U.S. Food & Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993 

www.fda.gov

MODIFIED RISK GRANTED ORDERS– EXPOSURE MODIFICATION

22nd Century Group Inc. 

Attention: Karen E. Delaney, Program Manager

8560 Main Street, Suite 4

Williamsville, NY 14221

FDA Submission Tracking Numbers (STNs): MR0000159-MR0000160, see Appendix A

Dear Karen Delaney: 

We completed review of your MRTPAs1 and are issuing modified risk granted orders for the tobacco 

products identified in Appendix A. 

Based on our review of your MRTPAs, we determined that the proposed modified risk tobacco

products, as described in your applications and specified in Appendix A, have satisfied the 

requirements of section 911(g)(2)(A) and (B), including that they are appropriate to promote the 

public health and are expected to benefit the health of the population as a whole taking into 

account both users of tobacco products and persons who do not currently use tobacco products. 

We authorize marketing of the tobacco products as modified risk tobacco products with reduced 

exposure claims, including2

: 

1. “95% less nicotine”

2. “Helps reduce your nicotine consumption”

3. “...greatly reduces your nicotine consumption”

Where any of the reduced exposure claims listed in Appendix A are used in the product label, 

labeling, or advertising (LLA), under section 911(h)(1) and 911(h)(3)(B), this order requires that the 

LLA must also include the following condition of use: “Helps you smoke less.” Additionally, we 

recommend that the LLA include the disclaimer:

3 “Nicotine is addictive. Less nicotine does NOT 

mean safer. All cigarettes can cause disease and death.”

Under the provisions of section 911, you may introduce or deliver for introduction into interstate 

commerce the modified risk tobacco products, in accordance with this exposure modification order. 

Under section 911(g)(2)(C)(ii), this order is conditioned on your agreement to conduct postmarket 

surveillance and studies (PMSS) in accordance with a protocol approved by FDA and to submit the 

results of such PMSS annually. See Appendix B for information on required PMSS. This order also 

1 Modified Risk Tobacco Product Applications (MRTPAs) submitted under section 911(d) of the Federal Food, Drug, and 

Cosmetic Act (FD&C Act). 2 See Appendix A for additional claims. 

3 In your MRTPAs, you refer to the statement, “Nicotine is addictive. Less nicotine does NOT mean safer. All cigarettes can cause 

disease and death.” variously as a “disclaimer” (Section V “Labels, Labeling, and Advertising,” p. 3; Section VII “Summary of All 

Research Findings,” p. 72) and “voluntary warning” (Section V “VLNTM Cigarettes: Labels, Labeling, and Advertising,” pp. 2, 8-9). 

In this order, the word “disclaimer” refers to your use of this term and does not reflect FDA’s independent conclusion regarding 

characterization of the information. 
MR0000159-MR0000160, see Appendix A Page 2 of 14 

includes requests related to other record retention and reporting, as outlined in all attached 

appendices.

This order expires five years from the issue date of this letter. If you wish to renew your order, we 

recommend a request for renewal is received by FDA at least 360 days prior to the expiration date. 

Your renewal may cross-reference your MRTPAs that are subject to these orders. 

The requirements in this exposure modification order are intended to help ensure that your modified 

risk tobacco products will continue to satisfy the requirements of section 911(g)(2)(A) and (B). 

However, compliance with these requirements alone is not a guarantee that the modified risk

tobacco products will continue to be appropriate to promote public health and continue to be 

expected to benefit the health of the population as a whole, particularly if, despite these measures, 

there is a significant increase in youth initiation or initiation by non-users. FDA will continue to 

monitor the marketing of your products and their impact on the population. 

This order authorizing the marketing of these modified risk tobacco products does not mean FDA

“approved” the products specified in Appendix A; therefore, you may not make any express or 

implied statement or representation directed to consumers that conveys, misleads, or would mislead 

consumers into believing, among other things that the modified risk tobacco products specified in 

Appendix A, are “approved” by FDA (see Section 301(tt) of the FD&C Act). Moreover, because these 

products have not been authorized under section 911(g)(1) (risk modification order), you may not 

market these products with reduced risk claims.

The exposure modification order under 911(g)(2), that these modified risk tobacco products are

subject to, is subject to withdrawal as described in section 911(j) of the FD&C Act.

We remind you that the modified risk tobacco products specified in Appendix A are subject to 

the requirements of the associated December 17, 2019 PMTA order and appendices, FD&C Act, 

and its implementing regulations, and Federal Cigarette Labeling and Advertising Act (15 U.S.C. 

1333). It is your responsibility to ensure the tobacco products specified in Appendix A comply

with all applicable statutory and regulatory requirements. FDA will monitor your compliance 

with all applicable statutes and regulations.

In accordance with 40 CFR 1506.6, we will make your Environmental Assessment (EA) publicly 

available.

. 
MR0000159-MR0000160, see Appendix A Page 3 of 14 

We encourage you to submit all regulatory correspondence electronically via the CTP Portal4,5 using 

eSubmitter.6 Alternatively, submissions may be mailed to:

Food and Drug Administration

Center for Tobacco Products

Document Control Center (DCC)

Building 71, Room G335

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

The CTP Portal and FDA’s Electronic Submission Gateway (ESG) are generally available 24 hours a day,

seven days a week; if the upload is successful, submissions are considered received by DCC on the day of 

upload. Submissions delivered to DCC by courier or physical mail will be considered timely if received

during delivery hours on or before the due date7

; if the due date falls on a weekend or holiday, the

delivery must be received on or before the preceding business day. We are unable to accept regulatory

submissions by e-mail. 

If you have any questions, please contact Kristopher Van Amburg, Regulatory Health Project Manager, at 

(301) 348-3032 or Kristopher.VanAmburg@fda.hhs.gov.

If you have any questions regarding postmarket activities for the tobacco products subject of these

orders, please contact Michael Gu, Acting Director, Division of Enforcement and Manufacturing, at CTPOCE-Postmarket@fda.hhs.gov. 

Sincerely,

/S/

Matthew R. Holman, Ph.D.

Director

Office of Science

Center for Tobacco Products

Enclosures:

Appendix A – Tobacco Products Subject of This Letter

Appendix B – Postmarket Surveillance and Studies 

Appendix C – Recordkeeping and Retention

Appendix D – Manufacturing Information

4 https://www.fda.gov/tobacco-products/manufacturing/submit-documents-ctp-portal 5 FDA’s Electronic Submission Gateway (ESG) is still available as an alternative to the CTP Portal. 6 https://www.fda.gov/industry/fda-esubmitter 7 https://www.fda.gov/tobacco-products/about-center-tobacco-products-ctp/contact-ctp
MR0000159-MR0000160, see Appendix A Page 4 of 14 

Appendix A8

8

Tobacco Products Subject of This Letter 

 Common Attributes of MRTPAs

Submission date May 17, 2019

Receipt date May 20, 2019

Applicant 22nd Century Group Inc.

Product Manufacturer NASCO Products LLC

Product Category Cigarettes

Product Sub-Category Combusted, Filtered 

Product order under 911(g) 911(g)(2) Exposure Modification Order

Reduced Exposure Claims • “95% less Nicotine

• “Helps reduce your nicotine consumption”

• “...greatly reduces your nicotine consumption”

• “VLNTM cigarettes are substantially lower in nicotine content than any 

other cigarettes currently available to smokers in the United States. 

VLNTM cigarette contain an average of just 0.27 mg of nicotine.” 

• “Without exception, VLNTM cigarettes contain at least 95% less 

nicotine than the top 100 cigarette brands in the United States.” 

• “22nd Century's VLNTM cigarettes contain an average of 0.27 mg 

nicotine - -at least 95% less nicotine compared to conventional 

cigarettes.” 

• “22nd Century's VLNTM cigarettes feature the same nicotine content 

as the lowest nicotine style of the Company's SPECTRUM research 

cigarettes."

• “VLNTM cigarettes contain 0.27 ± 0.1 mg nicotine.” 

• “As a result of our unique technology and plant breeding expertise, 

VLNTM tobacco grows with 95% less nicotine than conventional 

tobacco.” 

• Graph depicting nicotine levels of VLNTM cigarettes compared to 

several other cigarette brands. 

Attributes Tobacco Product

MR0000159: VLNTM King

Package type Hard Pack

Package quantity 20 Cigarettes

Characterizing flavor None

Length 83 mm

Diameter 7.9 mm 

Ventilation 13 %

MR0000160: VLNTM Menthol King

Package type Hard Pack

Package quantity 20 Cigarettes

Characterizing flavor Menthol

Length 83 mm

Diameter 7.9 mm 

Ventilation 13 %

8 Brand/sub-brand or other commercial name used in commercial distribution.
MR0000159-MR0000160, see Appendix A Page 5 of 14 

8 
MR0000159-MR0000160, see Appendix A Page 6 of 14 

Appendix B

Postmarket Surveillance and Studies (PMSS) 

Under Section 911(g)(2)(C)(ii) of the FD&C Act, an order under 911(g)(2) is conditioned on the 

applicant’s agreement to conduct postmarket surveillance and studies in order to “determine the 

impact of the order on consumer perception, behavior, and health, and to enable the [FDA] to review 

the accuracy of the determinations upon which the order was based in accordance with a protocol 

approved by the [FDA].” 

I. PMSS Content

MRTP Use Behavior and Consumer Understanding and Perception

After receiving authorization, the determination of whether the tobacco products, which are the subject 

of this order, continue to satisfy the requirements of section 911(g)(2)(A) and (B), is driven, in part, by 

use behavior. 

Your proposed postmarketing surveillance and studies (PMSS) include a 6-month cross sectional study 

(n=1,000) to assess product knowledge, use, and attitudes among people who started smoking VLNTM 

cigarettes within the past 6 months (Section X “Postmarket Surveillance Program,” pp. 5-6). Primary 

objectives of the study would be to assess VLNTM product knowledge, use patterns, and demographic 

characteristics of VLNTM smokers (age, gender, ethnicity, three-digit zip code). Secondary objectives 

would be to assess the use of other tobacco products at the time of initiation of VLNTM cigarettes, 

describe how users learned about VLNTM cigarettes, and describe personal factors motivating initiation 

of VLNTM cigarette use. You also propose to recruit a subset of the cross-sectional study participants into 

a longitudinal study that would evaluate reductions in cigarette use among VLNTM smokers prospectively 

over a 12-month period. We agree with the constructs you propose to assess in your 6-month crosssectional study (e.g., knowledge of VLNTM’s product features – including understanding of the health 

risks associated with various patterns of use – as well as demographic characteristics and current, 

previous, and subsequent use patterns with VLNTM and other cigarettes). In your longitudinal study, 

monitoring use of the products that are the subject of this order in terms of uptake, dual use, and 

complete switching is required. In particular, your PMSS must assess the extent to which new MRTP 

users were never, former, or current smokers, or other tobacco product users before initiating the 

MRTPs and the extent to which new users of the MRTPs become exclusive VLNTM cigarette users, dual 

users with combusted cigarettes or other tobacco products, or transition to normal nicotine content 

(NNC) cigarette smoking over time. These studies must be designed to observe behavior over a 

sufficient period of time to examine, for instance, the extent to which dual use of VLNTM cigarettes and 

combusted cigarettes is a transitional versus stable pattern of use. 

Your studies must also include an assessment of consumers’ understanding of the modified risk claims 

and perceptions of the products. In particular, PMSS must assess the extent to which users of these 

products understand that VLNTM cigarettes are just as toxic as other cigarettes when used in the same 

way (i.e., with the same frequency and for the same duration). Additionally, you must assess the extent 

to which VLNTM cigarette users understand that to get long-term benefits, they have to use VLNTM 

cigarettes to substantially reduce the amount of cigarettes that they smoke. Thus, you must assess 

whether current smokers who take up VLNTM understand that they should cut down on their overall 

cigarette smoking and that replacing their other cigarettes with VLNTM without substantially cutting 

down is not sufficient to yield long-term benefits. 
MR0000159-MR0000160, see Appendix A Page 7 of 14 

Your studies must have clear research objectives, including assessing whether the MRTPs are leading to 

changes in product use behaviors that are expected to benefit population health. Your protocol must 

include a statistical analysis plan describing, among other things, how you plan to conduct inferential 

statistical analyses to address these objectives. 

Your PMSS must also include a postmarket study testing the effects of the disclaimer10 (“Nicotine is 

addictive. Less nicotine does NOT mean safer. All cigarettes can cause disease and death.”) on consumer 

understanding of VLNTM cigarettes’ health risks and conditions of use. The disclaimer has several features 

that are inconsistent with expert recommendations for designing disclaimers, and poorly designed 

disclaimers have the potential to confuse consumers and change their perceptions, attitudes, or 

decisions in a manner opposite of that intended (Green & Armstrong, 2012). Conducting a postmarket 

study to test the disclaimer can provide FDA with evidence about whether the disclaimer helps enable 

consumers to understand that VLNTM cigarettes present the same disease risks as other cigarettes if 

smoked in the same way, or if it worsens existing misperceptions about the health risks of cigarettes 

containing reduced nicotine levels. If FDA determines that the disclaimer causes such misperceptions, 

then FDA will require that you remove the disclaimer from the modified risk labels, labeling and 

advertising and any advertising where it is included. 

FDA also recommends that, if you seek to use any modified risk ads that are potentially youth-appealing, 

then you should conduct consumer testing of the ads to determine whether they would increase the 

likelihood of use among nonsmokers, particularly minors (under age 21). For example, FDA found that 

some of the original advertising submitted with these applications contained potentially youth appealing 

imagery. Although you subsequently withdrew it from the MRTPAs, this is an example of advertising that 

FDA has concerns about and we suggest that if you seek to use ads that are potentially youth appealing, 

then you first study them to determine the effect on initiation by non-users, particularly youth; imagery 

and themes known to resonate with youth include aspirational content depicting tobacco use as “cool,” 

attractive, rebellious, or risky, or as a means to make one more popular, desirable, or independent (U.S. 

Department of Health and Human Services, 2012). 

In addition, FDA has determined that assessing the impact of your MRTP orders on uptake of the 

products requires surveillance of MRTP sales and distribution, which provide information to assess 

tobacco consumption at the population level. Your PMSS protocols must describe procedures for 

monitoring and reporting MRTP sales and distribution in the U.S. by product, major metropolitan areas, 

and channels where the products are sold (e.g., convenience stores, food and drug stores, internet and 

digital retailers, tobacco specialty shops). Your annual PMSS report must include:

• U.S. sales and distribution of the tobacco products by quarter since the date of issuance of your 

modified risk granted orders (for the initial reporting period) or the previous reporting period 

(for all reports that follow), including, for each MRTPA STN, total U.S. sales and distribution 

reported in dollars and units, and broken down by major metropolitan areas, and channels 

where the products were distributed and sold during the reporting period (e.g., convenience 

stores, food and drug stores, internet and digital retailers, tobacco specialty shops).

• A brief synthesis and summary of the sales and distribution data for the initial reporting period 

or the previous reporting period (for all reports that follow), including annual and quarterly 

10 In your MRTPAs, you refer to the statement, “Nicotine is addictive. Less nicotine does NOT mean safer. All cigarettes can 

cause disease and death.” variously as a “disclaimer” (Section V “Labels, Labeling, and Advertising,” p. 3; Section VII “Summary 

of All Research Findings,” p. 72) and “voluntary warning” (Section V “VLNTM Cigarettes: Labels, Labeling, and Advertising,” pp. 2, 

8-9). In this order, the word “disclaimer” refers to your use of this term and does not reflect FDA’s independent conclusion 

regarding characterization of the information. 
MR0000159-MR0000160, see Appendix A Page 8 of 14 

growth rate (percent change) in total U.S. sales and distribution of the tobacco products for 

each MRTPA STN, post-MRTP authorization. 

MRTP Use and Health Risk – Serious and Unexpected Adverse Experiences

In order for FDA to determine whether the tobacco products that are the subject of this order continue 

to be appropriate to promote the public health and continue to be expected to benefit the health of the 

population as a whole taking into account both users of tobacco products and persons who do not 

currently use tobacco products (section 911(g)(2)(A-B)), your PMSS must include ongoing surveillance of 

all adverse experiences including those that are both serious and unexpected associated with the use of 

the MRTPs. These experiences may become known to you through any source, including a customer 

complaint, request, or suggestion made as a result of an adverse experience; or tobacco product defect, 

or failure, reported to you, or identified in the literature or media. Your PMSS protocols must include 

procedures for monitoring and analyzing adverse experiences and your annual PMSS report must 

include: 

• A summary of reported serious and reported unexpected adverse experiences for the tobacco 

products, which includes a listing of all serious and unexpected adverse experiences during the 

reporting period and a cumulative list including all serious and unexpected adverse experiences 

previously reported. The summary must be accompanied by an analysis of the reports and a 

statement of any changes to risk information related to the products including nature, 

frequency, and potential aggravating factors. 

In addition, the PMTA order for your tobacco products, issued on December 17, 2019, requires you to 

report to the FDA all adverse experiences that are serious, whether expected or unexpected, and your 

analysis of the association between the adverse experience and the tobacco product within 15 calendar 

days after the report is received by you. These experiences may become known to you through any 

source, including a customer complaint, request, or suggestion made as a result of an adverse 

experience, tobacco product defect, or failure, reported to you, or identified in the literature or media. 

We request that when submitting such reports, you reference both your PMTAs and your MRTPAs for 

these products. Your information should be submitted with a cover letter that includes the following 

text in the subject line: SERIOUS ADVERSE EXPERIENCE REPORT FOR STNs PM0000491-PM0000492 and 

MR0000159-MR0000160. 

For purposes of this reporting, serious adverse experience means an adverse experience that results in 

any of the following outcomes: 

• Death; 

• A life-threatening adverse event; 

• Inpatient hospitalization or prolongation of existing hospitalization; 

• A persistent or significant incapacity or substantial disruption of the ability to conduct normal 

life functions; 

• A congenital anomaly/birth defect; or 

• Any other adverse experience that, based upon appropriate medical judgment, may jeopardize 

the health of a person and may require medical or surgical intervention to prevent one of the 

other outcomes listed in this definition. 

For purposes of this reporting, unexpected adverse experience means an adverse experience occurring in 

one or more persons in which the nature, severity, or frequency of the experience is not consistent with: 
MR0000159-MR0000160, see Appendix A Page 9 of 14 

• The known or foreseeable risks associated with the use or exposure to the tobacco product as 

described in the PMTA (including the results of human subject investigations) and other relevant 

sources of information, such as postmarket reports and studies; 

• The expected natural progression of any underlying disease, disorder, or condition of the 

person(s) experiencing the adverse experience and the person’s predisposing risk factor profile 

for the adverse experience; or 

• The results of nonclinical laboratory studies. 

Surveillance of New Research Study Findings on the MRTPs and Consumer Perception, Behavior, or 

Health 

In order for FDA to determine whether the tobacco products that are the subject of this order continue 

to be appropriate to promote the public health and continue to be expected to benefit the health of the 

population as a whole, your PMSS must include surveillance of new research study information about 

the MRTPs and consumer perceptions, behavior, or health. In particular, your PMSS protocol must 

include procedures for monitoring and assessing previously unreported (new) findings both in published 

or unpublished studies conducted by you or on your behalf and in published or otherwise available 

studies regarding the MRTPs and consumer perceptions, behavior, or health. Your annual PMSS report 

must include: 

• A summary of significant findings about the tobacco products from research studies conducted 

by you or on your behalf, whether or not such studies were specifically required under this 

order. 

• A summary of significant findings in publications not previously reported and full copies of the 

articles. These must include any new scientific data (published or otherwise) on the MRTPs and 

consumer perception, behavior, or health. 

Modeling the Impact of the MRTP on Population Health

In order for FDA to determine whether the tobacco products that are the subject of this order continue 

to be appropriate to promote the public health and continue to be expected to benefit the health of the 

population as a whole, your PMSS must include computational modeling of the impact of the MRTPs on 

population health. Such modeling must incorporate data and information collected through PMSS, 

including the percentage of former smokers who start using VLNTM cigarettes; the percentage of current 

smokers who start using VLNTM cigarettes and become dual users; the percentage of current smokers 

who switch completely to VLNTM cigarettes; the percentage of youth and young adults under the federal 

minimum age of sale who start using VLNTM cigarettes; and the percentage of individuals who start using 

VLNTM cigarettes and then initiate or re-initiate NNC combusted cigarettes. Postmarket modeling must 

also incorporate the latest information on acute and long-term health effects of using the proposed 

MRTPs relative to NNC combusted cigarette smoking in order to assess the short and long-term 

population health impacts of the marketing. Your annual PMSS report must include:

• A description of the methodological approach used in the model;

• A copy of the model or its underlying code, such that FDA can independently run and verify the 

model inputs and outputs;

• A description of all model inputs, including the justification for input values and how they were 

derived from postmarket data and information; and

• A summary of the modeling results and their implications for assessing whether the MRTPs 

continue to be appropriate to promote the public health and continue to be expected to benefit 

the health of the population as a whole.
MR0000159-MR0000160, see Appendix A Page 10 of 14 

II. Submitting PMSS Protocols and Reports

As required under section 911(g)(2)(C)(ii) of the FD&C Act, your modified risk order is conditioned on 

your agreement to conduct PMSS under an approved protocol, and to submit the results for FDA to 

determine the impact of the order and review the accuracy of determinations on which the order is 

based. Within 30 days of receiving this notice, you must submit your agreement to conduct PMSS and 

complete protocols for your PMSS. Label your submission clearly as a “PMSS Protocol” and reference 

your MRTPA Submission Tracking Numbers (STNs). If you have more than one protocol, each protocol 

should be a separate submission. If applicable, each protocol should include the name(s) of the principal 

investigator(s) and materials that demonstrate the relevant professional credentials and training that 

qualify them to lead the study. Within 60 days of receipt of the protocol(s), FDA intends to review the 

protocol(s) and evaluate if the principal investigator proposed to be used in the surveillance has 

sufficient qualifications and experience to conduct the surveillance and if the protocol(s) will result in 

collection of data or other information that has the potential to enable FDA to accurately determine the 

impact of the order on consumer perception, behavior and health and to review the accuracy of the 

determinations upon which the order was based, pursuant to section 911(g)(2)(C)(ii) of the FD&C Act. 

FDA will notify you of, and provide opportunities to address, any deficiency in the submission. If the 

PMSS protocol is amended subsequent to FDA approval, FDA must receive the amended protocol 

promptly. For protocol amendments that are administrative in nature (e.g., corrections in punctuation 

or titles), the amended protocol must be received by FDA within 30 days of the update. For protocol 

amendments that seek to modify the study design (including endpoints, sites, questionnaires, 

methodology, etc.) or other scientific parameters, you may not initiate the change until you receive FDA 

approval.

As part of the requirement to conduct PMSS, you must initiate and conduct your PMSS per the 

timeframes established in your protocols and approved by FDA. Note that for PMSS that involve human 

subjects, the anticipated start date for each study must account for the time required for securing IRB 

approval, as needed. In addition to specifying the start date, your protocols must contain timelines for 

completion of major study milestones including, as applicable, the start and completion of participant 

recruitment, initiation of data collection (per wave, if applicable), completion of data collection, analysis, 

and report writing. If you deviate from these timelines, we request that you report the deviation within 

30 days to FDA.

Section 911(g)(2)(C)(iii) requires that the results of the PMSS be submitted on an annual basis. These 

reports must be identified as “PMSS Report” and the MRTPA STNs should be referenced for each report. 

The PMSS Report must indicate the beginning and ending date of the period covered by the report and 

must include accomplishments since the last reporting period. For quantitative updates on studies in 

progress (e.g., participant accrual), reports should describe both interim (since the last reporting period) 

as well as cumulative (since study initiation) accomplishments. The PMSS Report describing studies in 

progress must describe the status of PMSS, including, as applicable, the status of recruitment, data 

collection, and analysis; a summary of the study milestones achieved and any deviations from the 

approved timelines in the protocol; a summary of protocol amendments; and a summary of any 

preliminary analyses conducted. Once a study is completed, the PMSS Report should include the 

complete final study report.
MR0000159-MR0000160, see Appendix A Page 11 of 14 

Appendix C

Recordkeeping and Retention

The exposure modification order for your modified risk tobacco products is effective for five years form

the issue date of the order. If you wish to renew your order, we recommend you submit a request for

renewal 360 days prior to the end of your effective timeframe. In order to help ensure that your

exposure modification order meets the standard for renewal and to help expedite the review of any

renewal applications, we request that you establish and maintain the records listed below. The records

should be retained for a period of not less than four years from the date of distribution of the last batch

of the tobacco products listed in your orders under section 911(g)(2). The records should be legible,

written in English, and available for inspection and copying by officers or employees duly designated by

the Secretary upon request. Please note that Appendix B requires you to periodically submit some of

these records to FDA (e.g., in PMSS reports). Additionally, we remind you that the PMTA order for your

tobacco products issued on December 17, 2019, also requires you to establish and maintain records,

some of which overlap with the records listed below: 

• The MRTPAs submitted prior to the orders

• Postmarket reports, as described in Appendix B, and adverse experience reports, including all

relevant documentation associated with the experience

• Records of all nonclinical or clinical studies, including:

o Source data;

o Study protocols (including statistical analysis plan);

o Amendments showing the dates and reasons for any protocol revisions;

o Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approvals or nonapprovals;

o Informed consent forms;

o Correspondence with study monitors/investigators/contract research

organizations/sponsors/IRB/IEC;

o Investigator financial disclosure statements;

o Progress reports;

o Monitoring reports;

o Adverse experience reports;

o Case report forms/subject diaries/medical records/laboratory reports;

o Subject data line listings/observation records;

o Test article accountability records;

o Study results/protocol summaries/study reports; and

o Certifications and amendments to certifications

• Records pertaining to the manufacture, in process and release testing, production process 

(including any changes to the process, facility, or controls), packaging, storage, and stability 

monitoring and testing (including protocol and results) of the products

• Records pertaining to the sale, distribution, or other disposition of the products, specifically:

o A list of distributors and retailers of the products, including brick-and-mortar and digital. For 

the purposes of this order, here and throughout the document, “digital” includes 

internet/online and mobile; 

o Any available information (not to include personally identifiable information) about product 

purchases, such as purchasers’ demographics (e.g., age, gender, race/ethnicity, geographic 

region) and previous or current use of other tobacco products (i.e., dual use); 

o With respect to individuals under the federal minimum age of sale of tobacco products, 

policies and procedures regarding restrictions on access to the products, including purchaser 

age and identity verification processes
MR0000159-MR0000160, see Appendix A Page 12 of 14 

• Records pertaining to the products’ labeling, advertising, marketing, and/or promotion – 

whether conducted by you, on your behalf, or at your direction – including: 

o Specimens of all labeling (including all labeling variations, such as those reflecting different 

required warnings), labels, inserts/onserts, instructions, and other accompanying 

information;

o Copies of all advertising, marketing, and/or promotional materials published, disseminated 

to consumers, or for use in engaging or communicating with consumers;

o Copies of any formative research studies conducted among any audiences in the formation 

of the labeling, advertising, marketing, and/or promotional materials, including qualitative 

and quantitative research studies used to determine message effectiveness, consumer 

knowledge, attitudes, beliefs, intentions, and behaviors toward using the products, and 

including copies of the stimuli used in testing;

o Copies of any consumer evaluation research studies conducted among any audiences to 

determine the effectiveness of labeling, advertising, marketing, and/or promotional 

materials and any shifts in consumer knowledge, attitudes, beliefs, intentions, and behaviors 

toward using the products, and including copies of the stimuli used in testing;

o Copies of any contractual agreements regarding the creation and/or dissemination of the 

products’ labeling, advertising, marketing, and/or promotional materials, including for 

example, in print media, online or through digital platforms (e.g., social media and mobile 

applications), such as influencers, bloggers, and ambassadors, on your behalf, or at your 

direction; 

o Copies of all advertising and marketing plans, including strategic creative briefs and paid 

media plans, by channel and by product, and the dollar amount(s) and flighting of such 

plans, by channel and by product, including any:

 Use of competent and reliable data sources, methodologies, and technologies to 

establish, maintain, and monitor highly targeted advertising and marketing plans and 

media buys, including a list of all data sources used to target advertising and marketing 

plans and media buys; 

 Targeting of specific adult audiences by age-range(s), including young adults, ages 21-

24, and other demographic and/or psychographic characteristics that reflect your 

intended target audience;

 With respect to individuals under the federal minimum age of sale of tobacco products, 

actions taken to restrict access to the product and limit exposure to the products’ 

labeling, advertising, marketing, and/or promotion; 

 Use of owned, earned, shared, and/or paid social media to create labeling for, advertise, 

market, and/or promote the product;



 Use of partners, influencers, bloggers, and/or brand ambassadors to create labeling for, 

advertise, market, and/or promote the product; 

 Consumer engagements – whether conducted by you, on your behalf, or at your 

direction – including events at which the products were demonstrated and how access 

will be restricted to individuals at or above the federal minimum age of sale of tobacco 

products; or

 Use of public-relations or other communications outreach to create labeling for, 

advertise, market, and/or promote the products; 

o Copies of all records pertaining to the actual delivery of advertising impressions, including 

media tracking and optimization, by channel, by product (if applicable), by program (where 

applicable), and by audience demographics (e.g., age, gender, race/ethnicity, geographic 

region), media buy summaries, program lists, number of units by program, percent audience 

compositions by age breakouts (i.e., 21+, 2-11, 12-17, 18-24, 25-54, 55+) by program, 
MR0000159-MR0000160, see Appendix A Page 13 of 14 

audience indices by age breakouts (i.e., 2-11, 12-17, 18-24, 25-54, 55+) by program, reach 

and frequency, any other parameters purchased against the buying demographics, and all 

post-launch delivery-verification reports for other paid media submitted to you or entities 

working on your behalf or at your direction from an accredited source; and 

o Policies and procedures for real-time digital media monitoring to identify, correct, and 

prevent delivery of advertising impressions to individuals under the federal minimum age of 

sale of tobacco products, including documentation of such monitoring activities and 

implementation of corrective and preventive measures

• Health hazard analyses, if performed voluntarily or directed by FDA

• Records pertaining to any and all complaints associated with any of the products that you 

receive or of which you are aware; such records may also include your analysis of those 

complaints
MR0000159-MR0000160, see Appendix A Page 14 of 14 

Appendix D

Manufacturing Information

The PMTA order for your tobacco products, issued on December 17, 2019, requires you to report to the 

FDA manufacturing information. We request that when submitting such reports, you reference both 

your PMTA and your MRTPA for the product. When cross-referencing, please provide the date of 

submission and location in the submission where the information is covered.

For each twelve-month reporting period, the annual reports should include:

• A cover letter that includes the following text in your subject line: ANNUAL REPORT for 

PM0000491-PM0000492 and MR0000159-MR0000160. The cover letter should include the 

STN(s), static product ID if applicable, and corresponding tobacco product name(s), firm name, 

date of report, reporting period.

• A description of each change made to the manufacturing process, facilities, or controls during 

the reporting period including:

 A comparison of each change to what was described in the PMTA/MRTPA;

 The rationale for making each change; and

 A certification that the reported change did not result in any modification (including a 

change in design, any component, any part, or any constituent, including a smoke or aerosol 

constituent, or in the content, delivery, or form of nicotine, or any other additive or 

ingredient) of the tobacco products and the basis for concluding that each manufacturing 

change did not result in any modification to the products.11

• A summary of all manufacturing deviations, investigations, and corrective and preventive 

actions, including, but not limited to, those deviations associated with processing, testing, 

packing, labeling, storage, holding, and distribution and indicate any deviation(s) that may affect 

the characteristics of the products. For additional information on manufacturing deviations, see 

below.

Manufacturing Deviations

You should promptly investigate all manufacturing deviations including, but not limited to, those 

associated with processing, testing, packing, labeling, storage, holding, and distribution. The PMTA order 

for your tobacco product, issued on December 17, 2019, requires that, for products that have been 

distributed, if a deviation occurs that you determine presents a reasonable probability that the tobacco 

product contains a manufacturing or other defect not ordinarily contained in tobacco products on the 

market that would cause serious, adverse health consequences or death you are required to report the 

deviation to FDA within 15 calendar days of identification. We request that when submitting such 

reports, you reference both your PMTA and your MRTPA for the product.

Discontinuation and Reintroduction 

If you discontinue the manufacture, preparation, compounding, or processing for commercial 

distribution of the modified risk tobacco product and later decide to reintroduce the modified risk 

tobacco product into the market, please contact the Office of Compliance and Enforcement prior to 

reintroduction. Section 905(i)(3) of the FD&C Act requires you to update your product listing biannually 

to reflect any products that have been discontinued and/or reintroduced into interstate commerce.

11 We note that any modifications made to a tobacco product that render it a new tobacco product are subject to

the premarket review requirements under section 910 of the FD&C Act.