DEPARTMENT OF HEALTH & HUMAN 

SERVICES 

Food and Dmg Administration 

Center for Tobacco Products 

Office ofScience 

Premarket Tobacco Application (PMTA) 


Technical Project Lead (TPL) Review 


Submission Information 

Applicant Swedish Match N01th America, fuc . 

Submission Date March 11, 2015 FDA Receipt Date March 11, 2015 

PMOOOOOlO: General Loose 

Product Category Smokeless Tobacco 

Product Sub-Category Loose Snus 

Package Type Car dboard Can with Plastic Lid 

Package Quantity 45.0 g 

Tobacco Cut Size: 

Characterizing Flavor None 

PMOOOOOll: General Dn Mint Portion Orhdnal Mini 

Product Category Smokeless Tobacco 

Product Sub-Category P01tioned Snus 

Package Type Plastic Can 

Package Quantity 6.0 g 

P01tion Count: 20 pouches 

P01tion Mass: 300 mg 

P01tion Length: 28 Illlll 

P01tion Width : 14 Illlll 

P01tion Thickness: 5 mm 

Tobacco Cut Size: 

Characterizing Flavor Mint 

PM0000012: General Portion Original Large 

Product Category Smokeless Tobacco 

Product Sub-Category P01tioned Snus 

Package Type Plastic Can 

Package Quantity 24.0g 

P01tion Count: 24 pouches 

P01tion Mass: 1000 mg 

P01tion Length: 33 Illlll 

P01tion Width : 18 Illlll 

P01tion Thickness: 6 mm 

Tobacco Cut Size: 

Characterizing Flavor None 

1 The applicant provided (b) 4) buckets to characterize the tobacco cut size. Therefore, the tobacco 

cut size cannot be repres ente<l wttli a single value and cotTesponding range limit. 
TPL Review for: PM0000010-PM0000017 

PM0000013: General Classic Blend Portion White Lar2e - 12ct 

Product Category Smokeless Tobacco 

Product Sub-Category Portioned Snus 

Package Type Plastic Can 

Package Quantity 10.8 g 

Portion Count: 12 pouches 

Portion Mass: 900 mg 

P01iion Length: 34 mm 

P01iion Width : 14 mm 

P01iion Thickness: 5 mm 

(b) (4) Tobacco Cut Size: 

Characterizing Flavor None 

PM0000014: General Mint Portion White Large 

Product Category Smokeless Tobacco 

Product Sub-Category P01iioned Snus 

Package Type Plastic Can 

Package Quantity 24.0 g 

P01iion Count: 24 pouches 

P01iion Mass: 1000 mg 

P01iion Length: 34 Illlll 

P01iion Width : 18 Illlll 

P01iion Thickness: 5.5 mm 

Tobacco Cut S (b) (4) ize: 

Characterizing Flavor Mint 

PM0000015: General Nordic Mint Portion White Lar2e - 12ct 

Product Category Smokeless Tobacco 

Product Sub-Category P01iioned Snus 

Package Type Plastic Can 

Package Quantity 10.8 g 

P01iion Count: 12 pouches 

P01iion Mass: 900 mg 

P01iion Length: 34 Illlll 

P01iion Width : 14 Illlll 

P01iion Thickness: 5 mm 


Tobacco Cut Size: 


Characterizing Flavor 
 Mint 

(t>f(4) 

Page 2 of67 
TPL Review for : PM0000010-PM0000017 

PM0000016: General Portion White Lar2e 

Product Category Smokeless Tobacco 

Product Sub-Category Portioned Snus 

Package Type Plastic Can 

Package Quantity 24.0 g 

Portion Count: 24 pouches 

Portion Mas s: 1000 mg 

P01iion Length: 34 mm 

P01iion Width : 18 mm 

P01iion Thickness: 5.5 mm 

Tobacco Cut Size: {b) (4) 

Characterizing Flavor None 

PM0000017 : General Wintergreen Portion White Large 

Product Category Smokeless Tobacco 

Product Sub-Category P01iioned Snus 

Package Type Plastic Can 

Package Quantity 24.0 g 

P01iion Count: 24 pouches 

P01iion Mas s: 1000 mg 

P01iion Length: 34 mm 

P01iion Width : 18 mm 

P01iion Thickness: 5.5 mm 

Tobacco Cut Size: (b) (4 ) 

Characterizing Flavor Wintergreen 

STN Submission Date Solicited Y IN 

PM0000018 3/31/2015 y 

PM0000019 3/31/2015 y 

PM0000020 3/3 1/2015 y 

PM0000021 3/3 1/2015 y 

Amendment(s) PM0000022 3/31/2015 y 

PM0000023 3/3 1/2015 y 

PM0000024 3/3 1/2015 y 

PM0000025 3/31/2015 y 

PM0000026 6/3/2015 y 

PM0000027 6/23/2015 y 

PM0000029 7/8/2015 y 

Page 3 of67 
TPL Review for: PM0000010-PM0000017 

Related 

Submissions 

Cross Referenced 

Submission Industry Meetings 

Other Related 

Submission ST N(s) 

MR0000020 SE0000140, SE0010524 

MR0000021 SE0000139, SE0010525 

MR0000022 SE0000143, SE0010526 

MR0000024 SE0010528 

MR0000025 SE0000141 , SE0010529 

MR0000027 SE0010531 

MR0000028 SE0000144, SE0010532 

MR0000029 SE0000145, SE0010533 

Product Use IZJ For Consumer Use D For Fmi her Manufach1ring 

Product Type IZJ Complete D Component, Prui, or Accessory 

DISCIPLINES REVIEWED DATE OF REVIEW 


Behavioral Phrumacology October 21, 2015 


Chemistry October 30, 2015 

Clinical Phrumacology October 21, 2015 

Engineering October 2, 2015 

Environmental Science October 8, 2015 

Epidemiology October 6, 2015 

Medical October 20, 2015 

Microbiology October 15, 2015 

OCE Review (DEM & DPAL) October 6, 2015 

Social Science October 2, 2015 

Statistics September 28, 2015 

Toxicology October 16, 2015 

Page 4 of67 
TPL Review for: PM0000010-PM0000017 

Recommended Action(s) 

[8J Issue a Marketing Authorization letter; application contains sufficient evidence to 

demonstrate the product is appropriate for the protection ofpublic health. 

D Issue a No Marketing Authorization letter; application does not contain sufficient evidence 

to demonstrate the product is appropriate for the protection of public health. 

Technical Project Lead Name: 

CTP/OS 	 Ii-Lun Chen, MD 

Director, Division of Individual Health Science 

Digita lly s ig , ~~ Chen -S 

Date: 201 s. _l lf.~i ?~'o9 -05'00' 

Signatory Decision: 

I:8J 

D 

D 

I concm with TPL recommendation and basis of recommendation 

I concm with TPL recommendation and am providing additional comments (see separate 

memo) 

I do not concm with TPL recommendation as stated in my separate memo 

Signatory: 	

CTP/OS 	

David Ashley, Ph.D. 

RADM, U.S. Public Health Service 

Director 

Office ofScience 

Digitally signed by David Ashley -S 

Date: 2015.11.03 13:25:56 -05'00' 

Page 5 of67 
TPL Review for: PM0000010-PM0000017 

Premarket Tobacco Application Technical Project Leader Review 

I. Executive Summary 

On March 11, 2015, Swedish Match North America (SMNA) submitted eight General brand 

snus premarket tobacco product applications (PMTAs) to FDA seeking authorization under 

Section 910(b) of the Federal Food, Drug and Cosmetic Act (FD&C Act). 

Scientific review of these eight applications demonstrates that these eight products have the 

following qualities: 

x	 

x	 

x	 

Produced with a voluntary, proprietary standard using acceptable manufacturing processes 

as confirmed by both application review and on-site inspections. The applicant’s heat 

treatment process distinguishes Swedish snus from other types of smokeless tobacco (ST), 

including snus-like products sold in the US market. The proprietary quality standard for 

Swedish snus products was developed to ensure product quality. The principal 

components of this standard include constituent standards, manufacturing standards, 

manufacturing process requirements, and consumer package labeling with a “best before” 

date. The constituent standards set maximum levels that must not be exceeded for selected 

constituents in the finished products. 

The proposed products contain significantly lower levels of NNN and NNK compared to 

over 97% the ST products currently on US market. Since NNN and NNK are among the 

most carcinogenic constituents in tobacco products, reduction of NNN and NNK levels in 

ST products could reduce the cancer risk for consumers using ST products. Assuming 

persons who would have used other US ST products use these product instead, an 

individual using these products with reduced NNN levels could decrease the excess 

cancer risk2 by 90% compared to use of moist snuff (market share: 82%), 67% compared 

to use of chewing tobacco (market share: 15%), 38% compared to use of United States 

(US)-style snus, and 92% compared to use of dry snuff. Even further reductions in excess 

cancer risk could occur with the corresponding reductions in NNK; however, a 

quantitative contribution cannot be determined at this time due to the absence of a NNK 

cancer slope factor. 

Levels of other harmful and potentially harmful constituents (HPHC)(including As, Cd, 

acetaldehyde, crotonaldehyde, formaldehyde, and BaP) are similar to or lower than levels 

of ST products currently on the US market. Certain HPHCs (such as acrolein, 

acetaldehyde, cadmium, and nickel) have been identified as constituents of more toxic 

concern in the smoke of combusted products as compared to smokeless products. 

When used as exclusively instead of other smokeless tobacco products or cigarettes on the 

US market, these products offer potential for reductions in oral cancer risk. 

2

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 6 of 67 
TPL Review for: PM0000010-PM0000017 

x

x

x

x

When used as exclusively instead of combusted tobacco products, these products offer 

lower risk of developing respiratory diseases (i.e., chronic obstructive pulmonary disease 

(COPD), emphysema, chronic bronchitis) and cancers (such as oral, esophageal, and lung) 

than smokers. 

If nonusers were to initiate or users decrease cessation, there would be negative health 

consequences. 

Use of Swedish snus products is not risk-free and its use is associated with adverse health 

risks such adverse pregnancy outcomes, oral disease, increased risk of fatal cardiovascular 

events, pancreatic cancer, diabetes, and all-cause mortality. 

It is anticipated that the marketing of the proposed products, as described in the PMTAs, 

there is a low likelihood of nonuser uptake of these products, decreased or delayed 

cessation, or other significant shifts in user demographics. 

Information from national tobacco use studies and other studies submitted by the applicant 

indicate that migration of smokers to exclusive use of these proposed snus tobacco products 

while possible is expected to be limited. It is more likely that uptake of the proposed products 

occurs among current smokeless tobacco users. Given the above listed justifications based on 

information gathered from nonclinical and clinical product evaluations as well as substantial 

epidemiological studies, the totality of evidence provided in the applications support 

authorization of these products so that current ST product users will have additional options 

for less toxic tobacco products, thereby potentially decreasing the negative health impact from 

tobacco product use making the marketing of these proposed products appropriate for the 

protection of public health. 

II. Review of PMTA 

1. Background and Regulatory History 

A new tobacco product, including a tobacco product modified in any way (“including a change 

in design, any component, any part, or any constituent, including a smoke constituent, or in the 

content, delivery, or form of nicotine, or any other additive or ingredient” (section 

910(a)(1)(B)), after February 15, 2007 requires premarket review and an order from FDA 

authorizing the marketing of the product. 

A PMTA must be submitted to FDA under section 910(b) of the FD&C Act and a marketing 

authorization order must be received from FDA under section 910(c)(1)(A)(i) prior to 

marketing any new tobacco product, unless FDA has found that the product is substantially 

equivalent to a tobacco product commercially marketed in the US as of February 15, 2007 (see 

section 910(a)(2)(A)(i)) or is exempt from a substantial equivalence determination pursuant to 

regulation (see section 910(a)(2)(A)(ii)). 

Page 7 of 67 
TPL Review for: PM0000010-PM0000017 

FDA will deny a PMTA and issue a no marketing authorization order that the product may not 

be introduced or delivered for introduction into interstate commerce under section 

910(c)(1)(A)(ii) where FDA finds that: 

x	 

x	 

x	 

x	 

there is a lack of a showing that marketing the product is appropriate for the protection 

of the public health; 

the methods, facilities, or controls used in manufacturing, processing, or packing do 

not conform to manufacturing regulations issued under section 906(e) (21 U.S.C. 

387f(e)); 

the proposed labeling is false or misleading; or 

it is not shown that the product complies with any tobacco product standard in effect 

under section 907 (21 U.S.C. 387g), and there is not adequate information to justify 

deviation from the standard. 

The statute provides that the finding as to whether the marketing of a product for which a 

PMTA is submitted would be appropriate for the protection of the public health shall be 

determined with respect to the risks and benefits to the population as a whole, including users 

DQG QRQXVHUV RI WKH WREDFFR SURGXFW DQG WDNLQJ LQWR DFFRXQW ņ

(A) the increased or decreased likelihood that existing users of tobacco products will 

stop using such products; and 

(B) the increased or decreased likelihood that those who do not use tobacco products 

will start using such products. 

Regulatory History 

On March 11, 2015, Swedish Match North America (SMNA) submitted eight General brand 

snus PMTAs to FDA seeking authorization under Section 910(b) of the Food, Drug and 

Cosmetic Act. The PMTAs [PM00000010-PM00000017] were submitted in connection with 

the June 10, 2014 Modified Risk Tobacco Product Applications (MRTPA) for the same eight
 

snus products. However, the PMTAs are for the eight General brand snus products without any
 

modified risk claims (proposed product labeling submitted March 31, 2015 [PM0000018­

PM0000025]). 

Significant regulatory interactions include the following:
 

x

x

x

x

x	 

March 11, 2015: FDA received PMTAs for eight snus products.
 

March 25, 2015: FDA issued eight acknowledgment letters.
 

March 26, 2015: FDA held a teleconference with SMNA requesting SMNA submit one 

label that includes one of the health warnings for each tobacco product because SMNA did 

not submit specimen labels specific to the PMTAs. 

March 31, 2015: SMNA submitted amendments, PM0000018-PM0000025, in response to 

a teleconference held on March 26, 2015. 

March-April 2015: FDA conducted on-site clinical and manufacturing inspections of 

domestic and foreign clinical sites related to the SMNA MRTPAs. FDA inspected clinical 

study sites (Indianapolis, IN and Serbia), manufacturing sites (Sweden), and a SMNA 

laboratory facility (Sweden). 

Page 8 of 67 
TPL Review for: PM0000010-PM0000017 

x

x

x

x

x

x

x

x

x

x

April 2, 2015: FDA conducted a follow-up teleconference with SMNA regarding the status 

of samples being shipped to Southeastern Regional Laboratory (SRL) for testing. 

April 23, 2015: FDA issued eight Sample Acknowledgement letters acknowledging SRL’s 

receipt of samples on April 15, 2015 from SMNA. 

April 9-10, 2015: A meeting of the Tobacco Products Scientific Advisory Committee 

(TPSAC) discussed the ten submitted MRTPAs, including the adequacy of the scientific 

evidence to support proposed health claims of substantially reduced health risk in 

comparison with cigarettes. 

May 7, 2015: FDA determined that the eight PMTAs met the filing requirements for a 

PMTA seeking a marketing order under section 910(c)(1)(A)(i) of the FD&C Act. A Filing 

letter was issued to SMNA. 

May 20, 2015: FDA issued an Advice/Information (A/I) Request letter to SMNA. 

June 3, 2015: SMNA submitted an amendment, PM0000026, in response to FDA’s May 

20, 2015 A/I letter. 

June 12, 2015: FDA issued an A/I Request letter to SMNA. 

June 23, 2015: SMNA submitted an amendment, PM0000027, in response to FDA’s June 

12, 2015 A/I letter. 

June 29, 2015: FDA held a teleconference with SMNA to discuss engineering deficiencies 

for their PMTA and MRTP applications. 

July 8, 2015: SMNA submitted an amendment, PM0000029, in response to a 

teleconference held on June 29, 2015. 

Current Submission Tobacco Product 

Swedish Match General brand snus is an oral ST product that is moistened to facilitate use in 

the oral cavity. The applicant defines “snus” as an ST product that is produced and used in 

Sweden and manufactured using a heat treatment process according to a proprietary standard. 

This process distinguishes Swedish snus from other types of ST, including snus-like products 

sold in the US market. Swedish snus is made mainly from air-dried tobacco varieties, various 

salts, flavoring, and moisture-preserving substances. SMNA describes the snus products as 

“moist ( (b) (4)% moisture) to semi-moist (b) (4) % moisture) oral smokeless products which are 

typically placed between the upper lip and the gum and do not require expectoration during 

use.” In contrast, American ST products are typically placed between the lower lip and gum 

and require expectoration during use (Hatsukami et al., 1988). In Sweden, the product is 

classified as food, contains only food-approved ingredients, and is manufactured in a way that 

is consistent for food production. 

Swedish Match currently markets other snus products in the US in two packaging formats: 

loose snus and portioned snus. 

x

x	 

Loose Snus: Traditional variant of Swedish snus that is formed by pinching a desired 

amount upon use. 

Portioned Snus: Consists of pre-packed pouches wrapped in a non-woven fabric for 

discrete and hygienic usage. The pouches are available in different sizes and weights 

(e.g., from 0.3 g to 1.0 g/pouch). Swedish Match produces two types of pouch 

products, original and white. 

Page 9 of 67 
TPL Review for: PM0000010-PM0000017 

2. Overview of ST Products on the US Market 

According to the August 2014 Emomonitor Intemational rep01i, in 2013 the tobacco industry 

had US sales totaling $ 112.2 billion (including cigarettes, cigars, ST tobacco, cigarettes 

including RYO stick equivalent). ST accounted for $7.4 billion. Therefore, ST accounted for 

6.6% of tobacco sales in 2013 . ST products are marketed in the US in categories such as USstyle moist snuff, chewing tobacco, Swedish-style snus, illy and hard snuff. US style m oist 

snuff comprises greater than 82% of the ST market based on sales in the US . ST users 

pmchase moist snuff as pouched products or loose tobacco products. Chewing tobacco, 

Swedish-style snus, illy snuff, hard snuff products account for approximately 18% ofthe US 

ST market. Chewing tobacco consists ofproducts such as plug, twist, and chew. Dry snuff is 

often inhaled through the nose, or may be a pouched product placed in the mouth . The eight 

new snus products in this PMTA are categorized as Swedish-style snus, which follows the 

manufactming procedmes provided by a voluntary indust:I·ial quality standard for Swedish 

snus. This standard aims to reduce selected, undesired constituents in the finished products, 

such as tobacco-specific nit:I·osamines (TSNAs), metals, benzo(a)pyrene(BaP), and nit:I·ite, by 

implementing a series of procedmes that includes: tobacco leafselection, cont:I·olled heat 

t:I·eatment that reduces the natmal microbial flora, and manufactming in a closed system to 

prevent extemal microflora contamination . 

3. Product Science (Chemistry/Engineering/Microbiology) 

General Product Description -.-.-------. 

The eight Swedish snus products are made from (t>) (4) , and ) t tobaccos 

along with various salts, flavorings, and moistme-preservm suostan ces. T~~ applicant 

indicates that all the products are designed to contain (b) (4) %(weight) nicotine with 

moistme levels between . • % and ~ and QH values between 11 u and '>1'' . The total nicotine 

in the eight snus products ranges from (o) (4) mg/g for PM0000010 and PM0000012-17, and 

4 > ( mg/g for PM0000011 . These nicotine values are within the rep01ied ranges for other 

mar eted US moist snuff, therefore the abuse potential for these products is similar to other 

marketed sm okeless tobacco products. Other than tobacco, the basic fonnulations for all the 

products consist of various salts, flavorings, processing aid, and humectants. The applicant 

claims that all ingredients other than tobacco are approved for food use. In tenus of quantity, 

water b) (4) %), a humectant according to the applicant, is the m ost abundant ingredient 

besides tooacco in each product. Exce t for PM0000011 , all of the roducts also contain 

(t>) (4) or bot~bJ 141j and (b) (4) as humectantsj (b) (4) % . (b) (4) 

(b) (4) % is used as a taste enhancer and preservative. (b) (4) 

b) (4) (b) (4) %) are used as pH adj usters. Small quantities of (b) (4) b) (4) %) are 

used as a processing aid. For non-mint and non-wintergreen flavored roducts (PM0000010, 

PM0000012-PM0000013, and PM0000016), flavors account for(6){4) % ofthe finished 

products by weight. However, the three mint-flavored products (PM0000011 and PM0000014­

PM000001 and one wintergreen-flavored product (PM000001 7) contain higher levels of 

flavor b) 4) %by weight). The flavored products also contain an miificial sweetener, 

(t>) 4) 6)l4fl%) . For most ofthe products included in these PMTAs, the vast maj ority 

of tlieingreilients ot her than tobacco m·e listed as flavor, which are typically present at very 

low concent:I·ations (ppm or ppb levels), except for the mint and wintergreen flavor ingredients 

Page 10 of67 
TPL Review for: PM0000010-PM0000017 

as described. Non-portioned snus (PM0000010) is not allocated into a defined serving size; 

instead, the consumer decides the amount per use. Portioned snus (PM0000011-PM0000017) 

is allocated into a defined serving size via pouch paper, individual pieces, or other means. In 

this case, the products utilize pouch paper. 

The chemistry evaluation took into consideration product formulation (including HPHCs), 

chemistry design (nicotine, moisture, pH), tobacco blend, ingredients other than tobacco, 

manufacturing steps and controls, performance criteria and stability. More specifically, 

HPHCs evaluated include: acetaldehyde, arsenic, BaP, cadmium, crotonaldehyde, 

formaldehyde, nicotine (free and total), NNN (N-nitrosonornicotine), NNK ((4­

methylnitrosamino)-1-(3-pyridyl)-1-butanone), and pH. Compared to the literature data, we 

found that the levels of NNK, NNN, B[a]P, and crotonaldehyde in these new snus products are 

significantly lower than those in the major types of traditional smokeless tobacco products 

(STPs) on the US market (e.g., moist snuff). These reductions can be mainly attributed to the 

differences in the types of tobacco (no use of dark-fire cured and fermented tobacco) and 

manufacturing process (steam heat-treatment versus fermentation). Also, there are no 

increased levels of formaldehyde, acetaldehyde, arsenic, and cadmium compared to the 

traditional STPs. Additionally, these new snus products do not contain a wide range of HPHCs 

that are typically found in mainstream cigarette smoke. 

The applicant states that the product for PM0000010 is packed in paraffin-coated cardboard 

cans with plastic lids and the products for PM0000011-PM0000017 are packed in either round 

or square plastic cans with plastic lids. The applicant provides the ingredients (e.g., 

) contained in the packaging materials and states that all ingredients and 

materials in the new products are food grade, generally recognized as safe (GRAS), or are 

approved for food contact. The plastic lid, plastic base, cardboard can base, and wax coating 

used in the new products are the same as other products currently on the market from SMNA. 

No chemistry or toxicology concerns with the containers were identified based on the 

information provided. Overall, the chemistry evaluation determined that there was adequate 

information to characterize the proposed products and that the property parameters, 

manufacturing and processing were acceptable. Refer to the individual chemistry, engineering 

and microbiology reviews for a full description of unique properties by product. This review 

only provides an overview of the products. 

(b) (4) (b) (4)

Page 11 of 67 
TPL Review for : PM0000010-PM0000017 

Tobacco Blend 

Quantity (Tar get with minimum and maximum 

limits in par enthesis) (m;Vg or mg/pouch)* 

PMTA Product Tobacco 

Leaf

Tobacco 

Leaf

Tobacco 

Stem 

Total 

_ (b) - (b) -

<t> r (4) i<br<4)1 

PMOOOOOlO General Loose (b) (4) 

PMOOOOOll General Dry Mint 

P01iion Original 

Mini 

PM0000012 General P01iion 

Original Large 

PM0000013 General Classic 

Blend P01iion 

White Large 

(12 ct) 

PM0000014 General Mint 

P01iion White 

Large 

PM0000015 General Nordic 

Mint Portion 

White Large 

(12 ct) 

PM0000016 General P01iion 

White Large 

PM0000017 General 

Wintergreen 

P01iion White 

Lar ge 

* mg/g for PMOOOOOl O and mg/pouch for PM0000011-PM0000017. 

Page 12 of67 
TPL Review for : PM0000010-PM0000017 

Overview of Produce 

B1·and 

FDA Submission 

Trackin2 Number 

(STN) 

Packa2e 

T ype 

Can 

Weight 

Can 

Dimension 

Pouch 

Size 

Pouches 

per Can 

P01·tion 

Mass 

General 

Loose PM0000010 

Cardboard 

Can with 

Plastic Lid 

45.0 g 70.5 X 23 

nun 

General Dty Mint 

P01t ion Original 

Mini 

PMOOOOOll Plastic Can 6.0 g 66x19nun 14 X 28 X 

5 nun 

20 0.3 g 

General Portion 

Original Large PM0000012 Plastic Can 24.0 g 70 x 24 nun 

18 X 33 X 

6nun 24 1.0 g 

General Classic 

Blend P01t ion 

White Large 

PM0000013 Plastic Can 10.8 g 56.6 X 86 

x18 nun 

14 X 34 X 

5 nun 

12 0.9 g 

General Nordic 

Mint Portion 

White Large PM0000014 Plastic Can 13.5 g 56.6 X 86 

x18 nun 

14 X 34 X 

5 nun 

24 0.9 g 

General Nordic 

Mint Portion 

White Large 

PM0000015 Plastic Can 10.0 g 56.6 X 86 

x18 nun 

14 X 34 X 

5 nun 

12 0.9 g 

General Portion 

White Large PM0000016 Plastic Can 24.0 g 70 x 24 nun 

18 X 34 X 

5.5 mm 24 1.0 g 

General 

Wintergreen 

Portion White 

Large 

PM0000017 Plastic Can 24.0 g 70 x 24 nun 

18 X 34 X 

5.5 llllll 

24 1.0 g 

General Product Design 

The applicant identifies the products' components and subcomponents (e.g. , tobacco, pouch, 

can) as well as some of the applicable specifications and a description of the intended function 

for each. Design parameters are assessed to understand the comprehensive design ofthe 

products as each parameter contributes to the overall constituent yields: 

• 	 Tobacco cut size is directly related to the pa~ticle smface a~·ea and the 

accessibility of saliva to tobacco smfaces, thereby affecting the amount an d rate 

of constituents released from the product. 4 

3 This table supersedes the tables presented in the clinical pharmacology, behavioral pharmacology, and medical 

revrews. 

4 Dash S, Mmthy PN, Nath L, Chowdhmy P (2010). Kinetic modeling on dmg release from controlled dmg 

Page 13 of67 
TPL Review for: PM0000010-PM0000017 

x

x

x

x

x

x	 

x	 

x	 

Tobacco moisture (tobacco leaf, blend, and final) may affect microbial growth 

in the product, extraction efficiency, and total exposure to nicotine, NNN, and 

NNK.5, 6, 7 

Portion mass may affect user exposure to the tobacco product and, in turn, the 

HPHCs contained in each portion.8 

Portion length may affect the constituents in each portion.8 

Portion width is directly related to product surface area, which is proportional 

to the amount and rate of constituents released from the product.9 

Portion thickness is directly related to product surface area, which is directly 

proportional to the amount and rate of constituents released from the product.9 

Pouch paper basis weight, the weight of paper per meter area, influences the 

interactions between the tobacco and oral cavity, thereby affecting the amount 

and rate of constituents released from the product.10 

Pouch paper porosity/permeability influences the interactions between the 

tobacco and oral cavity, thereby affecting the amount and rate of constituents 

released from the product.10 

Pouch paper wicking allows the transport of tobacco constituents from the 

tobacco filler to the pouch surface, thereby affecting the amount and rate of 

constituents released from the product.11 In this submission, the applicant’s 

nicotine uptake trials demonstrate the nicotine extraction rates differ even in the 

products with the same pouch material, indicating the wicking rates are not 

affecting the nicotine absorption rates in these new products. Therefore, 

wicking values are not needed for these products. 

Compared to currently-marketed smokeless products, the applicant provided some of the target 

specifications and upper and lower range limits necessary to evaluate ST products. Industry 

average ranges are used to compare the design parameters of PM0000010-PM0000017 to 

typical values that FDA anticipates based on previous submissions. The products chosen for 

delivery systems. Acta Poloniae Pharmaceutica – Drug Research 67(3):217-223.

5 U.S. Food and Drug Administration (2013). Evaluation and Definition of Potentially Hazardous Foods ­

Chapter 3: Factors that Influence Microbial Growth. Available at: 

http://www.fda.gov/Food/FoodScienceResearch/SafePracticesforFoodProcesses/ucm094145.htm (The “tobacco 

juice” generated when snus is consumed can be ingested similar to foods, thus this reference is relevant here.) 

6 Gale N, Errington G, McAdam K (2013). Effects of product format on nicotine and TSNA extraction from snus
 

pouches. British American Tobacco 67th Tobacco Science Research Conference, Williamsburg, VA, September
 

15-18, 2013.

7 Djordjevic MV, Hoffman D, Glynn T, Connolly GN. U.S. commercial brands of moist snuff, 1994. I. 

Assessment of nicotine, moisture, and pH. Tob Control. 1995;4:62–6.

8 Stepanov I, Jensen J, Biener L, Bliss R, Hecht SS, Hatsukami DK (2012). Increased pouch sizes and resulting
 

changes in the amounts of nicotine and tobacco-specific N-nitrosamines in single pouches of camel snus and 

malrboro snus. Nicotine Tob Research 14(10):1241-1245.

9 Zhang H, Zhang J, Streisand JB (2002). Oral mucosal drug delivery: Clinical pharmacokinetics and therapeutic 

applications. Drug Deliv Sys 41(9):661-680.

10 Lewis S, Subramanian G, Pandey S, Udupa N (2006). Design, evaluation and pharmacokinetic study of
 

mucoadhesive buccal tablets of nicotine for smoking cessation. Indian J Pharm Sci 68:829-31. 11 Morrow NR (1970). Physics and thermodynamics of capillary action in porous media. Ind Eng Chem Res
 

62(6): 32-56.
 

Page 14 of 67 
TPL Review for : PM0000010-PM000001 7 

comparison are those that ar e in similar product categories an d subcategories as the new 

products. The table below lists typical smokeless design parameter ranges. 

Aver a2e I n d u stry Ran 2es f or S mo kl e ess D es1. 2n Par a meters"' 

Design Parameter Industty Range 

P110000010-P110000017 

Within Industty Range** 

Final11oisture (%) 3.6-57 Yes 

Portion 11ass (mg) 230-1820 Yes 

Portion Length (llllll) 10-36 Yes 

Portion Width (rmn) 6.65 -18 Yes 

Portion Thickness (rmn) 5-5.79 Yes 

Pouch Paper Basis Weight (g/m') 1-29 Yes 

Caliper (!J.m) 195 Yes 

*Data som·ce rs FDA database ofengmeenng parameters fotmd 111 SE Rep01ts subnutted to FDA 


(version 5/9/ 14); fmal moisttu·e range determined fi:om portioned and non-portioned smokeless products; 


portioned parameters determined from p01tioned smokeless products. 


**Due to testing variability, values for the new products that are out ofindustry range by less than 5% are 


considered to be w-ithin range and acceptable. 


The fmal tobacco moisture level is within the industry range an d no other issues are identified. 

Also, portion m ass, length, width, thickness, an d caliper are within the industry ranges for all 

of the new products an d no other issues are identified . Fmi he1more, the tobacco types utilized 

in the new products are similar to or the same as products cmTently marketed . Therefore, the 

new products do not appear to be different from available sm okeless products with regard to 

the tobacco and the design parameters provided. In summruy, the results analyzed indicate 

these products fall in the n01mal range, and the actual design feature values do not apperu· to 

raise concem s related to how these products might adversely impact public health through risk 

to the user, increased initiation or decreased cessation as compru·ed to the existing ST market. 

Sample Testing 

The applicant submitted samples of each of its products in supp01t ofits PMTAs to FDA's SRL on 

April 15, 2015. Samples were shipped via UPS fi:om Swedish Match N01th Europe to the Swedish 

Match N01th America Owensboro, Kentucky facility. These samples were then shipped at ambient 

temperatme fi:om the Owensboro facility to SRL. 

The CTP Office ofScience (OS) requested testing ofthe PMTA product samples and examples of 

testing pe1fonned: 

• 	

• 	

• 	

• 	

Nicotine (filler/SL), pH, TSNA (filler), nicotine (free), NNN, NNK, pouch thickness, 

pouch width, pouch length, % oven volatiles, p01tion mass 

Chemisny Tests: Three to fom replicates at 1g each; composite fi:om at least two 

pouches; quantity expressed in units/gram ("as is" [wet] weight) 

Engineering Tests : Three to four replicates; quantity expressed in mm for length, width, 

thickness; p01tion mass in g per pouch (including pouch material and filler) and in g per 

filler 

Micro Tests: Three to four replicates at 1 g each (combined with chemisny tests) from at 

least two pouches 

Page 15 of 67 
TPL Review for: PM0000010-PM0000017 

Division of Product Science scientists reviewed the analysis provided by SRL and evaluation 

of the sample testing did not raise any concerns. 

Clinical Microbiology 

Product stability (including moisture content, pH, water activity, bacterial counts and 

validation parameters), heat treatment process, additives, fermentation, storage and microbial 

concerns were evaluated. The clinical microbiology content of the submission was considered 

adequate as: 

x

x

x

x

x

x	 

x	 

x

x

Descriptions of manufacturing steps and quality control measurements were 

established and followed. 

A written testing program designed to assess the stability characteristics of the tobacco 

products was established and followed. 

Sample size and test intervals were determined based on statistical criteria for each 

attribute examined to assure valid estimates of stability. 

Evaluation of stability was made using the same container-closure systems in which 

the tobacco products are intended to be marketed. 

Expiration dates were related to storage conditions stated on the labeling, as 

determined by stability studies. 

Written procedures, designed to prevent the growth of objectionable microorganisms 

(including the mycotoxin ochratoxin A and aflatoxins B1, B2, G1 and G2) were 

established and followed. 

Written procedures designed to determine the physical and chemical attributes that 

affect microbial activity and/or are susceptible to change during product storage were 

established and followed for pH, moisture content, and water content. Written 

procedures for sampling and testing parameters were established, described, and 

followed including method of sampling and the number of batches tested. 

Validation protocols showing the accuracy, sensitivity, specificity, and reproducibility 

of test methods employed by the applicant were established and documented. 

Statistical quality control criteria including appropriate acceptance levels and/or 

appropriate rejection levels were established and followed. 

Shelf Life 

The applicant recommended retail shelf lives of 14 weeks for loose snus, 20 weeks for 

pouched snus (White and Original) and 30 weeks for “dry” pouched snus. These shelf lives are 

supported by the provided data. 

Manufacturing, Processing, and Controls 

The applicant has provided descriptions about tobacco procurement, grading method, countries 

of origin, curing method for each type of tobacco, tobacco storage conditions, criteria for 

choosing suppliers, and criteria for acceptance of raw tobacco based on chemical testing 

results and tolerance levels of certain constituents (see the discussion about the applicant’s 

internal quality standard below). According to the applicant, the tobacco grade is based on the 

country of origin, curing process, and plant position. 

Briefly, manufacture of these products includes grinding, blend processing, and packaging. 

Page 16 of 67 
TPL Review for: PM0000010-PM0000017 

During the April 2015 FDA inspection, several issues were observed regarding manufacturing 

equipment (e.g., the scale for weighing tobacco flour was not calibrated; the calibration of the 

temperature probes for blenders was outdated). However, these issues are not expected to have 

a major impact on the quality of the new products because: 1) the applicant will not routinely 

manufacture the new products unless FDA issues the marketing authorization orders, and 2) 

the applicant responded that it would take corrective actions in a timely manner and the issues 

were noted by OCE reviewer to have been corrected on or before May 30, 2015. Furthermore, 

during the inspection, FDA reviewed the manufacturing processes that would be applied to the 

new products according to the applicant and found no significant deviations from the process 

described in the PMTAs. 

The applicant states that it uses analytical methods, chemical quality control programs, brands 

testing programs, and agrochemical management programs according to its proprietary quality 

standard for snus products to ensure product quality. The principal components of this 

standard include constituent standards, manufacturing standards, manufacturing process 

requirements, and consumer package labeling with a “best before” date. The constituent 

standards set maximum levels that must not be exceeded for selected constituents in the 

finished products. Currently, the Swedish Match standard has limits for the following nine 

constituents: 

x

x

x

x

x

x

x

x

x

NDMA: ng/g (dry weight basis); ng/g (as is) 

Nitrite: μg/g (dry weight basis); μg/g (as is) 

BaP: ng/g (dry weight basis); ng/g (as is) 

Arsenic: ng/g (dry weight basis); ng/g (as is) 

Lead: μg/g (dry weight basis); μg/g (as is); 

Cadmium: μg/g (dry weight basis); μg/g (as is) 

Chromium: μg/g (dry weight basis); μg/g (as is) 

Nickel: μg/g (dry weight basis); μg/g (as is) 

NNN+NNK: μg/g (dry weight basis); μg/g (as is) 

(b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) ( (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4)

In addition to the Swedish Match standard, the applicant states that the Swedish National Food 

Agency and the Swedish Medical Product Agency have also set regulatory limits for the 

following constituents: 

x

x

x

x

Lead: 3 mg/kg (as is) 

Propylene glycol: 40 g/kg (as is) 

Aflatoxins (sum of B1, B2, G1, and G2): 0.005 mg/kg (as is) 

Ethanol: 2.25% v/v (as is) 

The applicant states that all snus products are analyzed three to four times a year in its 

Chemical Control Program. The applicant has provided the chemical testing data on all the 

products included in these from the 2011 Chemical Quality Control Program and the 2012 

Brands Testing Program. All products have constituent levels below the Swedish Match limits 

and the Swedish national regulatory limits. 

Additionally, the applicant states that their proprietary standard also includes Guidance 

Residue Limits (GRL) for agrochemical residues in raw tobacco and finished snus products. 

Testing of raw tobacco is performed and results are reviewed prior to the tobacco’s release for 

Page 17 of 67 
TPL Review for : PM0000010-PM000001 7 

snus manufach1ring (if results are acceptable) . Testing of the fmished products is perfonned 

annually. For all the products that are the subjects of these PMTAs, the applicant provided the 

2011 testing results, and the levels of the agrochemical residues tested all fell below the 

applicant 's GRL. The reported an alyses and use ofvoluntruy standru·ds apperu· acceptable. 

Inspections of Swedish Match Manufacturing Facilities and Laboratory 

The Office of Regulatory Affairs (ORA), accompanied by Subject Matter Expe1is (SMEs) 

from the Division of Enforcement and Manufacturing (DEM) in the Office ofCompliance and 

Enforcement (OCE) an d the Office of Science (OS) within the Center for Tobacco Products 

(CTP), conducted an inspection of Swedish Match manufacturing an d testing facilities from 

April 13, 2015 -April 17, 2015 (April 13-14 at two Gothenburg sites; April 15-16 at the 

Kungalv site; an d April17 at the Stockhohn site). Manufach1ring, product analysis, packaging, 

distribution, recalls and complaints, shipping, laborat01y accreditation, validations, raw data, 

and procedures were evaluated at the different sites. DEM 's review of both the application and 

the manufach1ring facilities an d laborat01y inspection results did not identify any issues of 

concem for the methods used in, or the facilities or controls used for, the manufach1re, 

processing, or packing of the tobacco products for which the applications were submitted . 

DEM inspectional review recommends classification as V AI (voluntruy action indicated) for 

facilities inspected other than the Stockholm laborat01y facility which was recommended as 

NAI (no action indicated). 

4. Toxicological Risk (Nonclinical Science) 

The applicant provided HPHC data for each of the eight snus products in the PMTA based on 

wet-weight (as is weight). The FDA converted the wet-weight levels into my -weight levels 

using the product moisture levels provided by the applicant in the application in order to allow 

HPHC level comparisons to be made between the eight new snus products and other 

smokeless tobacco products on the market that rep01i ed the HPHC levels as dry-weight levels 

in the respective publications. 

HPHC L eves1 C a I cu 1 a t e d on a D1ry-we1

. 21 ht B ast

.s I Cadmium I Crotonal I Formald I Nicotine I Nicotine I 

Product 

NNN I NNK I ~~~~de I Arsenic I BaP 

(5) (4) 

dehyde ehyde (total) (free) 

PMOOOOOIO 

PMOOOOO I I 

PM00000 12 

PM0000013 

PM0000014 

PM00000 15 

PM00000 16 

PM0000017 

Averag e 

Page 18 of 67 
TPL Review for: PM0000010-PM0000017 

HPHCs, Excess Cancer Risk, Relative Risk of Specific Cancers 

The PMTA products were compared to other ST products (including moist snuff, chewing 

tobacco, American snus, and dry snuff) and cigarette products currently on the US market. The 

eight new Swedish snus products have significantly lower levels of NNN and NNK compared 

to over 97% the ST products currently on US market. NNN and NNK are arguably the most 

concerning carcinogenic HPHCs in smokeless tobacco products. They showed strong dose 

response relationships with cancer development, are specific to tobacco products, and 

biomarkers of exposure are present in minimal to below levels of detection in most nonusers of 

tobacco products. Since NNN and NNK are among the most carcinogenic constituents in 

tobacco products, reduction of NNN and NNK levels in ST products could reduce the cancer 

risk for consumers who use these products instead of other US smokeless products. Assuming 

tobacco product use pattern to be consistent, for an individual the use of PMTA products with 

low levels of NNN could decrease the excess cancer risk by 90% compared to use of moist 

snuff (market share: 82%), 67% compared to use of chewing tobacco (market share: 15%), 

38% compared to use of US-style snus, and 92% compared to use of dry snuff. Even further 

reductions in excess cancer risk could occur with the corresponding reductions in NNK; 

however, a quantitative contribution cannot be determined at this time due to the absence of a 

NNK cancer slope factor. 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, in this assessment, NNN. 

Other HPHCs in these PMTA products, including arsenic, cadmium, acetaldehyde, 

crotonaldehyde, formaldehyde, and BaP exist at similar or lower levels than in the other types 

of ST products on US market. The estimated levels of exposure to these HPHCs are typically 

at or below dietary intake levels or the reference levels set by government agencies, and are 

therefore not considered to be a significant toxicological concern. Dietary intake levels are 

used as comparison as the “tobacco juice” generated when snus is consumed can be ingested 

similar to foods. 

Data showed that ST use in general is associated with elevated risks of oral cancer in the US, 

but not associated with oral cancer in Nordic countries where Swedish snus with lower levels 

of NNN and NNK is used by Swedish ST users (Boffetta, 2008). This suggests that the lower 

levels of NNN and NNK in the Swedish snus may reduce the risk of oral cancer in US 

consumers who use a low NNN- and NNK-containing snus product as compared to other ST 

products. 

Comparison to Cigarette Smoke 

FDA’s established list of HPHCs includes over 40 more carcinogenic constituents in cigarette 

smoke than in ST products. Certain HPHCs -- such as acetaldehyde, cadmium, acrolein, and 

nickel have been identified as constituents of more toxic concern in the smoke of combusted 

products as compared to smokeless products. Direct comparisons of HPHC levels using 

urinary biomarker information and estimated absolute HPHC levels, which would allow a 

comparative risk assessment of the proposed Swedish snus products and cigarettes, is difficult. 

Inherent differences in the products -- such as combusted vs. non-combusted, route of HPHC 

exposure (oral vs. inhalation), and the complex mechanisms of target organ-specific toxicity 

Page 19 of 67 
TPL Review for: PM0000010-PM0000017 

by each individual HPHC, as well as toxicity resulting from the complex mixture of HPHCs, 

make a direct comparison challenging in terms of nonclinical toxicological assessment. While 

smokeless tobacco is associated with many health problems, epidemiology studies discussed 

later in this review, provide evidence that smokeless tobacco users have much lower relative 

risk of developing oral cancers, respiratory diseases (COPD, emphysema and chronic 

bronchitis) and lung cancers as compared to smokers. Overall death rate is also lower in 

smokeless tobacco users as compared to smokers. 

5.	 Abuse Liability, Exposure/Response, and Use Behavior (Clinical
 

Pharmacology/Behavioral Pharmacology)
 

Abuse Liability 

The applicant acknowledges the abuse liability (addictive and reinforcing effects) of its 

Swedish snus products given their nicotine content. Although the applicant did not submit 

formal abuse liability studies or predictions about uptake and use specific to the proposed snus 

products, the reinforcing and addictive effects of the proposed snus products are acknowledged 

and the abuse potential of the proposed products is understood to be within the range of similar 

marketed products. Also, the proposed snus products expose individuals to nicotine levels that 

are broadly similar to traditional combusted tobacco products (e.g., cigarettes). Data provided 

demonstrate that snus products produce reinforcing effects, as indicated by positive ratings of 

“liking” and “good effects.” The behavioral pharmacology review focuses on the effects of 

Swedish snus products in general on tobacco use behaviors. This includes consideration of the 

expected rates of use of snus products by current tobacco users, use of the snus products in 

conjunction with other tobacco products, the potential for abuse and misuse of the snus 

products, the potential for experimenters to become addicted, and the impact on cessation 

rates. 

Pharmacokinetics and Exposure/Response 

The applicant submitted four clinical pharmacology studies. Three evaluated the nicotine 

pharmacokinetics after single and multiple administrations of Swedish snus. The nicotine 

maximum concentration (Cmax) values after use of a single snus portion ranged from about 

10.8-29 ng/mL, with the highest Cmax values reported after use of “General” and “Catch” 

brands. Nicotine pharmacokinetics were dose proportional, a finding consistent with previous 

literature (Digard et al., 2013). Estimations of area under the curve (AUC) values are 

hampered by the use of varied time collection periods across studies and varied product use 

characteristics (e.g., amount and duration). The format of the products (i.e., loose or pouched) 

had little influence on the nicotine pharmacokinetic parameters. After overnight abstinence, 

time to maximum nicotine plasma concentration (Tmax) appeared to be dependent on product 

use time. Similarly, other studies examining Swedish snus reported Tmax values between 30 

and 37 minutes (Holm et al., 1992; Lunell and Curvall, 2011; Lunell and Lunell, 2005). In 

comparison, after cigarette smoking, nicotine reaches peak venous concentrations within eight 

minutes and peak arterial plasma concentrations within five minutes (Arcavi and Benowitz, 

2004; Benowitz et al., 2009; Gori et al., 1986; Lunell et al., 2000; Lunell and Curvall, 2011; 

Schaedeli et al., 2002). As used by consumers, the proposed snus products expose individuals 

to nicotine levels that are broadly similar to cigarettes and traditional ST products. Thus, from 

Page 20 of 67 
TPL Review for: PM0000010-PM0000017 

a clinical pharmacology perspective, systemic exposure to nicotine following use of the 

proposed snus products is expected to produce reinforcing effects and have an abuse liability 

similar to traditional cigarettes and other ST products. 

One study measured the pre- and post-use levels of lead, cadmium, nicotine, and TSNAs in 

Swedish snus products; however, systemic exposures were not assessed. The systemic 

exposures to TSNAs and other HPHCs after use of some snus products including Swedish 

snus are described in peer-reviewed literature (Hatsukami et al., 2004; Sarkar et al., 2012). 

Summaries of the four clinical pharmacology studies submitted by the applicant are presented 

below. 

SW WS 02: This study was an open-label, crossover study of nicotine plasma levels after the 

use of four types of snus and nicotine chewing gum. In the study, male snus users aged 18-23 

were administered snus portions [General (8.8±0.4 mg nicotine/portion), Catch Licorice 

(7.0±0.1 mg nicotine/portion), Catch Mini (4.5±0.3 mg nicotine/portion), Catch Dry Mini 

(4.8±0.6 mg nicotine/portion)] or nicotine gum (Nicorette, 1.9±0.1 mg nicotine) once an hour 

for 11 hours (12 doses total). Subjects were instructed to keep the snus between the upper lip 

and gum for 30 minutes. In the Nicorette gum condition, subjects were administered 2 mg 

Nicorette chewing gum and instructed to chew each piece for 30 minutes. For each condition, 

serial venous blood samples, were drawn to assess nicotine levels. After multiple doses (12 

doses over 11 hours) of the four types of snus or Nicorette gum, nicotine pharmacokinetic 

parameters were reported, but only after the last use (Cmax and AUC11-12). The mean±SD 

nicotine amount extracted per dose was calculated as 2.74±0.80, 1.55±0.68, 2.00±0.56, 

1.08±0.94 and 0.84±0.12 mg/portion for General, Catch Licorice, Catch Mini, Catch Dry Mini 

snus, and Nicorette gum, respectively. 

After the multiple dosing regimen, nicotine plasma concentrations reached the following 

mean±SD Cmax values (ng/mL) for the snus products: General, 29.00± 8.53; Catch Licorice, 

23.79± 8.60; Catch Mini 20.95 ±6.90; Catch Dry Mini, 10.85 ±5.65; and nicotine gum, 12.75± 

4.67. For the first three snus products, nicotine Cmax values were similar to Cmax values 

observed in smokers (Benowitz et al., 1982;Benowitz, 2008;Kotlyar et al., 2007). Mean±SD 

AUC values (ng·h/mL) following the last dosing interval reached the following values for the 

snus products: General, 26.2 ± 3.4; Catch Licorice, 21.6 ± 8.8; Catch Mini, 19.0 ± 6.7; Catch 

Dry Mini, 9.8 ± 5.1; and Nicorette, 11.6 ± 4.5. Mean Cmax and AUC11-12 values were dose 

proportional, with R2 values of 0.82 and 0.81, respectively. Thus, from the comparison of 

these parameters, the nicotine pharmacokinetics did not differ across all products. 

SW WS 06: This study was an open label, single center, three-way cross-over study, designed 

to examine the nicotine plasma concentrations and subjective effects of a single dose (1 g) of 

General Onyx and General White portion snus relative to Nicorette chewing gum (4 mg). The 

study involved male and female subjects aged 18-50 years who smoked more than seven 

cigarettes per day. After baseline measurements and dosing, plasma nicotine concentrations 

were monitored for eight hours. Subjective effects assessments were performed using visual 

analog scale (VAS) assessments. Following the use of Nicorette gum, the extracted dose of 

nicotine was about 2.56 mg compared to 2.12 and 2.18 mg for Onyx portion snus and General 

Page 21 of 67 
TPL Review for: PM0000010-PM0000017 

White snus, respectively. Mean Cmax values for Onyx portion snus and General White snus 

were 14.76 and 13.72 ng/mL, respectively, both higher than Nicorette gum (12.77 ng/mL). 

Tmax was reached about 30 minutes after snus use, faster than the 45 min Tmax observed 

following Nicorette administration. The faster absorption of nicotine following snus 

administration was reflected in higher VAS ratings of “head rush” following snus use relative 

to nicotine gum. The applicant concluded that snus provides a higher Cmax in a shorter 

amount of time (e.g., decreased Tmax) relative to Nicorette, and that the faster onset may 

account for the increased ratings of “head rush” compared to the gum. However, despite the 

lower Cmax of Nicorette relative to the snus comparators, Nicorette had a larger AUC, which 

is consistent with the increased amount of extracted nicotine. This study was limited to single 

dose administrations, which may not reflect actual use. 

SM WS 12: This study compared the nicotine pharmacokinetics and subjective effects of 

single doses of sublingual nicotine (Nicorette Microtab, 6 mg) to Swedish snus. The study was 

an open-label, five-way, crossover study involving 18 healthy snus users. The goal of the study 

was to examine the interaction between nicotine amount and portion size; the study involved 

four snus products with two nicotine concentrations. Four Swedish snus products with 

different nicotine concentrations were administered in different portion sizes: 8 mg nicotine in 

a 1 g portion; 8 mg nicotine in a 0.5 g portion; 16 mg nicotine in a 1 g portion; and 16 mg 

nicotine in a 2 g portion (composed of two 1 g portions of 8 mg each). Blood plasma samples 

were taken over a six-hour time period and VAS assessments were performed. For the four 

snus products, the extracted nicotine doses were 1.56 ±0.95 mg, 1.90±0.82 mg, 3.0 ±1.65 mg, 

and 3.0 ±1.35 mg, respectively. Nicotine was absorbed more slowly from Nicorette Microtab 

tablets, but systemic exposure was within the range of the snus products. All products 

increased “head rush” and reduced craving over the first 30 minutes. The effects were 

strongest for the portioned snus (i.e., two 1 g portions of 8 mg each), although the effects were 

not statistically significant from Nicorette Microtab. According to the applicant, the similar 

nicotine absorption for both 16mg conditions indicates that absorption kinetics were dependent 

on total nicotine extraction (i.e., dose) rather than mode of administration (i.e., portioned or 

single dose). Both 16 mg conditions displayed similar pharmacokinetic (e.g., AUC values) and 

pharmacodynamic effects (e.g., VAS scores) compared to 6 mg Nicorette Microtab sublingual 

tablets. This study was limited to single dose administration. 

SM WS 03: This study examined the in-vivo extraction of cadmium, lead, and TSNAs from 

four brands of Swedish snus [General Large (1 g), Catch White Licorice Large (1 g), Catch 

Licorice Mini (0.5 g), and Catch Licorice Dry Mini (0.3 g)] in regular snus users. The study 

was an open-label, randomized, four-way, single dose study in 32 males. Snus portions were 

administered once every hour (four administrations/brand) and were kept between the upper 

lip and the gum for 30 minutes. The received dose of cadmium (Cd), lead (Pb), and TSNAs 

was calculated by comparing pre- and post-use levels of constituents in used and unused snus 

products. Systemic exposures to Cd, Pb, and TSNAs were not examined. In this study, the 

mean±SD extracted amounts of Cd from General Large, Catch White Licorice Large, Catch 

Licorice Mini, and Catch Licorice Dry Mini were , and 

ng/portion, respectively. The mean extracted amount of Pb was negative for all products and 

the applicant has not explained this finding, the impact of this to the study as a whole is 

(b) (4) (b) (4)

Page 22 of 67 
TPL Review for: PM0000010-PM0000017 

unknown. The mean±SD sum of extracted TSNAs from the four brands was calculated as 

, and ng TSNA/portion, respectively. 

(b) (4) (b) (4) (b) 

(4)

In summary, the studies focused on nicotine pharmacokinetics and nicotine exposures and 

found that Swedish snus products were similar to other marketed ST products. None of the 

submitted studies evaluated exposure-response relationships (i.e., changes in biomarkers and 

clinical outcomes related to systemic exposures to HPHCs). The health impacts (influence on 

the disease development and endpoints) of the new tobacco products were not specifically 

assessed in these sponsored clinical pharmacology studies. Prospectively-designed clinical 

pharmacology studies that compare systemic toxicant exposures following the use of the 

proposed Swedish snus products relative to other tobacco products would provide more data to 

evaluate actual exposure and response differences. However, substantial epidemiological data 

is submitted by the applicant evaluating health impact of similar Swedish snus products 

informing anticipated health impact from use of these products. 

Use Behavior 

ST products are usually chewed, placed in the oral cavity between the cheek and gum, or 

inhaled or snorted through the nose. The applicant provides a description of data relating to the 

frequency, amount, duration, and overall use profile of snus products. While the applicant 

describes general use of the proposed products, the proposed labels do not include a 

description of “intended use”. With traditional ST, topography measures include: self-reported 

measures of tobacco use such as ST tins used per week, total dips per day, total daily dip 

duration, and total daily dipping time (time from first to last dip of the day) (Lemmonds et al., 

2005). According to the applicant, the most common method of snus use is to place 1-2 grams 

of product (loose or pouched) in the vestibular area inside the upper lip. Survey data of 

Swedish snus users suggest that this is the manner of use for 96% of pouched users and 99% 

of loose snus users, although movement of the product inside the mouth is common (Digard et 

al., 2009). In a telephone survey of 2,914 Swedish snus users (359 females and 2555 males), 

pouch snus use was much more common among females (92.8%) than males (42.1%). The 

survey also indicated that average “loose” snus consumption per day was approximately equal 

for both genders (29.3 g for men and 29.0 g for women). Similarly, total consumption of 

portioned/pouched snus was similar for men (32.1 g/day) and women (33.8 g/day). However, 

men used snus portions for a longer duration (69.6 min vs. 56.1 min for women). These data 

are broadly similar to values reported in the Norwegian Tobacco report, which found that snus 

users reported about 9.5 “pinches” of snus per day, with each “pinch” weighing about 2.5 g for 

a total use of 23.75 g/day. 

Snus products are generally placed in the oral cavity but there are some differences in oral 

placement among users as US studies indicate that American ST users typically place ST 

between lower lip and gum. Whether the same snus product is placed near upper lip or lower 

lip, the health impacts from these products are expected to be similar given oral exposures to 

the product itself. Total snus consumption per day by Swedish users while informative may 

not be directly transferrable to the US experience. 

Acceptability 

Receptivity to snus use in Indianapolis, Indiana and Dallas/Fort Worth Texas (two cities with 

the greatest exposure to the major snus brands) was examined in a telephone and mail survey 

Page 23 of 67 
TPL Review for: PM0000010-PM0000017 

conducted in 2011 and 2012 (Biener et al., 2014) . More than 5000 adults completed smveys 

assessing trial, ever use, cmTent use, and reasons for using or quitting snus after the trial. 

Among m ale sm okers, 29.9% had ever tried snus (95% CI [confidence inteival]=22.7-38 .1) 

and 4.2% were cunent users (CI=1.6-10.7). Among female smokers, 8.5% had tried snus 

(CI=4.4-15 .7) and cmTent use was unknown. CmTent use was low am ong f01mer smokers and 

never sm okers. Conventional ST use was a major predictor of any snus use. Those who tried 

and gave up snus cited cmiosity (41.3%) and the fact that it was available at low or no cost 

(30%). Reasons for not continuing snus use included prefening another f01m oftobacco 

(7 5.1%) and disliking the mouth feel (34. 6%) . Almost all cmTent snus users indicated that they 

were trying to cut down on cigarettes, but few (3.9%) were using snus to quit sm oking 

entirely. Low acceptability ofsnus use has been found elsewhere in the US (Hatsukami et al., 

2011; Hatsukami et al., 2013; O'Connor et al., 2011; O'Connor et al. , 2014). The low rate of 

snus adoption suggests that any adverse effects confened on the population as a whole will be 

minimal especially given that the proposed snus products have lower NNN, NNK and other 

HPHC levels compared to other US sm okeless tobacco products cmrently on the market. 

Flavors 

Ofthe eight snus products that are the subjects ofthese PMTAs, one contains mint and the 

ingredients b) (4) One product 

includes (b) (4) (b) (4) I S a major chemical 

com onent o (b) (4) (World Health Organization, 2002). These ingredients (e.g., 

(5) 4) ) can give the new products a characterizing mint flavor that is 

distinct from other Swedish Match Snus products described in the published literatme and in 

the submitted studies. Fmi he1more, the two products (General Mint P01i ion White Large 0.9 

oz. [24g] and General Nordic Mint P01iion White Large .38 oz. [1 0.8g]) may be sweeter than 

other Swedish Match Snus products because they contain the miificial sweetener (b) (4) 

. A recent study (Choi et al., 2012) rep01ied that young adults view new ST products 

including snus) favorably because these products are available in flavors . 

It is possible that introducing the products with new flavor ingredients may make the products 

more appealing to consumers. It has been suggested that flavored products have a unique and 

important role with respect to initiation and m aintenance of tobacco-use pattems, pmi icularly 

am ong young adults (Kenny et al., 1996;Lisnerski et al. , 1991;Villanti et al. , 2012). There is 

also evidence to suggest smokeless tobacco users typically initiate with a flavored product and 

that brand switching from a non-flavored to flavored product can occm (Hatsukmni et al., 

2007; Oliver et al. , 2013b). 

Access and utilization of ST remains a public health issue am ong American middle and high 

school students, with more than 25 different types ofsmokeless tobacco (ST) available in the 

United States (Bromberg et al., 2012). Analyzing data from Legacy's Young Adult Cohort 

Study, a nationally representative sample collected in January 2012, Villanti et al. (Villanti et 

al., 2013) sought to determine the prevalence offlavored tobacco use, dual use offlavored and 

menthol tobacco products, and sociodem ographic predictors of flavored tobacco product use in 

young adults aged 18-34 years (n=4 196). Overall, 18.5% oftobacco users rep01i using 

flavored products, and dual use ofmenthol and flavored product use ranged from 1% (nicotine 

products) to 72% (chewing tobacco products). In a multivm·iable model controlling for 

menthol use, younger adults were more likely to use flavored tobacco products (OR=1. 89, 

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95% CI=1.14, 3.11), and those with a high school education had decreased use of flavored 

products (OR=0.56; 95% CI=0.32, 0.97). The authors concluded that individuals most likely to 

use flavored products are also those most at risk of developing established tobacco-use 

patterns that may persist through their lifetime. 

The proposed products are reported to have flavors such as mint, wintergreen, or tobacco 

character with citrus. While flavored smokeless tobacco products are a potential concern of 

youth initiation, these proposed flavors are consistent with traditionally available ST flavors 

and are not novel flavors that likely increase appeal to youth. Overall uptake of snus products 

including among youth in the US is low even with such flavors available in currently marketed 

products and unexpected to dramatically increase with the marketing of the PMTA products at 

this time. Postmarket data describing sales of these proposed snus products may be 

informative in better understanding appeal and use of newly marketed flavored products. 

6. Health Impact (Medical/Epidemiology/Statistics) 

Health Risks of Swedish Snus 

The Applicant cites data spanning several decades, derived from numerous cohort, casecontrol, and cross-sectional studies, to describe the impact of snus use on health risks in 

Scandinavian countries. In particular, the Applicant discusses the health risks of Swedish snus 

compared with cigarette smokers and nonusers, and the health risks of dual use and switching 

from cigarette smoking to Swedish snus use compared with quitting completely and nicotine 

replacement therapy (NRT) use. 

Comparison to Smoking and Nonuse 

There is no evidence that snus causes lung cancer and COPD, which together are estimated to 

account for over 50% of smoking-attributable mortality in the US (CDC, 2008). This alone 

suggests a difference between cigarette smoking and snus in overall risks to health. Use of 

snus is not associated with significant ‘second-hand’ exposure which, in this respect, decreases 

risk for both users and nonusers. With regards to the risk of oral cancer, the literature12 

indicates that the risk from snus is significantly less than the risk from smoking cigarettes. 

However, the literature presented does not support use of snus as having no effect on dental 

health. Gingival recession was noted at increased frequency in several studies, even with 

younger subjects exposed for shorter periods of time. Snuff-induced lesions (SIL) were found 

to be almost universal among snuff users in Scandinavia. The long-term health implications of 

these lesions are unknown. The incidence of oral cancer in Sweden is low and the use of oral 

snuff is high indicating that malignant transformation of the lesions is uncommon. The 

prevalence of SIL is lower in the United States but it is not clear whether this is related to the 

product, patterns of use, differences in diet or dental care, or exposure to other agents. In 

general, the published literature presented confirms the health risks of snus for the individual 

user are less, or at least no greater, than those associated with cigarette smoking. 

12 Note that the volume of published literature addressing the risk of oral cancer with snus use is much lower than 

that for the risk of oral cancer associated with cigarette smoking. 

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While the available evidence suggests that there are likely to be differences in health risks 

between snus and cigarettes for some endpoints, the magnitude of these differences appears to 

vary considerably by endpoint. For example, the available evidence suggests that risks to the 

fetus due to snus use and cigarette smoking during pregnancy may not be very different. The 

applicant notes that pregnant or lactating women should not use products containing nicotine, 

including Swedish snus. Maternal snus use has been reported to be associated with increased 

rates of stillbirth. The fetal and neonatal effects related to cigarette smoking are well known. 

NRTs are considered a “safer alternative” but use during pregnancy is discouraged. In addition 

to adverse pregnancy outcomes, multiple studies have reported associations between Swedish 

snus use and increased risk of fatal cardiovascular events, pancreatic cancer, diabetes, and allcause mortality. Finally, the applicant does not address the potentially negative effect of 

nicotine on the developing brain in youth, however, this is a universal concern of all nicotine 

containing products. Given that the nitrosamines in snus are still elevated and that there are 

suggestive associations between snus and a number of diseases, it is unlikely that switching to 

snus is comparable to quitting tobacco completely with or without using NRTs. 

Thus, while the proposed snus products may be a less toxic product compared to cigarettes, the 

proposed snus products are not risk-free. Nonusers never starting tobacco use and current users 

quitting tobacco completely are still the optimal outcomes. 

Impact on Cessation 

Use behavior is described in the above section. Understanding use patterns is important 

because using the product frequently, using larger portions, or increasing deposition time in 

the mouth are behaviors known to affect nicotine exposure (Hatsukami et al., 1988; Hatsukami 

et al., 1991; Hatsukami et al., 2004). Snus appears to increase cigarette smoking cessation rates 

in some studies (Rutqvist 2012) but the Swedish population appears to be more homogenous, 

have a higher socioeconomic status, and greater access to healthcare services including dental 

care relative to individuals in the US. Swedish Match conducted two clinical trials designed to 

examine if Swedish snus use could decrease smoking. The subjects recruited for these studies 

were motivated to quit smoking and the product was provided free of charge; however, the 

success rate for smoking cessation was low. Of note, the placebo group used a snus product 

with no nicotine, making the placebo an “active control”. Neither study demonstrated that 

current cigarette smokers are likely to use snus as a smoking cessation aid. Thus, although 

snus was not associated with certain significant health risks for the users, the studies did not 

provide evidence that US smokers will use snus to reduce or replace cigarettes. It is unlikely 

that we can expect to see a large migration of cigarette smokers to switch completely to use of 

these snus products and decrease individual risk, however, some switching behavior may 

occur. 

SM 07 01: This was a randomized, placebo-controlled, double blind study in Serbia designed 

to examine whether ad libitum snus use could affect smoking relative to placebo. Subjects 

(n=319) could choose between two pouch sizes (0.5 and 1.0 g) and two flavors of snus. 

Placebo pouches were identical to the “active” pouches in size and appearance, including 

flavoring, pH, and other sensory characteristics. Subjects were young adults aged 20-65 who 

had smoked daily for more than one year and who were motivated to quit. This study involved 

a smoking reduction stage (weeks 1 to 24 post-randomization) and a smoking cessation stage 

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(weeks 25 to 48). The primary outcome measure was smoking reduction at week 24. At the 

week 24 visit, the snus and placebo groups did not differ in the proportion of subjects who 

achieved the protocol definition of a >50% smoking reduction. However, a higher proportion 

of participants in the snus group (9.5% vs. 2.5%, p<0.01) reported >75% reduction in average 

number of smoked cigarettes per day compared to baseline, particularly during the first six 

months of the trial. Fagerström dependence scores were similar in both groups. ST is not 

available in Serbia; therefore, experience with ST was limited in this population. Because 

participants were motivated to quit and counseling was offered during the study, the results 

may not be applicable to the general snus user population; however, the data suggest that some 

individuals may switch from smoking combusted cigarettes to snus. 

SM 08 01: This study was a multi-center, randomized, double-blind, placebo controlled trial in 

the US comparing snus vs. placebo to examine whether snus use increases quit rates among 

cigarette smokers aged 25-65 (n=152) who wished to stop smoking. Snus in 0.5 or 1.0 g 

sachets or matching placebo (without tobacco or nicotine) was used ad libitum. The study 

consisted of four phases: pre-randomization screening (up to two weeks), a study product test 

period (four weeks), an intervention phase (12 weeks), and a follow-up phase (12 weeks). The 

primary outcome measure was complete abstention during weeks 6 to 28. This was a smoking 

cessation trial with participants who were motivated to quit, and study counseling was offered 

as part of study participation. During the test period, participants were instructed to use the 

study product when they had an urge to smoke, without requiring complete abstention from 

cigarettes; instructions were the same during the intervention phase, but participants were 

encouraged to completely stop smoking. Biologically verified (e.g., expired air carbon 

monoxide (CO) < 8 ppm), continuous abstinence rates during weeks 6 to -28 were 4.0% for 

snus and 1.6% for placebo. Minnesota Withdrawal Scale scores for craving were not 

statistically significant between the groups. Nearly two-thirds of the participants had tried 

other pharmaceutical smoking cessation aids. Given US and Swedish population differences, 

the results may not be generalizable to the US population. 

In the two clinical trials conducted by SMNA, the studies were performed in generally healthy 

subjects. Reported adverse events (AEs) were generally mild and non-serious and were not 

unexpected reactions to these products; most reported AEs were either related or possibly 

related to the study product. In the US study, 616 AEs were reported by 200 subjects (350 in 

the snus group and 266 in the placebo group). No deaths occurred. Overall, the most common 

AEs reported were gastrointestinal disorders (45%; gingival pain, dyspepsia, nausea, 

toothache, diarrhea, dry mouth, gingivitis, salivary hypersecretion, abdominal pain, and 

sensitivity of teeth), infections and infestations (34%; viral upper respiratory tract infection, 

upper respiratory tract infection, sinusitis, pharyngitis, bronchitis, otitis media, and viral 

infection), nervous system disorders (20%; headache, dizziness, and dysgeusia), respiratory, 

thoracic, and mediastinal disorders (17%; cough, hiccups, oropharyngeal pain, nasal 

congestion, and rhinorrhea), musculoskeletal and connective tissue disorders (13%; back pain, 

arthralgia, and myalgia), injury, poisoning, and procedural complications (10%; skin 

laceration, back injury, and joint sprain), psychiatric disorders (10%; insomnia, anxiety, and 

mood alterations), general disorders and administration site conditions (6%; irritability), and 

skin and subcutaneous tissue disorders (6%; acne). The most frequently reported AEs were 

gingival pain, headache, dyspepsia, and nausea. 

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Six subjects discontinued study participation due to AEs (5 from snus group, 1 from placebo 

group). The AEs leading to discontinuation from the snus group were mild gingival pain 

(definitely product related), severe vaginal bleeding (unlikely related), glossitis and pharyngitis 

(probably related), pregnancy (not related), and dyspepsia, diarrhea, and acne vulgaris 

(unlikely related). A total of five serious AEs were reported in the study, however, none were 

reported to be related to the study product. 

Bioresearch Monitoring (BIMO) Inspection 

In March and April 2015, FDA conducted inspections at clinical study sites (Indianapolis, IN 

and Serbia), manufacturing sites (Sweden) and an SMNA laboratory facility (Sweden). The 

clinical site inspections included the review of paper and electronic source data, electronic case 

report forms, and administrative files. Documents were reviewed for issues such as: protocol 

adherence, randomization, informed consent, eligibility, investigational product dispensing, 

study endpoints, adverse events and subject final status. Overall, the inspection teams report 

that while there were some missing and inconsistent data, there was no overt fraud reported. 

The limited missing and inconsistent data are not considered substantive to prevent product 

authorization. 

During one of the manufacturing inspection visits, the inspection team noted that 256 

consumer complaints were received by SMNA during the period from January 2013 to April 

2015, and only two of these were health-related complaints (burning of mouth/throat and 

esophagus). 

7. Population Health (Epidemiology/Social Science/Behavioral Pharmacology) 

Initiation 

In Sweden and Norway, snus initiation is more prevalent among former cigarette smokers than 

among nonusers. Generally, in these populations, tobacco initiation is gender-dependent; 

males are more likely to initiate snus and females are more likely to initiate cigarette smoking. 

Adolescent males initiate snus use at a median age of 15 while females who used snus usually 

started by age 18. In the US, tobacco users (male and female) are more likely to initiate with 

cigarettes, but no specific data compare the likelihood of initiation with snus versus cigarettes. 

In 2014 according to the National Survey on Drug Use and Health, 3.3% of the US population 

aged 12 or older used ST in the past month (SAMHSA, 2015). National estimates of ST use 

have been reported by a variety of sources and provide relatively consistent results. For 

example, across several representative surveys, ST use rates were reported as follows: National 

Adult Tobacco Survey 3.9%; National Health and Nutrition Examination Survey, 2.3%; 

Tobacco Use Supplement, Current Population Survey, 1.6%; and National Health Information 

Survey, 2.8% (Agaku et al., 2015). More specifically, overall prevalence of current daily snus 

use in the US adult population was reported to be 1.8% from National Adult Tobacco Survey 

data (CDC, 2014). These data indicate that the adoption and initiation of ST product use in the 

US is relatively low and therefore, overall initiation of the proposed snus products would be 

expected to be quite low given Swedish snus are a low percentage of the US ST market. 

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Due to methodological and data rep01iing limitations, the data from this study do not offer 

fi1m conclusions about consumer perceptions evaluated. However, studies from the US 

literature indicate low acceptability ofsnus use has been found, as discussed earlier, and it 

does not appear there would be significant shift in these snus product use by nonusers or 

cmTent tobacco users; although cmTent ST users m ay be more inclined to consider these snus 

products use. Other General brand snus products are cmTently available on the market in round 

and square cans with disposal compartment. 

Transition from Snus to Smoking 

According to the applicant, there is little evidence that snus use leads to future cigarette 

smoking and that longitudinal and cross-sectional studies conducted on snus use in Sweden 

and other Scan dinavian countries suggest that snus use is associated with a reduced risk of 

becoming (or continuing to be) a regular smoker. These longitudinal studies suggest that users 

will transition from cigarettes to snus, rather than switching from snus to cigarettes. The 

applicant summarizes studies examining the transitioning ofsnus users to combusted 

cigarettes. 

Researchers (Tam et al., 2015) conducted a review ofpublished estimates of the prop01iion of 

US adults and adolescents transitioning between ST and cigarettes. Six studies of US 

populations were published since 2000 with longitudinal data on some or all of the transitions 

between STand cigarette use. There was considerable heterogeneity across studies in design 

and tobacco use definitions. Despite these differences, the existing data fairly consistently 

indicated that switching behaviors fr om exclusive smoking to exclusive ST use are limited 

(adults: 0-1.4%, adolescents: 0.8-3 .8%) but switching from ST use to sm oking may be more 

common (adults: 0.9-26.6%, adolescents: 16.6-25 .5%). Among adults, exclusive cigarette 

smoking was generally stable and consistent (79.7-87.6%) during follow-up across studies but 

less stable in adolescents (46.8-78.7%). Exclusive ST use was less stable than exclusive 

cigarette sm oking over time (adults: 59.4-76.6%, adolescents: 26.2-44.8%). A potential 

limitation ofthis study is that the data were collected more than a decade ago. Available US 

data do not address snus specifically and are inconclusive regar ding whether prior ST use is 

associated with or leads to subsequent cigarette smoking in adults. Researchers (Meier et al. , 

2015) also examined the use of various nicotine-containing products on a tobacco-free college 

campus and whether the first product tried predicts subsequent tobacco use. The authors 

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concluded that uptake of emerging tobacco products (including snus) was poor, and does not 

appear to lead to use of cigarettes and traditional ST products. 

In sum, existing data indicate that switching behaviors from exclusive smoking to exclusive 

smokeless tobacco use are limited. Findings from Tam et al. indicate that in the US, switching 

from ST use to smoking is more common than switching from smoking to ST use. 

Nevertheless, limited data suggest overall that the adoption of snus use in the US is low and 

therefore, unlikely to lead to use of other tobacco products. Thus, it is anticipated that the 

marketing of these products, as described in the PMTAs, is unlikely to lead to significant 

increases in initiation of tobacco product use. 

Likelihood of Cessation 

Cessation is discussed in the Health Impact section above. In addition, the SMNA MRTP 

Warning Label Evaluation study presented data on the likelihood of quitting or reducing use of 

different tobacco products. More than 13,000 subjects were enrolled and six warning labels 

were tested in this online experimental study. Due to study limitations, it is difficult to draw 

concrete conclusions and implications from the data. Nevertheless, one pattern evident across 

the different harm measures was that a portion of participants (about 25%) reported not 

knowing the risks of snus or snus use risks compared to those of other tobacco products. Also, 

18% of tobacco users ages 18 to 24 believed that there was little or no risk from using snus. 

Risk perceptions are often related to use behavior; however, it is unclear from the data 

presented how risk perceptions will influence use behavior. One caveat is that studies have 

found that perceptions of relative harm of snus depend on how the question is framed. 

Preliminary data from the Population Assessment of Tobacco and Health (PATH) Study 

indicate that nearly 40% of adults and 43% of youth who are current tobacco users use more 

than one tobacco product. The significant proportion of tobacco users who use multiple 

products was not accounted for in the MRTP Warning Label Evaluation study. Product labels 

with appropriate warning labels and educational campaigns to increase awareness of various 

tobacco product health impacts are important tools to utilize in increasing likelihood of 

cessation of tobacco products. These proposed product labels do include mandated warnings. 

Dual Use 

The availability of snus may result in dual use. While relatively uncommon in Sweden, dual 

use may be more likely in the US. SMNA provided a summary of available scientific evidence 

addressing snus use and behavior patterns; however, most studies were conducted in Sweden 

and other Scandinavian countries. Limited data related to US snus use are available, and most 

relevant studies include the broader category of ST products and are not specific for snus 

products. 

The 2014 NYTS reports that 24.6% of high school students report using tobacco products and 

more specifically, 1.9% use snus products (prevalence of middle school student snus use is 

0.5%). Given the historically low and stable rates of ST use in the US, there is no compelling 

reason to believe the marketing these products, as described in the PMTAs, that concomitant 

use of snus and cigarettes will exceed concomitant use of traditional ST products and 

cigarettes. However, it is possible that a market authorization order may increase dual use due 

to the perceived favorable profile associated with an “FDA authorization” marketing order 

which could lead to benefit if tobacco users who use multiple tobacco products then transition 

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to exclusive use of less toxic tobacco products and then ultimately quit all tobacco products. 

Conversely, there could be harm if the perceived favorable profile discourages transition to 

exclusive use of less toxic tobacco products and cessation. 

According to the applicant, the Swedish National Tobacco Survey indicates that the prevalence 

of daily snus and cigarette smoking (i.e., dual use) has remained stable at 2% since 2004. 

Norway and Sweden have reported roughly similar results with the percentage of dual users 

ranging from 2-10%. In the MONICA cohort study (representative of Northern Sweden from 

1986-1999), dual use was reported to be around 2-5% (Rodu et al., 2002; Stegmayr et al., 

2005). In the Norway Tobacco Statistics survey, 7% of individuals reported dual use of snus 

and cigarettes. In a study of Norwegian youth, dual use was reported to be10%. Overall, the 

applicant concluded that males and individuals with low educational background were more 

likely to be dual users of cigarettes and snus. The applicant also notes that data suggests 

slightly lower overall tobacco use among dual tobacco users. 

Concomitant use of two tobacco products may increase the risk of adverse health 

consequences relative to use of a single tobacco product. Few representative US national data 

sets on the prevalence of concomitant smoking and ST use exist. The few data sets available 

suggest that 25% or more of current adult ST users also smoke cigarettes, whereas 2.5-5% of 

adult smokers also use ST (CDC, 1993; CDC, 2000; SAMHSA, 2001). Using data from the 

Working Well Trial, a large cancer prevention study that tested the effectiveness of worksite 

health promotion interventions in reducing cancer risk behavior, researchers (Wetter et al., 

2002) examined correlates of concomitant smoking and ST use. The researchers found that the 

prevalence of concomitant smoking and ST use exists among males (5%) but is nonexistent 

among females. The characteristics of dual users were relatively distinct from those of 

exclusive smokers and exclusive ST users (e.g., more likely to live with a smoker, younger, 

less educated), and indicators of nicotine dependence predicted tobacco cessation for both 

smokers and ST users but were unrelated to tobacco cessation for dual users. Swedish studies 

indicate low prevalence of dual use is possible. While this is not the situation in the US, further 

understanding of factors leading to high rates of multiple tobacco use in the US is important in 

being able to decrease rates of multiple tobacco use in US with the goal of decreasing risk of 

adverse health consequences. The most effective way to decrease morbidity and mortality 

from tobacco use remains to never start or to quit tobacco product use as early in life as 

possible. 

Likelihood Product Used as Designed 

The proposed label does not include statement of “intended use”. In particular, as noted in 

section 2.4, differences in the manner of use between traditional US ST products and Swedish 

snus include the placement of the product in the mouth and expectoration. Given these 

differences and the lack of instructions, it is likely that individuals in the US will use the 

products which are the subject of these applications in a manner that may be different than 

users of snus in Sweden. It is unknown if and how these different use patterns would impact 

the health effects associated with these products; however, while discrepancies may be 

possible, overall, similar health impacts are expected from these snus products given oral 

exposure whether it is placed near upper lip versus lower lip. 

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Population Modeling 

The applicant describes the implementation of a Dynamic Population Model to track 

population-based tobacco use and hrum and presents results from analyses conducted with the 

model to assess the h othetical effects of ci ru·ette and snus use in the US o ulation in a 

vru'!e ofscenru·ios. (b) (4) 

The model and analyses provide for a range of tobacco use behaviors including initiation and 

cessation ofsnus and cigarettes, switching between the products, and, to some extent, dual use. 

fu general, it is difficult to dete1mine from these population m odel results what effect, if any, 

the marketing and sale ofthe PMTA would have on tobacco use 

and health effects in the US 

fu general, it would have been useful ifthe applicant had provided a clearer description ofthe 

model and its use, including detailed explanations ofhow all data inputs were derived from the 

original data sources and a complete listing of all tobacco use behaviors that were used in the 

model along with their transition probabilities. It also would have been helpful if the applicant 

had provided additional inf01mation to aid in the inte1pretation of model analyses and results, 

including cigarette and snus use prevalence estimates for each model scenru·io, in order to 

facilitate an evaluation ofthe plausibility and relevance of these scenru·ios for the U.S. 

population. However, given the prui icular situation that these PMTAs offer epidemiologic data 

on Swedish snus use and health impact ("The Swedish Experience"), as well as experience 

from sales ofsimilru· Swedish snus products in the US, CTP reviewers can develop a 

reasonable understanding ofpotential impact from mru·keting ofthe proposed products as 

discussed in their reviews. 

ill. Tobacco Product Science Advisory Committee Meeting 

On April 9-10, 2015, the Tobacco Product Scientific Advis01y Committee (TPSAC) met to 

discuss MRTPAs submitted by S:MNA for 10 General brand snus tobacco products, ofwhich 

eight were submitted for PMTA consideration. S:MNA submitted MRTPAs seeking risk 

modification orders under Section 911(g)(1) of the FD&C Act specifically requesting certain 

modifications to the health wamings cmTently required by the Comprehensive Sm okeless 

Tobacco Health Education Act for smokeless tobacco products: 

• 	

• 	

• 	

Remove "WARNING: This product can cause gum disease and tooth loss." 

Remove "WARNING: This product can cause m outh can cer. " 

Revise "WARNING: This product is not a safe altemative to cigarettes" to 

"WARNING: No tobacco product is safe but this product presents substantially lower 

risks to health than cigru·ettes." 

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The FDA identified several topics for discussion for which TPSAC recommendations were 

sought with respect to the relative health risks to individual users of the snus tobacco products 

that are subject to the proposed MRTPAs: 

1.	 The relative health risks to individual users of the snus tobacco products that are 

subject to the proposed MRTPAs, particularly with respect to gum disease, tooth loss, 

and oral cancer, and a comparison to risks of cigarette smoking 

2.	 The behavioral aspects of snus use, particularly as they relate to: 

x	 

x	 

The likelihood that existing users of tobacco products who would otherwise 

stop using those products will switch to the snus tobacco products that are 

subject to the proposed MRTPAs 

The likelihood that persons who do not use tobacco products will start using the 

snus tobacco products that are subject to the proposed MRTPAs 

3.	 Comprehension of the modified risk information and perception of the product in the 

context of total health 

4.	 Postmarket surveillance and studies 

As per section 911(f)(1), any MRTPAs must be referred to TPSAC for discussion. In the case 

of PMTAs, the FDA or the applicant may refer applications to TPSAC for discussion but no 

requirement exists [section 910 (b)(2)(A&B)]. Many of the issues for TPSAC discussion 

regarding the MRTPAs for the General brand snus products overlap with potential issues 

related to premarket authorization consideration, such as considerations of health impact from 

these snus products. FDA determined that there were no issues specific to the PMTAs that 

would require a second TPSAC meeting to discuss these same products. 

TPSAC members generally agreed that Swedish snus products when used exclusively confer 

lower health risks than cigarettes in terms of respiratory and cardiovascular diseases; however, 

for other disease end points, the situation is not as definitive that there is lower health risks as 

compared to cigarette use. 

IV. Labeling (DPAL/Social Science) 

Labeling for each of the eight snus products without any proposed claims (as compared to 

those submitted for the respective MRTPAs) were evaluated by reviewers from Social Science 

Branch and Division of Product Advertising and Labeling (DPAL, Office of Compliance and 

Enforcement). The MRTP Warning Label Evaluation study included questions about warning 

claim believability and intention to use based on warning claim; these data have limited 

applicability to the PMTAs as they focused on the warning label and not the labeling as a 

whole. This was primarily a test of modified warning labels. While no studies were conducted 

to evaluate consumer perceptions of the entire labeling, the FDA reviewers concluded that the 

labeling does not appear to be false or misleading. 

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Of note, the labeling for General Classic Blend Portion White Large - 12ct (PM0000013) and 

General Nordic Mint P01iion White Large -12 ct (PM0000015) indicates that a disposal 

co ~ruim t is included in the packaging for these two products in ruiicular. The Febmary 

201 O:>) 4) Study as discussed earlier in this review b) (4) 

methodology an d design limitations of the study, no fi1m conclusions can be drawn from the 

study. However, other General brand snus products ru·e currently available with disposal 

compruiment. Thus, this feature does not raise new questions that these products m ay have 

increased appeal for users or nonusers. 

Instm ctions for Use 

Instm ctions for use ru·e not included with the actual products. The applicant does state in the 

PMTAs that a pouched snus or a pinch of loose snus is typically placed between the gum and 

the upper lip at the front of the oral cavity; furthe1more, the pouch may be pre-wet on the 

tongue before being placed in the m outh an d is most often worked on orally during use. The 

applicant states that none of the proposed products "require specific instm ctions for use or 

storage to get the proposed reduction in risk ... or on how to avoid using the products in a way 

that could reduce or eliminate the potential benefit or increase the risk of use the products ." 

The applicant refers to the population-based telephone survey of 2,9 14 randomly selected 

respondents in Sweden investigating snus use pattem s and behaviors (Digru·d et al., 2009) . It 

found that the typical usage time for one portion snus pouch is 60-70 minutes, and the total 

usage time is 10-12.5 hours per day. The study fuiiher found that the typical usage time is 

approximately the sam e among users of loose snus products an d users of pouched snus 

products. 

ST products including ve1y similar products to these proposed products have been mru·keted 

for many years an d the reviewers are unawru·e of rep01is of serious adverse experiences from 

unexpected uses of snus products. N onetheless, it is recommended that with marketing 

authorization that the applicant provides with the proposed products an y appropriate 

instructions for use. 

V. Conclusions and Recommendation 

Section 910(c)(4) of the FD&C Act specifies that FDA deny a PMTA where it fmds that, 

am ong other things, a new tobacco product is not "appropriate for the protection of public 

health ." One of FDA's goals is to decrease m orbidity and m ortality from tobacco use and to 

change the status quo so that nearly half a million Americans no longer die every yeru· from 

tobacco use. Therefore, the broad overall obj ective of authorizing new tobacco products to be 

marketed through the PMTA process is to reduce the morbidity an d mo1iality fr om tobacco 

use. In evaluating how marketing authorization fo r these eight Swedish snus products impact 

the cun ent mru·ket, FDA considered it is possible that a PMTA order m ay increase use and 

initiation of snus due to its perceived favorable profile. Given this possibility, the products' 

impact on health, impact on sm oking cessation, impact on snus initiation an d uptake, and 

impact on cun ent ST users must be considered. 

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TPL Review for: PM0000010-PM0000017 

Impact on health: SMNA provided a comprehensive review of published literature on the 

health effects related to Swedish Match snus use and specific disease states. In general, the 

literature presented confirms that individual snus user health risks are lower, or at least no 

greater, than those associated with cigarette smoking. The applications provide evidence that 

use of the products which are the subject of these applications is not likely to be associated 

with lung cancer, COPD, or chronic respiratory disease. Data are insufficient to support a lack 

of association between product use of these products and the other disease endpoints specified 

in the applications (e.g., stomach, pancreatic cancers, CVD, stroke, all-cause mortality). Use of 

these products is not associated with significant “second-hand” exposure, which decreases 

disease risks for the general population. 

With regard to oral cancer risk, the scientific evidence provided in this application suggests 

that the risk from these proposed Swedish snus products is lower than the risk from smoking 

cigarettes or use of other smokeless tobacco products. However, the literature presented 

indicates that Swedish snus use does have a negative effect on dental health. Gingival 

recession was noted at increased frequency in several studies, even in younger subjects 

exposed for shorter periods of time. SIL were found to be almost universal among snuff users 

in Scandinavia. The long-term health implications of these lesions are unknown. Of note, the 

lesions typically reverse when the user quits using ST. At least one long-term study involving 

1,115 individuals with SIL followed for > 25 years (Roosaar et al., 2006) found no cases of 

oral cancer at the site of snuff placement. The incidence of oral cancer in Sweden is low and 

the use of oral snuff is high, indicating that malignant transformation of the lesions is 

uncommon. But, overall the evidence supports that the use of the products which are the 

subject of these applications has a lower risk of disease for the individual user than the use of 

other smokeless tobacco products. 

Where we may see the greatest impact is among current users of ST products. Given that (1) 

the full characterization, manufacturing, processing, and labeling of the eight snus products are 

considered to be acceptable and (2) their toxicological risk is considered to be significantly 

lower than that of similar products on the market, for current smokeless tobacco users it is 

likely appropriate to allow access to these tobacco products. Otherwise, available options 

would be limited to the existing grandfathered products and similar products. 

Impact on smoking cessation: SMNA provided data from two clinical studies, one of which 

was conducted in the United States. Both studies were small and subject discontinuation rates 

were high (~40%). Although study subjects were motivated to quit smoking and the Swedish 

snus test products were provided free of charge, the success rate for smoking cessation was 

low. Stated alternatively, neither study demonstrated that current cigarette smokers are likely 

to use snus as a smoking cessation aid. The studies’ analyses of health effects, including AEs 

and other information related to product use, showed no significant unexpected concerns for 

individual users. 

In contrast, considerable data in the Scandinavian literature support the use of snus to facilitate 

smoking cessation; this would clearly benefit the individual user as well as the population as a 

whole due to reduced tobacco smoke exposure. Swedish longitudinal studies indicate that snus 

use is associated with a reduced risk of becoming or continuing to be a regular cigarette user. 

Page 35 of 67 
TPL Review for: PM0000010-PM0000017 

Additionally, studies of Swedish adolescents show that snus use is neither a precursor to 

exclusive cigarette smoking nor a predictor of future cigarette smoking. Similar data for the 

US is unavailable. But, given the evidence as described in the PMTAs, it is reasonable to 

conclude that the marketing of these products which are the subject of these applications will 

not significantly reduce smoking but some smokers may switch to use of these products and 

quit smoking. 

Impact on snus initiation and uptake: The applicant does not provide U.S. product use data 

demonstrating that the proposed Swedish Match snus products will be used similarly to 

traditional American ST products; however, since snus and traditional ST products are broadly 

similar, use behaviors are not expected to differ. Snus products are a small minority of tobacco 

products sold in the US and epidemiological data indicate that use rates remain relatively low; 

thus, there is no compelling reason to consider the marketing of these products, as described in 

the PMTAs, would result in uptake and initiation of these proposed products will exceed that 

of traditional ST products. Furthermore, the marketing of snus (including very similar General 

brand snus) does not appear to have increased overall ST use rates. It is unlikely that a 

significant portion of US cigarette smokers will switch exclusively to these Swedish Match 

snus products, given cultural and population differences as discussed in numerous FDA 

scientific discipline reviews evaluating these PMTAs. It is also expected that uptake of these 

products by nonusers is also likely to be very low, given that other very similar Swedish snus 

products currently exist and no increase in these product use has been reported. 

In general, the availability of a product with abuse potential might lead to a number of 

consumers who sustain their addiction to nicotine or individuals who initiate use of the new 

product; therefore, it is important to understand how different characteristics such as nicotine 

dose delivered, nicotine delivery pharmacokinetics, and nonpharmacologic factors such as 

taste and other sensory aspects affect a product’s abuse liability (Carter et al., 2009; Fant et al., 

1999; Kotlyar et al., 2007). The proposed Swedish snus tobacco products have nicotine 

content that are considered to have abuse potential. However, several similar Swedish Match 

snus products are currently marketed in the US, and widespread use of snus has not been 

reported. A clinical study conducted in five US locations showed no evidence of smokers 

beginning to use snus along with their cigarettes (i.e., dual use). Several studies have reported 

low acceptability of snus in the US (Biener et al., 2014; Hatsukami et al., 2011; Hatsukami et 

al., 2013; O'Connor et al., 2011; O'Connor et al., 2014). Current low snus adoption rates 

suggest that, any detrimental effects to the US population from marketing these products are 

likely to be minimal. Overall, it is anticipated that unless use patterns change in unfavorable 

ways (increased youth initiation, delayed/decreased cessation), the products which are the 

subject of these applications may decrease the individual risk among current ST user due to 

their favorable toxicological profile (see below) without posing increased risk to the general 

population. 

Top-line reasons for granting authorization for the proposed eight products include the 

following: 

Produced with a voluntary, proprietary manufacturing process that distinguishes Swedish 

snus from other types of ST, including snus-like products sold in the US market. The 

proprietary standard for Swedish snus products was developed to ensure product quality. 

Page 36 of 67 

x
TPL Review for: PM0000010-PM0000017 

The principal components of this standard include constituent standards, manufacturing 

standards, manufacturing process requirements, and consumer package labeling with a 

“best before” date. The constituent standards set maximum levels that must not be 

exceeded for selected constituents in the finished products. 

The proposed products have significantly lower levels of NNN and NNK compared to 

over 97% the ST products currently on US market. Since NNN and NNK are among the 

most carcinogenic constituents in tobacco products, reduction of NNN and NNK levels in 

ST products could reduce the cancer risk for consumers. Assuming that the only users of 

these products are persons who would have used other ST products currently on the US 

market, individuals using these products with lower NNN levels could decrease their 

excess cancer risk by 90% compared use of moist snuff (market share: 82%), 67% 

compared to use of chewing tobacco (market share:15%), 38% compared to use of USstyle snus, and 92% compared to use of dry snuff. 

x

x

x

x

Levels of other HPHCs (including As, Cd, acetaldehyde, crotonaldehyde, formaldehyde, 

and BaP) are similar to or lower than levels of ST products currently on the US market. 

Certain HPHCs (such as acetaldehyde, cadmium, acrolein, and nickel) have been 

identified as constituents of more toxic concern in the smoke of combusted products as 

compared to smokeless products. 

When used exclusively instead of other US market smokeless tobacco products or 

cigarettes, offer potential for reductions in oral cancer. 

When used exclusively instead of cigarettes, offer lower risk of developing respiratory 

diseases (i.e., COPD, emphysema, chronic bronchitis) and certain cancers (such as oral, 

esophageal, and lung). 

It is anticipated that the marketing of the proposed products, as described in the PMTAs, 

there is a low likelihood of nonuser uptake of these products, decreased or delayed 

cessation, or other significant shifts in user demographics. 

The most effective way to decrease morbidity and mortality from tobacco use remains to never 

start or to quit tobacco product use as early in life as possible. However, given the reasons 

described above, authorization of these products is recommended so that current ST 

product users who chose to continue using tobacco products will have additional options for 

less toxic smokeless tobacco products, thereby potentially decreasing the negative health 

impact from tobacco product use. 

Environmental Decision 

A finding of no significant impact (FONSI) was signed by Kimberly Benson, Ph.D. on 

October 8, 2015. The FONSI was supported by an environmental assessment prepared by 

FDA on October 8, 2015. 

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Required Postmarketing Reports 

1.	 Serious and Unexpected Adverse Experience Reporting 

x	 Report to the FDA all serious and unexpected adverse experiences associated with the 

tobacco product that have been reported to you within 15 calendar days after the 

report is received by you. These experiences may become known to you through a 

response to a customer complain, request, or suggestion made as a result of an adverse 

experience, tobacco product defect, or failure reported to you; or identified in the 

literature/media. 

2.	 Manufacturing Deviations 

x	 Promptly identify and investigate all manufacturing deviations, including those 

associated with processing, testing, packing, labeling, storage, holding and distribution. 

For products that have been distributed, if there is a potential for that deviation to 

impact public health, promptly identify and report to your regional FDA Office of 

Regulatory Affairs. 

3.	 Periodic Reporting 

On an annual basis, beginning October 2016, provide the following postmarketing 

reports: 

x	 

x	 

x	 

x	 

A cover letter listing the PMTA submission tracking number, tobacco product name(s), 

company name, date of report, reporting period, and worldwide marketing 

authorization status. 

A summary of how the tobacco product continues to be appropriate for the protection 

of the public health. 

If you have not already submitted specimens of all final printed labeling (actual 

labeling distributed with the product) including labels, insert/onserts, instructions and 

other accompanying information or materials for this product as a result of this 

authorization, include the labeling in your first annual report. Also include descriptions 

of all labeling changes. 

A description of all changes made to the manufacturing, facilities, or controls during 

the reporting period, including: 

i. A comparison of each change to what was described in the PMTA 

ii.	 The rationale for making each change 

iii.	 A certification that the reported change did not result in any modification 

(including a change in design, any component, any part, or any constituent, 

including a smoke constituent, or in the content, delivery or form of nicotine, or 

any other additive or ingredient) of the tobacco product; 

iv.	 The basis for concluding that each change did not result in any modification to 

the final product 

x	 

x	 

A summary of all manufacturing deviations, including those associated with 

processing, testing, packing, labeling, storage, holding and distribution and 

indicate a deviation that may affect the characteristics of the final product. 

An inventory of ongoing and completed studies about the tobacco product conducted 

by, or on behalf of, the applicant. 

Page 38 of 67 
TPL Review for: PM0000010-PM0000017 

x	 

x	 

x	 

x	 

x	 

A summary of reports on scientific investigations and full articles from literature about 

the tobacco product and significant findings from publications not previously reported. 

Any new scientific data (published or otherwise) should also be reported on the 

likelihood of product use by current users of tobacco products within the same tobacco 

product category, current users of tobacco products in other tobacco product categories, 

former users of any tobacco product, and youth and young adults. 

A list of each, and a summary analysis of all, adverse experiences associated with the 

tobacco product that have been reported to the applicant, accompanied by a statement 

of any changes to the reference risk information and a summary of important risks, 

including the nature, frequency, and potential risk factors. 

A summary of sales and distribution of the tobacco product: Total U.S. sales reported 

in dollars, units, and volume with breakdowns by U.S. census region, major retail 

markets, and channels in which the product is sold (e.g. convenience stores, food and 

drug markets, big box retailers, internet/online sales, tobacco specialty shops); 

Data on current product users. Data should be collected about new users, current users, 

those who have switched tobacco products, and multiple product users. The results 

should be broken down by key demographic variables including age, gender, and 

race/ethnicity. Also, any change in the intended target market for the product should be 

reported. The data described above may include sales data and postmarketing analysis. 

Full-color copies of all advertising for the tobacco product that has not been previously 

submitted, along with the original date the materials were first disseminated and the 

date when their dissemination was completely terminated. 

Recommended Action 

Instructions for use are not included for the proposed products. We recommend that you add 

consumer instructions for product use and disposal. 

Page 39 of 67 
TPL Review for: PM0000010-PM0000017 

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APPENDICES 

Full Characterization of Products 

l.l.Appendix A 

The following info n nation is applicable to PMOOOOOlO, General Loose: 

Ch ermshy Product S>pect t 'ficahons 

Category Unit of Target J Range 

Measure Va lue Limit 

Nicotine Design % (b) (4) 

Moisture Design % 

pH Design 

Tobacco b) (4) I fugredient m g/g 

Tobacco (b) (4) 1 fugredient m g/g 

Tobacco (b) (4) I fugredient mg/g {6) (4) fugredient mg/g 

fugredient mg/g 

fu gredient mg/g 

fugredient mg/g 

fugredient mg/g 

fugredient mg/g 

fugredient mg/g 

fugredient mg/g 

fugredient mg/g 

fugredient mg/g 

fugredient mg/g 

fugredient m g/g 

Design Parameters 

Design Parameter Target Value nge Limit_ L 

Tobacco Cut Size 

(%)13 

(b) (4) 

Final Moisture(%) 

Blend Moisture(%) 

Leaf Tobacco 

Moisture (%) 

13 The applicant provided t>) 4 ) buckets to characterize tobacco cut size. Therefore, the tobacco 

blend cannot be represented w!tli a smgle size value and cotTesponding range limit. In each cell, the data (given 

in%) repres ents the following buckets, from top to (b) (4) 

~------------------------~ 

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Perfon nance Criteria 

Phase JTest IMethod14 Perf01mance 

Tolerance 

(b) (4) 

Grinding 

Grinding 

Snus 

blend 

processmg 

Packaging 

14 QEMS: Swedish Match' s proprietary Quality and Environmental Management System 

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TPL Review for: PM0000010-PM0000017 

1.2.Appendix B 

The fo llowing infon nation is applicable to PMOOOOOll , General Dry Mint P01i ion Original 

Mint: 

Chermstry Product S>pect 1'fi catwns 

Category Unit of Target Range 

Measure Value Limit 

Nicotine Design % (b) (4) 

Moisture Design % 

pH Design 

Tobacco b) (4) I Ingredient mg/pouch 

Tobacco (b) (4) 1 Ingredient mg/pouch 

Tobacco (b) (4) I Ingredient mg/pouch ~6f4) Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

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D es1gn parame t ers 

Design Parameter Target Va lue l_ ange Limit I 

(b) (4) 

Tobacco Cut Size (%) 15 

Final Moisture(%) 

Blend Moisture(%) 

Leaf Tobacco Moisture 

Pmiion Mass (m12:) 

Portion Le ~Zth (nnn) 

Portion Width (nnn) 

Pmiion Thickness (nnn) 

Pouch Paper Basis 

Weight (g/m2

) 

Pouch Paper Air 

Petmeability (Lim2

/s) 

Pouch Paper Wicking1 1 

Pouch Paper Caliper 

(f.llll) 

15 The applicant provide{f>) (4) buckets to characterize tobacco cut size. Therefore, the tobacco 


blend cannot be representedWitli a smgle size value and COITesponding range limit. In each cell, the data (given 


in %) repres ents the following buckets, from top to bottom: b) (4) 


16 The range limits for the portion mass in MR0000021 are wliat tlie applicant defmes as acceptance criteria. 


FDA' s definition for range limits matches the applicant's definition for acceptance criteria. 


17 In this subrnission, the applicant's nicotine uptake evaluation demonstrates the nicotine extraction rates differ 


even in the products with the same pouch material, indicating the wicking rates are not affecting the nicotine 


absorption rates in this new product. Therefore, wicking values are not needed for this product. 


Page 48 of67 
TPL Review for: PM0000010-PM0000017 

Perfon nance Criteria 

Phase 

Grinding 

Test 

(b) (4) 

Method18 Perf01mance 

Tolerance 

Grinding 

Snus 

blend 

processing 

Packaging 

Packaging 

Packaging 

18 QEMS: Swedish Match' s proprietary Quality and Environmental Management System 

Page 49 of67 
TPL Review for : PM0000010-PM000001 7 

1.3.Appendix C 

The following inf01mation is applicable to PM000001 2, General P01tion Original Large: 

Ch ermstry Prod uct S>pect 'fi1catwns 

Category Unit of Target I Range 

Measme Value Limit 

Nicotine Design (b) (4) _ 

% 

Moistme Design % 

p H Design 

Tobacco b) (4) I Ingredient mg/pouch 

Tobacco (b) (4) 1 Ingredient mg/p ouch 

_Tob accd(b) (4) I Ingredient mg/pouch (b) (4) Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

,_ 

Page 50 of67 
TPL Review for: PM0000010-PM0000017 

D es1gn . P arame ters 

Design Parameter 

Tobacco Cut Size (%) 19 

Target Value IRange Limit I 

(b) (4) 

Final Moisture(%) 

Blend Moisture (%) 

LeafTobacco Moisture 

(%) 

P01iion Mass (mg) 

P01iion Length (mm) 

P01iion Width (mm) 

P01iion Thickness (mm) 

Pouch Paper Basis Weight 

(g/m2) 

Pouch Paper Air 

Petmeability (L!m2

/s) 

Pouch Paper Wicking:.w 

Pouch Paper Caliper (f.lm) 

19 The applicant provided (t>) (4 ) buckets to characterize tobacco cut size. Therefore, the tobacco 


blend cannot be representedWitli a smgle size value and cotTesponding range limit. In each cell, the data (given 


in %) represents the following buckets, from top to bottom: (t>) 4) 


20 In this submission, the applicant's nicotine uptake valua'":-.,.. io__n d;-___-::- str -:.tes-: -_.,.. ic ":"' tine ex-:tr _.ction rates differ 

even in the products with the same pouch material, indicating the wicking rates are not affecting the nicotine 

absorption rates in this new product. Therefore, wicking values are not needed for this product. 

Page 51 of67 
TPL Review for: PM0000010-PM0000017 

Perf01mance Criteria 

Phase Test IMethod21 

(b) (4) 

Perf01mance 

Tolerance 

Grinding 

Grinding 

Snus 

blend 

processmg 

Packaging 

Packaging 

Packaging 

21 QEMS: Swedish Match' s proprietary Quality and Environmental Management System 

Page 52 of67 
TPL Review for: PM0000010-PM0000017 

1.4.Appendix D 

The following info n nation is applicable to PM0000013 , General Classic Blend P01iion White 

Large - 12 ct: 

Ch ermstry Prod uct S>pect 'fi1catwns 

Categ01y Unit of Target I Range 

Measm e 

Nicotine Design % (b) (4 ) 

Moistme Design % 

p H Design 

Tobacco b) (4) I fugredient mg/pouch 

Tobacco (b) (4) 1 fugredient mg/pouch 

Iohaccd(b) (4) I fugredient mg/pouch U>f{4) fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

Page 53 of67 
TPL Review for: PM0000010-PM0000017 

D es1gn . P arame ters 

Design Parameter Target Value l_g_ange Limit I 

Tobacco Cut Size (%)22 

Final Moisture(%) 

Blend Moisture (%) 

LeafTobacco Moisture 

(b) (4) 

(%) 

P01iion Mass (mg) 

P01iion Length (mm) 

P01iion Width (mm) 

P01iion Thickness (mm) 

Pouch Paper Basis 

Weight (g/m2) 

Pouch Paper Air 

Petmeability (Lim2

/s) 

Pouch Paper Wickingzj 

Pouch Paper Caliper 

(f.llll) 

22 The applicant provided (t>) (4 ) buckets to characterize tobacco cut size. Therefore, the tobacco 


blend cannot be representedWitli a smgle size value and cotTesponding range limit. In each cell, the data (given 


in%) represents the following buckets, from top to bottom: t>) (4) 


23 In this submission, the applicant's nicotine uptake evalua'":-.,.. io__n d;-___-::- str -:.tes-: -_.,.. ic ":"' tine ex-:tr ction rates differ 

even in the products with the same pouch material, indicating the wicking rates are not affecting the nicotine 

absorption rates in this new product. Therefore, wicking values are not needed for this product. 

Page 54 of67 
TPL Review for: PM0000010-PM0000017 

Perfon nance Criteria 

Phase JTest 

(b) (4) 

Grinding 

Grinding 

Snus 

blend 

ocessin~ 

Packaging 

Packaging 

Packaging 

Packaging 

et od24 IPerf01mance I 

Tolerance 

24 QEMS: Swedish Match' s proprietary Quality and Environmental Management System 

Page 55 of67 
TPL Review for : PM0000010-PM00000 17 

1.5.Appendix E 

The following inf01m ation is applicable to PM00000 14, General Mint P01iion White Large: 

Ch ermstry Prod uct S>pect 'fi1catwns 

Categ01y Unit of Target Range 

Measure Value Limit 

N icotine Design % of(4) 

Moisture Design % 

pH Design 

Tobacco b) (4) 

Tobacco (b) (4) 

I 

1 

fugredient 

fugredient 

mg/pouch 

mg/pouch 

rr.:"'"i'~-,-Jobacco (b) (4) 

(b) (4) 

I fugredient 

fugredient 

mg/pouch 

mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

Page 56 of67 
TPL Review for: PM0000010-PM0000017 

D es1gn . P arame ters 

Design Parameter Target Value l_~ange Limit I 

(b) (4) 

Tobacco Cut Size (%)25 

Final Moisture(%) 

Blend Moisture (%) 

LeafTobacco Moisture 

(%) 

P01iion Mass (mg) 

P01iion Length (mm) 

P01iion Width (mm) 

P01iion Thickness (mm) 

Pouch Paper Basis 

Weight (g/m2

) 

Pouch Paper Air 

Petmeability (Lim2

/s) 

Pouch Paper Wickingzt> 

Pouch Paper Caliper 

(f.llll) 

25 The applicant provide{f>) (4) buckets to characterize tobacco cut size. Therefore, the tobacco 

blend cannot be representedWitli a smgle size value and cotTesponding range limit. In each cell, the data (given 

in%) represents the following buckets, from top to bottom {b) (4) 

26 In this submission, the applicant's nicotine uptake evalu ... at:-:- io_ _n d';"em_ _ _ _ ons':"" tr-at:-e-s -:; th-e-n""' ic-o"":' tt·'""n_e_e-xtr:---' act·ion rates differ 

even in the products with the same pouch material, indicating the wicking rates are not affecting the nicotine 

absorption rates in this new product. Therefore, wicking values are not needed for this product. 

Page 57 of67 
TPL Review for: PM0000010-PM0000017 

Perfonnance Criteria 

Phase Test Method27 Perf01mance 

Tolerance 

Grinding 

(b) (4) 

Grinding 

Snus 

blend 

processmg 

Packaging 

Packaging 

Packaging 

Packaging 

27 QEMS: Swedish Match' s proprietary Quality and Environmental Management System 

Page 58 of67 
TPL Review for : PM0000010-PM0000017 

1.6.Appendix F 

The following infonnation is applicable to PM0000015 , General Nordic Mint P01iion White 

Large - 12 ct: 

Chemistry Product Specifications 

Categ01y Unit of Target I Range 

Measure Value Limit 

Nicotine Design % (b) (4) 

Moisture Design % 

pH Design 

Tobacco {b) (4) I fugredient mg/pouch 

Tobacco (b) (4) 1 fugredient mg/pouch 

Tobacco (b) (4) I fugredient mg/pouch ?6} 4) fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

fugredient mg/pouch 

,_ 

Page 59 of67 
TPL Review for: PM0000010-PM0000017 

D es1gn . P arame ters 

Design Parameter J. Target Value ... ange Limit I 

(b ) (4) 

Tobacco Cut Size (%)28 

Final Moisture(%) 

Blend Moisture (%) 

LeafTobacco Moisture 

(%) 

P01iion Mass (mg) 

P01iion Length (mm) 

P01iion Width (mm) 

P01iion Thickness (mm) 

Pouch Paper Basis 

Weight (g/m2

) 

Pouch Paper Air 

Petmeability (Lim2

/s) 

Pouch Paper ckingz~ 

Pouch Paper Caliper 

(f.llll) 

28 The applicant provide{f>) (4) buckets to characterize tobacco cut size. Therefore, the tobacco 

blend cannot be representedWitli a smgle size value and cotTesponding range limit. In each cell, the data (given 

in %) represents the following buckets, from top to bottom {b) (4) 

29 In this submission, the applicant's nicotine uptake evalu ... at:-:- io_ _n d';"em_ _ _ _ ons':'"tr-at:-e-s -:; th-e-n""' ic-o"":' tt.,..n_e_e-xtr:---' act·ion rates differ 

even in the products with the same pouch material, indicating the wicking rates are not affecting the nicotine 

absorption rat es in this new product. Therefore, wicking values are not needed for this product. 

Page 60 of67 
TPL Review for: PM0000010-PM0000017 

Perfonnance Criteria 

Perf01mance

Tolerance 

Phase Test Method30 

(b) (4 ) 

Grinding 

Grinding 

Snus 

blend 

processmg 

Packaging 

Packaging 

Packaging 

Packaging 

30 QEMS: Swedish Match' s proprietary Quality and Environmental Management System 

Page 61 of67 
TPL Review for : PM0000010-PM000001 7 

1. 7.Appendix G 

The following infonnation is applicable to PM000001 6, General P01tion White Large: 

Ch ermstry Prod uct S>pect 'fi1catwns 

Category Unit of Target I Range 

Measme Value Limit 

Nicotine Design % (b) (4) 

Moistme Design % 

pH Design 

Tobacco (b) (4) I Ingredient mg/pouch 

Tobacco (b) (4) I Ingredient mg/pouch 

(b) (4) Ingredient mg/pouch (b) (4) Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Page 62 of67 
TPL Review for: PM0000010-PM0000017 

D es1gn . P arame ters 

Design Parameter Target Value IRange Limit I 

I'(Df(4) 31 Tobacco Cut Size (%)

Final Moisture(%) 


Blend Moisture (%) 


LeafTobacco Moisture 

(%) 


P01iion Mass (mg) 


P01iion Length (mm) 


P01iion Width (mm) 


P01iion Thickness (mm) 


Pouch Paper Basis 


Weight (g/m2

) 


Pouch Paper Air 


Petmeability (Lim2

/s) 


Pouch Paper Wicking.sz 


Pouch Paper Caliper 


(f.llll) 


31 The applicant provided (o) (4 ) buckets to characterize tobacco cut size. Therefore, the tobacco 

blend cannot be representedWitli a smgle size value and cotTesponding range limit. In each cell, the data (given 

in%) represents the following buckets, from top to bottom {b) (4) 

32 In this submission, the applicant's nicotine uptake evalu ... at:-:- io_ _n d';"em_ _ _ _ ons':"" tr-at:-e-s -:; th--""'ic "":' tt'""__xtr:- tio rates differ

even in the products with the same pouch material, indicating the wicking rates are not affecting the nicotine 

absorption rates in this new product. Therefore, wicking values are not ne.eded for this product. 

Page 63 of67 
TPL Review for: PM0000010-PM0000017 

Perfonnance Criteria 

Phase Test et od33 Perf01m ance 

Tolerance 

I

(b

I 

) (4) 

Grinding 

Grinding 

Snus 

blend 

processmg 

Packaging 

Packaging 

Packaging 

Packaging 

33 QEMS: Swedish Match' s proprietary Quality and Environmental Management System 

Page 64 of67 
TPL Review for: PM0000010-PM000001 7 

1.8.Appendix H 

The following inf01mation is applicab le to PM000001 7, General Wintergreen P01tion White 

Large: 

Chemistry Product Specifications 

Categ01y Unit of Measure Target IRange Limit 

Value 

Nicotine Design % (b) (4) 

Moisture Design % 

pH Design 

Tobacco (o) (4) I Ingredient mg/pouch 

Tobacco (b) (4) l Ingredient mg/pouch 

Tobacco (b) (4) I Ingredient mg/pouch 

(6)"(4) Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Ingredient mg/pouch 

Page 65 of67 
TPL Review for: PM0000010-PM0000017 

D es1gn . P arame ters 

Design Parameter Target Value IRange Limit I 

(b) (4) 

Tobacco Cut Size (%)34 

Final Moisture(%) 


Blend Moisture (%) 


LeafTobacco Moisture 


(%) 


P01iion Mass (mg) 


P01iion Length (mm) 


P01iion Width (mm) 


P01iion Thickness (mm) 


Pouch Paper Basis 


Weight (g/m2) 


Pouch Paper Air 


Petmeability (Lim2

/s) 


Pouch Paper Wicking5 ) 


Pouch Paper Caliper 


(f.llll) 


34 The applicant provide{f>) (4) buckets to characterize tobacco cut size. Therefore, the tobacco 


blend cannot be representedWitli a smgle size value and cotTesponding range limit. In each cell, the data (given 


in%) represents the following buckets, from top to bottom: b) (4) 


35 In this submission, the applicant's nicotine uptake valua'":-.,.. io__n d;-___-::- str -:.tes-: -_.,.. ic ":"' tine ex-:tr ction rates differ 

even in the products with the same pouch material, indicating the wicking rates are not affecting the nicotine 

absorption rates in this new product. Therefore, wicking values are not ne.eded for this product. 

Page 66 of67 
TPL Review for: PM0000010-PM0000017 

Perfon nance Criteria 

Phase J. Test I 36 Method

(b) (4) 

Perf01mance 

Tolerance 

Grinding 

Grinding 

Snus 

blend 

processmg 

Packaging 

Packaging 

Packaging 

Packaging 

36 QEMS: Swedish Match' s proprietary Quality and Environmental Management System 

Page 67 of67