Driven Sports Inc. 4/4/14
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Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
5100 Paint Branch ParkwayCollege Park, MD 20740
April 4, 2014
VIA OVERNIGHT DELIVERY
Mr. Matthew J. Cahill
Driven Sports Inc.
672 Dogwood Avenue
Franklin Square, NY 11010
Re: Case # 413379
Dear Mr. Cahill:
This letter concerns your product CRAZE, which is labeled and promoted as a dietary supplement. The supplement facts panel on your product label declares “Dendrobex™ (Dendrobium Extract) (stem) (concentrated for alkaloid content including Dendrobine, Dendroxine, Dendramine, B-Phenylethylamine, N,N-Dimethyl-B-Phenylethylamine, and N,N-Diethyl-B-Phenylethylamine))” (hereinafter referred to as Dendrobex™) as a dietary ingredient. Your product label does not declare N,α-diethylphenylethylamine as an ingredient. According to the statement dated January 8, 2014, on your website, drivensports.com, due to reports of the presence of N,α-diethylphenylethylamine in CRAZE, which you dispute, you had stopped distributing CRAZE and were in the process of completing destruction of any remaining inventory to which you have access. You have not conducted a recall of this product. In addition, you have announced plans to market new products, but have not specified whether they will contain Dendrobex™. As explained below, even if CRAZE does not contain N,α-diethylphenylethylamine, the presence of Dendrobex™ in CRAZE renders this product adulterated under the Federal Food, Drug, and Cosmetic Act (the Act).
The term “dietary supplement” is defined in section 201(ff) of the Act [21 U.S.C. 321(ff)]. Given that you have declared Dendrobex™ as a dietary ingredient in the labeling of your product, we assume you have a basis to conclude that Dendrobex™ is a “dietary ingredient” under section 201(ff)(1) of the Act [21 U.S.C. 321(ff)(1)]. Assuming that Dendrobex™ is a “dietary ingredient,” it would also be a “new dietary ingredient” for which a notification is required under section 413(a)(2) of the Act [21 U.S.C. 350b(a)(2)] and 21 CFR 190.6.
Under section 413 of the Act (21 U.S.C. 350b), a dietary supplement that contains a new dietary ingredient (i.e., a dietary ingredient not marketed in the United States before October 15, 1994) shall be deemed adulterated under section 402(f) of the Act [21 U.S.C. 342(f)] unless it meets one of two requirements:
1. The dietary supplement contains only dietary ingredients that have been present in the food supply as articles used for food in a form in which the food has not been chemically altered; or
2. There is a history of use or other evidence of safety establishing that the dietary ingredient, when used under the conditions recommended or suggested in the labeling of the dietary supplement, will reasonably be expected to be safe and, at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or dietary supplement provides FDA with information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe.
To the best of FDA’s knowledge, there is no information demonstrating that Dendrobex™ was lawfully marketed as a dietary ingredient in the United States before October 15, 1994, nor is there information demonstrating that this ingredient has been present in the food supply as an article used for food in a form in which the food has not been chemically altered. In the absence of such information, Dendrobex™ is subject to the notification requirement in section 413(a)(2) of the Act and 21 CFR 190.6. Because the required notification has not been submitted, your product is adulterated under sections 402(f)(1)(B) and 413(a) of the Act [21 U.S.C. 342(f)(1)(B) and 350b(a)].
Even if the required notification had been submitted, we know of no evidence that would establishe that your product is not adulterated. In the absence of a history of use or other evidence of safety establishing that Dendrobex™, when used under the conditions recommended or suggested in the labeling of your products, will reasonably be expected to be safe, CRAZE is adulterated under sections 402(f)(1)(B) and 413(a) because it contains a new dietary ingredient for which there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury. Introduction of such a product into interstate commerce is prohibited under sections 301(a) and (v) of the Act [21 U.S.C. 331(a) and (v)]. To the best of FDA’s knowledge, there is no history of use or other evidence of safety establishing that Dendrobex™ will reasonably be expected to be safe when used as a dietary ingredient.
We request that you take prompt action to correct the violations cited above, as well as any other violations associated with CRAZE and any other products marketed by your firm that contain Dendrobex™. We acknowledge the email from your attorney, dated February 11, 2014, stating your plans to destroy the existing stock of CRAZE held by your distributors. However, you have not provided any written assurances that you will be correcting the violations listed above.
We also remind you that the new dietary ingredient notification requirement applies to all dietary supplements that contain new dietary ingredients that have not been present in the food supply as articles used for food in a form in which the food has not been chemically altered. It is your responsibility to ensure that your firm complies with all requirements of federal law and regulations.
Further distribution of all products containing Dendrobex™ may result in enforcement action by FDA without further notice. The Act provides for seizure of violative products and injunction against the manufacturers and distributors of violative products.
Additionally, we have the following comments:
- You declare Dendrobex™ is Dendrobium Extract. As described below, based on our review of peer-reviewed, credible scientific literature, phenethylamine-type alkaloids (PEAs) - such as B-Phenylethylamine, N,N-Dimethyl-B-Phenylethylamine, and N,N-Diethyl-B-Phenylethylamine - which you declare as part of Dendrobex™, do not appear to be present in the Dendrobium species. Therefore, if the Dendrobium Extract in Dendrobex™ contains PEAs, as indicated on the label for CRAZE, please explain how the PEAs are present.
In a study by Wang et al. (2010)
, the main alkaloid of Dendrobium
(collected from Guizhou Province, P.R. of China in 2004—which is referred to as D. nobile (Guizhou) in the literature referenced below, Xu et al. (2010)) was dendrobine (90.7% of the extract with ratio 308:1). Other alkaloids were Dendramine (2.31%), 3-Hydroxy-2-oxodendrobine (1.29%), and Nobilonine (4.47%). In the study by Li et al. (2011)
, the composition of alkaloids in Dendrobium nobile
Lindl is identical to the alkaloid composition as determined in the study by Wang et al. (2010). Neither of these studies identifies PEAs as a constituent of Dendrobium
Furthermore, in the study by Xu et al (2010)
, several species of Dendrobium
were investigated for five components, including two alkaloids: dendrobine and dendronobilin A. The Dendrobium
was collected from different provinces of China; specifically, Yunnan, Anhui and Guizhou. Dendrobine was found in only one species (D. nobile
from Yunnan Province and Guizhou Province), and dendronobilin A was not found in any of the species investigated. For example, D. huoshanense
(Anhui and commercial) contained neither alkaloid.
These studies established the presence of several alkaloids in the Dendrobium species; however, none revealed the presence of B-Phenylethylamine, N,N-Dimethyl-B-Phenylethylamine, or N,N-Diethyl-B-Phenylethylamine. Based on these studies, it is unclear on what information you rely in asserting that Dendrobium contains PEAs.
- A recent study indicates that your product may contain N,α-diethylphenylethylamine, an ingredient not listed on your product label. This ingredient has been reported in this recent study to be found in excess of 20 mg per serving in your product. FDA is not aware of any information demonstrating that N,α-diethylphenylethylamine was lawfully marketed as a dietary ingredient in the United States before October 15, 1994, nor is FDA aware of any information demonstrating that this ingredient has been present in the food supply as an article used for food in a form in which the food has not been chemically altered. In the absence of such information, dietary supplement products containing N,α-diethylphenylethylamine as a dietary ingredient are also subject to the notification requirement for a new dietary ingredient in section 413(a)(2) of the Act and 21 CFR 190.6. Products that contain N,α-diethylphenylethylamine for which the required notification has not been submitted would be adulterated under sections 402(f)(1)(B) and 413(a) of the Act.
We request that you advise us in writing, within 15 days of receipt of this letter, as to the specific steps that have been or will be taken to correct these violations, including any steps taken with respect to product currently in the marketplace. Your response should also include an explanation of each step taken to ensure that similar violations do not recur, as well as documentation to support your response, including documentation of the destruction of CRAZE.
In addition to your legal responsibility to file a notification with FDA for certain new dietary ingredients under Section 413 of the Act, we are requesting that you come in for a meeting to discuss the products that you intend to market.
Please send your response to Mr. Quyen Tien, Compliance Officer, at the following address:
U.S. Food and Drug Administration
Office of Compliance
Division of Enforcement
5100 Paint Branch Parkway
College Park, MD 20740
If you have any questions, please contact Mr. Tien at 215-717-3705 or Quyen.Tien@fda.hhs.gov
. You may also contact Mr. Tien to request the meeting referred to above.
Amy A. Barringer
Office of Compliance
Center for Food Safety
and Applied Nutrition
cc: FDA New York District Office
 Wang et al. (2010) Neuroprotective effects of Dendrobium alkaloids on rat cortical neurons injured by oxygen-glucose deprivation and reperfusion, Phytomedicine 17: 108–115.  Li et al. (2011) Inhibitory Effects of Dendrobium Alkaloids on Memory Impairment Induced by Lipopolysaccharide in Rats, Planta Med, 77: 117–121.  Xu et al. (2010) Fast determination of five components of coumarin, alkaloids and bibenzyls in Dendrobium spp. using pressurized liquid extraction and ultra-performance liquid chromatography, J. of Separation Science, 33: 1580–1586.  Cohen et al. (2013) A methamphetamine analog (N,α-diethylphenylethylamine) identified in a mainstream dietary supplement. Drug Testing and Analysis DOI 10.1002/dta.1578