Letter to HHS Secretary Tommy Thompson calling on the government to seize 10 products containing synthetic ephedra (HRG Publication #1608)
Tommy Thompson, Secretary
January 31, 2002
FDA has concluded that synthetically produced ephedrine alkaloids are not “dietary ingredients” as defined in 21 USC §321 (ff)(1)…FDA has further concluded that products containing synthetic ephedrine alkaloids do not fall under the dietary supplement regulatory scheme and should be regulated as drugs.
Under this interpretation of the FDCA, the FDA has recently taken action against E’OLA International and its contract manufacturer Nature's Energy, Inc, by seizing their adulterated product, Amp II Pro Drops, and the bulk Ephedrine HCl used to manufacture it.
In its complaint requesting product seizure against E’OLA, the FDA asserts that synthetic Ephedrine HCl cannot be considered a legitimate dietary supplement ingredient because it is a new drug that was not marketed as a dietary supplement prior to its approval in 1948. This court-proven argument invariably holds true for other synthetic ephedrine alkaloids such as PPA and pseudoephedrine.
These companies are specifically advertising their products as “pharmaceutical grade” and consistently make strong efforts to distinguish them from herbal based ephedrine alkaloid dietary supplements. For example, the company which manufactures Overdrive warns potential ephedrine alkaloid dietary supplement consumers to “be sure that the product [they] purchase contains only pharmaceutical grade ingredients and not herbal derivatives.” Given that the FDA has determined that synthetic drugs are not legitimate ingredients for dietary supplements, and since Ephedrine HCl and PPA are defined as drugs, these products should also be seized on the basis of being unapproved new drugs.
· 3308 adverse events for all dietary supplements, of which 1398 (42%) are associated with ephedrine alkaloid dietary supplements (EADS)
· 137 reports of death, 81 (59%) associated with EADS
· 38 reports of myocardial infarction/heart attack, 32 (84%) associated with EADS
· 98 reports of cardiac arrhythmias, 62 (63%) associated with EADS
· 144 reports of hypertension, 91 (63%) associated with EADS
· 85 reports of stroke, 69 (81%) associated with EADS
· 121 reports of seizure, 70 (58%) associated with EADS
In addition to seizing the ten drug products mentioned in this letter, the broader goal of banning all ephedrine alkaloid dietary supplements demands your immediate attention.
The sale of these dangerous products over the Internet is a cause for added concern. By forgoing the physical limitations of the traditional marketplace these products are readily accessible to minors who may not be fully aware of the abuse and injury potential of these dangerous drugs. The marketing techniques used on a majority of these websites promotes usage of these products for the indications of weight loss and energy enhancement. Coupling these indications with explicit language describing these drugs as synthetic chemicals surely promotes substance abuse. In fact, the makers of Hollywood Cuts explicitly state that the ingredient ““1R, 2S Norephedrine [PPA] is a close cousin to the pharmaceutical “amphetamine.” Also, the presence of both caffeine and ephedrine alkaloids increases the abuse potential of these drugs. The scientific literature shows that the combination of ephedrine and caffeine at individually sub-threshold quantities are synergistically able to produce an effect that is similar to that of amphetamine, an illegal drug.Therefore, we believe that sale of these alleged dietary supplements over the Internet increases the risk of substance abuse, especially by minors and young adults.
In summary, we have compiled a list of nine manufacturers who are publicly selling ten mislabeled drugs in the United States over the Internet. These products and the materials used to manufacture them are subject to seizure under the laws and regulations detailed above. Failure to act swiftly and decisively in this matter as required by law and to ban all ephedra alkaloids will result in a continuation of the harm and injury of dietary supplement consumers nationwide and will emphasize how fraudulent your concerns about food safety are.
Amer K. Ardati
Sidney M. Wolfe, MD
Health Canada. Advisory not to use products containing Ephedra or ephedrine. [Advisory] June 14th, 2001. http://www.hc-sc.gc.ca/english/protection/warnings/2001/2001_67e.htm
Health Canada. Health Canada requests recall of certain products containing Ephedra/ ephedrine. [Advisory] January 9th, 2002. http://www.hc-sc.gc.ca/english/protection/warnings/2002/2002_01e.htm
Ephedrine alkaloids include: ephedrine, pseudoephedrine, methylephedrine, norephedrine, and norpseudoephedrine. Norephedrine (also known as phenylpropanolamine - PPA) was recently banned by the FDA. These compounds are able to elicit physiological responses similar to sympathetic nervous system catecholamines and are hence known as sympathomimetics. These compounds are known to increase the risk for hypertension, stroke and heart attacks.
FDA Talk Paper “U.S. Marshals Seize Unapproved Drug in FDA Case.” October 31st, 2001. The FDA announced the seizure of 140,000 bottles of dietary supplements containing synthetic ephedrine and the bulk ephedrine used for production purposes from Biogenics, Inc. of St. George, Utah.
21 USC 321(ff) (1)
Baker, Dennis E. Letter to Laura Nagel, Deputy Assistant Administrator for the Office of Diversion Control of the Drug Enforcement Administration. June 21st, 2001.
Plaisier, Melinda K. Letter to Representative Henry Waxman. October 31st, 2001.
FDA Talk Paper, op cit.
Warner, Paul M. United States complaint filed with United States District Court for the District of Utah, Central Division. October 22nd, 2001 (Civil No. 2:01CV-820C). The complaint cites 21 USC 321 (ff) (3) (B) which prohibits the marketing of new drugs in dietary supplements. 21 USC 321 (ff) (3) (A) does not apply to Ephedrine HCl because it was not marketed as a dietary supplement prior to its approval as a new drug in 1948.
Pharmanex v. Shalala, 221 F.3d 1151 (2000); here the court states “that approval of active ingredients is integral to the overall new drug approval process,” and concludes that the term “an article that is approved as a new drug” 21 USC 321 (ff) (3) (B) applies to both final drug products and their ingredients. Therefore active ingredients of approved drugs may not be used in the production of dietary supplements unless they meet the criteria of 21 USC 321 (ff) (3) (A).
Warner, Paul M. op cit. These products are considered drugs under the definition of drugs as articles intended for the diagnosis, cure, mitigation, treatment, or prevention of disease in man. In this case, the supplements are marketed as weight-loss drugs. They are new drugs because the safety and efficacy of these drugs have not been evaluated, and hence they must apply for approval. 21 USC 321 (g)(1)(c) also 321 (p) and 355 (b).
Federal Register 48(224):52513 November 18, 1983
Federal Register 66(157):42665 August 14, 2001
The American Herbal Products Association, the Consumer Healthcare Products Association, the National Nutritional Foods Association and the Utah Natural Products Alliance. Citizen Petition to the FDA. October 25th, 2000 (FDA Docket # 95N-0304/CP2). The petitioners propose that “neither finished consumer goods nor raw materials used in their manufacture are to contain any synthetically derived ephedrine alkaloids or their salts.” Moreover, they suggest that industry has already “effectively” implemented a voluntary program for ephedra and that it has been adopted by “virtually all major manufacturers and distributors of ephedra products.”
Public Citizen Health Research Group and Raymond Woosley. Petition to the Secretary of Health and Human Services. September 5th, 2001. (FDA Docket # 01P-0396)
Young, R.; Gabryszuk, M.; Glennon, R. A. (-)Ephedrine and caffeine mutually potentiate one another's amphetamine-like stimulus effects. Pharmacology Biochemistry and Behavior, 1998; 61:169-73