Ii 

Technical Project Lead {TPL} Review of PMTAs 

New Products Subject of this Review1 

Submission tracking numbers (STNs) PM0000SSl, PM0000553, PM0000560 

Common Attributes 

Submission date October 10, 2019 

Receipt date October 17, 2019 

Applicant R.J. Reynolds Vapor Company 

Product manufacturer R.J. Reynolds Vapor Company 

Application t ype Standard 

Product category ENDS (VAPES) 

Product subcategory ENDS Component, Closed E-Cigarette 

Cross-Referenced Submissions 

All STNs ]{5) (~) I 

Supporting FDA Memoranda Relied Upon in this Review 

All STNs None 

Recommendation 

Issue marketing granted order for the new products that are the subject of this review. 

Technical Project Lead (TPL): 

Signatory Decision: 

Digitally signed by Berran Yucesoy -S 

Date: 2021.10.12 10:35:33 -04'00' 

Berran Yucesoy, PhD, ATS, DABT 

Deputy Director 

Division of Nonclinical Science 

Concur with TPL recommendation and basis of recommendation 

Digitally signed by Matthew R. Holman -5 

Date: 2021.10.12 10:53:11 -04'00' 

Matthew R. Holman, Ph.D. 

Director 

Office of Science 

1 Tobacco product details, amendments, and dates provided in the Appendix. PMTA means premarket tobacco application. 
 

 

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TABLE OF CONTENTS 

1. EXECUTIVE SUMMARY....................................................................................................................4 

2. BACKGROUND................................................................................................................................5 

2.1. NEW TOBACCO PRODUCTS ............................................................................................................. 5 

2.2. REGULATORY ACTIVITY.................................................................................................................... 5 

2.3. SCOPE OF REVIEW ........................................................................................................................... 5 

3. SCIENTIFIC REVIEW.........................................................................................................................6 

3.1. COMPARISON PRODUCTS................................................................................................................ 6 

Discipline key findings ..................................................................................................... 6 

 Synthesis.......................................................................................................................... 7 

3.2. PRODUCT CHARACTERIZATION ....................................................................................................... 7 

Discipline key findings ..................................................................................................... 7 

 Synthesis........................................................................................................................ 10 

3.3. ABUSE LIABILITY............................................................................................................................. 11 

Discipline key findings ................................................................................................... 11

 Synthesis........................................................................................................................ 12 

3.4. USER POPULATIONS ...................................................................................................................... 12 

Discipline key findings ................................................................................................... 12

 Synthesis........................................................................................................................ 19 

3.5. TOXICANT EXPOSURE .................................................................................................................... 21 

Discipline key findings ................................................................................................... 21

 Synthesis........................................................................................................................ 21 

3.6. HEALTH EFFECTS............................................................................................................................ 22 

Discipline key findings ................................................................................................... 22

 Synthesis........................................................................................................................ 25 

3.7. POPULATION AND PUBLIC HEALTH ............................................................................................... 26 

Discipline key findings ................................................................................................... 26

 Synthesis........................................................................................................................ 26 

3.8. STATUTORY REQUIREMENTS ......................................................................................................... 27

 Public health conclusion ................................................................................................ 27

 Tobacco product manufacturing practices.................................................................... 27

 Labeling ......................................................................................................................... 27

 Product standards ......................................................................................................... 27 

4. ENVIRONMENTAL DECISION ......................................................................................................... 27 

4.1. DISCIPLINE FINDINGS..................................................................................................................... 27 

4.2. ENVIRONMENTAL CONCLUSION ................................................................................................... 27 

5. CONCLUSION AND RECOMMENDATION ........................................................................................27 

6. REFERENCES................................................................................................................................. 29 

7. APPENDIX .................................................................................................................................... 33
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LIST OF TABLES 

Table 1. Disciplines reviewed ........................................................................................................................ 5 

Table 2. Consultations ................................................................................................................................... 6 

Table 3. New tobacco products subject to Granted Orders .......................................................................33 

Table 4. Amendments received.............................................................................................................................34
 

 

 

 

 

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1. EXECUTIVE SUMMARY 

Based on the information provided in the application and other scientific data, as described in this 

Technical Project Lead review, I find that permitting the marketing of the new products listed above 

(“new products” or “subject ENDS”) is appropriate for the protection of the public health (APPH) 

(subject to certain marketing restrictions). 

FDA’s evaluation of these premarket tobacco product applications (PMTAs) determined that there 

are adequate process controls and quality assurance procedures to help ensure both the device and 

e-liquids are manufactured consistently. Based on the information provided in the PMTAs, the new 

products’ abuse liability—i.e., ability to promote continued use, addiction, or dependence—is lower 

than combusted cigarettes and is similar to, or lower than, that of other ENDS. The overall 

toxicological risk to the users of the new products is lower compared to cigarettes due to significant 

reductions in aerosol HPHCs of the new products compared to cigarettes, as evidenced by results of 

nonclinical studies. Further, significant reductions in blood and urinary biomarkers of exposure (e.g., 

volatile organic compounds (VOCs), tobacco-specific nitrosamines (TSNAs), and polycyclic aromatic 

hydrocarbons (PAHs)) after switching from cigarettes to the new products indicate that exposure to 

carcinogens and other toxicants present in cigarette smoke was greatly reduced in smokers who 

switched completely to the use of the new products. In the applicant’s analysis, among all user 

groups (current established cigarette users, current established non-cigarette tobacco users, former 

tobacco users, and never tobacco users), current established cigarette users indicated the highest 

intentions to purchase Vuse Solo products, and the most preferred flavor among these individuals 

was the tobacco (original) flavor compared to non-tobacco flavors (e.g., mint, nectar, and tropical). 

Therefore, the applicant has demonstrated that current adult smokers are particularly interested in 

the new products to assist in intended switching, and these products have the potential to benefit 

that group as compared to continued exclusive cigarette use. 

In terms of the risks to non-users, youth are considered a vulnerable population for various reasons, 

including that the majority of tobacco use begins before adulthood and thus youth are at particular 

risk of tobacco initiation. Existing evidence consistently indicates that use of tobacco-flavored ENDS 

is less common compared to non-tobacco flavored ENDS among youth. In addition, the applicant’s 

study findings demonstrated low intention to purchase the new products among adult never and 

former established tobacco users. Nonetheless, given the strong evidence regarding the impact of 

youth exposure to marketing on youth appeal and initiation of tobacco use, a marketing 

authorization should include marketing restrictions and postmarket requirements to help ensure 

that youth exposure to tobacco marketing is limited. Together, based on the information provided in 

the PMTAs and the available evidence, the potential to benefit smokers who switch completely or 

significantly reduce their cigarette use would outweigh the risk to youth, provided the applicant 

follows post-marketing requirements aimed at reducing youth exposure and access to the products. 

. However, the applicant did not provide microbial data that would allow FDA to evaluate 

whether the products are microbially stable over . The applicant instead provided data 

that supports microbial stability of the products over . Because the microbial stability 

data for is acceptable and indicates that the products are low-risk for microbial growth 

over a period and because there are no other stability concerns, the lack of microbial data 

for does not preclude an APPH finding for the products. 

Regarding product stability, the applicant stated that the shelf life of the new products is 

(b) (4)

The applicant provided chemistry data to support that the new products are chemically stable over 

(b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) . 
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FDA has examined the environmental effects of finding the new products APPH and made a Finding 

of No Significant Impact (FONSI). 

2. BACKGROUND 

2.1. NEW TOBACCO PRODUCTS 

The applicant submitted information for the three new tobacco products listed on the cover 

page and with more detail in the Appendix, sold under the brand names Vuse and Vuse Solo. 

Briefly, a complete Vuse Solo ENDS is composed of a rechargeable Power Unit (device) 

(PM0000SSl), a prefi lled replacement cartridge containing thee-liquids, and an accessory USS 

charger for the power unit. The power unit and cart ridge settings are not adjustable by the user. 

There are two cartridge designs: generation 1 (Gl) (PM0000553) and generation 2 (G2) 

(PM0000560). The primary differences between the t wo designs are the outer tube material (Gl 

stainless steel, G2 6 4 ) and the placement of the authentication/memory chip. 

Each cart ridge design contains e-liquids in original (t obacco) flavor. 

2.2. REGULATORY ACTIVITY 

On October 17, 2019, FDA received 3 PMTAs from R. J. Reynolds (RJR) Vapor Company. FDA 

issued an Acceptance letter to the applicant on October 30, 2019. FDA issued a Filing letter to 

the applicant on November 22, 2019. FDA issued a Deficiency letter to the applicant on 

May 19, 2020. 

Refer t o the Appendix, Table 4 for a complete list of amendment s received by FDA. 

2.3. SCOPE OF REVIEW 

This review captures all compliance and scientific reviews completed for the new tobacco 

product s subject of this review. 

Table 1. Disciplines reviewed 

Discipline Cycle 1 Cycle 2 

Reviewer(s) Review Date Reviewer(s) Review Date 

Engineering Ryan Andress 5/18/2020 Ryan Andress 10/12/2021 

Chemistry Jikun Liu 5/19/2020 Jikun Liu 10/07/2021 

Microbiology David Crah 5/18/2020 Aimee Cunningham 10/12/2021 

Toxicology Steven Yee 5/18/2020 Thomas Hill 10/08/2021 

Behavioral & Clinical Mollie Miller 5/18/2020 Allison Kurti 10/12/2021 

Pharmacology 

Medical Lester Lacorte 5/19/2020 Lester Lacorte 10/08/2021 

Epidemiology Blair Coleman 5/19/2020 Jamal Jones 10/12/2021 

Social Science Katherine Margolis 5/18/2020 Andrea Ruybal 10/12/2021 

Environmental William Brenner 5/18/2020 Yasmin Termeh- 10/06/2021 

Science Zonoozi 

OCE - Lara Williams 5/19/2020 N/A N/A Manufacturing/Lab 

OCE - BIMO Tara C. Singh 5/19/2020 N/A N/A 
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Table 2. Consultations 

Discipline or Office Reviewer(s) Review Date 

Statistics Ruben Montes de Oca 5/19/2020 

OCE- DPAL Julie Nguyen 5/19/2020 

Tobacco Product Surveillance Team (TPST) Susan Rudy 3/04/2021 

OHCE Emily Talbert 10/12/ 2021 

3. SCIENTIFIC REVIEW 

3.1. COMPARISON PRODUCTS 

3.1.1. Discipline key findings 

The following discussion is based on key findings provided in the discipline reviews: 

• Newport Gold data was chosen as cigarette comparison data. The applicant stated 

that the reason to use this data was because Newport Gold was the only RJR 

cigarette that had received a marketing order at the t ime of testing. Newport Gold 

was used for the HPHC comparative analysis studies, in vitro toxicity studies, and in 

vivo inhalation studies. The chemistry review found Newport Gold as an 

appropriate combusted tobacco comparison product as the applicant provided 

adequate data and rationale to support their chosen comparison product. However, 

since it may not represent the U.S. cigarette market, the chemistry review 

introduced additional datasets from other combusted tobacco comparison products 

(3R4F research cigarette and the FDA 50 cigarettes) for comparative HPHC analysis 

to comprehensively elucidate the differences in product characteristics between the 

tw o different categories of tobacco products. 

• Data from three closed ENDS market comparison products were chosen to cover a 

range of aerosol deliveries and flavors (tobacco, menthol, and fruit ) and because of 

their significant market share among closed ENDS at the time studies w ere initiated. 

In comparative HPHC analysis studies, the new products were compared against 

select ENDS market comparison product data (Siu PLUS+ Classic Tobacco, 

Magnificent Menthol, and Cherry Crush; Logic Pro Tobacco, Menthol, and Cherry; 

and Mistie 2.0 Tobacco, Menthol, and Strawberry Splash) and for in vitro toxicit y 

studies, comparisons were made against Siu PLUS+ Classic Tobacco, Magnificent 

Menthol, and Cherry Crush. The chemistry review concluded that the applicant' s 

rationale for the selection of ENDS comparison data is reasonable. 

• The engineering review indicates that the applicant provided draw resistance and 

aerosol mass-based particle size distribution data for Vuse Vibe and Vuse Ciro 

products as market comparison data. 

• The behavioral and clinical pharmacology (SCP) review indicates that the applicant 

used data from usual brand (US) cigarettes or Newport Gold Non-menthol King 

cigarettes (CSD170304) as comparison data in clinical studies that provided data on 

abuse liabilit y and BOE. While 4mg NRT (nicotine replacement therapy) gum was 

used as a comparison product in three clinical studies (CSD170401, CSD1303, and 

CSD1304) that provided data on abuse liability and biomarkers of exposure (BOE) 

associated with using the new products, blu PLUS Classic Tobacco, Logic Pro 

Tobacco, M istie 2.0 POD MOD products w ere used as comparison ENDS in another 
 

 

 

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clinical study (CSD170304) that provided data on abuse liability of the products in 

PM0000553 and PM0000554. From a BCP perspective, the comparison products are 

appropriate comparisons for the new products. 

  The previous version of Vuse Solo G1 Original product was used in four of the

clinical studies (CSD1302, CSD1303, CSD1304, and CSD1503). Per chemistry and 

engineering reviews, the applicant provided sufficient information to determine that 

ingredients, aerosol constituent levels, and design parameters of the previous 

version are comparable with the Vuse Solo G1 product in the PMTA. 

Synthesis 

As TPL, I agree with chemistry and engineering reviews that the applicant’s rationale for the 

selection of cigarette and ENDS as comparison products of the new products is appropriate 

and the applicant provided adequate data to support the comparison between the new 

products and their chosen comparison products. In addition, selection rationale for 

cigarette and ENDS market comparators are reasonable and the information provided by 

the applicant demonstrates that product composition and design parameters for the 

previous versions of the Vuse Solo G1 original product used in submitted clinical studies are 

comparable with their current versions in the PMTAs. I also agree with the BCP review that 

comparison data used in the BOE and abuse liability studies are appropriate. 

3.2. PRODUCT CHARACTERIZATION 

Discipline key findings 

The following discussion is based on key findings provided in the discipline reviews: 

3.2.1.1. Product design and composition 

Per the chemistry review: 

  The new product e-liquids contain nicotine salt formulations (nicotine lactate and

nicotine levulinate), which may be easier (i.e., less irritating) to inhale at high 

nicotine concentrations1-3, thereby facilitating initiation and use of ENDS with high 

amounts of nicotine. Chemistry deferred to toxicology, medical, BCP, and social 

science disciplines for the evaluation of toxicological and sensory effects of the 

nicotine salts in the new products. As discussed in Sections 3.3-3.6, based on clinical 

and nonclinical studies provided by the applicant, these disciplines did not find any 

potential concerns regarding the impact of nicotine salts in the new products. 

Per the engineering review: 

  For the previous version of Vuse Solo G1, used in clinical studies CSD1302, CSD1303,

CSD1304, and CSD1503, the applicant did not provide specifications for air flow rate, 

coil temperature, power delivery unit wattage operating range, inhaled aerosol 

temperature, and e-liquid viscosity. Although these design parameters may affect 

HPHC yields and related toxicities4-10, chemistry and toxicology disciplines concluded 

that, given the magnitude and statistical significance of the decreases in HPHC yields 

in the Vuse Solo aerosol compared to combusted tobacco products and comparable 

HPHC levels with ENDS market comparison data, it is unlikely that the absence of 

these design parameters will raise concerns. 

  For the previous version of the new products in PM0000553, used in clinical studies

CSD1302, CSD1303, CSD1304, and CSD1503, the wick material is different than the 
 

 

 

 

 

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wick material used in the new product according to the material safety data sheet. 

The difference in wick material may affect wicking rate6,11 and, therefore, the impact 

of wick material on HPHC yields is deferred to chemistry for evaluation. Chemistry 

concluded that changes in aerosol constituent levels of the prior and current 

versions of the new products are comparable. 

For all PMTAs, the air flow rate is uncontrolled and may affect HPHC yields.4 The impact 

of uncontrolled air flow rate on HPHC yields is deferred to chemistry for evaluation. 

Chemistry concluded that the HPHC yields of the new products are significantly lower 

than the combusted cigarettes despite any potential effect of the air flow rate.

For PM0000553, the Design Failure Mode Effects Analysis shows an increased risk for eliquid exposure when external force is applied. There is an occasional probability of 

occurrence of the external tube separating from the mouth end cap. Oral, dermal, or 

ocular exposure to e-liquids containing nicotine can cause adverse health effects, 

including seizures, anoxic brain injury, vomiting, and lactic acidosis, and may be fatal.12

Engineering defers the health impact of e-liquid exposure to medical for evaluation. 

Medical concluded that the health risk of fluid leakage and subsequent exposure to 

leaked chemical constituents cannot be ascertained or quantified, particularly since 

exact quantities of constituent exposure from potential e-liquid leakage is unknown. 

However, although the possibility of accidental exposure remains, these concerns have 

been reduced by the product design (i.e., closed pod-based non-refillable system). In 

addition, post-market manufacturer reporting obligations will allow FDA to monitor and 

assess any issues with accidental exposure.

For PM0000553, the applicant does not provide a target specification for cartridge

resistance. Cartridge resistance may affect HPHC yields11, 13 and, therefore, engineering 

deferred the impact of cartridge resistance on HPHC yields to chemistry for evaluation. 

Chemistry concluded that it is unlikely that product characteristics negatively impact the 

aerosol constituent levels of the new products as the aerosol constituent levels are 

significantly lower than the combusted cigarette.

Per the microbiology review: 

Stability data indicate that the new products in the PMTAs are low-risk for microbial

growth over a

(b) (4)

 time period (see 3.1.2.3 for details).

3.2.1.2. Manufacturing 

FDA has conducted an inspection of the applicant’s manufacturing facility at 7855 KingTobaccoville Road, Tobaccoville, NC 27050 in February 2020. From the chemistry, 

engineering, and microbiology perspectives, the applicant demonstrates that the new 

products are manufactured in a consistent manner that minimizes variability in product 

quality.

3.2.1.3. Product stability 

Per the chemistry review: 

The analytical methods used in the stability studies were fit for purpose and fully

validated.

The aerosol yields of nicotine, propylene glycol (PG) and vegetable glycerin (VG)

from the new products fell within their acceptance limits 

(b) (4)

% of T0 aerosol 

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constituent levels) over 

(b) (4)

. From a chemistry perspective, the new products 

are chemically stable within the applicant-proposed 

(b) (4)

shelf life. 

Variation in atmospheric CO2 levels caused the variation in the measured air pH but did 

not affect the aerosol emissions of the new products in the stability studies.

Per the microbiology review: 

 time period. However, the applicant’s proposed shelf life is .

The applicant also provided bulk e-liquid aw data at time and at .

However, FDA only considers finished product data (in this case, up to )

because further manufacturing from a bulk e-liquid into the finished product could

affect microbiological stability (i.e., possible introduction of contaminants during

filling, or use of a different container closure system). Therefore, the data provided

are sufficient to demonstrate the microbial stability of the products over 

but not sufficient to demonstrate the microbial stability of the products over the

applicant-proposed shelf life of 

The microbial stability data is necessary for the proposed shelf life as bacterial

communities change as a function of storage time.14, 15 Increased microbial growth

over time can impact stability of the product and may result in an increased risk to

public health as the product sits in storage. Microbial stability study data (total

aerobic microbial counts (TAMC), total yeast and mold counts (TYMC), and water

activity (aw)) were provided for the new finished products at times 

The data provided indicates that the products are low-risk for microbial growth over

a 

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

3.2.1.4. Product test data 

Per the chemistry review: 

The aerosol HPHC yields of the new products are tested using the power unit in

PM0000551. There are significant reductions in HPHCs from the new products’

aerosols compared to cigarette comparison data under intense and non-intense

regimens.

The intense and non-intense aerosol yields of some constituents (e.g., PG, VG,

acetaldehyde, and formaldehyde) from the new products are increased compared

to ENDS market comparisons. However, aerosol levels of these HPHC are

significantly below the levels present in cigarette smoke.

(b) (4)

The discrepancy between the intense aerosol formaldehyde yields of

(b) (4)

 and

may be caused by different carbonyl

methods used, high method variation in the determination of low formaldehyde

yields, unstable coil temperature in the intense aerosol testing, occurrence of drypuff phenomenon, and device manufacturing variability. The amount of

formaldehyde only accounts for less than 0.5% of total aerosol constituent weight,

and the aerosol level of formaldehyde is lower than that of the levels in cigarette

smoke. The variation of aerosol formaldehyde will not impact the stability of the

new products.

The e-liquid ingredients and aerosol constituent yields of the current new product in

PM0000553 differ from their previous version. Chemistry deferred to BCP discipline to 

determine whether the test results of the prior version of the new product in clinical 

studies CSD1302 – CSD1304 and CSD1503 can be bridged to the current version. BCP 

concluded that nicotine yield comparisons for the predecessor used in these clinical 

studies and the new product in PM0000553 are sufficiently comparable to support 

bridging.

(b) (4) .

(b) (4) ,

(b) (4) .

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Per the engineering review: 

The power unit (PM0000551) contains a rechargeable lithium battery and printed

circuit board assembly (PCBA) and is packaged with a universal serial bus (USB)

charger. The battery is certified to IEC 62133:2012, UN38.3, and UL 1642 standards.

The applicant controls battery cycle life by limiting the power unit to

(b) (4)

 cycles,

which is below the battery vendor specification. Charging and output power is

controlled by the PCBA. The applicant provides power, temperature, and

functionality test data to show that specifications have been met. The new products

do not have user settings and cannot be modified by the user.

The replacement cartridges are closed systems and contain e-liquid and a heater

wick assembly. The cartridges have a proprietary snap-fit connection, unique to

Vuse Solo ENDS, and a cartridge authentication system. The heater is pressure

activated and will remain on for up to 4 s of puff time, with a minimum 

(b) (4)

between activations. Additionally, the replacement cartridges are factory

programmed to have

(b) (4)

 s of puff time stored in the microchip memory. These

design features prevent product tampering and may mitigate dry puffing.

For the new products, measured wet bulb aerosol temperatures do not exceed 44°C, 

however, dry bulb aerosol temperatures up to 90°C were reported. 60°C saturated air is 

the hottest air that can be breathed without injury16, but wet bulb temperatures up to 

50°C can be tolerated for up to one hour.17 Therefore, engineering deferred the health 

impact of aerosol dry bulb temperatures above 60°C to medical for evaluation. From a 

medical perspective, based on published literature and the lack of consumer reports for 

the adverse experiences (AEs)2, the health risk of thermal and aerosol inhalation injury 

appears to be low.

For the new products, coil temperature is uncontrolled and, in general, increases with 

each puff. Heater coil temperature is generally correlated with carbonyl emissions18-20 

and, therefore, the impact of uncontrolled coil temperatures on HPHC yields is deferred 

to chemistry for evaluation. Chemistry concluded that it is unlikely that product 

characteristics negatively impact the aerosol constituent levels of the new products as 

the aerosol constituent levels are significantly lower than the combusted cigarette.

For the new products, the measured maximum surface temperatures, including the

mouth end cap, external tube, and power unit, are at or below 40°C and are appropriate 

from an engineering perspective.

Based on the information provided in the PMTAs for the device and replacement

cartridges, adequate manufacturing processes and controls were used to ensure that 

the new products meet manufacturer’s specifications and they will operate consistently 

throughout the life of the product.

Synthesis 

As TPL, I agree with engineering, chemistry, and microbiology conclusions that these PMTAs 

contain sufficient information to characterize the product design and adequate 

manufacturing processes and controls to help ensure that the new products will operate 

consistently throughout the life of the product and according to the manufacturer’s 

specifications. I also agree with these discipline reviews that there is sufficient information 

for product design and manufacturing and the new products contain significantly lower 

2 Adverse experiences refer to any adverse report (experience or effect or event) associated with the use of the new products. 

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levels (greater than 65% decreases in aerosol HPHCs such as aromatic amines, carbonyls, 

and TSNAs) of measured HPHCs when compared to combusted comparison data. 

Per the microbiology review, the microbial stability data (TAMC, TYMC, and a

finished new products support microbial stability for 

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

w) for the

. However, the applicant’s 

proposed shelf life is . To determine the stability of these products for the entire 

shelf life, microbiology would need additional data beyond . I agree with this 

conclusion. However, because the stability data for is acceptable and indicates 

that the products are low-risk for microbial growth over a period and because 

there are no other stability concerns, the lack of microbial stability data for does 

not preclude an APPH finding for the new products. 

3.3. ABUSE LIABILITY 

Discipline key findings 

The following discussion is based on key findings provided in the BCP review. 

3.3.1.1. Current tobacco users 

Per the BCP review: 

‘Abuse liability’ refers to the ability of the product to promote continued use, and the 

development of addiction and dependence. This can be relevant to determining the 

likelihood that addicted users of one nicotine product would switch to another. For 

example, if a new tobacco product has a low abuse liability, current addicted tobacco 

users may find it to be an inadequate substitute for the product they are currently using. 

On the other hand, low abuse liability makes it less likely that new users will become 

addicted. In ENDS naïve exclusive smokers, the abuse liability of the new products in 

PMTAs is lower than that of combusted cigarettes. For PM0000560, the abuse liability is 

slightly greater than 4mg NRT gum, evidenced by similar nicotine uptake and subjective 

effects after acute use, which may increase the likelihood of its use and adherence 

compared to NRT in smokers interested in quitting combusted cigarette smoking. 

Overall, the low abuse liability of the new products among adult naïve ENDS users 

suggests a low likelihood of initiation with any of the products in the PMTAs among 

adult current tobacco product users.

The abuse liability of the new product in PM0000553 is lower than the abuse liability of 

combusted cigarettes following acute use (CSD170304 and CSD1303), and after five 

days of complete switching from combusted cigarettes to PM0000553

(CSD1304). The abuse liability of PM0000553 is similar to, or lower than, that of other 

ENDS device comparisons evaluated (CSD170304). Similarly, the abuse liability of the 

new product in PM0000560 is lower than the abuse liability of combusted cigarettes 

following acute use (CSD170401 and CSD1502), and after five days of switching from 

combusted cigarettes to PM0000560 (CSD170501). Although PM0000560 was not 

explicitly compared to other ENDS like PM0000553, BCP determined that the new 

product in PM0000553 could be bridged to the new product in PM0000560.

The abuse liability of the new products following extended use cannot be determined as 

the switching studies were conducted over five-day in-clinic studies among exclusive 

smokers who used the new products over a short-term period. The

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abuse liability of these new products used long-term in one’s naturalistic 

environment was not evaluated. However, previous research has shown 

experienced ENDS users can achieve comparable nicotine uptake from ENDS relative 

to combusted cigarettes. Therefore, extended use of the new products may permit 

users to obtain higher nicotine uptake than what was observed in the applicant’s 

clinical studies. Although more extended use may facilitate switching, long-term use 

of the new products was not explicitly examined by the applicant. 

Synthesis 

Per the BCP review, the evaluation of nicotine pharmacokinetic (PK) and subjective effects 

indicate that the abuse liability of the new products is lower than cigarettes in ENDS naïve 

exclusive smokers. Based on (a) existing literature showing that inexperienced users may 

obtain less nicotine from ENDS than experienced users, and (b) applicant-submitted 

information indicating low abuse liability of the new products under acute use conditions, it 

is possible that a naïve/non-user may not be able to achieve nicotine levels that would 

sustain ongoing use and the development of dependence. However, evidence shows that 

experienced ENDS users can attain higher Cmax plasma nicotine concentrations than 

inexperienced users,21, 22 and these levels can even reach similar levels to those of cigarette 

smokers.23, 24 Therefore, extended use of the new products may result in higher nicotine 

uptake than seen in the applicant’s clinical studies and this may facilitate switching among 

current smokers. However, long-term use was not explicitly examined. In addition, as 

compared to non-daily ENDS use, daily use of the new products with concomitant reduction 

in cigarettes per day (CPD) may result in equivalent or lower nicotine dependence compared 

to exclusive cigarette smoking. 

Although conclusions on long-term health benefits cannot be made at this point, as TPL, I 

agree with the BCP conclusion that based on the findings across all clinical studies included 

in the PMTAs, the abuse liability of the new products is lower than combusted cigarettes 

and are similar to, or lower than, that of other ENDS comparisons evaluated. However, with 

experience, users might reach higher nicotine levels to satisfy the withdrawal and craving 

symptoms. This is potentially beneficial for smokers trying to switch to ENDS as they are 

more likely to have satisfactory results and not resume cigarette smoking. In addition, 

slightly greater abuse liability of the new products than 4mg NRT gum may increase the 

likelihood of use of these products compared to nicotine gum among smokers interested in 

quitting. The nicotine levels may pose an addiction risk for non-tobacco users; however, the 

risk is no higher than other currently available tobacco products due to relatively low abuse 

liability of the new products. 

3.4. USER POPULATIONS 

Discipline key findings 

The following discussion is based on key findings provided in the discipline reviews: 

3.4.1.1. Intended user population 

Per the BCP and epidemiology reviews: 
 

 

 

 

 

 

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  The applicant states that use of the new products is likely to be higher among

current tobacco users (in particular, current cigarette smokers) than among nonusers of tobacco. 

Per the social science review: 

  The applicant notes that the mean projected product use rate among adult current

established combusted cigarette users for the new products is 9.1%. However, due 

to limitations identified with the algorithm study in cycle 1 review (e.g., it was not 

validated with ENDS or the new products, the algorithm overestimated combusted 

cigarette purchases), this is likely an overestimation and the results of the study 

should be taken with caution. 

  In another study, the applicant provided data on predicted product use, intentions

to use the products based on main reasons for interest, and behavioral intentions 

regarding how the products will be used. Based on this information, the likely users 

of the new products include current established combusted cigarette users. In this 

study, 66.8% of current established tobacco users were interested in the new 

products. Although it is unclear which products they typically use (i.e., combusted 

cigarettes and ENDS, only combusted cigarettes, other tobacco products), many 

questions asked respondents about intentions to quit or reduce smoking. 

3.4.1.2. Current tobacco users 

Per the social science review: 

  The applicant’s algorithm study was not validated with ENDS or the new products

and as such may overestimate product purchase of combusted cigarettes. However, 

among adults, the projected product use rate was highest among current 

established combusted cigarette users (9.1%), followed by current established noncombusted cigarette tobacco users (2.2%). 

  Among adult current combusted cigarette users sampled, 45% said they intended to

stop smoking completely and use the new products instead. However, the 

applicant’s analysis of data from the Population Assessment of Tobacco and Health 

(PATH) Study (across Waves 1-3) indicated that 1.5% of adults who were exclusive 

combusted cigarette users transitioned to exclusive ENDS use. It is plausible that 

the discrepancy in values between behavioral intention and complete switching may 

be due to the fact that the applicant study assessed intention to completely switch 

for the new products while the PATH Study assessed complete switching for general 

ENDS. The discrepancy may also be attributed to the moderate relationship 

between behavioral intention and future tobacco use behavior due to the addictive 

nature of tobacco products.25, 26 

  Among current combusted cigarette users with intentions to purchase the Vuse Solo

products, 28.6% preferred “original”3/tobacco flavored, 23.2% preferred menthol 

flavored and interest in non-tobacco/non-menthol flavored products4 varied from 

6.4% to 14.7% depending on the specific flavor. Overall, 51.9% preferred original or 

menthol and 47.6% preferred the non-tobacco and non-menthol flavored products. 

  Regarding main reasons for interest in the new products, few statistical differences

were observed across product flavors in 84 different comparisons that compared 

3 “Original” refers to the applicant-provided characterizing flavor for PM0000553 and PM0000560 which are tobacco-flavored. 4 FDA uses the term ‘tobacco-flavored products’ to reflect products which are sometimes referred to as “non-flavored” or 

“unflavored” in the published literature. FDA uses the term ‘non-tobacco flavored products’ for all other products. 
 

 

 

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each flavor to all other flavors across all reasons for use. Combusted cigarette users 

with any purchase intent who selected original (26.4%) as their most preferred 

flavor were more likely to report intentions to use these flavors to stop smoking, 

compared to users who selected mint flavor (12.7%). There were no significant 

differences among other flavors and interest in each flavor to help quit smoking 

ranged from 16.1-23.7%. 

  The main reasons for interest in purchasing the new products among combusted

cigarette users were to either reduce combusted cigarette usage (14.6-19.7%) or to 

stop smoking all together (12.7-26.4%). Other common reasons included curiosity 

(8.8-16.4%) and enjoyable flavors (3.3-14.3%). Percentages varied based on specific 

flavor. 

  Most respondents indicated that their intended behavioral change with the new

products was to switch to the product (38.5-52.8%) or to dual use (combusted 

cigarettes and the new products, 39.7-52.8%) with the intention of using fewer 

combusted cigarettes. 

  The mean rating for likelihood of switching back to combusted cigarettes after

adopting the new products among adult current established users was 4.3 (95% CI, 

4.1- 4.5) on a 1 (not at all likely to switch back to cigarettes) to 10 (very likely to 

switch back to cigarettes) scale. Among those likely to quit combusted cigarettes, 

the mean rating for likelihood of switching back after adopting the new products 

was 3.9 (95% CI, 3.5-4.3). 

Per the epidemiology review: 

  Evidence from observational studies submitted in the PMTAs, as well as evidence

from the peer-reviewed literature, suggests that adult use of closed ENDS, and the 

subject new products in particular, is predominately non-daily and concurrent use 

with cigarettes is common. 

Dual or poly use 

  Per the BCP review, the applicant-submitted survey data show that

approximately 2-5% of adult exclusive combusted cigarette smokers or dual 

cigarette and ENDS users switched completely to ENDS use at subsequent 

waves, suggesting a high likelihood of dual tobacco use with the new products. 

However, this estimate is based on use patterns of ENDS in general because the 

applicant did not conduct longitudinal studies on use patterns with the new 

products.5 

  From an epidemiology perspective, the applicant did not provide any

prospective data to assess long-term trajectories of use, so it is unclear to what 

extent dual use is a transient state along a pathway to switching versus a 

permanent state. 

5 Determining whether marketing a new product is APPH includes evaluating the risks and benefits to the population as a 

whole. This requires FDA to balance, among other things, the negative public health impact for nonusers against the potential 

positive public health impact for current tobacco users. Accordingly, for marketing of a new product to be found to be APPH, 

any risks posed by a new product to youth would need to be overcome by a sufficient benefit to adult users, and as the known 

risks increase, so too does the burden of demonstrating a substantial enough benefit. In the case of a new non-tobacco flavored 

ENDS product, the risk of youth initiation and use is substantial, given the clearly documented published evidence. In contrast, 

the risk of youth initiation for tobacco-flavored ENDS products is less substantial, thus the level of evidence demonstrating 

benefit to adult smokers may not need to be as high. 
 

 

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Switching 

  Per the BCP review, survey data suggest that, while a small proportion of adult

tobacco users are likely to switch completely to the new products, daily and 

exclusive users have an increased likelihood of switching completely compared 

to non-daily and dual-users. 

  Per the epidemiology review, the applicant examined the association between

ENDS use (“original”/tobacco flavor vs. all other flavors) and smoking status 

(current vs. former smokers). The extent to which the new products (or ENDS in 

general) facilitated cessation was unknown, and therefore the conclusion made 

by the applicant that the availability of flavors may help smokers completely 

switch was unsupported by the data. The applicant used longitudinal studies to 

examine tobacco use transitions from exclusive cigarette smoking to exclusive 

ENDS use in the first cycle review. Rates of switching from combusted cigarette 

use to exclusive ENDS use reported in the application (1.5-6.7%) were 

comparable to rates in the published literature (3.4-5.9%).27-29 However, the 

applicant did not provide information that examined the role of flavors on 

tobacco use transitions. Additionally, the applicant did not provide evidence on 

tobacco use transitions overall or the role of flavors on tobacco use transitions 

for cycle 2 of PMTA review. In the absence of product-specific (longitudinal) 

data on switching in this PMTA, it may be reasonable to infer that switching 

rates for this product would be somewhere within the range found in the 

published literature and presented in the PMTA. However, based on the 

applicant’s analysis and available evidence showing higher preference of 

original flavored ENDS among adult smokers, the new products could help 

current adult smokers in quitting or reducing cigarette smoking. 

Cessation 

Per the BCP review: 

  Existing studies have shown that daily ENDS use is associated with significant

reductions in combusted cigarette use; however, non-daily ENDS use does not 

appear to be associated with these reductions. 

  Published literature and survey data show that some closed ENDS (e.g., cig-alike) may deliver sufficient nicotine to effectively replace some cigarettes.

  The new products in PM0000553 (used in CSD1303) and PM0000560

(CSD170401) were associated with slightly greater abuse liability than 4mg NRT 

gum, which may increase the likelihood of use and adherence of these three 

products compared to nicotine gum among smokers interested in quitting 

cigarette smoking. 

3.4.1.3. Tobacco non-users (including youth) 

Per the BCP review: 

  Due to the lower abuse liability of these products compared to cigarettes, former

and non-tobacco users (including youth) who initiate use of the new products are 

less likely to progress to regular use of the new products. 

  Overall, the applicant submitted two human abuse liability studies (CSD1303 and

CSD170401) and four nicotine PK studies (CSD1502, CSD1503, CSD170303, and 

CSD170304) that collectively indicate lower abuse liability for the new products in 

PMTAs relative to combusted cigarettes. Although tobacco non-users including 

youth were not included in the applicant-submitted clinical studies, the comparably 
 

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low abuse liability of the new products relative to combusted cigarettes suggests 

initiation and sustained use of the new products among tobacco non-users is likely 

to be lower than initiation and sustained use of tobacco products with greater 

abuse liability (e.g., combusted cigarettes). 

Per the social science review: 

  The applicant study findings indicate that among most adult non-tobacco users,

both former (84.3%) and never users (74.7%), indicated they were not interested in 

the new products. Additionally, according to an algorithm created by the applicant, 

adult never tobacco users had a projected product use rate of 0.4%. While findings 

indicated that those susceptible to combusted cigarette use had a significantly 

higher projected product use rate than those not susceptible, these projected 

product use rates are low, which is consistent with previous literature.30 The mean 

projected product use rate among former adult tobacco users was 1.4% and 1.8% 

among current tobacco experimenters. Based on the respondent data, the applicant 

concludes that adult never users are not likely to become users of the new products. 

  The applicant examined intentions to purchase Vuse Solo products on a 1 (definitely

would not purchase it to use) to 10 (definitely would purchase it to use) point scale. 

Current established cigarette users (4.6; 95% CI 4.5 – 4.8) indicated the highest 

intentions to purchase. Current established non-cigarette users (3.6; 95% CI 3.3 – 

3.9), former established tobacco users (1.9; 95% CI 1.8 – 2.0), and never established 

tobacco users (2.5; 95% CI 2.4 – 2.6) reported low intentions to purchase. 

  In 2020, approximately 19.6% of high school students and 4.7% of middle school

students reported current use of ENDS.31 Additionally, longitudinal research using 

2013-2015 PATH data indicated that 42.2% of past 30-day youth ENDS users 

remained past 30-day ENDS users one year later.29 These published findings indicate 

risk of ENDS use among youth. However, youth are less likely to initiate tobaccoflavored ENDS and subsequently progress to regular use than with non-tobacco 

flavored ENDS. For instance, in Wave 1 of the PATH Study from 2013-2014, over 

80% of youth aged 12-17, 75% of young adults 18-24, and 58% of adults 25 and 

older reported that the first ENDS that they used was non-tobacco flavored. In 

another PATH Study, more youth, young adults, and adults who initiated ENDS use 

between Wave 1 and Wave 2 reported use of a non-tobacco flavored product than a 

tobacco-flavored product. Finally, in PATH Wave 4 from 2016-2017, 93.2% of youth 

and 83.7% of young adult ever ENDS users reported that their first ENDS product 

was flavored compared to 52.9% among adult ever users 25 and older.32 

Additionally, existing literature on non-tobacco flavored product use suggests that 

non-tobacco flavors not only facilitate initiation, but also promote established 

regular ENDS use. For example, regional studies have found that the use of nontobacco flavored ENDS was associated with a greater frequency of ENDS used per 

day among a sample of adolescents in Connecticut in 201433 and continuation of 

ENDS use in a sample of adolescents in California from 2014-2017.34 Use of nontraditional flavors (vs. tobacco, mint/menthol, flavorless) was associated with 

increased likelihood of continued use and taking more puffs per episode.34 Data 

from a regional survey in Philadelphia, PA found initial use of a non-tobacco flavored 

vs. tobacco flavored ENDS was associated with progression to current ENDS use as 

well as escalation in the number of days ENDS were used across 18 months. Finally, 

similar effects have been found in the PATH study among young adults (18-24 

years), where “ever use” of non-tobacco flavored ENDS at Wave 1 was also 
 

 

 

 

 

 

 

 

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associated with increased odds of current regular ENDS use a year later at Wave 2. 

Collectively, these findings indicate that while all ENDS pose risks to youth, youth 

are less likely to initiate tobacco-flavored ENDS and subsequently progress to 

regular use, than with non-tobacco flavored ENDS. 

 The applicant did not provide direct data on youth. In the applicant’s “Likelihood of 

Use, Label Comprehension, and Risk Perceptions Testing for Vuse Solo E-Cigarette” 

study, adults 18 to 30 were oversampled to provide a sufficient sample of young 

adults ages 18 to 24 to serve as a proxy for youth. However, some subsamples of 

young adults were small and not all analyses were broken down by age to allow for 

young adults to serve as a proxy for youth. Further, data on most preferred flavor 

was not broken out by young adult and adult age categories which would have 

helped FDA in determining the appeal of the new products among youth in the 

absence of youth data. 

 Generally, interest in tobacco flavors is low among youth. The available evidence 

(NYTS 2019) indicates that non-tobacco flavored ENDS are more likely to be used by 

youth than tobacco flavored ENDS.35 The applicant’s data demonstrate that adults 

had the highest purchase intent for original (28.6%), compared to menthol (23.2%) 

and mint/fruit flavors (between 6.4-14.7% depending on the flavor). 

 According to National Youth Tobacco Survey (NYTS) 2020 data, prefilled pods or 

cartridges are the most common ENDS device types used among youth.36 Sleek 

design, ability to use products discreetly, and user-friendly nature make pod mod 

(rechargeable cartridge-based ENDS) products appealing among youth.33, 37, 38 

Although the new products are not pod mods, they are sleek and small in design, 

user friendly cartridge-based, and easily rechargeable. Although there is some risk 

of youth uptake of these products, in general, tobacco-flavored ENDS are less 

appealing to youth compared to non-tobacco flavored ENDS, making the risk of 

youth initiation low for these products. Findings from a discrete choice experiment 

showed that non-tobacco flavors were associated with more curiosity, less 

perceived danger, and greater perceived ease-of-use among high school students, 

compared to tobacco flavor.39 Additionally, the published literature indicates that 

youth report significantly higher preference for non-tobacco flavored ENDS 

compared to tobacco flavored ENDS.33, 37, 38 Moreover, the evidence indicates that 

tobacco flavored ENDS are less likely to be used by youth who initiate or regularly 

use ENDS compared to non-tobacco flavors. The findings from the 2020 Monitoring 

the Future (MTF) survey provide evidence that youth use of tobacco flavored ENDS 

is less common compared to other flavored ENDS including mint.40 According to the 

2020 MTF data, the prevalence of tobacco flavor was 2.9% among 10th and 12th 

graders while mint was the second most often used flavor (26.9%) after fruit 

(59.3%).40 

 In addition, the digital marketing and TV and radio restrictions recommended by 

OHCE will help to mitigate the risk of youth initiation. 

Per the epidemiology review: 

 Observational evidence submitted by the applicant in both review cycles 

demonstrates that prevalence of use of the applicant’s products among young 

adults declines with younger ages, and the majority of new product users (both 

experimental and established) are more likely to be older (>30 years of age). 

 Some evidence in the peer-reviewed literature on youth device type preferences 

suggests youth report using closed systems (i.e., disposable devices or those that 
 

 

 

 

 

 

 

 

 

 

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use pre-filled pods or cartridges similar to the new products) most often.41 The 

literature shows that non-tobacco flavor use is very common in both youth and 

adult ENDS users (irrespective of the device type). Furthermore, the proportion of 

reported youth use of the brand “Vuse” significantly increased from 2019 (1.2%) to 

2020 (7.3%).40 However, the study did not specify the type of Vuse-branded 

products or the flavor used by youth, so it is uncertain whether use of Vuse Solo 

products increased among youth. As previously discussed, the published literature 

shows that prevalence of youth use of tobacco-flavored ENDS is low and that 

tobacco flavored ENDS are less likely to be used by youth who initiate or regularly 

use ENDS compared to non-tobacco flavors. 

  Overall, the available evidence to date does not adequately address whether new

product use in youth and young adults leads to regular smoking. 

3.4.1.4. Vulnerable populations (other than youth) 

  Per social science and epidemiology reviews, the applicant did not provide

information on use of the new products among vulnerable populations—i.e., groups 

that are susceptible to tobacco product risk and harm due to disproportionate rates 

of tobacco product initiation, use, burden of tobacco-related diseases, or decreased 

cessation. Evidence from the published literature indicates that all age groups with 

substance use or mental health issues are more likely to use ENDS compared to 

those without.42-44 Additionally, the prevalence of ENDS use is higher among other 

vulnerable populations (e.g., pregnant persons, and lesbian, gay, and bisexual 

individuals).45-49 While the evidence indicates that some vulnerable populations 

experience disproportionate ENDS use, there is a lack of currently available 

evidence to show whether the new products would help facilitate adult combusted 

cigarette smokers from vulnerable populations to switch or reduce CPD. 

  Per the BCP review, no clinical studies were provided or reviewed by the applicant

addressing use of the new products among vulnerable populations. Given the 

existing high rates of tobacco product use among vulnerable populations and the 

known difficulties that these populations have with cessation, ENDS use may serve 

as a harm reduction approach if users are able to completely switch or dramatically 

reduce other combusted tobacco use. Further, the applicant submitted two human 

abuse liability studies (CSD1303 and CSD170401) and four nicotine PK studies 

(CSD1502, CSD1503, CSD170303, and CSD170304) indicating lower abuse liability for 

the new products relative to combusted cigarettes, which suggests the new 

products will not pose greater initiation and addiction risks among vulnerable 

populations than combusted cigarettes. Nevertheless, due to insufficient 

information, from a BCP perspective, the impact of the new products on abuse 

liability and product use behavior in vulnerable populations other than youth is 

unknown. 

3.4.1.5. Actions taken to mitigate risk of unintended use 

Per the OHCE consult: 

  The applicant submitted information on their proposed marketing restrictions in

two letters dated November 9, 2018 and April 29, 2019. 

  OHCE’s review raised concerns about the potential broad reach of the applicant’s

plan for digital and broadcast marketing and concluded that, if the products are 
 

 

 

 

 

 

 

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authorized to be marketed, FDA should place restrictions on digital marketing and 

TV and radio marketing to protect youth. 

  Additionally, OHCE noted concerns with the applicant’s plans for print and point-ofsale advertising and recommended that any marketing granted order (MGO) letter

encourage the applicant to take additional steps to limit youth exposure to print 

and point-of-sale advertising, including, for example, limiting advertising to print 

publications where 85% or more of the readership is 21 years of age or older 

and/or selecting publications that do not over-index for youth. 

  The applicant describes the following measures it would take to help reduce the

youth-appeal of its marketing materials: “No testimonials by sports figures or 

celebrities or any person with special appeal to persons under 21 years of age; No 

person appearing in any advertising materials shall be under age 25 or be styled to 

look under age 25; Content shall not include characters, images, or themes 

designed to target youth; Content shall not be related to youth or youth-oriented 

activities; Content shall not suggest that use of R.J. Reynolds Vapor Company's 

("RJRV") products is essential to social prominence, distinction, success or sexual 

attraction, nor shall any content picture a person using any RJRV products in an 

exaggerated manner; and Content shall not depict persons participating in, or 

obviously just having participated in, a physical activity requiring stamina or 

athletic conditioning beyond that of normal recreation.” OHCE noted support for 

the use of these measures because they are likely to further help mitigate risks to 

youth. OHCE recommended that any MGO letter for these products encourage the 

applicant to implement these measures. 

3.4.1.6. Labeling and advertising 

  The applicant provided labels that did not appear to contain anything potentially

false or misleading. 

  The applicant assessed label comprehension with a series of questions that

measured knowledge about the products. The percentage of correct responses 

ranged from 74% to 94% across items and user groups. 

  The applicant did not include information that indicates whether consumers will

use the products as intended or designed. However, nothing in the applications 

suggest that potential issues would arise. 

Synthesis 

Per BCP, social science, and epidemiology reviews, the applicant states that use of the new 

products is likely to be higher among current tobacco users (in particular, current cigarette 

smokers) than among non-users of tobacco. Although the social science review indicates 

limitations with the applicant’s algorithm study, self-reported measures from respondents 

were also provided. These data indicate that the mean projected product use rates are 

highest among current established cigarette smokers. Most non-tobacco users in the study 

were not interested in the new products (74.7% never established tobacco users, 84.3% 

former established tobacco users); whereas two-thirds of current established tobacco users 

(66.8%) and about half of current established non-combusted tobacco users were interested 

(52%). In addition, based on the applicant’s analysis, switching from conventional cigarettes 

to ENDS does occur among a small proportion of users, typically through a period of dual 

use. The applicant reported that approximately 5% of dual users switched to exclusive ENDS 
 

 

 

 

 

 

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use at follow-up, which is consistent with published analyses of the PATH Study data looking 

at ENDS and cigarette transitions from Wave 1 to Wave 2.27 

Per social science and epidemiology reviews, findings from the applicant’s likelihood-of-use 

study suggest that current established cigarette smokers are more likely to prefer original 

(tobacco) flavor relative to other flavors (i.e., menthol, mint and fruit). In addition, 

respondents with a purchase intent of 2+ (on a 10-point scale) who selected original (26.4%) 

flavor were more likely to report intentions to use this flavor to stop smoking compared to 6 

other flavors (12.7%, 20.0%, 23.7%, 22.3%, 16.1%, and 26.3% for mint, nectar, melon, 

tropical, fusion, and menthol, respectively). In Wave 2 of the PATH Study, tobacco flavor was 

used by 50.5% of adult ENDS users aged 25 years and older who used a single flavor while 

menthol/mint was used by 23.3%, fruit by 15.9%, and candy or sweets by 7.8%.50 In 

addition, among adult dual users (18+) who used nonmenthol cigarettes, 32.3% reported 

exclusive tobacco flavor use.51 

The evidence shows that original (tobacco) flavored ENDS are less likely to be used by youth 

who initiate or regularly use ENDS compared to non-tobacco flavors. The findings from the 

2020 MTF survey provide evidence that youth use of tobacco flavored ENDS is less common 

compared to other flavored ENDS including mint.40 According to the 2020 MTF data, the 

prevalence of tobacco flavor was 2.9% among 10th and 12th graders while mint was the 

second most often used flavor (26.9%) after fruit (59.3%).40 Although youth report using 

prefilled pods or cartridges most often, more data is needed to determine overall youth 

appeal of cig-a-like ENDS. The evidence from the peer-reviewed literature demonstrates 

that, while youth use of ENDS is common, the proportion of youth who report Vuse Solo as 

their usual brand is low. Although the overall youth use of ENDS has decreased from 2019 to 

2020 among high school and middle school students,36 the proportions of reported youth 

use of the brand “Vuse” significantly increased from 2019 to 2020 (1.2% to 7.3%) though the 

study did not specify by Vuse subbrands or by flavor, so specific findings for the new 

products are unknown.40 Though youth use of ENDS is concerning, as previously discussed, 

the published literature shows that prevalence of youth use of tobacco-flavored ENDS is low 

and that tobacco-flavored ENDS are less likely to be used by youth who initiate or regularly 

use ENDS compared to non-tobacco flavors. 

With respect to youth appeal and mitigation, I agree with OHCE’s evaluation of the 

applicant’s marketing plans and all recommendations in the OHCE consult. Accordingly, I 

recommend that the MGO letter include additional marketing requirements and 

recommendations. 

The evidence summarized in this section describes relatively high interest among smokers in 

using the tobacco-flavored products. Although nicotine delivery is lower than for cigarette 

smoking, available evidence indicates that experienced ENDS users can increase nicotine 

uptake compared to inexperienced users, which increases the likelihood of switching. Use of 

these products would benefit smokers who switched completely or substantially reduced 

their cigarette smoking. The available information also shows that youth appeal/uptake of 

tobacco-flavored products is generally low among youth. Overall, I agree that the benefit of 

the new products to adult smokers is significant enough to overcome the risk to youth. 

(b 
 

 

 

 

 

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While the DPAL recommendation was for the marketing order for the new products to 

include an explicit reminder in the order that the applicant must comply with all applicable 

requirements, including the nicotine warning statements for covered tobacco products 

required under 21 CFR 1143.3, this is already covered. The main body of the order letter 

contains language reminding applicants of their responsibility to ensure the new products 

comply with all applicable statutory and regulatory requirements and notes that FDA 

monitors for compliance. 

3.5. TOXICANT EXPOSURE 

Discipline key findings 

The following discussion is based on key findings provided in the discipline reviews: 

3.5.1.1. Toxicity 

  Overall, there are significant reductions in HPHCs tested using the power unit

(PM0000551) from the new products’ aerosols compared to cigarette comparison 

data under both regimens. Elevations in glycerin and propylene glycol of the new 

products’ aerosols were outweighed by decreases in other respiratory toxicants 

(i.e., acetaldehyde, acetyl propionyl, ammonia, anabasine, acrolein, crotonaldehyde, 

diacetyl, ethylene glycol, and formaldehyde) in the cigarette comparators. Observed 

glycerin and propylene glycol levels were comparable to levels seen in other ENDS 

market comparisons. 

3.5.1.2. Biomarkers of exposure 

Per the BCP review: 

  Switching from cigarette smoking to ad libitum use of the new products in

PM0000553 or PM0000554 (CSD1304), and PM0000560 (CSD170501) for five days 

resulted in significant reductions in the urinary and blood BOEs of similar magnitude 

to the reductions in the participants who abstained from smoking. While the longterm effects of switching were not assessed, these changes in systemic exposures 

are likely to provide the health benefit of reduced exposure to these HPHCs for 

current adult smokers should they completely switch to the products in the PMTAs. 

  Changes in BOE and the associated health risks of dual use of cigarettes and the new

products in the PMTAs have not been evaluated in longitudinal studies or under 

extended exposure conditions, thus conclusions on such long-term health risks 

cannot be made at this point. 

Synthesis 

Based on the toxicology review, the overall toxicological risk to the users of the new 

products is lower compared to cigarettes due to significant reductions in HPHC yields in 

the new products’ aerosol compared to cigarette comparators and results of nonclinical 

studies. Per the BCP review, significant reductions in blood and urinary BOE (e.g., VOCs, 

TSNAs, and PAHs) indicate that exposure to carcinogens and other toxicants present in 

cigarette smoke were greatly reduced with use of the new products. The magnitude of 

reductions in biomarker levels was similar to the reductions that occurred when smokers 

switched to nicotine gum. Although the impact on long-term disease risk has not been 
 

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evaluated, the applicant’s results and existing evidence support that complete switching 

reduces exposure to tobacco-related toxicants and may result in less risk of tobaccorelated diseases. A recent study examining Waves 1 and 2 of the PATH data reported that 

participants with moderate to high reductions in CPD had also lower levels of 

biomarkers.52 The impact of dual use on BOE levels and the associated health risks were 

not assessed; however, based on the currently available evidence, reducing CPD likely 

leads to less exposure to harmful toxicants than continued smoking and may help for 

eventual quitting. Longitudinal data are needed to follow individuals over time to 

accurately determine use trajectories and potential impact of dual use on health risk. 

I agree with the conclusion that available toxicological data, the demonstrated reductions 

in measured HPHC levels, and significant reductions in BOEs indicate the potential for a 

relative benefit compared to cigarette smoking for smokers who completely or partially 

switch to the new products. 

3.6. HEALTH EFFECTS 

Discipline key findings 

The following discussion is based on key findings provided in the discipline reviews: 

3.6.1.1. Toxicology 

  Results from the in vitro toxicology studies demonstrated that combusted cigarette

smoke fractions (total particulate matter (TPM), gas vapor phase (GVP), or both) 

were mutagenic, cytotoxic, and genotoxic. By contrast, even at the maximum dose 

levels tested, neither the TPM nor GVP from any of the aerosols of all the new 

products or ENDS market comparisons was mutagenic, cytotoxic, or genotoxic under 

the test conditions. 

  For the in vivo inhalation studies, the new products’ aerosols consistently resulted in

substantially lower nonclinical toxicity and histopathological changes compared to 

Newport Gold cigarette smoke. The Newport Gold cigarette was the only cigarette 

available with a market order at the time the in vitro and in vivo studies were 

started, and the cigarette measured many of similar HPHCs as the new products 

under both non-intense and intense puffing regimens. Therefore, the supportive 

findings relative to Newport Gold cigarette were considered sufficient for 

comparative determination. 

  No in vivo studies were conducted comparing the new products’ aerosols to the

aerosols from ENDS market comparisons as none of the comparison products had 

received a positive marketing order at the time of PMTA submission. However, 

chemistry had determined that HPHC levels in the aerosol from the new products 

were comparable to similar closed ENDS market products. Based on these similar 

HPHC levels, as well as the accompanying in vitro studies, additional in vivo 

inhalation studies between the new products and marketed ENDS comparison 

product are not needed for a toxicological assessment. 

  The BOE data from clinical studies indicated that exposure to carcinogens and other

toxicants present in cigarette smoke were greatly reduced with use of the new 

products for five days in a controlled in-clinic setting. 
 

 

 

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3.6.1.2. BIMO inspection findings 

  FDA has not conducted bioresearch monitoring (BIMO) inspections of clinical study

sites used in these PMTAs, as studies were not pivotal and reported AEs did not 

raise clinically significant concerns. 

3.6.1.3. Addiction as a health endpoint 

Per the BCP review: 

  The abuse liability of the new products is less than that of a cigarette in ENDS naïve

exclusive smokers. Current cigarette smokers are likely to dual use the new products 

with cigarettes; however, daily use of the new products may be associated with 

reduced CPD. Exclusive daily users of the new products in the PMTAs are likely to 

have equivalent or lower overall nicotine dependence levels compared to exclusive 

cigarette smoking. 

3.6.1.4. Short and long-term health effects (clinical and observational) 

Per the medical review: 

  In general, the published literature on the health effects of ENDS suggests that

many ENDS aerosol constituents (e.g., TSNAs, VOCs, and PAHs) may be decreased 

compared with combusted cigarettes.53-55 The National Academies of Sciences, 

Engineering, and Medicine (NASEM) states that ENDS aerosol contains lower levels 

of most toxicants than combusted cigarette smoke.12 Some literature also reports 

that not all ENDS aerosol constituents are reduced (e.g., acrolein, acrylamide, 

acrylonitrile, and xylene)54, 56, which may potentially off-set the potential health 

benefit of short and long-term reductions in exposure to other ENDS constituents. 

However, the ability to draw conclusions on the health effects of ENDS from the 

published literature is limited due to small sample sizes and short durations of 

exposure. 

  Several study design issues limit the interpretation of health effect data from the

applicant’s short-term switching, abuse liability, and PK studies including small 

sample sizes, short-term exposure durations, and generally healthy participants. In 

addition, the applicant’s switching studies did not assess dual use as it would be 

more likely to occur in real-world conditions. 

Per the epidemiology review: 

  Some published literature suggest that ENDS use compared to never tobacco use

may be associated with a higher likelihood of some health outcomes such as 

cardiovascular disease, respiratory disease, and oral health.57-59 As many of these 

studies utilized cross-sectional surveys to examine these relationships, the timing of 

ENDS use and disease onset cannot be established with certainty. 

  Few observational studies have been published on the short- and long-term health

effects of ENDS use. Biomarker data from observational studies generally show that 

ENDS users have higher exposure to nicotine, some VOCs, and TSNAs than do nontobacco users.53, 60 Some biomarker data from observational studies have also 

found that dual users can have higher levels of certain biomarkers of exposure than 

exclusive cigarette smokers.53, 61 

  A meta-analysis found that compared to heavy smokers, dual users who are able to

reduce the number of cigarettes they smoke by at least 50% had a significant 

reduction in lung cancer risk.62 However, reductions in cigarette smoking have not 
 

 

 

 

 

 

 

 

 

 

 

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been found to lower the risk of all-cause mortality, all-cancer risk, or other 

smoking/tobacco-related cancers.62 

  Switching and smoking reduction likely reduce exposure to tobacco-related

toxicants. In an observational study where smokers switched to ENDS for two 

weeks, total nicotine and some PAH metabolite levels did not change, but levels of 

all other biomarkers, including VOCs and TSNAs, significantly decreased after one 

week of using ENDS.63 Another study, examining Waves 1 and 2 of PATH data, 

reported that participants with moderate reductions in cigarettes smoked per day 

had lower levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and 

1-hydroxypyrene and participants with heavy reductions in cigarettes smoked per 

day had lower levels of NNAL, 2-fluorene, and MHB3 at Wave 2.52 

3.6.1.5. Likelihood and effects of product misuse 

  Per the medical review, the PMTAs did not specifically address human use factors or

the potential for intentional product misuse (e.g., child resistant packaging). There is 

a potential risk of accidental exposure from misuse (using the product in ways other 

than intended such as product modifications, dripping, and stealth use), abuse, or 

unintended use resulting in exposure to nicotine and other toxicants. However, the 

new products have a closed system and are not intended to be opened. Therefore, 

the health risks are likely mitigated for accidental ingestion and exposure in 

children. Further, there have been no FDA reports of accidental exposure for these 

products. The authentication memory chip intended to minimize the potential for 

unintended use such as dry puffs (insufficient e-liquid) could also serve as a 

secondary safety feature preventing accidental ingestion and exposure in children. 

  Per the BCP review, the low abuse liability of the new products among ENDS naïve

users and added safety features help to contribute to a lower likelihood of the new 

product misuse. 

3.6.1.6. Adverse experiences 

Per the medical review: 

  In short-term new product exposure switching, abuse liability, and PK studies, the

numbers of AEs were generally low and characterized overall as mostly mild, 

transient, and expected. No deaths or serious AEs associated with use of the new 

products were reported. 

  Two of the four consumer health-related AEs associated with the new products

reported to the CTP Safety Reporting Portal were seizures. One was a “complex 

partial seizure” occurring 10 months after starting the new product and the other 

occurred after complete switching to the new product in one consumer without a 

prior medical history of seizures. Although additional follow-up information was not 

available, new product exposure may potentially be associated with seizures under 

real-world use conditions. However, it is premature to determine whether current 

seizure reports indicate an association with complete switching to the new 

products. 

  The evidence is inconclusive for drawing health risk determinations based on the

TPST AE data. The numbers of self-reported AEs were small (n=4 health-related 

AEs), and consumers did not specifically associate the AEs with the new products. 

  FDA is aware of several health issues regarding the use of ENDS, specifically e
 

 

 

 

 

 

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cigarette or vaping use-associated lung injury (EVALI), seizures, and 

overheating/fire/explosion-related thermal burn injuries (OH/F/Exp): 

EVALI is a potential respiratory health effect that could occur in individuals who 

use vaping products. There were no reports of EVALI in the applicant’s 

foundational clinical studies and there did not appear to be any subjects who 

experienced the constellation of symptoms indicative of EVALI as an AE that 

required hospitalization. However, since EVALI is associated with use of vaping 

products, CTP is interested in evaluating any additional information related to 

respiratory illness in association with ENDS and specifically the new products. 

There were no seizures reported as an AE in the applicant-submitted clinical 

studies. Two seizures were reported with new product use in the CTP Safety 

Reporting Portal. While this data is insufficient to fully evaluate the potential 

association of the new products with seizures, CTP is interested in monitoring an 

on-going evaluation of this potential health consequence of ENDS use. 

No OH/F/Exp were reported in the PMTAs. However, the risk is still an issue 

regarding ENDS use overall. 

Therefore, to further monitor and evaluate potential ENDS health effects such as 

EVALI, seizures, and OH/F/Exp, medical recommends that post-market reporting 

include a specific plan to monitor respiratory-related illnesses, neurological 

symptoms, and AEs related to overheating and thermal burns associated with the 

products in the PMTAs. 

The Establishment Inspection Report (EIR) EX 33 reports only one verified case of a 

thermal burn which is described as a “blister” associated with use of Vuse Kit 

Original Solo 4.8% (RJRV-COMP-170669). No other cases of verified consumerreported physical thermal burns or inhalational aerosol injuries were reported for 

the new products. Generally, consumer complaints of “hot/excessive heat” 

appeared to be a subjective sensation of increased temperature rather than actual 

corporeal burn injuries requiring medical treatment or hospitalization. Although 

consumer-reported data suggest that the risk is low, there is still a potential risk of 

burns associated with use of ENDS. 

Synthesis 

Per the toxicology review, the new products’ aerosols are significantly less toxic than the 

combusted tobacco comparisons based on available nonclinical, HPHC, and BOE data. Per 

the BCP review, short-term (five days) switching from cigarette smoking to the new products 

resulted in significant reductions in the urinary and blood BOE. Per the medical review, the 

numbers of AEs were generally low and mostly mild and transient in short-term clinical 

studies. However, the applicant’s switching studies did not assess the effects of long-term 

use and the impact of dual use which would be more likely to occur in real-world conditions. 

There is limited data about the long-term health effects of ENDS from large clinical studies 

or long-term epidemiological studies. In addition, the study design limitations (e.g., small 

sample size, generally healthy participants, short exposure periods) in the published 

literature make it difficult to draw definitive conclusions related to health effects of ENDS, 

specifically the new products. Therefore, the long-term health effects and potential short 

and long-term health effects from dual use could not be evaluated. However, based on 

available information, I agree that adult smokers who switch to these products (either 

completely or with a significant reduction in cigarette consumption) would benefit from 

•

•

•

•
 

 

 

 

 

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reduced exposure to many HPHCs. While the effects of dual use were not assessed, 

significant reductions in systemic exposures after short-term switching and the available 

evidence suggest that daily use of the new products with concomitant reduction in CPD may 

provide health benefits from a harm reduction perspective in terms of reducing exposure to 

HPHCs relative to continued use of cigarette smoking alone. 

Although available data show low risk for adverse effects, I agree with the medical review 

that, for the marketed new products, post-market reporting is needed to further monitor 

and evaluate potential health effects including EVALI, seizures, and OH/F/Exp. 

I also agree with medical and BCP reviews that there are health risks for accidental exposure 

in children, but these risks are likely mitigated with the product design (i.e., closed system 

and authentication/memory chip). 

3.7. POPULATION AND PUBLIC HEALTH 

Discipline key findings 

The following discussion is based on the key findings provided in the epidemiology review: 

3.7.1.1. Population health impact (PHI) model 

  The applicant submitted a model that has been used previously to estimate the

population health effects of the new products. The limitations of the model include 

an approach known to overestimate actual use of the product (i.e., using likelihood 

of use data without comparison to prevalence data observed under real-world 

conditions), overestimate product switching due to lack of consideration for periods 

of sustained dual use, and overestimate the net population health effect in the 

event of a marketing authorization given the optimistic risk reduction estimates 

used in the main analysis (i.e., the assumption of a 95% lower excess relative risk 

compared to cigarettes). Although the model description is clear, the model inputs 

do not rely on actual product use from surveys or real-world prevalence data (vs. 

likelihood of product use employed by the applicant) and do not account for periods 

of dual use. Therefore, it does not help evaluate mortality rates and survival 

estimates and the potential public health impact. 

Synthesis 

I agree with the epidemiology review conclusion that the model does not raise concerns in 

terms of model structure or tobacco use transitions. However, given the limitations 

associated with the model inputs described in the epidemiology review, the model is not 

particularly informative in the evaluation of whether the new products are appropriate for 

the protection of the public health. 
 

 

 

 

 

 

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3.8. STATUTORY REQUIREMENTS 

Public health conclusion 

Based on the findings and evaluations discussed in Sections 3.1-3.7, I find that permitting 

the marketing of the new products in accordance with the requirements in the marketing 

granted orders is APPH. 

Tobacco product manufacturing practices 

The PMTAs contain sufficient information to characterize the products’ design and adequate 

processes and controls to help ensure that the products meet the manufacturer’s 

specifications. The methods used in, and the facilities or controls used for, the manufacture, 

processing, and packing of these products do not fail to conform to the requirements in 

Section 906(e) of the FD&C Act. 

Labeling 

For all PMTAs, the applicant provided labels that did not contain any false or misleading 

information. 

Product standards 

There are no applicable product standards for these PMTAs. 

4. ENVIRONMENTAL DECISION 

4.1. DISCIPLINE FINDINGS 

Environmental science concluded that the environmental assessments for all PMTAs contain 

sufficient information to determine whether the proposed actions may significantly affect the 

quality of the human environment. As TPL, I agree with this conclusion. 

4.2. ENVIRONMENTAL CONCLUSION 

A finding of no significant impact (FONSI) was signed by Luis G. Valerio, Jr. on October 8, 2021. 

The FONSI was supported by an environmental assessment prepared by the applicant on 

October 20, 2020. 

5. CONCLUSION AND RECOMMENDATION 

In making a determination about whether permitting the marketing of a product is APPH, Section 

910(c)(4) directs FDA to consider the risks and benefits to the population as a whole, including users 

and nonusers of tobacco, taking into account, among other things, the likelihood that those who do 

not use tobacco products will start using them. FDA’s scientific review is not limited to considering 

only information in a PMTA, but also extends to any other information before the Agency, including 

the relevant existing scientific literature (see Section 910(c)(2)). 

FDA’s evaluation of these PMTAs determined that there are adequate process controls and quality 

assurance procedures to help ensure both the device and e-liquids are manufactured consistently. 

Based on the information provided in the PMTAs, the abuse liability of the new products is lower 

than combusted cigarettes and is similar to, or lower than, that of other ENDS. The overall 

toxicological risk to the users of the new products is lower compared to cigarettes due to significant 

reductions in aerosol HPHCs of the new products’ compared to cigarettes and as evidenced by 
 

 

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results of nonclinical studies. Further, significant reductions in blood and urinary biomarkers of 

exposure (e.g., VOCs, TSNAs, and PAHs) indicate that exposure to carcinogens and other toxicants 

present in cigarette smoke was greatly reduced in smokers who switched completely to the use of 

the new products. In addition, current established cigarette users indicated the highest intentions 

to purchase among all groups, and the most preferred product among current established cigarette 

users was the tobacco (original) flavor. Therefore, the applicant has demonstrated the potential for 

these new products to benefit adult smokers. 

In terms of the risks to non-users, youth are considered a vulnerable population for various reasons, 

including that the majority of tobacco use begins before adulthood and thus youth are at particular 

risk of tobacco initiation. Existing evidence consistently indicates that use of tobacco flavored ENDS 

is less common than non-tobacco flavored ENDS among youth. Nonetheless, given the strong 

evidence regarding the impact of youth marketing exposure to youth appeal and initiation of 

tobacco use, a marketing authorization should include postmarket requirements to help ensure that 

youth exposure to tobacco marketing is limited. In addition, the applicant’s study findings 

demonstrated low intention to purchase the new products among adult never and former 

established tobacco users. Together, based on the information provided in the PMTAs and the 

available evidence, the potential to benefit smokers who switch completely or significantly reduce 

their cigarette use would outweigh the risk to youth, provided the applicant follows post-marketing 

requirements aimed at reducing youth exposure and access to the products. 

. However, the applicant did not provide microbial data that would allow FDA to evaluate 

whether the products are microbially stable over . The applicant instead provided data 

that supports microbial stability of the products over . Because the microbial stability 

data for is acceptable and indicates that the products are low-risk for microbial growth 

over a h period and because there are no other stability concerns, the lack of microbial data 

for does not preclude an APPH finding for the products. 

Regarding product stability, the applicant stated that the shelf life of the new products is 

(b) (4)

The applicant provided chemistry data to support that the new products are chemically stable over 

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

Based on my review of your PMTAs, I find that permitting the marketing of the new products, as 

described in the applications and specified in Appendix, Table 3, is appropriate for the protection of 

the public health. The issuance of these marketing granted orders confirms that you have met the 

requirements of section 910(c) of the FD&C Act and authorizes marketing of your new products. 

Under the provisions of section 910, you may introduce or deliver for introduction into interstate 

commerce the products, in accordance with the marketing order requirements outlined in 

marketing granted orders. 

FDA has examined the environmental effects of finding the new products APPH and made a Finding 

of No Significant Impact (FONSI). 

Marketing granted orders should be issued for the new products subject to this review, as identified 

on the cover page of this review. 
 

 

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PM 0000551, PM0000553, PM0000560 

7. APPENDIX 

Table 3. New tobacco products subject to Granted Orders 

Common Attributes of PMTA 

Submission date October 10, 2019 

Receipt date October 17, 2019 

Applicant R.J. Reynolds Vapor Company 

Product manufacturer R.J. Reynolds Vapor Company 

Product category ENDS (VAPES) 

Attributes6 New Tobacco Product 

STN PM0000SSl 

Product name Vuse Solo Power Unit7 

Product Sub-Category ENDS Component 

Package type Paperboard Carton 

Package quantit y 1 Power Unit 

Characterizing flavors None 

Additional properties Length: 87 mm 

Diameter: 9.6 mm 

Battery capacity: 2: 270 milliAmpere hours (mAh) 

Wattage: 3.00 W 

Universal Serial Bus (USS) charger 

STN PM0000553 

Product name Vuse Replacement Cartridge Original 4.8% Gl7 

Product Sub-Category Closed E-cigarettes 

Package type Paperboard Carton/ Blister Pack 

Package quantit y 2 Cart ridges 

Characterizing flavor Original 

Nicotine Concentration 57.4 mg/ ml 

E-liquid Volume 0.5 ml/ cartridge 

PG/VG Ratio 21/ 79 

Additional Properties Length: 37.6 mm 

Diameter: 9.6 mm 

Gl Tube Material: Stainless Steel 

STN PM0000560 

Product name Vuse Replacement Cartridge Original 4.8% G27 

Product Sub-Category Closed E-cigarettes 

Package type Paperboard Carton/ Blister Pack 

Package quantity 2 Cartridges 

Characterizing flavor Original 

Nicotine Concentration 57.4 mg/ ml 

6 We interpret package type to mean container closure system and package quantity to mean product quantity within the 

container closure system, unless otherwise identified. 

7 Brand/sub-brand or other commercial name used in commercial distribution. The Vuse Solo "Original" e-liquid is a tobacco 

flavored e-liquid. 

8 Provided as part of product labeling 
TPL Review of PMTAs: Page 34 of 34 

PM 0000551, PM0000553, PM0000560 

E-liquid Volume 0.5 ml/ cartridge 

PG/VG Ratio 21/ 79 

Additional Properties Length: 37.6 mm 

Diameter: 9.6 mm 

G2 Tube Material{{5) (~) I 

Table 4. Amendments received 

Submission Receipt Amendment Applications Reviewed Brief Description 

Date Date being 

amended 

December December PM0000582 All STNs Yes Response to December 12, 

23, 2019 23, 2019 2019, Inspection Request 

Letter 

November November PM0004236 All STNs Yes Response to May 19, 2020, 

10, 2020 10, 2020 Deficiency letter