FDA Press Release

For Immediate Release: July 22, 2009

Media Inquiries: Siobhan DeLancey, 301-796-4668, siobhan.delancey@fda.hhs.gov 
Consumer Inquiries: 888-INFO-FDA

FDA and Public Health Experts Warn About Electronic Cigarettes

The U.S. Food and Drug Administration today announced that a laboratory analysis of electronic cigarette samples has found that they contain carcinogens and toxic chemicals such as diethylene glycol, an ingredient used in antifreeze.

Electronic cigarettes, also called e-cigarettes, are battery-operated devices that generally contain cartridges filled with nicotine, flavor and other chemicals. The electronic cigarette turns nicotine, which is highly addictive, and other chemicals into a vapor that is inhaled by the user.

These products are marketed and sold to young people and are readily available online and in shopping malls. In addition, these products do not contain any health warnings comparable to FDA-approved nicotine replacement products or conventional cigarettes. They are also available in different flavors, such as chocolate and mint, which may appeal to young people.

You can read the entire "Smoke and Mirrors" news release here.

Date: May 4, 2009 To: Michael Levy, Supervisor Regulatory Counsel, CDER, Office of Compliance, Division of New Drugs and Labeling Compliance

From: B.J. Westenberger, Deputy Director, CDER/OPS/OTR, Division of Pharmaceutical Analysis

Subject: Evaluation of e-cigarettes Background: The Center for Drug Evaluation and Research through the Office of Compliance (OC) has requested that the Division of Pharmaceutical Analysis (DPA) evaluate two brands of electronic cigarettes (e-cigarettes) for nicotine content and other impurities. An e-cigarette is advertised as an alternative to smoked tobacco products. It is a battery-powered device that provides inhaled doses of nicotine by delivering a vaporized propylene glycol/nicotine mixture as shown in Figure 1. The Center is concerned that in addition to nicotine delivery, the vapor may also provide other potentially harmful volatile components. DPA was asked to quantitate the amount of nicotine present in each brand and to evaluate each brand for the presence of tobacco specific nitrosamines (TSNA), certain tobacco specific impurities, ethylene glycol (EG) and diethylene glycol (DEG).

You can access the full FDA report here.

Then read the Technical Review and Analysis of the FDA Report

A recent report and press release issued by the Food and Drug Administration (FDA) assert that NJOY e-cigarette cartridges contain harmful levels of carcinogens and toxic chemicals. It was further implied that these chemicals are not found in other FDA-approved nicotine-containing products. Subsequently, a technical review and scientific analysis of the FDA's report was performed by scientists at Exponent. Results of the review identified the following limitations:

 The report failed to present standard protocols for proper study design with regards to the testing of the referenced control device, documenting the number of samples tested either within or across tests, or presenting statistical analyses when quantifiable results were obtained.

 The chemical content of similar nicotine-containing FDA-approved products was not completely described with respect to the presence of tobacco-specific nitrosamines (TSNAs) and other tobacco-associated impurities that have also been found in nicotine replacement therapy (NRT) devices at similar, if not higher, levels.

 In the lots that were tested by the FDA, none of the key chemicals of concern in this study such as TSNAs and tobacco-associated impurities were able to be quantifiably measured in the liquid of NJOYs cartridges because they were all below the limits of quantification (LOQ).

 All of the tobacco-associated impurities found in the NJOY products were present but at less than the level of the Nicotrol inhaler [manufacturer] specification according to the FDA report.

 There is no indication in the published scientific literature that cotinine or nicotyrine are carcinogenic or have toxicity ratings of concern. These were the only tobacco-associated impurities found in trace levels in the vapor phase of (some of) NJOYs products.

 The report does not reflect the actual dose of nicotine delivered to the user from the control Nicotrol inhaler device when used as recommended by the manufacturer (6 -16 cartridges/day or 24 -64 mg of nicotine, 50 mcg/100 mL puff). By comparison, NJOY devices delivered 46 mcg/100 mL in the highest-strength cartridge tested, according to the FDA report.

 Data presented in the report does not adequately support the opinion that users of NJOY products would actually be exposed to TSNAs and tobacco-specific impurities in the vapor phase during normal device use; and if exposed, that those levels would be a health concern as compared to other FDA-approved products.

In summary, the report Evaluation of e-cigarettes suffers from several limitations, that taken together result in it failing to adequately support the FDA claims of potential adverse health consequences from the use of NJOY e-cigarette products tested as compared to other FDA-approved nicotine containing products.

Concluding Statement
The detection of trace and non-measurable levels of TSNAs and tobacco-associated impurities in the liquid, rather than the vapor phase of NJOYs products, at levels that are many orders of magnitude below conventional cigarettes, and at or below FDA-approved nicotine containing products, should be considered as indicators of the regulatory acceptability of the NJOY products rather than reason for concern. When considering the relative potential health risks posed by these trace levels, it is worth noting that the approved NRTs, which have been shown to contain these substances, were not judged to contain levels sufficient to warrant toxicity information or reference to these substances in their own product literature.

Summary of Results:

Laboratory Analysis of Electronic Cigarettes

 Conducted By FDA

• FDA conducted a preliminary analysis on some samples of electronic cigarettes and components from two leading brands. Due to the variability among products, this analysis should not be used to draw conclusions about what substances are or are not present in particular electronic cigarettes or brands of electronic cigarettes. If this analysis was not to be used to draw conclusions about the substances present in particular electronic cigarettes or brands of cigarettes, exactly what did the FDA base their conclusions to boycott and ban this product on?

• FDA Center for Drug Evaluation, Office of Compliance purchased two samples of electronic cigarettes and components from two leading brands. These samples included 18 of the various flavored, nicotine, and no-nicotine cartridges offered for use with these products. These cartridges were obtained in order to test some of the ingredients contained in them and inhaled by users of electronic cigarettes. Since these tests were conducted and utilized as a mitigating factor in the products continued sales, why weren't samples tested in depth, including samples from all brands available, since most brands differ in their ingredients?

• FDA Center for Drug Evaluation, Division of Pharmaceutical Analysis (DPA) analyzed the cartridges from these electronic cigarettes for nicotine content and for the presence of other tobacco constituents, some of which are known to be harmful to humans, including those that are potentially carcinogenic or mutagenic. Since the product contains nicotine, which is derived from tobacco, wouldn't the expected results show as such? In order to provide both the consumer and the manufacturers with accurate information regarding acceptable levels of these potentially carcinogenic or mutagenic constituents, side by side testing will have to be performed requiring the electronic cigarette manufacturers to stay within these parameters set by the tobacco manufacturers.
  

• DPA analysis of the electronic cigarette samples showed that the product contained detectable levels of known carcinogens and toxic chemicals to which users could potentially be exposed. Aren't those same carcinogens and toxic chemicals also found in tobacco products, but at more lethal levels? An electronic cigarette shows the level of nitrosamines at approximitely 8.183 and Marlboro cigarettes show the nitrosamine level at 11190 ... if 8.183 is considered toxic enough to ban this product ... what warning level does 11190 account for and why hasn't the FDA taken steps to ban the tobacco products?

• DPA testing also suggested that quality control processes used to manufacture these products are inconsistent or non-existent. Would you please specify an example of which quality control processes are either inconsistent or non-existent? The manufacturers would then be able to rectify any problems you have concerns about.

• Specifically, DPA analysis of the electronic cigarette cartridges from the two leading brands revealed the following:

  • Diethylene glycol was detected in one cartridge at approximately 1%. Diethylene glycol, an ingredient used in antifreeze, is toxic to humans. This is the same ingredient which is widely used as a humectant for tobacco ... right? I believe the special warning states ... poison by inhalation, is moderately toxic to humans by ingestion and intravenous routes, is mildly toxic by subcutaneous route and is an experimental carcinogen, tumorigen and teratogen. It is also an eye and human skin irritant. Since there was only one cartridge that it was detected in, they can probably leave it out in the future and you'll break the news to the tobacco companies ... right?

  • Certain tobacco-specific nitrosamines which are human carcinogens were detected in half of the samples tested. They were detected in less than half the samples. Specific nitrosamines were found in 4 out of 24 samples from Smoking Everywhere and were detected in 12 out of 16 Njoy samples.

  • Tobacco-specific impurities suspected of being harmful to humans anabasine, myosmine, and β-nicotyrine were detected in a majority of the samples tested. According to Table 1, in the report, the Limit of detection Cotinine 20 ppb. Anabasine 10ppb, myosmine 69ppb, β-nicotyrine 170ppb is present but at less than the level of the Nicotrol specification, so where is the problem and will you be banning Nicotrol now also?

  • The electronic cigarette cartridges that were labeled as containing no nicotine had low levels of nicotine present in all cartridges tested, except one. HSGC-MS analysis was conducted at 60 C to simulate the temperature that would be encountered during activation of an e-cigarette. According to the test results, Nicotine was detepted in both products for all cartridges containing low, medium and high levels of nicotine but was not observed in cartridges identified as containing no nicotine.

  • Three different electronic cigarette cartridges with the same label were tested and each cartridge emitted a markedly different amount of nicotine with each puff. The nicotine levels per puff ranged from 26.8 to 43.2 mcg nicotine/100 mL puff. Levels found were consistent with the labeling (low, medium and high); however, the cartridge labeled no still delivered some nicotine by using a sparging apparatus to quantify the right amount of nicotine released during use. If I remember correctly, the tobacco product, level per puff also varies a great deal under these same testing conditions ... right? According to Health Canada, No smoking machine can accurately reproduce people's very complex smoking behaviour. Smokers' behaviour varies from cigarette to cigarette and from person to person. No differences in toxicity across cigarette brands should be concluded from the yield numbers. A small number of toxicity tests have been developed for this purpose, but their value for comparison has not yet been validated. .  

  • One high-nicotine cartridge delivered twice as much nicotine to users when the vapor from that electronic cigarette brand was inhaled than was delivered by a sample of the nicotine inhalation product (used as a control) approved by FDA for use as a smoking cessation aid. The cartridges labeled high delivered more nicotine than the approved Nicotrol product. Repeat testing of 3 different cartridges with the same label (menthol high) gave varying results from 26.8 to 43.2 mcg nicotine/100 mL puff. If the Nicotrol inhaler was used as a control, why aren't there any results provided, so as to compare these products properly? It would be a good isea to use tobacco cigarettes as a control next time so as to reach a full and complete conclusion as to whether or not the electronic cigarette is actually a safer product for the consumer to utilize.

FDA taking public comments on tobacco regulation

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA2009N0294]
Regulation of Tobacco Products; Extension of Comment Period
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; extension of comment period.

More Information
SUMMARY: The Food and Drug Administration (FDA) is extending to December 28, 2009, the comment period for the notice that appeared in the Federal Register of July 1, 2009 (74 FR 31457). In the notice, FDA requested comments on the implementation of the Family Smoking Prevention and Tobacco Control Act (the Tobacco Act). The agency is taking this action in response to a request for an extension to allow interested persons additional time to submit comments. 

Comments can be submitted to the agency online at http://www.regulations.gov, or by mail to the Division of Dockets Management [HFA-305], Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. Comments should be identified with the docket number, FDA-2009-N-0294.