeless tobacco (SLT) products for oral use traditionally produced in Sweden. The products (Figure 1) are placed between the upper lip and the gum and do not require expectoration. Swedish snus was developed in the early 1800s and has been in continuous use since.3 General Snus has been marketed in the U.S. since 2004.

Table 1. Product Name and FDA Authorization Information

Product Name General Loose General Dry Mint Portion Original Mini General Portion Original Large General Classic Blend Portion White Large-12 ct General Mint Portion White Large General Nordic Mint Portion White Large-12 ct General Portion White Large General Wintergreen Portion White Large

Product Category Smokeless Tobacco Smokeless Tobacco Smokeless Tobacco Smokeless Tobacco Smokeless Tobacco Smokeless Tobacco Smokeless Tobacco Smokeless Tobacco

STN MR0000020 MR0000021 MR0000022 MR0000024 MR0000025 MR0000027 MR0000028 MR0000029

3 For additional history, see Rutqvist, L.E., Curvall, M., Hassler, T. et al. Swedish snus and the GothiaTek® standard. Harm Reduct J 8, 11 (2011). https://doi.org/10.1186/1477-7517-8-11 Page 5 of 28
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Figure 1. Sample General Snus Products

2.1 Other Product Monitoring Studies (GOTHIATEK Standard)
While FDA did not require additional health risk studies as part of the PMSS requirements, we routinely collect data to monitor the General Snus products. Specifically, we test the General Snus products’ continued conformance with the GOTHIATEK standard, our proprietary quality standard for snus products, which, in part, ensures extremely low levels of TSNAs, NNN, NNK, polyaromatic hydrocarbons (B[a]P), and metals.4 To date, we are not aware of any other manufacturer that has voluntarily committed to ongoing monitoring against maximum constituent levels through a similar standard.
Recognizing the importance of TSNA levels, in 2017, FDA proposed an NNN product standard that would limit the level of NNN in SLT products to no more than 1 microgram per gram (g/g) of tobacco on a dry weight basis. The exceptionally low levels of TSNAs in General Snus meet this proposed standard and offer consumers who switch to these products a substantial reduction in harmful and potentially harmful constituents (HPHCs), which is likely to translate into improved health outcomes.
We conduct this extensive testing annually to confirm the General Snus products maintain their exceptionally low HPHC levels consistently over time. Figure 2 demonstrates the initial reduction and continued maintenance of exceptionally low TSNA and B[a]P levels in the General Snus portfolio over the past 20 years. Since the MRGOs were issued in 2019, the average observed levels of these HPHCs have remained low. This suggests the products, when used exclusively in place of cigarettes, will continue to reduce death and disease, consistent with the original authorization. Therefore, while not requested by FDA in PMSS, these data further support the TPSAC should recommend FDA authorize renewal of the MRGOs for these products.

4 https://www.swedishmatch.com/Snus-and-health/GOTHIATEK/ and https://www.coresta.org/sites/default/files/abstracts/2014_ST13_Lindholm.pdf
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Figure 2. Annual Measured Values for General Snus TSNA and B[a]P Levels (GOTHIATEK Monitoring)

SUMMARY OF PRIOR AUTHORIZATIONS

On June 10, 2014, and March 11, 2015, we submitted MRTPAs5 and PMTAs, respectively, for General Snus products. FDA issued MGOs for the products on November 10, 2015, concluding the products meet the APPH standard and should be authorized. The FDA decision6 was primarily predicated on the following:
· The products comply with the GOTHIATEK quality standard, which includes constituent standards that must not be exceeded in finished products, manufacturing standards, manufacturing process requirements, and consumer package labeling requirements.
· The products contain significantly lower levels of TSNAs (NNN and NNK) compared to over 97% of the SLT products currently on the U.S. market, and individuals using these products with reduced NNN levels could decrease their excess cancer risk7 by 90% compared to use of moist snuff.
· The levels of other HPHCs are similar to or lower than levels of SLT products currently on the U.S. market.
· There are significant reductions in oral cancer risk when the products are used exclusively instead of other SLT products or cigarettes on the U.S. market.
5 77 Fed. Reg. 20226, April 3, 2012 (https://www.fda.gov/media/83300/download). We submitted applications that conform to this nonbinding guidance.
6 Premarket Tobacco Application (PMTA) Technical Project Lead (TPL) Review (fda.gov) 7 The excess lifetime cancer risk is a toxicological tool to estimate the probability of cancer incidence in a population of individuals for a specific
lifetime from projected intakes (and exposures) and dose-response data (i.e., slope factors) for a specific chemical. Page 7 of 28
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· There are significantly lower risks of developing respiratory diseases and cancers when the products are used exclusively instead of combusted tobacco products.
· There is a low likelihood of nonuser uptake of these products, decreased or delayed cessation, or other significant shifts in user demographics.
FDA issued MRGOs for the submitted modified risk statements (Section 1) on October 22, 2019. The FDA decision8 was based on many of the same reasons listed above for the MGOs, as well as evidence demonstrating both the products’ potential to reduce death and disease amongst tobacco product users and consumer understanding of the modified risk information and relative risk of the products.
In total, FDA reviewed the extensive scientific evidence leading to the authorized PMTAs/MRTPAs and eight years of postmarket reporting. The postmarket data continue to support FDA’s conclusion that General Snus reduces risk of tobacco-related diseases and does not appeal to youth or nonusers of tobacco and nicotine products. General Snus continues to have tremendous potential to reduce the death and disease caused by continued combusted cigarette smoking and improve the lives of smokers in the U.S. by providing an acceptable alternative product.

SUMMARY OF POSTMARKET SURVEILLANCE AND STUDIES CONDUCTED BY SWEDISH MATCH

In the authorizations for each General Snus product, FDA outlined a series of PMSS to be conducted and submitted to FDA in Annual Reports. We conducted and submitted the required PMSS as well as additional postmarket studies to further characterize the impact of the products on health, beyond those required by the FDA. This evidence allows FDA to assess the continued appropriateness of the products for public health on a routine basis and, if necessary, exercise their authority to withdraw an authorization if these requirements are not met or if the submitted data raise new questions of public health.
As part of our PMSS, FDA required us to conduct an additional POU study to examine the impact of the orders on consumer health risks, perception, and behavior. FDA also required monitoring of awareness and use by youth and other unintended user populations (e.g., nonusers). In accordance with section 911(i)(2) of FD&C Act, FDA reviewed and approved all PMSS study plans before we executed the studies. We submitted comprehensive Annual Reports to the FDA demonstrating compliance with these PMSS requirements over the eight years following the first General Snus MGO.
The submitted PMSS data required by FDA during authorization are summarized in the remaining sections and include the following:
· Serious and unexpected AE monitoring · General Snus POU study · Secondary analysis of the Population Assessment of Tobacco and Health (PATH) survey · Secondary analysis of the National Youth Tobacco Survey (NYTS)

8 Scientific Review of MRTPA under Section 911(d) of the FD&C Act ­ Technical Project Lead, available at: https://www.fda.gov/media/131923/download?attachment
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· Surveillance of new research study findings
Additional evidence not specifically requested by the FDA was also collected and submitted to FDA. These data are also summarized in the remaining sections and include the following:
· Annual product monitoring to ensure GOTHIATEK standard compliance · Responsible marketing and controls in place to prevent use of these products amongst
unintended populations (e.g., youth, tobacco nonusers)
FDA accepted the submitted Annual Reports containing this evidence without major comment on the scientific data. The original orders remain in effect, indicating that FDA finds the submitted data sufficient to demonstrate the authorized products do not raise new questions of public health and thus, remain APPH.
4.1 Relative Health Risks of the MRTP to Individual Tobacco Users
4.1.1 Serious and Unexpected Adverse Experiences
When the General Snus products were authorized in 2015, we established a safety surveillance process to collect and manage all safety information related to the use of General Snus products. The aim of the safety surveillance process is to monitor and analyze, in a timely manner, all new safety information related to the use of our products.
Throughout the postmarket surveillance period from Oct. 1, 2015, to Oct. 31, 2023, no serious9 or unexpected10 AEs were reported for these products. There have been no changes in the nature and frequency of AEs. Further, we continue to comply with all FDA-required AE reporting. Therefore, when considering these data, the cumulative AEs support renewal of MRGOs for the authorized General Snus products.
4.2 Consumer Understanding and Perceptions
As outlined in the series of MRGOs for each General Snus product, FDA required us to conduct postmarket studies assessing consumer understanding and perceptions of the product over time to ensure users remain able to adequately understand the modified risk information. FDA stated this study must
“include an assessment of consumers’ understanding of the claim and perceptions of the products. In particular, PMSS must assess the extent to which users of these products understand that, to reduce their risk of disease relative to smoking as described in the modified risk
9 Per the MGO letters for General Snus, “a serious adverse experience means an adverse experience that results in any of the following outcomes: death; a life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect; or any other adverse experience that, based upon appropriate medical judgement, may jeopardize the health of a person and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.”
10 Per the MGO letters for General Snus, an “unexpected adverse experience means an adverse experience occurring in one or more persons in which the nature, severity, or frequency of the experience is not consistent with: the known or foreseeable risks associated with the use or exposure to the tobacco product as described in the PMTA and other relevant sources of information, such as postmarket reports and studies; the expected natural progression of any underlying disease, disorder, or condition of the person experiencing the adverse experience and the person’s predisposing risk factor profile for the adverse experience; or the results of nonclinical laboratory studies.” Page 9 of 28
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information, they must use General Snus exclusively. To adequately assess these impacts, you must conduct PMSS that include assessing users’ behavior and consumer understanding at multiple time points.11″
To accomplish this, we provided FDA with a study plan to conduct a POU study, which FDA approved in April 2020.
The POU study assessed consumer perception of risk associated with the MRTPs (i.e., relative risk compared to cigarettes), as well as understanding of elements of the modified risk information (i.e., the need to completely switch from cigarettes) post-MRTP authorization. The study consisted of a self- reported longitudinal survey examining patterns of past-30-day (P30D) tobacco and nicotine product (TNP) use among General Snus users in a baseline assessment (Wave 1, N = 1,655) and again, among the same General Snus users, at 6 months (Wave 2, N = 695), 1 year (Wave 3, N = 586), and 2 years (Wave 4, N = 451) after baseline (Figure 1Figure 3).
Figure 3. General Snus Patterns of Use Study Experimental Design

Across all four waves, surveyed consumers accurately maintained the correct relative risk perception associated with the MRTP product relative to cigarettes. When asked how using General Snus instead of cigarettes affects your risk for mouth cancer, heart disease, lung cancer, stroke, emphysema, and chronic bronchitis, the vast majority of consumer were able to identify that using General Snus puts you at a lower risk of these conditions (Figure 4). The longitudinal results also demonstrate consumers understand that fully switching to General Snus from cigarettes is needed to achieve risk reduction. Over the 24 months, greater than 80% of those who understood the modified risk messaging correctly responded that cigarette smokers must switch completely to General Snus (answered “zero cigarettes”) in order to reduce their risks of diseases (Figure 5). These results suggest the modified risk information is effectively educating consumers on the relative health risks of the product and the importance of completely substituting cigarettes with General Snus, and that consumer perceptions remain consistent over time.

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Figure 4. Respondents Overwhelmingly Comprehend Relative Risk of Using General Snus Instead of Smoking Cigarettes

n = number of respondents. Error bars = 95% CI. Source: General Snus POU study. This analysis was conducted using data from the 281 participants who completed all 4 waves. Participants were asked “Does using General Snus instead of cigarettes place you at a lower risk, the same risk, a higher risk, or no risk?”
Figure 5. Respondents Overwhelmingly Understand Necessity of Eliminating or Significantly Limiting Cigarette Smoking in Addition to Using General Snus to Maintain a Lower Risk of Disease

n = number of respondents. Error bars = 95% CI. Source: General Snus POU study. This analysis was conducted using data from the 281 participants who completed all four waves. This question was asked of only those respondents who correctly identified that using General Snus instead of cigarettes puts you at a lower risk of disease (see Figure 4).

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Therefore, the results of postmarket studies continue to support previously submitted premarket evidence showing all of the following:
· The perceived health risks associated with using General Snus are lower than the perceived health risks associated with smoking cigarettes, which is in line with the epidemiological data.
· There is a high level of understanding that completely switching to General Snus reduces the risk of disease compared to smoking.
Therefore, the availability of General Snus along with the modified risk information is improving legal age smokers’ ability to make informed, personal choices that could reduce their risk of tobacco-related disease. These study results were communicated to FDA in our Annual Report.
4.3 Tobacco Use Behavior and Impact to the Population as a Whole
FDA required us to also evaluate consumers’ use behaviors over time, which were intended to
“…assess the extent to which new MRTP users were non-users, smokers, or other tobacco product users before initiating the MRTPs and the extent to which new users of the MRTPs become exclusive users or dual users with cigarettes or other tobacco products over time.”12
We assessed use behaviors among U.S. General Snus users and nonusers as part of the previously described General Snus POU study. We provided FDA with the study plan, which they agreed to in April 2020. We also designed secondary analyses of nationally representative survey data to assess use patterns in General Snus users and nonusers, including monitoring youth uptake of the products. The relevant studies include the following:
· The General Snus POU study: Longitudinal survey of legal age General Snus users to assess use behaviors over time
· Secondary analysis: Estimation of prevalence of General Snus use by adults overall and by flavor category using the PATH study
· Secondary analysis: Estimation of use of General Snus among youth using the NYTS
4.3.1 Benefit to Legal Age Smokers
Legal age smokers who completely switch to General Snus are likely to reduce their risk of disease by replacing their cigarette consumption with a reduced risk alternative. Therefore, it is critical to ensure that General Snus is being used by the intended consumers (current, legal age smokers) and to monitor how they are using General Snus relative to cigarettes. These data inform the likelihood of consumers becoming complete switchers or dual users of General Snus and combusted cigarettes. These product use patterns were monitored using a combination of data collected from the POU study and the PATH survey.
Per the POU study, General Snus is primarily used by middle-aged, legal age consumers and does not have high rates of uptake in historically vulnerable populations (Table 2). Additionally, less than 8% of

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General Snus users were 21­24 years old, suggesting a continued low exposure to the products by those under the age of 25.

Table 2. Demographics of General Snus Users Completing All Four Waves

General Snus® Users

n=281

Geographic Region

Northeast (%)

39 (13.9%)

Midwest (%)

87 (31.0%)

South (%)

89 (31.7%)

West (%)

66 (23.5%)

Respondent Age

Mean age (years) + Std Dev 21-24 (%)

37 + 10 21 (7.5%)

25-34 (%)

105 (37.4%)

35-44 (%)

103 (36.7%)

45-54 (%)

35 (12.5%)

55+ (%)

17 (6.0%)

Gender

Male (%)

263 (93.6%)

Female (%)

18 (6.4%)

Racial or Ethnic Background

Caucasian/White (%)

252 (89.7%)

Black/African American (%)

2 (0.7%)

Hispanic (e.g., Latin American, Mexican, Puerto Rican, Cuban) (%)

7 (2.5%)

Asian or Pacific Islander (%)

5 (1.8%)

Native American or Alaskan native (%)

3 (1.1%)

Mixed racial background (%)

11 (3.9%)

Other (%)

1 (0.4%)

Highest Grade or Level of School Completed

Less than high school (%)

0 (0.0%)

Some high school, no diploma (%)

0 (0.0%)

General Educational Development (GED) (%)

13 (4.6%)

High school graduate – diploma (%)

14 (5.0%)

Some college but no degree (%)

72 (25.7%)

Associate degree (%)

38 (13.6%)

Bachelor’s degree (e.g., BA, AB, BS) (%)

101 (36.1%)

Post-graduate degree (e.g., MBA, PhD, JD, etc.) (%)

42 (15.0%)

Marital Status

Now married (%)

158 (56.2%)

Widowed (%)

4 (1.4%)

Divorced (%)

25 (8.9%)

Separated (%)

3 (1.1%)

Never married (%)

90 (32.0%)

Decline to answer (%)

1 (0.4%)

Household Income in the Past 12 Months

Less than $24,999 (%)

20 (7.1%)

$25,000 to $49,999 (%)

49 (17.4%)

$50,000 to $74,999 (%)

51 (18.1%)

$75,000 to $99,999 (%)

49 (17.4%)

$100,000 or more (%)

101 (35.9%)

Don’t know (%)

2 (0.7%)

Decline to answer (%)

9 (3.2%)

n = number of respondents

Source: General Snus POU study. This analysis was conducted using data from the 281 participants who completed

all four waves.

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Almost all General Snus users reported prior fairly regular use of TNPs (Figure 6) at Wave 1. The vast majority of established General Snus users reported prior use of cigarettes or traditional smokeless products, comprising 84% of users studied. Fairly regular users of other TNPs accounted for 15% of established General Snus users, with 4% reporting prior usage of other snus products, and 11% reporting prior use of another TNP. Only 1% of all established General Snus user study participants reported no prior use of TNPs. These data suggest that the vast majority of established General Snus users have a history of cigarette and/or SLT use and, therefore, could benefit from transitioning to General Snus based on the available epidemiological data.
Figure 6. Established General Snus Users Report Prior Fairly Regular Use of TNPs

Source: General Snus POU study. This analysis was conducted using participants’ reported tobacco use history at Wave 1. Participants were asked “Have you ever used any of the following tobacco or nicotine products fairly regularly?” Definition of fairly regular use was adapted from the PATH study.
Poly use of other TNPs was reported by several established General Snus users at Wave 1 (Figure 7). The five most common TNP categories used in the past 30 days were traditional smokeless products (MST or chew), nicotine pouches, snus (exclusive), and combustible products (such as cigars and cigarettes). When assessing past-30-day everyday use, the rates of poly use were dramatically lower for all categories except snus. Rates of poly use were particularly reduced for cigars and nicotine pouches. This suggests that much of the reported poly use of General Snus is likely due to situational use of TNPs and may be a temporary, transitional state as users transition from one product category or product to another. This highlights the importance of the modified risk information as it details the need to use snus instead of cigarettes, making it an important tool to encourage TNP users to adopt exclusive use of snus.

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Figure 7. Five Most Reported TNP Use Categories (Past-30-Day) Among Established General Snus Users at Wave 1 (Everyday and Some Day)

Source: General Snus POU study. This analysis was conducted using participants’ reported tobacco use history at Wave 1. Categories are not mutually exclusive.
When examining cigarette use among everyday smokers at Wave 1, 16.7% were no longer smoking at Wave 4, and an additional 33.3% had reduced their use from every day to some days (Figure 8). In this same subpopulation, a reduction of more than 50% in the mean cigarettes per day (CPD) was observed at Wave 4 (6.29 CPD) in comparison to Wave 1 (12.31 CPD) (Figure 9). General Snus consumers also demonstrated a reduction in the usage of noncombustible TNPs. When examining usage of other SLT products (MST or chewing tobacco), over 16% of prior fairly regular users were no longer using these products at Wave 1, and an additional 15% reported cessation of use at Wave 4.
We also rely on evidence collected in the PATH survey to monitor adult snus use and identify important factors that influence use behaviors. PATH queried adult established users about their use of flavored products, and roughly 80% of adult established snus users reported regularly using a flavored product (Figure 10). This indicates snus consumers have a clear preference for flavored products. Of these established adult users, roughly 80% used only mint and related flavors over the past 30 days, while roughly 10% reported use of only non-mint flavors (Figure 11). The other roughly 10% of established adult users reported using both mint and non-mint flavors. Therefore, maintaining a robust selection of noncombustible options with MRTP authorization, including flavored options, is likely to benefit consumers interested in switching to these products. These category-level data are consistent with our product-specific sales data that shows predominate adoption of mint-flavored General Snus varieties, which account for approximately two thirds of total sales volume (data not shown).

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Figure 8. Switching and Reduction in Smoking Among Everyday Smokers at Wave 1
n = number of respondents Source: General Snus POU study
Figure 9. Reduction in Cigarettes per Day Among Everyday Smokers at Wave 1

n = number of respondents Source: General Snus POU study

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Figure 10. Use of Flavored and Unflavored Snus Products by Adults in the PATH Survey

PATH is a nationally representative survey of youth (age 12 and older) and adults in the U.S. This survey is a collaboration between the National Institutes of Health (NIH) and the FDA.
Figure 11. Past-30-Day Use of Flavored Snus Products by Adults in the PATH Survey

PATH is a nationally representative survey of youth (age 12 and older) and adults in the U.S. This survey is a collaboration between the NIH and the FDA.

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The surveillance of new research also suggests the availability of reduced risk products with adequate nicotine delivery and in a variety of flavors is associated with switching away from combusted products.13 Furthermore, evidence has indicated the use of more than one flavor of product was common among users of reduced risk products and could potentially lead to greater rates of switching away from combusted cigarettes.14,15,16 Real-world data are supportive of these conclusions with sales data indicating a preference for flavored snus products, including mint varieties.17
Overall, the data from these postmarket studies are consistent with the data collected in premarket studies and demonstrate General Snus is providing a benefit to adult smokers and does not appeal to nonusers.
· General Snus consumers largely consist of existing tobacco users, especially those with a prior history of cigarette smoking and SLT use.
· Established General Snus users displayed cigarette switching and overall reduction in cigarette consumption. When examining cigarette use among everyday smokers at Wave 1, 16.7% were no longer smoking at Wave 4 (24 months), and an additional 33.3% had reduced their use from every day to some days. Additionally, the average number of cigarettes consumed per day decreased by approximately 50% from Wave 1 to Wave 4.
· General Snus does not appeal to adult nonusers of TNPs based on low prevalence of General Snus use among adults.
We reported these collective results to the FDA as part of annual reporting and received no feedback related to these scientific findings from the Agency. This further supports that these findings do not raise new questions of public health and are consistent with the prior evidence leading to authorization.
4.3.2 Risk to Youth
When authorizing the MRTPs, FDA noted the available evidence did not demonstrate significant youth initiation of snus products. We have continued to monitor youth TNP use patterns based on nationally representative survey data collected in both the NYTS and PATH surveys. Postmarket data continues to demonstrate an absence of appeal and uptake of snus among youth.
From 2011 to 2023, NYTS shows a consistently low and declining prevalence of snus use among high school students (Figure 12). In 2022, 0.5% of respondents indicated they have used snus at least
13 Gades MS, Alcheva A, Riegelman AL, Hatsukami DK. The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review. Nicotine Tob Res. 2022 Aug 6;24(9):1332-1343. doi: https://doi.org/10.1093/ntr/ntac073 PMID: 35305014; PMCID: PMC9356694
14 Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Spyrou A, Voudris V. Impact of flavour variability on electronic cigarette use experience: an internet survey. Int J Environ Res Public Health. 2013 Dec 17;10(12):7272-82. doi: https://doi.org/10.3390/ijerph10127272.PMID: 24351746; PMCID: PMC3881166
15 Romijnders KA, Krüsemann EJ, Boesveldt S, Graaf K, Vries H, Talhout R. E-Liquid Flavor Preferences and Individual Factors Related to Vaping: A Survey among Dutch Never-Users, Smokers, Dual Users, and Exclusive Vapers. Int J Environ Res Public Health. 2019 Nov 22;16(23):4661. doi: https://doi.org/10.3390/ijerph16234661. PMID: 31766776; PMCID: PMC6926905
16 Gentry SV, Ward E, Dawkins L, Holland R, Notley C. Reported patterns of vaping to support long-term abstinence from smoking: a crosssectional survey of a convenience sample of vapers. Harm Reduct J. 2020 Oct 6;17(1):70. doi: https://doi.org/10.1186/s12954-020-00418-8. PMID: 33023583; PMCID: PMC7541214
17 Liber AC, Seidenberg AB, Pesko MF. Tob Contrl Epub ahead of print: [accessed 7/13/2023]. doi:10.1136/tc-2022-057890
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once in the past 30 days. When considering ever use of snus, only 1% reported trying snus (even just one time). Furthermore, snus has the lowest prevalence of use among the other major categories of TNPs. These data are consistent with the prevalence of P30D use among youth in the PATH survey, which also shows low and declining rates of snus use among youth (data not shown). Taken together, data from NYTS and PATH demonstrate very low prevalence of snus use, including General Snus among underage individuals in the U.S.
Figure 12. NYTS P30D Use of Traditional Tobacco Products, Including Snus
MRTP Authorization Period
Current youth use of TNPs in NYTS is defined as use on one or more of the past 30 days. Recently published 2023 SLT use estimates include snus. Independent snus use data is not yet available. NYTS is a nationally representative survey of middle and high school youth in the U.S. This survey is a collaboration between the Centers for Disease Control and Prevention, Office on Smoking and Health (CDC, OSH) and the U.S. Food and Drug Administration, Center for Tobacco Products (FDA, CTP). The yellow box denotes the MRTP authorization period.
4.3.3 Impact to the Population on the Whole
We support FDA’s position on the continuum of risk across tobacco products, specifically that moving users of combusted products down the continuum of risk benefits the population at large.18 For tobacco harm reduction to be successful, there must be a diverse marketplace of innovative, FDA-authorized, reduced risk products. In this context, having multiple varieties and flavors of General Snus can help legal age consumers transition to products lower on the continuum of risk. In terms of tobacco use behavior, postmarket surveillance has continued to support the conclusions made in the initial MRGOs:
· The General Snus products are primarily used by consumers with a tobacco use history (cigarettes and SLT), with low rates of uptake among nonusers.
18 A recent publication authored by the current Director of the Center for Tobacco Products states that “the health risks for tobacco products exist on a continuum, with combustible products such as cigarettes being the most harmful. Decades of research have documented that cigarette smoking harms nearly every organ of the body; cigarette smoke contains nearly 7,000 chemicals, approximately 70 of which cause cancer. Non-combustible tobacco products, such as e-cigarettes, generally have lower health risks to the user than combusted tobacco products.” Toll BA, Smith TT, King BA. Nat Med. Epub ahead of print: [accessed 4/16/2024]. doi: https://doi.org/10.1038/s41591-02402926-7 Page 19 of 28 ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE FOR PUBLIC RELEASE

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· General Snus can facilitate switching from and reduction of combustible products that are high on the continuum of risk (e.g., cigarettes).
· There are consistently low levels of youth use of snus products.
The evidence demonstrates General Snus can benefit the health of the population as a whole by transitioning legal age cigarette smokers away from cigarettes. There is clear evidence of sustained long-term switching from combusted cigarette smoking among legal age General Snus users and, based on prevalence of General Snus among legal age nicotine users overall, the initiation of General Snus by nonusers of tobacco is unlikely. Further, the data demonstrate that snus use amongst youth and underage young adults is very low. Therefore, the continued marketing of General Snus as a MRTP will significantly reduce harm and the risk of tobacco-related diseases, and the modified risk order renewal should be granted.

SURVEILLANCE OF NEW RESEARCH STUDY FINDINGS IN PUBLISHED SCIENTIFIC

LITERATURE

We continually monitor the published scientific literature for new data on General Snus and provide our literature review to FDA in Annual Reports. The most recent literature review was conducted to summarize postmarket data focusing on the impact of Swedish snus, including General Snus, on health risks, consumer understanding and perceptions, and tobacco use behavior and impact to the population as a whole.
The original PMTAs and MRTPAs included long-term scientific evidence (e.g., decades of Swedish epidemiological studies) demonstrating consumers who exclusively used Swedish snus products had a lower risk of developing tobacco- related disease than consumers who smoked cigarettes. The well-established Swedish experience with snus continues to provide real-world evidence and epidemiological data demonstrating that these smoke-free products reduce tobacco-related morbidity and mortality. 19,20 Public health data show Sweden has the lowest smoking rate and incidence of tobacco-related diseases among men in Europe, due in large part to snus, which many Swedish men began switching to approximately 50 years ago.
Ongoing surveillance of the literature reinforces the reduced health risks associated with General Snus use in comparison to cigarettes and the continued validity of the modified risk claim. A complete list of the studies identified in the literature review is provided in the appendix (See Surveillance of Published Literature), with additional relevant publications being summarized in the remainder of this section.
5.1 Health Risks
As part of our surveillance efforts, Swedish Match identified numerous postmarket publications that provide additional evidence surrounding the health risks associated with General Snus use for the specific disease outcomes addressed in the modified risk claim.
19 Ramström, L., Borland, R., & Wikmans, T. (2016). Patterns of Smoking and Snus Use in Sweden: Implications for Public Health. International journal of environmental research and public health, 13(11), 1110. https://doi.org/10.3390/ijerph13111110
20 Snus Commission (2022). Relative Health Risks of Tobacco and Nicotine Products. https://snuskommissionen.se/wpcontent/uploads/2023/01/A-report-from- Swedens-Snus-Commission_2022.pdf
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In a systematic global review and meta-analysis of 37 studies examining associations between SLT use and oral cancer, Asthana et al. (2019)21 found that although many SLT products significantly increased oral cancer risk, there was no increased risk associated with snus. Additionally, in a similar meta-analysis of all SLT products sold in World Health Organization (WHO) regions, Gupta et al. (2022)22 linked many global SLT products to oral cancer but did not identify any association with snus. Although, in a previous meta- analysis of SLT products from WHO regions, Gupta et al. (2019)23 linked SLT products to increased risk of coronary heart disease (CHD), though a difference between SLT product types was not reported.
In another study of oral cancer risk, Araghi et al. (2020)24 found no association between snus use and oral cancer using the pooled analysis of nine prospective observational studies from the Swedish Collaboration on Health Effects of Snus Use Study. Kopperud et al. (2023)25 examined a small group (n = 1,363) of adolescents (18-20 years old) in southeastern Norway and found an increased instance of oral lesions and gingival retractions. Due to the small size of the study (only 216 participants used snus daily) and the homogenous population, this study does not provide conclusive evidence that can be extrapolated to the U.S. population. Further, in an analysis of Wave 1 through Wave 5 data from the PATH study examining the effects of tobacco product use on oral health, Silveira et al. (2022)26 found no associations between snus users and incidence of oral health outcomes.
In a study of peripheral artery disease (PAD), Yuan et al. (2022)27 found no increased risk of PAD for snus users. The study, which examined data from over 20,000 Swedish men across a decade (2009-2019), found while cigarette smoking was associated with higher risk of PAD, snus use did not increase PAD risk. Antoniewicz et al. (2022)28 examined the impact of chronic snus use on endothelial function and arterial stiffness. Although the results showed that chronic snus use altered endothelial function and increased arterial stiffness, it is important to note the extremely limited sample size of 50 healthy men. Additionally, the chronic snus user data were compared only to nonsmokers and the data indicated alcohol use as a statistically significant confounder.
21 Asthana, S., Labani, S., Kailash, U., Sinha, D. N., & Mehrotra, R. (2019). Association of Smokeless Tobacco Use and Oral Cancer: A Systematic Global Review and Meta-Analysis. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 21(9), 1162­1171. https://doi.org/10.1093/ntr/nty074
22 Gupta, A. K., Kanaan, M., Siddiqi, K., Sinha, D. N., & Mehrotra, R. (2022). Oral Cancer Risk Assessment for Different Types of Smokeless Tobacco Products Sold Worldwide: A Review of Reviews and Meta-analyses. Cancer prevention research (Philadelphia, Pa.), 15(11), 733­ 746. https://doi.org/10.1158/1940-6207.CAPR-21-0567
23 Gupta, R., Gupta, S., Sharma, S., Sinha, D. N., & Mehrotra, R. (2019). Risk of Coronary Heart Disease Among Smokeless Tobacco Users: Results of Systematic Review and Meta-Analysis of Global Data. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 21(1), 25­31. https://doi.org/10.1093/ntr/nty002
24 Araghi et al. 2020. No association between moist oral snuff (snus) use and oral cancer: pooled analysis of nine prospective observational studies. Scand J Public Health 2021 Vol. 49 Issue 8 Pages 833-840. https://www.ncbi.nlm.nih.gov/pubmed/32466721
25 Kopperud, S. E., Ansteinsson, V., Mdala, I., Becher, R., & Valen, H. (2023). Oral lesions associated with daily use of snus, a moist smokeless tobacco product. A cross-sectional study among Norwegian adolescents. Acta odontologica Scandinavica, 81(6), 473­478. https://doi.org/10.1080/00016357.2023.2178502
26 Silveira, M. L., Everard, C. D., Sharma, E., Lauten, K., Alexandridis, A. A., Duffy, K., Taylor, E. V., Tolliver, E. A., Blanco, C., Compton, W. M., Kimmel, H. L., Iafolla, T., Hyland, A., & Chaffee, B. W. (2022). Tobacco Use and Incidence of Adverse Oral Health Outcomes Among US Adults in the Population Assessment of Tobacco and Health Study. JAMA network open, 5(12), e2245909. https://doi.org/10.1001/jamanetworkopen.2022.45909
27 Yuan, S., Titova, O. E., Damrauer, S. M., Åkesson, A., & Larsson, S. C. (2022). Swedish snuff (snus) dipping, cigarette smoking, and risk of peripheral artery disease: a prospective cohort study. Scientific reports, 12(1), 12139. https://doi.org/10.1038/s41598-022-16467-x
28 Antoniewicz, L., Kabele, M., Nilsson, U., Pourazar, J., Rankin, G., Bosson, J. A., & Lundbäck, M. (2022). Chronic snus use in healthy males alters endothelial function and increases arterial stiffness. PloS one, 17(6), e0268746. https://doi.org/10.1371/journal.pone.0268746
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Two publications found no association between snus use and CVD, when controlling for confounders. Specifically, Titova et al. (2021)29 found no increase in CVD mortality in a prospective cohort study of middle-aged and older individuals. The authors conclude “In this middle-aged and elderly Swedish population, current Swedish snus use was not associated with the risk of major heart and valvular diseases, abdominal aortic aneurysm, or CVD mortality in the entire study population, but was linked to increased risk of stroke in never smokers.” They explain this finding as follows “[t]he possible explanation that we see the effect of snus use on the risk of stroke only in never smokers is that the majority of snus users in our study are former smokers (69%). Cigarette smoking is a well-established strong risk factor for CVDs and may mask the effect of snus in the analysis based on the entire cohort, i.e. residual confounding takes place.” Similarly, Frobert et al. (2019)30 found no increase in CVD mortality using data from the Swedish Coronary Angiography and Angioplasty Registry. The authors conclude “[s]nus use at admission for a first [Percutaneous Coronary Intervention] was not associated with a higher occurrence of all-cause mortality, new revascularization or heart failure hospitalization.”
In contrast, Byhamre et al. (2020)31 found an increase in CVD mortality in a pooled analysis of eight prospective studies of exclusive, Swedish male snus users compared to never tobacco users for data covering 1978-2010. Study design limitations and confounders include fixing tobacco use state at baseline (does not account for never-users initiating), the participants in the control group were not smokers, and the data were collected during a dramatic reduction in constituents. Further, the study observed an inverse- dose-response relationship between snus use and increased risk of CVD mortality. Overall and relative to the other publications, this study provides relatively weak evidence and does not address the risk of CVD in snus users relative to smokers. Rodu et al. (2021)32 published a critique of this paper, noting several methodological flaws “…that render their results uninformative and possibly misleading.”
In a systematic review of SLT products, Hajat et al. (2021)33 examined data collected from 53 studies from numerous geographical regions. There were significant differences in association with all-cause mortality (ACM), CVD, and cancer between SLT products in different regions. In regions where snus is not the predominate SLT used, such as Asia, the Middle East, and Africa, there is a correlation between SLT use and increased ACM, CVD, and cancer. In European regions where snus is used, there was no increased risk of ACM, CVD, or cancer. Although, in a systematic review assessing cancer risk and mortality for snus users, Valen et al. (2023)34 showed an association between snus use and increased cancer risk and cancer-specific mortality; the 15 studies included in the review spanned over 10 types of cancer and was limited to male data of snus users compared with nontobacco users. The study
29 Titova et al. 2021. Swedish snuff (snus) and risk of cardiovascular disease and mortality: prospective cohort study of middle-aged and older individuals. BMC Med 2021 Vol. 19 Issue 1 Pages 111. https://www.ncbi.nlm.nih.gov/pubmed/33957912
30 Frobert, O., Reitan, C., Hatsukami, D. K., Pernow, J., Omerovic, E., & Andell, P. (2019). Smokeless tobacco, snus, at admission for percutaneous coronary intervention and future risk for cardiac events. Open heart, 6(2), e001109. https://doi.org/10.1136/openhrt-2019001109
31 Byhamre et al. 2020. Swedish snus use is associated with mortality: a pooled analysis of eight prospective studies. https://doi.org/10.1093/ije/dyaa197
32 Rodu B and Plurphanswat N. Heterogeneity and other problems in a pooled analysis of snus use and mortality [version 1; peer review: 2 approved]. F1000Research 2021, 10:388 (https://doi.org/10.12688/f1000research.52127.1)
33 Hajat, C., Stein, E., Ramstrom, L., Shantikumar, S., & Polosa, R. (2021). The health impact of smokeless tobacco products: a systematic review. Harm reduction journal, 18(1), 123. https://doi.org/10.1186/s12954-021-00557-6
34 Valen, H., Becher, R., Vist, G. E., Holme, J. A., Mdala, I., Elvsaas, I. Ø., Alexander, J., Underland, V., Brinchmann, B. C., & Grimsrud, T. K. (2023). A systematic review of cancer risk among users of smokeless tobacco (Swedish snus) exclusively, compared with no use of tobacco. International journal of cancer, 153(12), 1942­1953. https://doi.org/10.1002/ijc.34643
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concluded that the use of snus carries a cancer risk, however, the magnitude of the risk may be affected by user history and individual susceptibility.
These individual studies should be evaluated in context of the totality of evidence surrounding the health risks associated with snus use, and in context of the modified risk claim, which communicates a modified risk in comparison to combusted cigarette smoking and does not communicate an absence of risk. Therefore, this postmarket evidence reinforces the validity of the modified risk claim and does not raise new questions regarding the health risks associated with snus use.
5.2 Consumer Understanding and Perceptions
We also examined the impact of snus messaging on consumer understanding and perceptions in the scientific literature. Wackowski and colleagues (2022)35 assessed MRTP claims related to snus and electronic nicotine delivery system (ENDS) products, with a focus on quantifying reductions in risk. A study of 57 current smokers and young adult nonsmokers participating in 12 focus groups, six of which focused on snus messaging and perceptions, found that messages stating snus and ENDS products have been estimated to be 90% and 95% less harmful than smoking cigarettes, respectively, are easy to understand and clearly communicate these products are less harmful than smoking cigarettes. The authors conclude such quantitative claims may be effective in gaining attention and persuading some audiences to switch to less harmful products like snus, although attribution to credible sources and active monitoring for unintended consequences (i.e., initiation by nonusers of tobacco) remain important considerations.
A separate study by Wackowski and colleagues (2021)36 used Wave 3 PATH data (collection period 20152016 prior to MRTP claim authorization in 2019) to assess the extent to which cigarette smokers had seen advertising for ENDS, SLT, or snus indicating using these products is less harmful than cigarette smoking. Such advertising was less commonly perceived among cigarette smokers for SLT and snus (approximately 5% for each product category, respectively) than for ENDS (nearly 30%). Nevertheless, 24-27% of smokers who noticed less harmful’ claims indicated they would use such products in the future, leading the authors to conclude MRTP claims may be an important motivator for some smokers to use reduced risk products. Lee et al. (2020) examined Wave 1-3 PATH data to find that use of SLT and snus was reported to predict increased quitting amongst smokers. One study related to snus and consumer understanding and perceptions reported an analysis of 11,631 snus-related Twitter posts collected between March 11, 2021, and February 26, 2022.37 The frequency of snus-related posts remained within a consistent range throughout the study period (generally 25-50 tweets per day), and a sentiment analysis indicated a positive sentiment was more prominent than a negative sentiment. Positive tweets focused on the harm reduction and smoking alternative properties of snus, whereas negative tweets focused on health concerns. Oral health concerns were the most commonly mentioned health category, although these were relatively 35 Wackowski OA, O’Connor RJ, Diaz D, et al95% less harmful’? Exploring reactions to quantitative modified risk claims for snus and ecigarettes. Tobacco Control 2022; 31:730-736. https://doi.org/10.1136/tobaccocontrol-2020-056303
36 Wackowski, O. A., O’Conner, R.J., and Pearson, J.L. (2021): Smokers’ Exposure to Perceived Modified Risk Claims for E-Cigarettes, Snus, and Smokeless Tobacco in the United States, Nicotine & Tobacco Research 2021; 23:605-608, retrieved from https://doi.org/10.1093/ntr/ntaa159
37 Chen, J., Xue, S., Xie, Z., Li, D. (2022): Perceptions and Discussions of Snus on Twitter: Observational Study. JMIR Med Inform 2022;10(8):e38174. Retrieved from: https://doi.org/10.2196/38174.
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infrequent at less than 5% of the total set of snus-related tweets. Taken together, the findings from this study related to snus and consumer understanding and perceptions are consistent with the position that General Snus (and snus overall) remain APPH.
Numerous additional studies highlight the importance of including modified risk claims38, 39, 40, 41 and demonstrate comprehension of the MRTP claims.42 DeAtley et al. (2023)43 examined the effects of MRTP claims on perceptions among racial and ethnic groups using three products authorized to include MRTP claims (General Snus Classic White, Philip Morris IQOS, and 22nd Century Group VLN cigarettes) and one not authorized (Juul Labs JUUL e-cigarette). This study found that “[n]ot including an MRTP claim resulted in an increased likelihood of trying a product, decreased concern of serious disease, lower perceived addictiveness” demonstrating consumers may misunderstand modified risk claims.
After the FDA authorized the MRTP claim for General Snus, Neilsen data from 19 U.S. states found no sales advantage gained from the claim relative to snus competitors but a relative increase in sales for all snus products. This indicates consumers may make determinations regarding product risk across the entire product class rather than attributing the modified risk to individual products44.
We also monitor the literature to ensure that there are no deficiencies in the responsible marketing and controls implemented to restrict access to unintended audiences, particularly youth. Recent studies show that the exclusive use of SLT products amongst school-based youth trended downwards45, 46. Cheng et al. (2023)47 found that “[l]ess than a quarter of youth (13­17 year olds) and less than a third of underage young adults (18­20 year olds) had heard of, or seen, snus”, illustrating the efficacy of the responsible marketing and controls.
38 Clarke, E., Thompson, K., Weaver, S., Thompson, J., & O’Connell, G. (2019). Snus: a compelling harm reduction alternative to cigarettes. Harm reduction journal, 16(1), 62. https://doi.org/10.1186/s12954-019-0335-1
39 Wackowski, O. A., Manderski, M. T. B., Lewis, M. J., & Delnevo, C. D. (2019). The Impact of Smokeless Tobacco Risk Information on Smokers’ Risk Perceptions and Use Intentions: A News Media Experiment. Health communication, 34(3), 325­332. https://doi.org/10.1080/10410236.2017.1407226
40 Wackowski, O. A., Rashid, M., Greene, K. L., Lewis, M. J., & O’Connor, R. J. (2020). Smokers’ and Young Adult Non-Smokers’ Perceptions and Perceived Impact of Snus and E-Cigarette Modified Risk Messages. International journal of environmental research and public health, 17(18), 6807. https://doi.org/10.3390/ijerph17186807
41 Lund, K. E., & Vedoy, T. F. (2019). Relative Risk Perceptions between Snus and Cigarettes in a Snus-Prevalent Society-An Observational Study over a 16 Year Period. International journal of environmental research and public health, 16(5), 879. https://doi.org/10.3390/ijerph16050879
42 Pillitteri, J. L., Shiffman, S., Sembower, M. A., Polster, M. R., & Curtin, G. M. (2020). Assessing comprehension and perceptions of modifiedrisk information for snus among adult current cigarette smokers, former tobacco users, and never tobacco users. Addictive behaviors reports, 11, 100254. https://doi.org/10.1016/j.abrep.2020.100254
43 DeAtley, T., Johnson, A. C., Stone, M. D., Audrain-McGovern, J., Mercincavage, M., & Strasser, A. A. (2023). Effects of Modified Tobacco Risk Products with Claims and Nicotine Features on Perceptions among Racial and Ethnic Groups. International journal of environmental research and public health, 20(15), 6454. https://doi.org/10.3390/ijerph20156454
44 Liber, A. C., Seidenberg, A. B., & Pesko, M. F. (2023). MRTP claim authorisation and General Snus sales in the USA: evidence from a difference- in-differences model. Tobacco control, tc-2022-057890. Advance online publication. https://doi.org/10.1136/tc-2022-057890
45 Dai, H. D., & Leventhal, A. M. (2023). Use of Traditional Smokeless, Snus, and Dissolvable Tobacco Among U.S. Youth. American journal of preventive medicine, 64(2), 204­212. https://doi.org/10.1016/j.amepre.2022.09.011
46 Cook, S., Ortiz Chavez, S., Zavala-Arciniega, L., Hirschtick, J. L., & Fleischer, N. L. (2023). Trends of Single, Dual, and Polytobacco Use Among School-Based Students in the United States: An Analysis of the National Youth Tobacco Survey. American journal of health promotion: AJHP, 37(8), 1078­1090. https://doi.org/10.1177/08901171231191557
47 Cheng, H. G., Vansickel, A. R., & Largo, E. G. (2023). Awareness and use of tobacco products among underage individuals: findings from the altria client services underage tobacco use survey 2020-2022. BMC public health, 23(1), 662. https://doi.org/10.1186/s12889-023-15610-1
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MRTP Renewal of MR0000020-MR0000022, MR0000024-MR0000025, MR0000027-MR0000029 Applicant: Swedish Match USA, Inc.
5.3 Tobacco Use Behavior and Impact to the Population as a Whole
We also monitor the literature for emerging evidence on population health impact of snus. One newly identified publication reported on the relationship between snus and alcohol use in a matched controlled population study of Norwegians (Watten and Watten, 2021).48 Alcohol consumption and drinking habits in a sample of snus users was compared to a sample of age- and gender- matched nonusers (n = 1,043 in both samples). Users of snus had higher frequencies of drinking, intoxication, and excess drinking when compared to the matched nonusers. However, the snus user group also differed significantly in several socioeconomic and health-related variables, including general mental health, that were found to be related to alcohol consumption habits. While this study on snus and use behavior has implications for alcohol and nicotine treatment and rehabilitation, the findings do not conflict with the position that General Snus remains APPH.
In addition to monitoring the literature, the recently established Rutgers Center of Excellence in Rapid Surveillance in Tobacco will provide FDA with unprecedented, real-time data on tobacco and nicotine marketing, products, and consumer behaviors. This comprehensive data will allow FDA to monitor the market and consumer changes as close to real time as possible and intervene as necessary.49
We have not received feedback from the Agency on the provided literature, indicating the required literature search does not raise new questions of public health. In fact, the literature and decades of epidemiological data continue to reinforce and strengthen the original FDA determination that General Snus products are APPH and that the products remain APPH, with smoke- free alternatives playing a critical role in helping legal age nicotine users abandon cigarettes and accelerate progress at the population level. Based on the collective findings in the published scientific literature and the studies and surveillance we conducted, renewal of the modified risk order should be granted.
6. RESPONSIBLE MARKETING AND CONTROLS
Upon MRGO renewal by FDA, under section 911(g)(1) of the FD&C Act, we intend to continue to market the products in a manner that restricts access to General Snus products by unintended audiences, particularly youth.
Our responsible marketing practices encompass labeling, advertising, marketing, promotion, and other consumer-directed activities. We conform with the requirements and marketing restrictions included in the MGOs and MRGOs, respectively, for those products, and we report to the FDA annually. In addition to annual reporting, Swedish Match also complies with all FDA- mandated marketing rules and regulations, as well as those required by law. Specifically, all General Snus product labeling carries the congressionally required, rotating warnings at 30% of the two primary panels. We also require retailers to merchandise General Snus in non-self-serve locations unless the facility is an adult-only facility.
In addition to these requirements, we take additional voluntary measures to ensure responsible marketing practices are applied to our entire portfolio of TNPs, including General Snus products. We
48 Watten R.G. and Watten, V.P. (2021): Snus and Alcohol: Mutually Rewarding Effects in the Brain? A Matched Controlled Population Study, Substance Abuse: Research and Treatment Volume 15: 1­9, retrieved from https://doi.org/10.1177/11782218211027124.
49 https://www.fda.gov/tobacco-products/ctp-newsroom/fda-and-nih-award- funding-new-center-rapid-surveillance-tobacco
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value transparency with our consumers and regulators, and we have a history of being proactive with marketing controls, including instituting age-gated marketing practices before they were required.
Specifically, we apply the following responsible marketing practices:
· We limit access to our website (GeneralSnus.com) to ONLY those confirmed to be at least 21 years old. We accomplish this through use of third-party age verification partners who match consumer information with government databases to confirm individuals’ identity and age;
· We limit access to our website to self-reported current users of TNPs;
· We do NOT advertise outdoors or through television and other mass media vehicles;
· We use models/talent who are visibly over the age of 35;
· We do NOT engage with consumers on social media platforms that are not age- restricted;
· We do NOT use paid professional athlete endorsements or sponsorship; and
· We do NOT use social influencers in our marketing.
We also routinely analyze data on sales and distribution, product purchasers, delivery of advertising impressions, and media tracking and optimization. The data shows 99.3% of General Snus purchasers who provided their age were over age 25, and none were reported to be under age 21, consistent with the practice of restricting owned-retail store entry and purchase, face-to-face engagement, and e-commerce purchase to adults verified as age 21+. Where tracking is available, advertising impressions were delivered predominantly (over 99.2% in all tracked channels) to persons over age 25. These results are consistent with implementation of responsible age restriction and verification practices.
We have also been conservative in our use of the authorized modified risk claim. Currently, the claim, which was authorized as part of our 2019 MRTP, is currently only communicated on the General Snus website behind the previously discussed age-gate. To view the claim, a consumer would need to take a series of steps to gain access to the webpage where the claim is visible (Figure 13). They must visit GeneralSnus.com, select “Register Now”, identify as a current tobacco user, provide personal information for age verification, be successfully age-verified, provide their communication preferences, create a username and password, and click on “Modified Risk.”
While this process drastically limits the likelihood that the claim will be viewed by unintended audiences, it also limits the utility of the claim, making it difficult to reach intended consumers, who could achieve a reduction in health risks by switching completely to the products. We remain open to discussion with the FDA on ways to adjust the use of the claim to reach more smokers and SLT product users who could benefit from using our products.

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MRTP Renewal of MR0000020-MR0000022, MR0000024-MR0000025, MR0000027-MR0000029 Applicant: Swedish Match USA, Inc.
Figure 13. Steps Required to Access the Modified Risk Claim

CONCLUSIONS

There is great opportunity to minimize harm from the use of combusted tobacco products by providing opportunities for legal age nicotine users to switch to modified risk alternatives like the authorized General Snus products. In addition, there is a need for effective education on the continuum of risk and ready access to authorized MRTP information by consumers. As Kozlowski and Abrams conclude, “[a] new reframing can align action plans to more powerfully and rapidly achieve population-level benefit and minimize harm to eliminate in our lifetime the use of the most deadly combustible tobacco products and thus prevent the premature deaths of 1 billion people projected to occur worldwide by 2100.”50 The combined evidence from the original and renewal applications submitted in support of these products demonstrate General Snus products continue to satisfy the requirements of section 911(g)(1) of the FD&C Act. These products are appropriate to promote public health and benefit the health of the population as a whole, taking into account both users of tobacco products and persons who do not currently use tobacco products. On March 16, 2023, FDA authorized U.S. Smokeless Tobacco Company’s Copenhagen Classic Snuff as an MRTP51, allowing the company to market the product with the claim, “IF YOU SMOKE, CONSIDER THIS: Switching completely to this product from cigarettes reduces risk of lung cancer.” While General Snus is not identical to Copenhagen Classic Snuff, they are both SLT products, and this authorization provides additional support for the continued use of products like General Snus as less harmful alternatives to combusted tobacco products.
50 Kozlowski, L.T., Abrams, D.B. Obsolete tobacco control themes can be hazardous to public health: the need for updating views on absolute product risks and harm reduction. BMC Public Health 16, 432 (2016). https://doi.org/10.1186/s12889-016-3079-9
51 https://www.fda.gov/media/166254/download?attachment Page 27 of 28
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There is converging public health consensus that non-combusted SLT is less hazardous than combusted cigarettes:
· “On the continuum of risk, non-combustible tobacco products are more likely to reduce harm than a smoked form of tobacco for individuals who would otherwise be using conventional cigarettes.”52
· “[U]sers of smokeless tobacco products generally have lower risk for tobacco-related morbidity and mortality than users of combustible tobacco products such as cigarettes.”53
· “[T]hough SLT products are generally considered higher-risk than NRT, they are of considerably lower risk than continued smoking. The overall epidemiological literature supports that cigarette smokers who completely switch to SLT products are likely to substantially lower their risks of cardiovascular disease, lung cancer, and respiratory disease compared to smoking.”54
As quoted in the last bullet, FDA’s evaluation of SLT tobacco products as a class only reinforces its initial evaluation of General Snus as a modified risk product and provides additional justification to renew this MRTP claim authorization.
The accuracy of the determinations upon which the original orders were based has not changed. The PMSS submitted over the past eight years have provided FDA ample time and data to review the information upon which the orders were based, and the FDA has not taken any enforcement action to remove the products from market or to remove the MRTP designations. We continue to provide realworld evidence and data over the past decade demonstrating General Snus is a viable tobacco harm reduction approach for legal age nicotine users who currently smoke but are either unable or unwilling to quit the use of combustible products. There is no new scientific evidence to change FDA’s original decision to grant these applications. The hierarchy of evidence supporting the modified risk information and authorization remains unchanged. Therefore, TPSAC should recommend FDA grant the MRGO renewals.

APPENDICES

· MGO Letters · MRGO Letters · TPL Executive Summaries
· Surveillance of Published Literature
52 Zeller, Hatsukami et al. The Strategic Dialogue on Tobacco Harm Reduction: A vision and blueprint for action in the US, Tobacco Control, 18(4), 324-332, 2009. http://www.jstor.org/stable/27798615
53 WHO Study Group on Tobacco Product Regulation (TobReg): The Scientific Basis for Tobacco Product Regulation, 951 Technical Reports Series (2008). https://books.google.com/books?id=-WpeaDp8sbcC
54 FDA memorandum from September 10, 2020, entitled “Summary of Health Effects of Smokeless Tobacco Products for Epidemiology Branch Product Application Review” https://vaping.org/wp- content/uploads/2023/02/SLTComparativeHealthEffects.pdf
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DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Dmg Administration Center for Tobacco Products
10903 New Hampshire Avenue Silver Spring, MD 20993

November 10, 2015

MARKETING ORDER

Swedish Match North America, fuc. Attention: Gerru·d Roerty, Jr., Vice President, General Cmmsel & Secretru.y Two Jru.nes Center 1021 East Cru.y Street, Suite 1600 Richmond, VA 23219 via Certified Mail

FDA Submission Tracking Number (STN): PM0000013

Dear Mr. Roeliy:

The Food and Dmg Administration (FDA) completed the review of your Premru.·ket Tobacco Product Application (PMTA) submitted under section 9 10(b) of the Federal Food, Dmg, an d Cosmetic Act (FD&C Act), for the following tobacco product:

Applicant: Tobacco Product Name: 1
Tobacco Product Category: Tobacco Product Sub-Category: Package Type: Package Quantity: Characterizing Flavor: Portion Count: Portion Mass: Portion Length: Portion Width: Portion Thickness: Tobacco Cut Size:2

Swedish Match North America, fuc. General Classic Blend Portion White Large 12ct Smokeless Tobacco P01tioned Snus Plastic Can 10.8 g None 12 pouches 900 mg 34 mm 14rmn 5 mm
{6)(4)r – – – – – – – .
(b)(4)
r )(4)

1 Brand/sub-brand or other conunercial name used in commercial distribution

2 The applicant provided ~ (b )( 4 )

to characterize the tobacco cut size. Therefore, the tobacco

cut size cannot be represented wrtli a smgle value an coiTesponding range limit.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

November 10, 2015

Food and Dmg Administration Center for Tobacco Products
10903 New Hampshire Avenue Silver Spring, MD 20993
MARKETING ORDER

Swedish Match North America, fuc. Attention: Gerru·d Roerty, Jr., Vice President, General Cmmsel & Secretru.y Two Jru.nes Center 1021 East Cru.y Street, Suite 1600 Richmond, VA 23219 via Certified Mail

FDA Submission Tracking Number (STN): PM0000011

Dear Mr. Roeliy:

The Food and Dmg Administration (FDA) completed the review of your Premru.·ket Tobacco Product Application (PMTA) submitted under section 9 10(b) of the Federal Food, Dmg, an d Cosmetic Act (FD&C Act), for the following tobacco product:

Applicant: Tobacco Product Name: 1 Tobacco Product Category: Tobacco Product Sub-Category: Package Type: Package Quantity: Characterizing Flavor: Portion Count: Portion Mass:
Portion Length: Portion Width: Portion Thickness: Tobacco Cut Size:2

Swedish Match North America, fuc.

General Dry Mint P01tion Original Mini Smokeless Tobacco P01tioned Snus Plastic Can 6.0 g Mint 20 pouches 300mg

28mm

14 mm

5mm

~)( 4)· -.

~

(b)(4)

f>l(4)

Based on our review of your PMTA, we fmd permitting the new tobacco product specified above to be marketed is appropriate for the protection of public health, and that you have met the other requirements of section 910(c) of the FD&C Act. Under the provisions of section 910, you may introduce or deliver for introduction into interstate commerce the new tobacco product specified above with the enclosed labeling.

1 Brand/sub-brand or other conunercial name used in commercial distribution

2 The applicant provided(b)(4)

to characterize the tobacco cut size. Therefore, the tobacco

cut size cannot be represented wrtli a smgle value an coiTesponding range limit.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

November 10, 2015

Food and Drug Administration Center for Tobacco Products
10903 New Hampshire Avenue Silver Spring, MD 20993
MARKETING ORDER

Swedish Match N01ih America, Inc. Attention: Gerard Roe1iy, Jr., Vice President, General Counsel & Secretmy Two James Center 1021 East Cmy Street, Suite 1600 Richmond, VA 23219 via Certified Mail

FDA Submission Tracking Number (STN): PM0000010
Dear Mr. Roe1iy:
The Food an d Dmg Administration (FDA) completed the review of your Premarket Tobacco Product Application (PMTA) subinitted under section 910(b) ofthe Federal Food, Dmg, an d Cosmetic Act (FD&C Act), for the following tobacco product:

Applicant: Tobacco Product Name: 1 Tobacco Product Category: Tobacco Product Sub-Category: Package Type: Package Quantity: C haracterizing Flavor: Tobacco Cut Size:2

Swedish Match N01ih America, Inc. General Loose Smokeless Tobacco Loose Snus Cardboard Can with Plastic Lid 45.0 g None
(b)(4) (b)(4)
f>H4l

Based on our review of your PMTA, we find pennitting the new tobacco product specified above to be marketed is appropriate for the protection of public health, and that you have met the other requirements of section 91 0(c) of the FD&C Act. Under the provisions of section 910, you may introduce or deliver for introduction into interstate commerce the new tobacco product specified above with the enclosed labeling.

1 Brand/sub-brand or other commercial name used in commercial distribution

2 The applicant provided (b)(4)

to characterize the tobacco cut size. Therefore, the tobacco

cut size cannot be represented wtth a smgle value and cotTesponding range limit.

3DJH 30
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DEPARTMENT OF HEALTH & HUMAN SERVICES

November 10, 2015

Food and Dmg Administration Center for Tobacco Products
10903 New Hampshire Avenue Silver Spring, MD 20993
MARKETING ORDER

Swedish Match North America, fuc. Attention: Gerru·d Roerty, Jr., Vice President, General Cmmsel & Secretru.y Two Jru.nes Center 1021 East Cru.y Street, Suite 1600 Richmond, VA 23219 via Certified Mail

FDA Submission Tracking Number (STN): PM0000015

Dear Mr. Roeliy:

The Food and Dmg Administration (FDA) completed the review of your Premru.·ket Tobacco Product Application (PMTA) submitted under section 9 10(b) of the Federal Food, Dmg, an d Cosmetic Act (FD&C Act), for the following tobacco product:

Applicant: Tobacco Product Name: 1
Tobacco Product Category: Tobacco Product Sub-Category: Package Type: Package Quantity: Characterizing Flavor: Portion Count: Portion Mass:
Portion Length: Portion Width: Portion Thickness: Tobacco Cut Size:2

Swedish Match North America, fuc. General Nordic Mint Portion White Large 12ct Smokeless Tobacco P01tioned Snus Plastic Can 10.8 g Mint 12 pouches 900 mg
34 mm 14 rmn 5 mm
( b) {4 )
(b){4)
r ){4)

1 Brand/sub-brand or other conunercial name used in commercial distribution

2 The applicant provided(b){4 )

to characterize the tobacco cut size. Therefore, the tobacco

cut size cannot be represented wrtli a smgle value an coiTesponding range limit.

3DJH 30
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POSTMARKET REPORTS
I. Serious and Unexpected Adverse Experiences Reporting
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II. Manufacturing Deviations
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III. Periodic Reporting
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