Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 1 of 10 PageID# 28134
`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 1 of 10 PagelD# 28134
`
`EXHIBIT A
`EXHIBIT A
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 2 of 10 PageID# 28135
`
`Enforcement Priorities for
`Electronic Nicotine Delivery
`Systems (ENDS) and Other
`Deemed Products on the Market
`Without Premarket
`Authorization (Revised)*
`
`Guidance for Industry
`
`Comments may be submitted at any time for Agency consideration. Electronic comments may be
`submitted to https://www.regulations.gov. Alternatively, submit written comments to the
`Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
`Room 1061, Rockville, MD 20852. All comments should be identified with docket number
`FDA-2019-D-0661.
`
`For questions regarding this guidance, contact the Center for Tobacco Products at (Tel) 1-877-
`CTP-1373 (1-877-287-1373) Monday-Friday, 9 a.m. — 4 p.m. ET.
`
`Additional copies are available online at https://wwwida.gov/tobacco-products/products-
`guidance-regulationskules-regulations-and-guidance. You may send an e-mail request to
`SmallBiz.Tobacco@fda.hhs.gov to receive an electronic copy of this guidance. You may send a
`request for hard copies to U.S. Food and Drug Administration, Center for Tobacco Products,
`Attn: Office of Small Business Assistance, Document Control Center, Bldg. 71, Rm. G335,
`10903 New Hampshire Ave., Silver Spring, MID 20993-2000.
`
`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Tobacco Products
`
`April 2020
`
`* This is a revision to the first edition of this guidance, which issued in January 2020.
`
`1199_RESP00014118
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 3 of 10 PageID# 28136
`
`Contains Nonbinding Recommendations
`
`For ENDS products marketed without FDA authorization, FDA intends to prioritize enforcement
`against:
`
`• Any flavored, cartridge-based ENDS product (other than a tobacco- or menthol-flavored
`ENDS product);
`• All other ENDS products for which the manufacturer has failed to take (or is failing to
`take) adequate measures to prevent minors' access; and
`• Any ENDS product that is targeted to minors or whose marketing is likely to promote use
`of ENDS by minors.3
`
`Further, FDA intends to prioritize enforcement of any ENDS product that is offered for sale after
`September 9, 2020, and for which the manufacturer has not submitted a premarket application
`(or after a negative action by FDA on a timely submitted application).
`
`This guidance does not in any way alter the fact that it is illegal to market any new tobacco
`product without premarket authorization. FDA is continuously evaluating new information and
`adjusting its enforcement priorities in light of the best available data, and it will continue to do so
`with respect to these products. FDA will take appropriate action regarding tobacco products that
`are marketed without premarket authorization, including as warranted based on changed
`circumstances, new information, or to better address minors' use of those products.
`
`FDA's guidance documents, including this guidance, do not establish legally enforceable
`responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should
`be viewed only as recommendations, unless specific regulatory or statutory requirements are
`cited. The use of the word should in Agency guidances means that something is suggested or
`recommended, but not required.
`
`II. BACKGROUND
`
`A. Statutory and Regulatory History
`
`The Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) (Public
`Law 111-31) granted FDA the authority to regulate the manufacture, marketing, and
`distribution of cigarettes, cigarette tobacco, roll-your-own (RYO) tobacco, and smokeless
`tobacco products to protect the public health and to reduce tobacco use by minors. The
`Tobacco Control Act also gave FDA the authority to issue regulations deeming other
`products that meet the statutory definition of a tobacco product4 to be subject to chapter IX of
`the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 387 through 387u)
`(section 901(b) of the FD&C Act).
`
`3 For purposes of this Final Guidance, FDA's use of the term "minor" refers to individuals under the age of 21. This
`is consistent with the Further Consolidated Appropriations Act, 2020 (H.R. 1865), signed into law on December 20,
`2019, which included a provision amending section 906(d) of the Federal Food, Drug, and Cosmetic Act to increase
`the federal minimum age to purchase tobacco products from 18 to 21, and adding a provision that it is unlawful for
`any retailer to sell a tobacco product to any person younger than 21 years of age. In addition, FDA is working to
`update our regulations within 180 days, consistent with the timeline set forth in the law.
`
`4 21 U.S.0 321(rr) (section 201(rr) of the FD&C Act).
`
`3
`
`1199_RESP00014121
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 4 of 10 PageID# 28137
`
`Contains Nonbinding Recommendations
`
`In accordance with that authority, on May 10, 2016, FDA issued a final rule deeming all
`products that meet the statutory definition of a tobacco product, except accessories of deemed
`tobacco products, to be subject to FDA's tobacco product authority. This included electronic
`nicotine delivery systems (ENDS), cigars, waterpipe (hookah) tobacco, pipe tobacco,
`nicotine gels, and dissolvables that were not already subject to the FD&C Act (81 FR 28974
`at 28976 (May 10, 2016)).
`
`The requirements in Chapter IX of the FD&C Act now apply to deemed products.
`Particularly relevant to this guidance is section 910, which imposes certain premarket-review
`requirements for "new tobacco products"—i.e., those that were not commercially marketed in
`the United States as of February 15, 2007. Accordingly, after the rule's effective date,
`deemed new tobacco products were required to obtain premarket authorization under Section
`910. Deemed new tobacco products that remain on the market without marketing
`authorization are marketed unlawfully in contravention of the Tobacco Control Act. Through
`the premarket review process, FDA conducts a science-based evaluation to determine
`whether a new tobacco product meets the applicable statutory standard for marketing
`authorization—for example, whether the product is appropriate for the protection of public
`health with respect to the risks and benefits to the population as a whole, including users and
`nonusers, and taking into account, among other things, the likelihood that those who do not
`use tobacco products will start using them.
`
`The preamble to the May 10, 2016, final deeming rule explained that FDA intended to defer
`enforcement for failure to have premarket authorization during two compliance periods
`related to premarket review: one for submission and FDA receipt of applications and one for
`obtaining premarket authorization. The first compliance period depended on the type of
`application. The compliance date was 12 months from the effective date of the rule for
`substantial equivalence exemption requests (EX REQs), 18 months for substantial
`equivalence reports (SE Reports), and 24 months for premarket tobacco applications
`(PMTAs). In addition, the preamble explained that under the second compliance period:
`
`Unless FDA has issued an order denying or refusing to accept the submission,
`products for which timely premarket submissions have been submitted will be subject
`to a continued compliance period for 12 months after the initial compliance period
`described previously. For such products, FDA does not intend to initiate enforcement
`for failure to have premarket authorization during this continued compliance period.5
`
`The preamble further explained that this compliance policy did not apply to any new tobacco
`product that was not on the market on August 8, 2016. Significantly, this policy did not
`confer lawful marketing status on new tobacco products being marketed without the
`necessary premarket authorization.
`
`In May 2017, FDA published a guidance document, Three-Month Extension of Certain Tobacco
`Product Compliance Deadlines Related to the Final Deeming Rule, under which the Agency, as
`
`5 81 FR at 29011.
`
`4
`
`1199_RESP00014122
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 5 of 10 PageID# 28138
`
`Contains Nonbinding Recommendations
`
`E-liquids are a type of ENDS product and generally refer to liquid nicotine and nicotine-
`containing e-liquids (i.e., liquid nicotine combined with colorings, flavorings, and/or other
`ingredients). Liquids that do not contain nicotine or other material made or derived from tobacco,
`but that are intended or reasonably expected to be used with or for the human consumption of a
`tobacco product, may be components or parts and, therefore, subject to FDA's tobacco control
`authorities.
`
`Label means a display of written, printed, or graphic matter upon the immediate container of any
`article. Section 201(k) of the FD&C Act.
`
`Labeling means all labels and other written, printed, or graphic matter (1) upon any article or any
`of its containers or wrappers, or (2) accompanying such article. Section 201(m) of the FD&C
`Act.
`
`New tobacco product means (1) any tobacco product (including those products in test markets)
`that was not commercially marketed in the United States as of February 15, 2007; or (2) any
`modification (including a change in design, any component, any part, or any constituent,
`including a smoke constituent, or in the content, delivery or form of nicotine, or any other
`additive or ingredient) of a tobacco product where the modified product was commercially
`marketed in the United States after February 15, 2007. Section 910(a) of the FD&C Act.
`
`Tobacco product means any product made or derived from tobacco that is intended for human
`consumption, including any component, part, or accessory of a tobacco product (except for raw
`materials other than tobacco used in manufacturing a component, part, or accessory of a tobacco
`product). The term "tobacco product" does not mean an article that under the FD&C Act is a
`drug (section 201(g)(1) (21 U.S.0 321(g)(1))), a device (section 201(h)), or a combination
`product (section 503(g) (21 U.S.0 353(g))). Section 201(rr) of the FD&C Act.
`
`IV. ENFORCEMENT PRIORITIES REGARDING CERTAIN ENDS PRODUCTS ON
`THE MARKET WITHOUT PREMARKET AUTHORIZATION
`
`A. Overview
`
`The Tobacco Control Act provides that new tobacco products (i.e., non-grandfathered products)
`may not legally be marketed without premarket authorization. Accordingly, all deemed new
`tobacco products on the market without authorization are illegally marketed products.
`
`Beginning February 6, 2020, FDA intends to prioritize enforcement of the premarket review
`requirements for certain ENDS products, including against retailers selling such products.
`Specifically, FDA intends to prioritize enforcement against:
`
`(1) Flavored, cartridge-based ENDS products (except for tobacco- or menthol-flavored
`products);
`(2) All other ENDS products for which the manufacturer has failed to take (or is failing to
`take) adequate measures to prevent minors' access; and
`
`10
`
`1199_RESP00014128
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 6 of 10 PageID# 28139
`
`Contains Nonbinding Recommendations
`
`(3) Any ENDS products targeted to, or whose marketing is likely to promote use by,
`minors.
`
`In addition, FDA intends to prioritize enforcement of any ENDS product that is offered for sale
`in the United States after September 9, 2020, and for which the manufacturer has not submitted a
`premarket application (or after a negative action by FDA on a timely submitted application).22
`
`FDA will make enforcement decisions on a case-by-case basis, recognizing that it is unable, as a
`practical matter, to take enforcement action against every illegally marketed tobacco product,
`and that it needs to make the best use of Agency resources. This guidance does not in any way
`alter the fact that it is illegal to market any new tobacco product without premarket authorization,
`or to sell any tobacco product to minors. The Agency also retains discretion to pursue
`enforcement action at any time against any deemed new tobacco product marketed without
`premarket authorization, regardless of whether it falls within one of these categories of
`enforcement priorities.
`
`B. Data Show Substantial Increase in Youth Use of ENDS Products, Particularly Certain
`Flavored, Cartridge-Based ENDS Products
`
`At the time FDA issued the August 2017 Compliance Policy to announce changes in its approach
`to enforcement regarding premarket authorization (as described in the preamble to the final
`deeming rule), data from the 2016 NYTS showed a decrease in prevalence of current e-cigarette
`use (i.e., past 30-day use) among high school students, from 16 percent in 2015 to 11.3 percent in
`2016.23 Results from the 2017 NYTS later confirmed that in regards to youth use there was no
`statistically significant rise at the time, with data suggesting that high school student use had
`leveled off between 2016 (11.3 percent)24 and 2017 (11.7 percent).25
`
`However, multiple survey results over the past several years demonstrate that there is significant
`initiation by youth. The recent surge in youth use of ENDS products has caused us to reevaluate
`our July 2017 assessment and to modify our enforcement priorities for ENDS products. Recent
`data show an alarming increase in youth use of ENDS products in the past two years. They also
`show youth are more likely to use certain flavored, cartridge-based ENDS products.
`
`22 We note that FDA would be enforcing the priorities discussed in Section IV of this guidance regardless of the
`court's decision in the AAP case. As discussed in this Final Guidance, FDA is implementing this policy to address
`the alarming increase in youth use of ENDS products as well as other recent health and safety issues regarding such
`products.
`
`23 Jamal, A, A. Gentzke, S.S. Hu, et al., "Tobacco Use Among Middle and High School Students — United States,
`2011-2016," Morbidity and Mortality Weekly Report, 66:597-603, 2017, available at:
`https://www.cdc.gov/mmwevolumes/66/wrimm6623a1 .htm.
`
`241d
`
`25 Wang, T.W., A. Gentzke, S. Sharapova, et al., "Tobacco Product Use Among Middle and High School Students —
`United States, 2011-2017," Morbidity and Mortality Weekly Report, 67:629-633, 2018, available at:
`hitp://dx doi.org/ 1 0.15585/mmwtmm6722a3.
`
`11
`
`1199_RESP00014129
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 7 of 10 PageID# 28140
`
`Contains Nonbinding Recommendations
`
`FDA also remains concerned about health and safety issues connected to ENDS products—e.g.,
`cases of lung injuries associated with use of vaping products69 as well as battery explosions with
`ENDS products70—particularly given that these products have been marketed without premarket
`evaluation. These current public health issues affirm the importance of the premarket review
`process, as contemplated by the Tobacco Control Act, to scientifically evaluate products based
`on a public health standard. For example, FDA review of premarket tobacco product
`applications considers the risks and benefits of the product to the population as a whole,
`including tobacco product users and non-users. In reviewing premarket tobacco product
`applications, FDA will consider, among other things: the product's components, ingredients,
`additives, and properties; manufacturing practices; and any studies or investigations into the
`health risks of the tobacco product.
`
`D. Enforcement Priorities for ENDS Products
`
`In the discussion that follows, we describe our current intent regarding prioritizing our
`enforcement resources with respect to certain illegally marketed ENDS products.
`
`FDA will prioritize enforcement of flavored, cartridge-based ENDS products (other than
`tobacco- and menthol-flavored products), which are produced primarily by large manufacturers.
`This policy should have minimal impact on small manufacturers (e.g., vape shops) that primarily
`sell non-cartridge-based ENDS products, unless they market to youth or fail to take adequate
`measures to prevent youth access. Specifically, FDA intends to prioritize enforcement regarding
`the lack of marketing authorization against:
`
`• Any flavored, cartridge-based ENDS product (other than a tobacco- or menthol-flavored
`ENDS product);
`• All other ENDS products for which the manufacturer has failed to take (or is failing to
`take) adequate measures to prevent minors' access; and
`• Any ENDS product that is targeted to minors or whose marketing is likely to promote use
`of ENDS by minors.
`
`FDA intends to prioritize enforcement beginning February 6, 2020.
`
`establishes a policy, practice, or precedent requiring the Agency to do so with respect to future iterations of this
`document or any other guidance document.
`
`69 See, e.g., Centers for Disease Control and Prevention, "Outbreak of Lung Injury Associated with E-cigarette Use,
`or Vaping," available at: https://www.cdc.gov/tobacco/basic_informationk-cigarettes/severe-lung-
`disease.html#latest-outbreak-information; Layden, J. E., I. Ghinai, I. Pray, et al., "Pulmonary Illness Related to E-
`Cigarette Use in Illinois and Wisconsin — Preliminary Report," New England Journal of Medicine, Sept. 2019; DOT:
`10.1056/NEJMoa1911614.
`
`7° See, e.g., Rossheim, ME., M.D. Livingston, E.K. Soule, et al., "Electronic Cigarette Explosion and Burn Injuries,
`US Emergency Departments 2015-2017," Tobacco Control, 2019; 28:472-474, available at:
`http://dx.doi.org/10.1136/tobaccocontrol-2018-054518.
`
`18
`
`1199_RESP00014136
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 8 of 10 PageID# 28141
`
`Contains Nonbinding Recommendations
`
`additives, and properties; manufacturing practices; and any studies or investigations into the
`health risks of the tobacco product. FDA also has stated its intention to issue a regulation that
`would ban the use of characterizing flavors in cigars, and FDA is actively working towards that
`proposed rule.
`
`After September 9, 2020, FDA will make enforcement decisions on a case-by-case basis,
`recognizing that it is unable, as a practical matter, to take enforcement action against every
`illegally marketed tobacco product, and that it needs to make the best use of Agency
`resources. FDA intends to prioritize enforcement based on the likelihood of youth use or
`initiation to make the most efficient use of its resources. In assessing this, factors the Agency
`intends to consider include, but are not limited to:
`
`• What FDA understands about the number of youth currently using the product or
`category of product;
`• The trends in those numbers, particularly since 2016;
`• Whether the product contains added flavors;
`• What FDA understands about how the product or category of product is typically sold
`and how that is likely to impact access and use by minors; and
`• What FDA understands about the frequency and other demographics of use by minors.
`
`To illustrate, based on these factors, FDA's lowest priority among these products will include
`relatively expensive, large hand-rolled cigars that do not have flavors (e.g., fruit, candy, or mint),
`given what FDA understands to be their comparatively lower youth usage rates.
`
`FDA is continuously evaluating new information and adjusting its enforcement priorities in light
`of the best available data, and it will continue to do so with respect to these products. FDA will
`take appropriate action regarding tobacco products that are marketed without premarket
`authorization, including as warranted based on changed circumstances, new information, or to
`better address minors' use of those products.
`
`VI. DOCUMENT HISTORY
`
`January 2020 — First edition of guidance issued.
`
`April 2020 — Guidance is revised to reflect the court's order in American Academy of Pediatrics,
`et at. v. Food and Drug Administration, et at., Case No. 8:18-cv-883 (PWG), (D. Md. Apr. 22,
`2020), Dkt. No. 182, granting a motion for a 120-day extension (until September 9, 2020) in
`light of the global outbreak of respiratory illness caused by a new coronavirus. Specific
`revisions include the following:
`
`• Section II.A — Added reference to order granting 120-day extension.
`
`• Section IV.A (and throughout) — Changed language stating that FDA's new enforcement
`priorities would begin "30 days after issuance of this Final Guidance" to "February 6,
`
`31
`
`1199_RESP00014149
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 9 of 10 PageID# 28142
`
`Contains Nonbinding Recommendations
`
`Draft guidance will kill innovation and force
`industry out of work.
`
`Draft guidance policy on marketing practices
`would violate the First Amendment as it
`represents an impermissibly broad commercial
`speech restriction.
`
`population level to be positive. If, on the other hand,
`there is significant initiation by youth, minimal
`q uitting, or significant dual use of combust[ed] and
`non-combust[ed] products, then the public health
`impact could be negative." As such policies are
`subject to change, manufacturers cannot have settled
`expectations to market unlawful products, especially
`in the face of evolving public health concerns.
`Therefore, FDA believes that manufacturers should
`have begun contemplating and/or preparing
`premarket applications at no later than the time of the
`final deeming rule.
`
`FDA disagrees that the Final Guidance will cause these
`results. The Final Guidance explains FDA's
`enforcement priorities for certain deemed new
`products that are being marketed without required
`premarket tobacco product authorization. The Final
`G uidance would only affect those products that are
`illegally on the market; none of the products affected
`by the guidance were ever in compliance with the
`premarket authorization requirements of the law. In
`a ny event, FDA believes that the use of premarket
`pathways will incentivize development of innovative
`tobacco products that meet the applicable statutory
`standards.
`
`FDA disagrees that the Final Guidance violates the
`First Amendment. Speech regarding an illegal activity
`— including distribution of a product that requires
`premarket review under the FDCA— is not protected
`u nder the First Amendment. See United States v.
`Caputo, 517 F.3d 935, 941 (7th Cir. 2008) (unapproved
`device); United States v. LeBeau, 654 Fed. App'x 826,
`831 (7th Cir. 2016) (unapproved drug); United States v.
`Cole, 84 F. Supp. 3d 1159, 11-66-67 (D. Or. 2015)
`(unapproved drug). Even if the First Amendment were
`applicable, the government has a substantial interest
`in protecting youth from tobacco products, and
`prioritizing enforcement actions with respect to ENDS
`products targeted to, or likely to promote use by,
`minors is a reasonable measure to directly advance
`that interest. See, e.g., Discount Tobacco City &
`Lottery, Inc. v. United States, 674 F.3d 509, 536 (6th
`Cir. 2012). We have provided additional examples for
`clarity in the Final Guidance.
`
`Modifications to ENDS Compliance Policy — Flavored ENDS except Tobacco, Mint, Menthol
`
`Comment
`
`Response
`
`36
`
`1199_RESP00014154
`
`

`

`Case 1:20-cv-00393-LO-TCB Document 1007-1 Filed 02/11/22 Page 10 of 10 PageID# 28143
`
`Contains Nonbinding Recommendations
`
`There is no evidence/limited evidence to connect
`liquid nicotine use with harmful health effects in
`youth.
`
`"Banning" flavors outside of tobacco, mint, and
`menthol would deter cigarette smokers from
`
`As discussed in the Final Guidance the studies of the
`effects of nicotine exposure in the naïve adolescent
`brain find that the adolescent brain is uniquely
`vulnerable to nicotine compared to the adult brain.
`Repeated exposure to nicotine during adolescence
`induces long-lasting structural and functional changes
`in brain regions involved in addiction, attention,
`learning, and memory.'
`
`Studies further suggest that nicotine-induced changes
`in the adolescent brain can lead to long-lasting effects
`on cognitive function, such as cognitive deficits
`following nicotine abstinence, and may contribute to
`the risk for mood and anxiety disorders. Nicotine is the
`primary addictive substance in tobacco products,
`including e-cigarettes and combustible cigarettes. The
`rate and extent of nicotine delivery significantly
`i mpact product abuse liability. Higher nicotine content
`and faster rates of nicotine delivery increase products'
`abuse liability due to the rapid absorption of nicotine
`into the brain. Some e-cigarettes are capable of
`achieving similar or greater nicotine delivery as
`cigarettes.'
`
`The Final Guidance does not ban any products but
`rather identifies FDA's priorities in connection with the
`enforcement of the statutory premarket review
`
`103 McDonald, C.G., A.K. Eppolito, J.M. Brielmaier, et. al., "Evidence for elevated nicotine-induced structural
`plasticity in nucleus accumbens of adolescent rats," Brain Research, 1151, 211-218, 2007; doi:
`10.1016/j.brainres.2007.03.019; Bergstrom, H.C., R.F. Smith„ N.S. Mollinedo, et al., "Chronic nicotine exposure
`produces lateralized, age-dependent dendritic remodeling in the rodent basolateral amygdala," Synapse, 64(10), 754-
`764, 2010; doi:10.1002/syn.20783; England, L.J., K. Aagaard, M. Bloch, et al., "Developmental toxicity of
`nicotine: a transdisciplinary synthesis and implications for emerging tobacco products," Neuroscience and
`Biobehavioral Reviews, 72:176-189, 2017.
`
`104 Hiler, M., A. Breland, T. Spindle, et al., "Electronic cigarette user plasma nicotine concentration, puff
`topography, heart rate, and subjective effects: Influence of liquid nicotine concentration and user experience,"
`Experimental and Clinical Pharmacology, 25(5), 380-392, 2017; doi:10.1037/pha0000140; Lopez, A.A., M.M.
`Hiler, E.K. Soule, et al., "Effects of Electronic Cigarette Liquid Nicotine Concentration on Plasma Nicotine and Puff
`Topography in Tobacco Cigarette Smokers: A Preliminary Report," Nicotine & Tobacco Research, 18(5):720-723,
`2016; doi:10.1093/ntrintv182; Maloney, S. F., A. Breland, E.K. Soule, et al. "Abuse liability assessment of an
`electronic cigarette in combustible cigarette smokers," Experimental and Clinical Psychopharmacology, 27(5):443-
`454, 2019; doi:10.1037/pha0000261; O'Connell, G., J.D. Pritchard, C. Prue, et al, "A randomised, open-label, cross-
`over clinical study to evaluate the pharmacokinetic profiles of cigarettes and e-cigarettes with nicotine salt
`formulations in US adult smokers," Internal and Emergency Medicine, 14(6):853-861, 2019; doi:10.1007/s11739-
`019-02025-3; Ramoa, C. P., M.M. Hiler, T.R. Spindle, et al. "Electronic cigarette nicotine delivery can exceed that
`of combustible cigarettes: a preliminary report," Tobacco Control, 25(e1): e6-9, 2016; doi:10.1136/tobaccocontrol-
`2015-052447; Yan, X. S., & C. D'Ruiz, "Effects of using electronic cigarettes on nicotine delivery and
`cardiovascular function in comparison with regular cigarettes," Regulatory Toxicology and Pharmacology, 71(1):24-
`34, 2015; doi:10.1016/j.yrtph.2014.11.004.
`
`37
`
`1199_RESP00014155
`
`