| Public Health Service Food and Drug Administration |
| Silver Spring, MD 20993-0002 |
Department of Health and Human Services
WARNING LETTER
September 8, 2010
Mr. Sihui (Sam) Han
Cixi E-Cig Technology Inc, Ltd.
E-Cig Technology Inc.
7488 Celosia St.
Las Vegas, NV 89113
Las Vegas, NV 89113
Dear Mr. Han:
This letter concerns the E-Cig Technology brand of electronic cigarettes, cigars, and USB cigarettes, and the components thereof, that are marketed by your firm (collectively "E-Cig Technology products").
Based on our review of the products' labeling, including your Internet website for these products, (www.e-cig.com), the E-Cig Technology electronic cigarettes, cigars, and USB cigarettes are constructed with a lithium ion rechargeable battery, a microprocessor, a heating element, and a cartridge that contains, or is intended to contain, various chemicals, including nicotine (in varying specified levels). Nicotine and/or other chemicals are intended to be volatilized when the user inhales through these electronic cigarette products. These electronic products do not contain tobacco leaf or stem. Each E-Cig Technology product is intended to heat air as it is drawn through it by the user. This heated air purportedly volatilizes the chemicals contained in the replaceable cartridge component of these products. The volatilized chemicals are then inhaled by the user.
The E-Cig Technology E-Liquid and Healthcare E-Liquid products, which may or may not contain nicotine, are intended and labeled for use with the electronic smoking products described above to fill depleted or empty cartridges that are components of these electronic smoking products. Additionally, E-Cig Technology offers the components of electronic cigarettes, cigars, and USB cigarettes such as cartridges, inhalers, cores, atomizers, E-Cigarillo lid, batteries, and chargers for sale.
E-Cig Technology also distributes various accessories for electronic cigarettes, cigars, and USB cigarettes, such as syringes with needles, plastic dropper bottles, and plastic bottles, which are intended and labeled to aid users of these electronic smoking products when transferring the E-Cig Technology E-liquid into depleted or empty cartridges of various brands/models of these products and/or into empty E-Cig Technology cartridges.
As presently labeled and promoted, these E-Cig Technology products violate provisions of the Federal Food, Drug, and Cosmetic Act (the Act). As described in more detail below, E-Cig Technology products are unapproved new drugs marketed in the United States in violation of section 505 of the Act (21 U.S.C. § 355), are misbranded under section 502 of the Act (21 U.S.C. § 352), and adulterated under section 501 of the Act (21 U.S.C. § 351).
Both the “drug” and “device” definitions in sections 201(g) and 201(h) of the Act (21 U.S.C. §§ 321(g) and (h)), encompass products intended either to affect the structure or function of the body or to cure, mitigate, treat, or prevent disease. Based on our review of the products and their associated labeling and promotional materials, these products are drug-device combination products, with a drug primary mode of action.
Statements in labeling and promotional materials, including your Internet website at www.e-cig.com, that reflect the intended uses for the products you market, include, but are not limited to, the following:
Home
“Why choose E-Cig? . . . E-Cig can help you reduce or quit smoking habits.”
Instruction Manuals
“E-Cigarillo Instruction Manual
"It can refresh the smokers and satisfy their smoking addiction, making them happy and relaxed, so as to relief [sic] the suffering of quitting smoking.
The essentially [sic] differences between the Electronic Cigarillo and the ordinary Cigarette are as follows: . . . 5. According to the smoke-quitting procedure, the target of quitting smoke can be reached non-painfully within a certain period of time . . . Suitable User . . . The smokers who want [sic] to quit smoking. Painless smoking abstention can be realized gradually by decreasing nicotine content.”
Consumer Testimonials
“Testimonials
I have published my recommendations in one of the largest newspapers in Israel and in many other forums I am a member of, and to all my closest friends who ordered and stopped smoking also. - - A. Rahamim
I have not had a real cigarette since Monday night . . . I feel this could be the first thing that really works to keep me off real cigarettes (have tried the gum, patch, zyban, etc ...).” . - - A. Bastarache”
“Read Reviews
James USA . . . I am extremely pleased with this product and I will be purchasing more cartridges to move from dangerous cigarettes to your safer invention.
Conrad CO . . . I LOVE your product and all my friends have ordered because I was able to quit smoking with your Ecig!”
Press
“Take Smoking To Next Level . . .
One product called E-Rimonabant promises to help users lose weight and combat their smoking addiction. This electronic cigarette produces vaporable Rimonabant, an anorectic anti-obesity drug. As an inverse agonist for the cannabinoid receptor CBI, Rimonabant helps reduce appetite by creating a full or satisfied feeling.
‘Rimonabant also reduces those strong cravings for smokers, which may help users quit smoking completely or reduce their smoking dependency. E-Rimonabant has the same characteristics and effectiveness as the original Rimonabant’, states Sam Han, owner of E-Cig Technology, Inc. Ltd.
Another innovative product that has recently come on the scene at E-Cig is called E-Cialis. This electronic cigarette helps improve sexual capacity for men who suffer with ED (erectile dysfunction). More than 50 percent of men between the ages of 40 and 70 years experience ED to some degree. E-Cialis provides a simple solution by enhancing sexual performance when smoking an electronic cigarette.
‘E-Cialis produces vaporable Cialis, an ED medication which is currently marketed in pill form and is more effective and longer lasting than Viagra.’”
News & Announcement
“5 July 2009 - New Product E-Cialis has been released . . . we have developed this new Vaporizable Cialis which have [sic] the same characteristic and the same effectiveness as the original Cialis. Now you can treat your ED or pulmonary arterial hypertension and improve your sexual capacity by smoking.
8 July 2009 - New Product E-Rimonabant has been released . . . this new Vaporizable Rimonabant which have [sic] the same characteristic and the same effectiveness as the original Rimonabant. Now you can Loss [sic] Your Weight and Reduce Your Smoking Addiction! by smoking.
5 May 2008 - Healthcare Liquid released . . . Healthcare Liquid is available now. These new developped [sic] Electronic Smoking Healthcare Liquid products not only give you the same feeling as a tobacco cigar or cigarette without suffering any tar and carbon monoxide smoking damages, but also give you the personal health care for your body.”
Product Page
“Electronic Smoking Liquid Vitamins are a great way to increase absorpion [sic] into the blood stream and produce maximum efficacy. It will give you not only the same feeling as a tobacco cigar or cigarette without suffering any tar and carbon monoxide smoking damages, but also give you the highest possible bodily absorption, and keeps your immune system running in tip-top shape. . . You can use it with any brand and model of E-Cig products.”
The above statements demonstrate that the E-Cig Technology products marketed by your firm are intended both to affect the structure or function of the body and to mitigate, treat, or prevent disease. See 21 C.F.R. § 201.128 (describing the meaning of “intended use”). In particular, these statements suggest that these products are intended for use as smoking deterrents or to reduce dependence on traditional tobacco products, and are also capable of delivering nicotine. The scientific and medical communities have determined that nicotine is a pharmacological agent,1 that nicotine addiction is a disease,2 and that nicotine withdrawal is itself a recognized medical condition.3 It is well understood that people smoke for the pharmacologically rewarding effects of nicotine, such as alleviation of stress and negative mood, enhancement of thinking, and increased alertness.4 For an addicted smoker, the body has adapted to nicotine, and abstinence produces withdrawal and craving.5 As a result, people also smoke to avoid the negative effects of nicotine withdrawal, such as anxiety, difficulty concentrating, negative mood, increased appetite, insomnia, and irritability.6 Therefore, the claims noted above demonstrate that the E-Cig Technology products are intended to affect the structure or function of the body and to mitigate, treat, or prevent disease.
Furthermore, the E-Cig Technology products and their components, described above, are also intended both to affect the structure or function of the body (e.g., by providing various vitamins for inhalation to supplement the diet, helping people lose weight, improving sexual capacity, and improving the overall health of the user) and to mitigate, treat, or prevent disease (e.g., mitigate, treat, or prevent erectile dysfunction).
As described in 21 C.F.R. § 310.544, any product that bears labeling claims that it “helps stop or reduce the cigarette urge,” “helps stop or reduce smoking,” or similar claims is a smoking deterrent drug product.7 Products that are labeled, represented, or promoted as smoking deterrents, such as the E-Cig Technology products marketed by your firm, are regarded as “new drugs” under section 201(p) of the Act (21 U.S.C. § 321(p)) because there is a lack of adequate data establishing that they are generally recognized as safe and effective for such use. See 21 C.F.R. § 310.544. These products are also “new drugs” under the Act because we are not aware of any data establishing that these E-Cig Technology products are generally recognized among scientific experts as safe and effective for the other drug uses described above and in the products’ labeling. “New drugs” require approval of an application filed in accordance with section 505 of the Act (21 U.S.C. § 355) to be legally marketed in the United States. None of the E-Cig Technology or any of their components marketed by your firm is so approved; therefore, marketing these products in the United States violates section 505 of the Act.
E-Cig Technology products are also misbranded under section 502(e)(1)(A)(ii) of the Act (21 U.S.C. § 352(e)(1)(A)(ii)) because their labeling fails to declare the quantity of each active ingredients for their Cialis, Rimonabant, and E-liquid products.
The E-Cig Technology products marketed by your firm are also misbranded under section 502 of the Act (21 U.S.C. § 352) because they are intended for use as smoking deterrents under 21 C.F.R. § 310.544 but are not covered by an approved new drug application. The E-Cig Technology products are further misbranded under section 502(f)(1) of the Act (21 U.S.C. § 352(f)(1)) because they do not bear adequate directions for their intended drug uses, including smoking deterrence and treatment of erectile dysfunction. “Adequate directions for use” is defined in 21 C.F.R. § 201.5 as “directions under which the layman can use a drug safely and for the purposes for which it is intended.”
FDA’s Division of Pharmaceutical Analysis (DPA) evaluated multiple samples of your products and in a sample of the Vitamin C E-Liquid, we detected DEG. The presence of DEG in the Vitamin C E-liquid drug product suggests that DEG has been added to a component in this drug product. DEG is an unexpected contaminant in Vitamin C E-liquid, perhaps tracing to DEG contamination of one of the ingredients used to manufacture Vitamin C E-liquid. The amount of this adulterant our lab found in Vitamin C E-liquid is fivefold in excess of the USP upper limit for DEG in Propylene Glycol and Glycerin, which are currently listed on your website as possible product ingredients.8 The USP monographs for Glycerin and Propylene Glycol have a DEG upper limit of 0.1% to prevent and detect DEG intentionally added as an adulterant. In certain instances outside the United States in which a drug manufacturer failed to detect DEG in an ingredient such as glycerin or propylene glycol, the health consequences from DEG poisoning have been serious and irreversible. According to section 801(a)(3) of the Act (21 U.S.C. §381(a)(3)), an imported drug that appears to be adulterated shall be refused admission into the United States. It appears that the DEG contamination renders your product adulterated under section 501(a)(2)(B) of the Act (21 U.S.C. 351(a)(2)(B)) and may not be imported into this country.
In addition, testing by FDA’s DPA revealed that several samples of your product were tested and revealed that the amount of active ingredient in the product did not correspond with that amount represented on the labeling. Specifically, the Rimonabant prefilled cartridges, the Rimonabant Healthcare E-Liquid, and the nicotine containing prefilled cartridges and E-Liquids did not contain the amount of active ingredients as represented on your labeling. The failure of your products to contain the amount of ingredients they purport to contain renders the products adulterated under section 501(c) of the Act. (21 U.S.C 351(c)). 9
Testing by FDA's DPA also revealed that the Cialis prefilled cartridges and the Cialis Healthcare E-Liquid contained amino-tadalafil, not tadalafil, the reference listed drug in Cialis. The substitution of this ingredient renders the products adulterated under section 501(d) of the Act. (21 U.S.C 351(d)).
Please be aware that the FDA has issued a letter addressed to the Electronic Cigarette Association (ECA) which explains, in detail, how the electronic cigarette industry can begin the drug approval process. For your convenience, we have enclosed a copy of that letter and encourage you to follow through with the recommendations.
The violations cited in this letterare not intended to be an all-inclusive list of deficiencies regarding your products, nor are the arguments raised here regarding them exhaustive. You are responsible for investigating and determining the causes of these violations and for preventing their recurrence and the occurrence of other violations. It is your responsibility to assure that your firm complies with all requirements of federal law and FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts.
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct the referenced violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction. Furthermore, please state what actions you will take to address products that you have already distributed. If another firm manufactures the products identified above, your reply should include the name and address of the manufacturer. If the firm from which you receive the products is not the manufacturer, please include the name of your supplier in addition to the manufacturer. Please direct your response to FDA's Electronic Cigarette Mailbox at FDAElectronicCigaretteMailboxCDER@fda.hhs.govor (301) 796-3110.
Sincerely,
/S/
Michael M. Levy, Jr., Esq.
Director, Division of New Drugs and Labeling Compliance
Office of Compliance
Center for Drug Evaluation and Research
1 E.g., P. Taylor, Agents Acting at the Neuromuscular Junction and Autonomic Ganglia, in Goodman & Gilman’s The Pharmacological Basis of Therapeutics 193, 193-218 (J.G. Hardman, L.E. Limbird & A.G. Gilman eds., 2001).
2 World Health Organization, ICD-10 International Statistical Classification of Diseases, 10th Revision (2nd ed. 2007).
3 American Psychiatric Association, Diagnostic and Statistical Manual -- Text Revision 192 (2000).
4 E.g.Pharmacologic Aspects of Cigarette Smoking and Nicotine, 319 New Eng. J. Med. 1318 (1988), N.L. Benowitz, Drug Therapy.
5 See World Health Organization, supra note 2.
6 E.g. T.B. Baker, T.H. Brandon & L. Chassin, Motivational Influences on Cigarette Smoking, 55 Ann. Rev. Psychol. 463 (2004).
7 We note that the determination as to whether e-cigarette products would be considered Rx or OTC will be made during the review of an NDA submission.
8 The website provides a choice of either the “propylene glycol” or “vegetable glycerin” base for the Vitamin C E-liquid.
9 The actual ingredient content found in the E-Liquids and prefilled cartridges were inconsistent in many cases with the amounts specified on the manufacturer’s website. Also, there were several incidences in which we detected nicotine in products represented as nicotine-free.
-
No comments:
Post a Comment