Posted by Monte_Alto in Jul 21, 2009, under Uncategorized
Center for Drug Evaluation and Research
Division of Pharmaceutical Analysis
St. Louis, MO 63101
Tel. (xxx) xxx-xxxx
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
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 Î²-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 10 ppb; myosmine 69 ppb; Î²-nicotyrine 170 ppb 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 detected 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 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?
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 idea to use tobacco cigarettes as a control next time so as to reach a full and complete conclusion and to whether or not the electronic cigarette is actually a safer product for the consumer to utilize.
The complete summary can be reviewed here.
The light blue comments are from the Analysis conducted by the FDA. The dark blue comments are mostly my own.
I was wondering … what’s up with this? I found this on page 6 Attachment A … in the FDA Report and in all honesty, it’s hard to tell what it says when the lettering is blocked like that, so maybe you can enlighten us?
Whole Cartridges: Detection and Quantitation of Nicotine by HPLC-UV Smokeless tobacco cartridges were extracted and analyzed using two different procedures:
* Methanol extraction and USP analytical procedure: cartridge components were weighed, extracted with methanol and reweighed. An aliquot of the methanol extract was diluted with mobile phase and analyzed by HPLC-UV following USP 31 p 2801 Nicotine Transdermal System Assay procedure.
*Extraction with __________________________________________________________________ (b) (4)_______________________________________ as described in NDA 20-714, Phamacia & Upjohn method Nicotine, Content Uniformity, Identification and Determination of Nicotine Related Substances in Nicotine Inhaler 10 mg method NM-046-6 dated 1999-07-16