FDA Issues Long-Delayed Proposal to Regulate E-Cigarettes

Health Letter, July 2014

By Sammy Almashat, M.D., M.P.H.

On April 24, 2014, three years after announcing its intention to do so, the Food and Drug Administration (FDA) released a long-awaited proposed rule that would, for the first time, bring e-cigarettes and certain noncigarette tobacco products under FDA regulation.[1] E-cigarettes have exploded in popularity over the past few years amid intensive promotional campaigns that often have mimicked earlier tobacco industry efforts to addict the American public en masse to the nation’s number one cause of preventable disease and death.[2] However, the widespread adoption of e-cigarettes has occurred in a regulatory vacuum, with no meaningful oversight of the production, distribution or advertising of these increasingly trendy alternatives to their lethal predecessors.

What are e-cigarettes?

E-cigarettes are battery-powered devices often shaped like cigarettes that deliver nicotine, a highly addictive drug found in tobacco, in the form of an aerosol or vapor. They were first introduced onto the U.S. market in 2007[3] and are mainly manufactured in China,[4] their liquid nicotine often “mixed on factory floors and in the back rooms of shops,” according to The New York Times.[5]

By 2013, e-cigarettes were generating $1.7 billion in annual sales,[6] due in no small part to intensive marketing campaigns in media long off-limits to traditional cigarette makers. Television ads, banned for cigarettes in 1970,[7] have begun to appear for e-cigarettes, and, honoring the tradition of Joe DiMaggio- and Ronald Reagan-hawked cigarettes, one e-cigarette maker recently hired celebrity Jenny McCarthy as the centerpiece of one of its ad campaigns.[8]

Also unlike traditional cigarettes, e-cigarettes are currently allowed to be marketed to all age groups, in flavors — such as chocolate, bubblegum and cola — with obvious appeal to children and adolescents.[9] (In 2009, Congress banned the addition of all such flavorings, with the notable exception of menthol, to traditional cigarettes.[10]) The Centers for Disease Control and Prevention recently reported that the percentage of middle school and high school children who have ever smoked an e-cigarette more than doubled between 2011 and 2012.[11]

In 2009, Congress passed the Family Smoking Prevention and Tobacco Control Act, which granted the FDA the authority to regulate tobacco and tobacco products.[12] The following year, the agency finalized a set of rules governing the production, manufacture and promotion of traditional cigarettes and smokeless tobacco (mainly snuff and chewing tobacco).[13]

This past April, after a three-year deliberative process, the FDA finally proposed extending these rules to e-cigarettes and other qualifying tobacco products (for example, some cigars) not included in the original rules. However, the long delay in releasing the new proposed rule frustrated some tobacco control advocates. “It is inexcusable that it has taken the FDA and the Administration so long to act,” said the Campaign for Tobacco-Free Kids in a statement on the release of the rule. “This delay has had serious public health consequences as these unregulated tobacco products have been marketed using tactics and sweet flavors that appeal to kids, and their use has skyrocketed.”[14]

The proposed FDA rule

The belatedly released rule would require the following:[15]

  • Registration of all marketed products with the FDA and disclosure to the FDA of all constituent ingredients;
  • FDA review prior to the marketing of any new e-cigarette products;
  • FDA permission to directly or implicitly claim that the product is associated with reduced risk (for example, use of the descriptors “light” or “mild” on the product label[16]) only if the agency confirms that scientific evidence supports the claim and that marketing the product will benefit public health generally; and
  • A ban on the distribution of free samples.

The FDA also proposed the following additional regulations for e-cigarette and other qualifying tobacco products:[17]

  • A minimum age, with accompanying identification requirements, for purchase;
  • Health warnings to accompany products; and
  • A ban on vending machine sales, unless the machine is located in a facility that never admits youth under 18 years of age.[18]

The rule’s flaws

The proposed rule has several flaws. For example, the FDA did not include a ban on the use of flavorings in e-cigarettes, despite acknowledging in its proposal that added flavorings are “especially attractive to children and young adults.”[19] However, the agency seemed open to the possibility for inclusion of a flavorings ban in a final rule, pending public feedback.[20] Nor did the agency go far enough in restricting the advertising or marketing of e-cigarettes to youth such as requiring rigorous age verification for online sales.[21] (A list of other critical suggestions from tobacco control experts to the FDA for inclusion in its final rule can be found at the following blog operated by the University of California, San Francisco’s Center for Tobacco Control Research and Education: http://tobacco.ucsf.edu/list-public-comments-fda-deeming-rule-ucsf-faculty-and-fellows-and-others-links-comments.)

Another flaw inherent to the FDA’s proposal is its classification of e-cigarettes as tobacco products, rather than drugs. The FDA considers nicotine a drug when it is marketed as an aid in smoking cessation. As such, currently approved nicotine replacement therapies must undergo clinical studies and be pre-approved by the FDA at specific dosages and potencies. Between 2008 and 2010, the FDA attempted to treat e-cigarettes as unapproved pharmaceuticals but was rebuffed by the courts, which ruled that, unless e-cigarette makers explicitly marketed their products as smoking cessation aids, the FDA could not regulate them as drugs.[22]

Under the the FDA’s current proposal, e-cigarette makers seeking to market a new product will only have to (a) submit a pre-market tobacco application (PMTA) or (b) demonstrate that their product is “substantially equivalent” to an e-cigarette version that was commercially available as of Feb. 15, 2007.[23] Because almost no e-cigarettes were on the market at that time,[24] most, if not all, e-cigarette makers will be required to submit PMTAs. Under current draft FDA guidance, PMTAs must contain, among other things, ingredient lists, manufacturing information and analytical summaries of all studies — conducted by the application sponsor or others — shedding light on the safety and addictiveness of the product and its impact on smoking cessation and adoption.[25]

However, there will, in all likelihood, be no requirement to conduct pre-marketing clinical studies on the effectiveness of e-cigarettes as smoking cessation aids like those mandated for nicotine replacement drugs.[26] And in the absence of such a requirement,[27] the agency will effectively codify a two-tier approval system for nicotine delivery products. Such a system would threaten to tilt the smoking cessation market in favor of e-cigarettes (even if they are not marketed for this purpose), at the expense of safe and effective nicotine replacement drugs that must undergo the lengthier and costlier drug approval process.

E-cigarette safety

Currently, not much is known about the safety of e-cigarettes. Because they contain no tobacco or other additives commonly used in traditional cigarettes, e-cigarettes almost certainly do not pose as high a risk to long-term health as do traditional cigarettes. However, as nicotine delivery devices, e-cigarettes are not without risk.

Nicotine is highly addictive, and the amount, potency and purity of the liquid nicotine used in e-cigarettes are currently unregulated. The FDA cited a study showing that in more than one-third of e-cigarette cartridges tested, the actual amounts of nicotine in e-cigarettes differed from those listed on the products’ labels by more than 20 percent.[28] The agency also pointed out the striking lack of standardization of nicotine content in e-cigarette devices, with up to a 30-fold variation between different brands in the amount of nicotine inhaled with each puff.[29]

In addition, liquid nicotine is often sold by the gallon or even the barrel, as well as in packages and smaller bottles that are not childproof.[30] Not surprisingly, the past few years have seen a dramatic rise in the number of calls to U.S. poison control centers reporting accidental exposure to liquid nicotine in young children.[31] (See the article on liquid nicotine in this issue of Health Letter to learn more.)

Contrary to popular belief, e-cigarette users inhale more than just nicotine. A recent study published in the journal Nicotine and Tobacco Research found that the heat generated inside a type of e-cigarette cartridge known as a “tank system” can release the carcinogenic chemical formaldehyde, which the user inhales along with the aerosolized nicotine.[32] The FDA cited several studies showing that numerous other toxic chemicals (among them lead, chromium, diethylene glycol and aromatic hydrocarbons) have been found in the vapor generated during the e-cigarette’s high-heat nicotine delivery process.[33] While it is unknown whether the dose of such chemicals inhaled with each breath is enough to cause adverse health effects, the use of the devices on a chronic basis raises concerns that any risks that do exist could accumulate over time.

Smoking cessation aids or risky enablers?

Besides the safety of the products themselves, a major concern with e-cigarettes is the possibility that they may serve as gateways to subsequent cigarette or other tobacco habits, especially in children and adolescents unable to legally access these more dangerous products until adulthood (approximately 80 percent of all cigarette smokers start before the age of 18[34]).

A parallel concern is the possibility, alluded to above, that e-cigarettes may be steering current smokers wishing to quit away from proven smoking cessation therapies. Because no pre-marketing studies like those required for approved nicotine replacement therapies have yet been mandated for e-cigarettes, little is currently known about the effectiveness of e-cigarettes as aids in smoking cessation.

In May 2014, researchers published the findings of a British national surveillance program called the Smoking Toolkit Study, which evaluated e-cigarettes’ effectiveness as smoking cessation aids.[35] The study, analyzing data collected between 2009 and 2014, interviewed 5,863 smokers ages 16 and older who had tried to quit at least once during the previous year using e-cigarettes, over-the-counter (OTC) nicotine replacement therapies or nothing. Multiple media outlets prominently reported the overall finding that e-cigarettes were associated with the highest successful quit rates.

However, experts not involved with the study pointed out several limitations of the study that cast doubt on the purported superiority of e-cigarettes. For example, the difference in quit rates was small (20 percent versus 10 percent versus 15 percent for e-cigarette, OTC nicotine replacement products and no aids, respectively), making it possible that random chance explained the findings. Further, the unusually low quit rate seen with the OTC nicotine replacement products (even lower than no aids), the reliance on self-reports and the study’s “cross-sectional” nature, which makes it impossible to distinguish whether those opting for e-cigarettes might have been disproportionately more motivated or able to quit smoking, makes it difficult to draw any firm conclusions on e-cigarettes as smoking cessation aids.[36]

Nevertheless, the study was an important addition to the otherwise scant literature on the topic, and e-cigarettes may indeed turn out to be an effective tool in the battle to lower smoking rates worldwide. Unfortunately, because the FDA’s proposal does not formally classify e-cigarettes as drugs, we may never know for sure.

FDA Rule Open for Public Comment

The FDA is soliciting comments from the public on its proposed rule until Aug. 8, 2014.[37] Online comments can be submitted at www.regulations.gov by typing “FDA–2014–N–0189” into the search box. Alternatively, comments can be mailed to the following address (be sure to list the Docket No. FDA–2014–N–0189 and RIN 0910–AG38):

Division of Dockets Management (HFA–305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852

NOTE: The article was updated on July 17, 2014, to reflect the following changes:

  • In the section titled “The rule’s flaws”, language has been added concerning the FDA’s failure to significantly regulate e-cigarette marketing and its unsuccessful efforts to regulate e-cigarettes as drugs, and a link has been inserted to an external blog containing comments to FDA from various tobacco control advocates.
  • In the text box at the end of the article, the deadline for submitting comments has been changed to Aug. 8, 2014, in response to an FDA announcement of an extension to the comment deadline.

References

[1] Food and Drug Administration. News Release. FDA proposes to extend its tobacco authority to additional tobacco products, including e-cigarettes. April 24, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394667.htm. Accessed May 28, 2014.

[2] Food and Drug Administration. Proposed Rule. 21 CFR Parts 1100, 1140, and 1143 [Docket No. FDA–2014–N–0189] RIN 0910–AG38. Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Regulations on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products. (Hereafter referred to as “FDA Proposed Rule”), p. 15. https://www.gpo.gov/fdsys/pkg/FR-2014-04-25/pdf/2014-09491.pdf. Accessed May 30, 2014.

[3] Pozin I. Electronic Cigarettes: Booming Industry Or Health Fiasco? Forbes. April 11, 2013. http://www.forbes.com/sites/ilyapozin/2013/04/11/electronic-cigarettes-booming-industry-or-health-fiasco/. Accessed June 12, 2014.

[4] Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. May 13, 2014;129(19):1972-86. http://circ.ahajournals.org/content/129/19/1972.full#xref-ref-1-1. Accessed May 28, 2014.

[5] Richtel M. Selling a Poison by the Barrel: Liquid Nicotine for E-Cigarettes. New York Times. March 23, 2014. http://www.nytimes.com/2014/03/24/business/selling-a-poison-by-the-barrel-liquid-nicotine-for-e-cigarettes.html. Accessed May 30, 2014.

[6] Richtel M. Some E-Cigarettes Deliver a Puff of Carcinogens. New York Times. May 3, 2014. http://www.nytimes.com/2014/05/04/business/some-e-cigarettes-deliver-a-puff-of-carcinogens.html?ref=health&_r=0. Accessed May 28, 2014.

[7] Glass A. Congress bans cigarette ads on the air, April 1, 1970. Politico. April 1, 2009. http://www.politico.com/news/stories/0309/20715.html. Accessed May 29, 2014.

[8] Felberbaum M. Old tobacco playbook gets new use by e-cigarettes. AP. August 3, 2013. http://bigstory.ap.org/article/old-tobacco-playbook-gets-new-use-e-cigarettes. Accessed May 28, 2014.

[9] FDA Proposed Rule, p. 17. For evidence on the popularity of other, similarly flavored tobacco products, see: Centers for Disease Control and Prevention. Preventing Tobacco Use Among Youth and Young Adults: A Report of the Surgeon General, 2012. Chapter 3: The Epidemiology of Tobacco Use Among Young People in the United States and Worldwide, p. 164. http://www.surgeongeneral.gov/library/reports/preventing-youth-tobacco-use/sgr_2012_chapt3.pdf. Accessed May 28, 2014.

[10] Tavernise S. F.D.A. Closer to Decision About Menthol Cigarettes. New York Times. July 23, 2013. http://www.nytimes.com/2013/07/24/health/fda-takes-steps-toward-ruling-on-menthol-cigarettes.html. Accessed May 30, 2014.

[11] Centers for Disease Control and Prevention. Notes from the Field: Electronic Cigarette Use Among Middle and High School Students — United States, 2011–2012. MMWR. September 6, 2013;62(35):729-730. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6235a6.htm?s_cid=mm6235a6_w. Accessed May 29, 2014.

[12] FDA Proposed Rule, p. 5.

[13] Food and Drug Administration. Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco. http://www.fda.gov/tobaccoproducts/protectingkidsfromtobacco/regsrestrictingsale/default.htm. Accessed May 29, 2014.

[14] Campaign for Tobacco-Free Kids. After Inexcusably Long Delay, FDA Takes First Step to Regulate E-Cigarettes and Cigars. April 24, 2014. http://www.tobaccofreekids.org/press_releases/post/2014_04_24_ecigarettes. Accessed May 29, 2014.

[15] Food and Drug Administration. News Release. FDA proposes to extend its tobacco authority to additional tobacco products, including e-cigarettes. April 24, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394667.htm. Accessed May 28, 2014.

[16] FDA Proposed Rule, p. 3.

[17] Food and Drug Administration. News Release. FDA proposes to extend its tobacco authority to additional tobacco products, including e-cigarettes. April 24, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394667.htm. Accessed May 28, 2014.

[18] FDA Proposed Rule, p. 4.

[19] FDA Proposed Rule, p. 6.

[20] FDA Proposed Rule, p. 17.

[21] Glantz S. (Center for Tobacco Control Research and Education). FDA to kids: Not 18? No problem! Buy your e-cigs (and cigars and other tobacco products) online! http://tobacco.ucsf.edu/fda-kids-not-18-no-problem-buy-your-e-cigs-and-cigars-and-other-tobacco-products-online. Accessed July 16, 2014.

[22] Food and Drug Administration. Stakeholder Letter: Regulation of E-Cigarettes and Other Tobacco Products. April 25, 2011. http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm252360.htm. Accessed July 16, 2014.

[23] FDA Proposed Rule, p. 34.

[24] Pozin I. Electronic Cigarettes: Booming Industry Or Health Fiasco? Forbes. April 11, 2013. http://www.forbes.com/sites/ilyapozin/2013/04/11/electronic-cigarettes-booming-industry-or-health-fiasco/. Accessed June 12, 2014.

[25] FDA. Draft Guidance. Applications for Premarket Review of New Tobacco Products. September 2011. http://www.fda.gov/downloads/TobaccoProducts/GuidanceComplianceRegulatoryInformation/UCM273425.pdf. The guidance requires “a showing that the new tobacco product is appropriate for the protection of public health,” (p. 15) which, in turn, requires, “when appropriate…well-controlled investigations” analyzing the comparative safety of the product to other tobacco products, the addictiveness of the product, and the effect of the product on tobacco cessation and adoption (p. 16). However, there are several problems with this guidance if applied to e-cigarettes. For one, well-controlled studies will only be required when the FDA deems them “appropriate” for the purposes of approval (although the FDA seems to make this a de facto requirement for all new tobacco products). Second, no quantitative safety or efficacy thresholds are laid out for any of the study outcomes, making it difficult to determine the standards by which the FDA will judge the studies. Finally, the new product will only need to be compared with other tobacco products and not with effective nicotine replacement drugs, setting the bar quite low with respect to both the safety and efficacy of e-cigarettes as smoking cessation aids. Of course, should an e-cigarette manufacturer want to market its product as a smoking cessation aid, the FDA would likely require it to submit a new drug application rather than go through the tobacco product approval process, obviating these concerns.

[26] Ibid.

[27] This seems unlikely. Although the FDA states that it is “seeking comment in this proposed rule as to how e-cigarettes should be regulated based on the continuum of nicotine-delivering products,” (FDA Proposed Rule, p. 3) the agency’s “continuum of nicotine-delivering products” is restricted to tobacco products and excludes nicotine replacement therapies approved as drugs (p. 7).

[28] FDA Proposed Rule, p. 17.

[29] FDA Proposed Rule, p. 15.

[30] Richtel M. Selling a Poison by the Barrel: Liquid Nicotine for E-Cigarettes. New York Times. March 23, 2014. http://www.nytimes.com/2014/03/24/business/selling-a-poison-by-the-barrel-liquid-nicotine-for-e-cigarettes.html. Accessed May 30, 2014.

[31] Chatham-Stephens K, Taylor E, Mestrom P, et al. Calls to poison centers for exposures to electronic cigarettes – United States, September 2010 – February 2014. MMWR. April 4, 2014;63(13):292-293. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6313a4.htm#Fig. Accessed May 30, 2014.

[32] Richtel M. Some E-Cigarettes Deliver a Puff of Carcinogens. New York Times. May 3, 2014. http://www.nytimes.com/2014/05/04/business/some-e-cigarettes-deliver-a-puff-of-carcinogens.html. Accessed May 28, 2014.

[33] FDA Proposed Rule, p. 17.

[34] Campaign for Tobacco-Free Kids. The Path to Tobacco Addiction Starts at Very Young Ages. http://www.tobaccofreekids.org/research/factsheets/pdf/0127.pdf. Accessed May 30, 2014.

[35] Brown J, Beard E, Kotz D, Michie S, West R. Real-world effectiveness of e-cigarettes when used to aid smoking cessation: a cross-sectional population study. Addiction. 2014 May 20. doi: 10.1111/add.12623. [Epub ahead of print] http://onlinelibrary.wiley.com/doi/10.1111/add.12623/pdf. Accessed May 30, 2014.

[36] Wickline S. HypeWatch: E-Cigs Best Cessation Tool Ever, Really? MedPage Today. May 20, 2014 (updated May 21). http://www.medpagetoday.com/PrimaryCare/Smoking/45894. Accessed May 30, 2014.

[37] Food and Drug Administration. Tobacco Products: Comment Opportunities. http://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/ucm198169.htm. Accessed July 16, 2014.