FOOD AND DRUG ADMINISTRATION
Cold, Cough, Allergy, Bronchodilator,
and Antiasthmatic Drug Products for
Over-the-Counter Human Use;
Proposed Amendment of Monograph
for OTC Bronchodilator Drug
Docket No. 95N-0205
JOINT COMMENTS OF
DURK PEARSON AND SANDY SHAW;
LIFE ENHANCEMENT INTERNATIONAL; WILL BLOCK;
LIFE EXTENSION FOUNDATION; WILLIAM FALOON;
LIFE PRIORITY; GREG PRYOR AND MICHELLE PRYOR;
SMART BASICS; AND JIM ENGLISH
Durk Pearson and Sandy Shaw; Life Enhancement International; Will Block; Life
Extension Foundation; William Faloon; Life Priority; Greg Pryor and Michelle Pryor; Smart Basics; and Jim English, by their counsel and in accordance with Section 10.25 of the FDA's Rules, 21 C.F.R. ' 10.25, hereby submit the following joint comments in partial opposition to the proposed rule in the above-referenced docket.
I. BACKGROUND OF THE COMMENTERS AND THEIR INTERESTS
Durk Pearson and Sandy Shaw.
Durk Pearson and Sandy Shaw ("P & S") are scientists, resident in Nevada, who are widely respected for their best-selling books Life Extension: A Practical Scientific Approach (Adding Years to Your Life and Life to Your Years) (1982); The Life Extension Companion (1984); and The Life Extension Weight Loss Program (1986), as well as their new book Freedom of Informed Choice: FDA v. Nutrient Supplements (1993). Pearson and Shaw have designed several popular and safe lines of dietary supplements and personal care products (which they use themselves) that are marketed by license through companies worldwide. P & S have a direct interest in this proceeding because one of the dietary supplement formulas they license to companies is ephedra herb tea.
Life Enhancement International and Will Block.
Life Enhancement International ("Life Enhancement") is a California corporation established in August 1994. Will Block is the President of Life Enhancement. Life Enhancement is a P & S licensee. It sells the P & S ephedra herb tea under the name "Thermogen Tea." Life Enhancement and Will Block thus have a direct interest in this proceeding.
Life Extension Foundation and William Faloon.
The Life Extension Foundation ("LEF") is a Florida not for profit corporation, established in 1980. William Faloon is the Vice President of LEF. LEF is a P & S licensee. It sells their ephedra herb tea under the name "Thermogen Tea." It also sells its own ephedra herb tea supplement under the name "Smart Body Ephedra Herbal Tea." LEF and William Faloon thus have a direct interest in this proceeding.
Life Priority, Inc. and Greg and Michelle Pryor.
Life Priority, Inc. ("Life Priority") is a Kansas corporation established in December 1994. Greg Pryor is the President of Life Priority. Michelle Pryor is the Chief Operating Officer of Life Priority. Life Priority is a P & S formulation distributor. It sells the P & S ephedra herb tea under the name "WillPower Tea." Life Priority and the Pryors thus have a direct interest in this proceeding.
Smart Basics and Jim English.
Smart Basics was incorporated in California in August 1994; it is the successor to Smart Products, incorporated in 1992. Jim English is the President of Smart Basics. Smart Basics is a P & S formulation distributor. It sells their ephedra herb tea under the name "Thermogen Tea." Smart Basics and Jim English thus have a direct interest in this proceeding.
If the FDA classifies all ephedrine (even that occurring naturally in ephedra herb) as not generally recognized as safe (not "GRAS") for OTC purposes, the agency will either cause or lay a precedential foundation for ephedra herb teas and dietary supplement products to be subject to adverse agency action. It will do so despite the fact that as foods and dietary supplements, those products are fully protected against such action or reclassification as not GRAS under the Food, Drug and Cosmetic Act, as amended (the "Act"). Because an indiscriminate determination that all ephedrine is not GRAS would adversely affect the Joint Commenters' economic interests and their opportunity to continue marketing and consuming ephedra herb tea, they each have a direct interest in the outcome of this proceeding and feel compelled to request that the agency make clear that it does not intend for its final rule to affect ephedra herb food or dietary supplement products.
P & S, Life Enhancement, Will Block, LEF, William Faloon, Life Priority, the Pryors, Smart Basics, and Jim English (hereinafter "the Joint Commenters") urge the agency to make plain its intentions concerning ephedra herb in the final rule. Does the agency intend that the rule affect ephedra herb or does it intend its rule to be limited in impact to synthetic forms of ephedrine? For the reasons that follow, the Joint Commenters urge the agency to make explicit that ephedra herb is exempt from the final rule and to limit the final rule to synthetic ephedrine.
III. FACTUAL BASIS FOR COMMENTS
A. History of Ephedra Herb as a Food and a Dietary Supplement
Ephedra herb contains a mixture of the following alkaloids: ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, n-methylephedrine, and n-methylpseudoephedrine. Varro E. Tyler, Herbs of Choice: The Therapeutic Use of Phytomedicinals 88 (1994). Ephedra herb teas, including Chinese Ma Huang tea, have been consumed safely by populations the world over for the past 5,000 years. The herb appears in the 1569 A.D. pharmacopeia, The Chinese Dispensatory (Pentsao Kang Mu). The herb was used in Russia for many centuries. It has also been employed by the Indians and Spaniards of the Southwest United States. Mormon tea includes an American species of ephedra herb. See generally Tyler, Herbs of Choice at 88; Goodman & Gilman's The Pharmacological Basis of Therapeutics (1941). P&S, LEF, and Smart Products (predecessor to Smart Basics) have been marketing ephedra herb dietary supplement formulas and products for years (in the case of P&S and LEF, for nearly a decade). The products have a long history of safe use as foods and dietary supplements.
B. Ephedra Herb
Foods and Dietary Supplements
Ephedra herb contains very small amounts of ephedrine. It is for this principal reason that those who seek to engage in the illicit methamphetamine and methcathinone trade choose neither to import ephedra herb nor to harvest ephedra herbs which populate vast stretches of the American Southwest but to extract synthetic ephedrine from OTC drugs. Dr. Varro Tyler, one of the nation's leading experts on herbs, has remarked upon this common sense distinction between ephedra herb and synthetic ephedrine:
There are no reported cases in the scientific or forensic literature of an ephedra herb containing dietary supplement or food being diverted to the illicit manufacture of methamphetamine or methcathinone, although there have been numerous cases where OTC ephedrine pills have been diverted to such manufacture. The reason for this difference is simple: It is extremely difficult and entirely unprofitable to convert ephedra herb into methamphetamine or methcathinone.
A typical ephedrine tablet may contain 50 milligrams of ephedrine and 150 milligrams of inert tablet filler-binder. The ephedrine content is 25%. The ephedrine can be quickly, easily and economically extracted from the tablets and separated from the inert and frequently insoluble tablet filler-binder using a small amount of solvent. A typical ephedra herb tea contains 20 milligrams of ephedrine in 2 grams of ground ephedra herb (the amount of which is varied to standardize the ephedrine content per serving of tea). When occurring in foods (such as herb teas) and supplements, ephedra herb is mixed with 10 to 20 grams of other constituents consisting of 10 to 20 other herbs, spices, vitamins, minerals, flavor extracts, sugars, and other food ingredients. The ephedrine content of the herbal tea is typically 0.1% to 0.15%, not the 25% common in ephedrine tablets. Because of this, at least 200 times as much solvents would be required to extract ephedrine from the herbal tea than is needed to extract ephedrine from a typical ephedrine tablet. The equipment required to extract ephedrine from the herbal tea would have to be at least 200 times larger than that required to extract ephedrine from tablets. Indeed, the extraction of just 10 kilograms of ephedrine would require about 10,000 kilograms of herbal tea and about 100,000 to 200,000 kilograms of solvents--an operation that is neither economically feasible nor capable of being hidden from the authorities. Moreover, many of the other constituents of ephedra herb tea are far more difficult to separate from ephedrine than the simple tablet fillers and binders (such as dicalcium phosphate) found in ephedrine tablets.
In addition, a typical ephedra herb tea sells for fifty cents to one dollar per serving, a cost per milligram of contained ephedrine that is about 10 to 100 times higher than ephedrine tablets. It is unremarkable that ephedra herb tea is not used to make illicit methamphetamine or methcathinone. There are almost impossible burdens associated with extracting ephedrine from the ephedra herb: (i) far greater cost (by at least 200 times) for solvents to extract ephedrine from the herb as opposed to the tablet; (ii) the economic and practical infeasibility associated with purchasing and storing such a large quantity of solvents (without arousing suspicion); (iii) vastly greater cost (by at least 200 times) for processing ephedrine from the herb; (iv) far greater difficulty and cost and far lower efficiency associated with extracting ephedrine from such a dilute complex mixture; and (v) vastly greater difficulty and cost associated with maintaining a clandestine cover for the large extraction and purification equipment and the extraordinary quantity of solvents (to say nothing of disposing of the 100 to 200 tons of used solvents afterward!). It is thus not at all surprising that ephedra herb tea has never been diverted to methamphetamine or methcathinone manufacture. Because of this the state of Nevada has exempted ephedra herb teas, herbs, and supplements from its ban on ephedrine tablets and most other ephedrine containing products.
C. Ephedra Herb Is Far Less Likely to Be Abused than Ephedrine Tablets
It is very easy for a drug abuser to swallow several cheap 50 milligram ephedrine pills, and to repeat this foolish act every hour. Because of this, there have been several reported hospitalizations due to overdoses of ephedrine pills, and one overdose death. This frequency of abuse, hospitalizations, and death from misuse of ephedrine tablets is far lower than the reported frequency of abuse, hospitalizations, and deaths from misuse of acetaminophen tablets (e.g., Tylenol). There is no rational scientific justification for limiting the availability of ephedrine containing products on the basis of their relatively low level of reported abuse. Moreover, ephedrine is not a drug of abuse as determined by the gold standard animal experiment: Animals will not self-administer ephedrine, unlike the case with amphetamines, opiates, cocaine, and other true drugs of abuse. Finally, while it is quick and easy to consume 10 ephedrine tablets, it is not quick and easy to consume 10 cups of ephedra herb tea (and the quantity of ephedrine in the former would vastly exceed that in the latter). Because of this there is no rational scientific basis for applying the final rule to ephedra herb teas in addition to ephedrine tablets.
D. Ephedra Herb Products "Spiked" with Synthetic Ephedrine Are Readily Discernible
FDA has alleged that it is difficult to detect whether an ephedra herb product has been adulterated ("spiked") with synthetic ephedrine. The agency contends that this difficulty justifies banning ephedra herb products if OTC ephedrine tablets are banned. The purported difficulty is a false predicate. High Performance Liquid Chromatography ("HPLC") can detect such adulteration and HPLC analyses are readily available to, and used by, the herbal product industry. See Exhibit A: An Example. Synthetic ephedrine is much cheaper than the ephedrine contained in ephedra herb and ephedra herb extracts. Hence, law-abiding ephedra herb product formulators have an incentive to ferret out those who use cheap and illegal synthetic ephedrine. The FDA needs no new regulations to prosecute those offenders and no new technology is required to detect that illegal activity.
E. The Less Restrictive Alternative of Fully Informing Consumers
The Joint Commenters design, formulate, manufacture, and sell an ephedra herb containing herbal tea. Their products, like most ephedra herb containing products on the market, display all FDA required warnings and precautions for ephedrine containing OTC products. They also display additional warnings and precautions not required by the FDA. The Joint Commenters do not have on their labels the statement that each serving is standardized (by varying the amount of ground ephedra herb contained per serving) to contain 20 milligrams of ephedrine. The Joint Commenters would prefer to include that information on the label (along with a large amount of other quantitative nutrient content information) but have been informed by their counsel that the provision of such information might result in the FDA declaring the products to be drugs by dint of their labeling. If the FDA provides assurance to the Joint Commenters that the provision of such information will not result in their herbal tea being reclassified as a drug, they will provide that information on the label, along with other quantitative nutrient content data.
F. The Arbitrary and Capricious Nature of the Proposed Rule
The proposed rule is arbitrary and capricious because it sweeps too broadly, drawing within its compass all ephedrine, including that ensconced in common foods (ephedra herb teas) and dietary supplements. The proposed rule is also arbitrary and capricious because it recites a goal that the rule is incapable of achieving. The agency purports to seek the end of the illicit trade in extracting ephedrine from OTC drugs to produce methamphetamine and methcathinone. However, the rule is so underinclusive that it will have little or no effect upon restricting that practice.
The proposed rule bans ephedrine containing OTC drugs but expressly does not ban the far more widely used OTC drugs that contain pseudoephedrine (e.g., Sudafed) and phenylpropanolamine. The same simple efficient palladium catalyzed hydrogenation that converts ephedrine to methamphetamine will convert pseudoephedrine to methamphetamine and phenylpropanolamine to amphetamine with equal ease and efficiency. Pseudoephedrine is just as suitable as ephedrine as a precursor for the illicit manufacture of methcathinone. The amounts of pseudoephedrine and phenylpropanolamine used in the OTC drug industry are far larger than the amounts of ephedrine used. Hence, the proposed rule will likely have little, if any effect on the illicit trade it purports to combat because those in that trade will simply rely upon pseudoephedrine and phenylpropanolamine as precursor sources. The proposed rule is completely ineffective in controlling the supply of precursors for the manufacture of illicit methamphetamine, methcathinone, and amphetamine.
IV. LEGAL BASIS FOR COMMENTS
If the FDA does not exempt ephedra herb from its final rule, the agency will be acting in contravention of the Food, Drug and Cosmetic Act ("Act"), as amended, and the Administrative Procedure Act ("APA"). The facts presented above confirm that ephedra herb is a common food and a dietary supplement. The Joint Commenters have explained that the FDA's unqualified proposal to deem all ephedrine not GRAS poses a threat of adverse agency action against a food in common form, ephedra herb tea, and a dietary supplement, ephedra herb tea supplements. Indeed, as a substance not GRAS, use of them may be deemed to be the use of an adulterated substance by the agency, one punishable by the full civil and criminal penalties afforded by the Act. For the reasons that follow, the agency should exempt ephedra herb from its final rule to ensure that agency enforcement authorities understand that they are not to use the final rule as a basis for taking action against ephedra herb.
A. Foods in Common Form May Not Be Reclassified as Not GRAS
Foods in common form that have a history of safe use may not be reclassified as "not GRAS". Nor may foods be deemed adulterated "if the quantity of such substance in such food does not ordinarily render it injurious to health." 21 U.S.C. ' 342 (a)(1). Even if a poisonous or deleterious substance is added to any food that food may not be considered adulterated if the substance is inextricably a part of the food and the agency can promulgate regulations that limit the quantity of the food to levels that can be consumed safely. 21 U.S.C. ' 346.
Ephedra herb is a food, consumed as a tea, for over 5,000 years. When in food form, ephedra herb provides ephedrine in such small quantities that it poses no serious threat to public health. In this rulemaking, the agency has obtained no evidence sufficient to support a determination that ephedra herb (as opposed to synthetic ephedrine) is either not a food or is a substance that bears or contains a poisonous or deleterious substance which renders it "injurious to health." Rather, in its naturally occurring state, ephedra herb contains such small amounts of ephedrine that it is neither poisonous nor deleterious within the meaning of 21 U.S.C. ' 342. As a food in common form, ephedra herb is entitled to a presumption in favor of its safety which presumption the agency has not rebutted based on any evidence received in this rulemaking. Accordingly, the FDA should clarify its position by expressly exempting ephedra herb from its proposed rule wherein it seeks to declare the substance ephedrine not GRAS for OTC purposes.
B. Dietary Supplements May Not Be Reclassified as Not GRAS
Dietary supplements, not food additives, may not be reclassified as "not GRAS". Under the Dietary Supplement Health and Education Act of 1994, 21 U.S.C. ' 321 (ff)(1)(C), a "dietary supplement" includes "an herb or other botanical." Under that Act a dietary supplement is deemed to be a food. 21 U.S.C. ' 201(ff)(3)(B)(ii). Dietary Supplements may not be considered adulterated unless they present a "significant or unreasonable risk of illness or injury" under conditions of use recommended or suggested in labeling or under ordinary conditions of use. The FDA bears the burden of proof to show that a supplement is adulterated. 21 U.S.C. ' 342(f)(1)(A),(D). Dietary supplements (like the foods they are deemed to be under the Act) that have a long history of safe use are presumptively safe and that presumption may not be rebutted but by clear evidence to the contrary. No evidence has been presented in this rulemaking that would call into question the safety of supplements containing ephedra herb (as opposed to ephedrine tablets). Accordingly, the FDA should clarify its position by expressly exempting supplements containing ephedra herb from its proposed rule wherein it seeks to declare the substance ephedrine not GRAS for OTC purposes.
C. If the FDA Does Not Exempt Ephedra Herb from
Its Final Rule, It Will Violate the APA
The agency's proposed rule fails to define the ephedrine it seeks to label not GRAS as synthetic ephedrine. As a consequence, its final rule sweeps within the rule's proscriptive compass ephedra herb. Ephedra herb is a food, commonly consumed as a tea, in the United States and around the world. It is also consumed as a dietary supplement. Any action that calls into question the safety of this food or dietary supplement without proof that the food or supplement itself (as opposed to synthetic ephedrine) is injurious to health violates the Act. A rule in violation of the Act also violates the APA because it constitutes arbitrary and capricious agency action contrary to law. 5 U.S.C. ' 706(2)(A). Likewise, agency action contrary to the weight of factual evidence before it (or in the absence of requisite factual evidence) constitutes arbitrary and capricious action. See generally Citizens to Preserve Overton Park v. Volpe, 401 U.S. 402, 414 (1971); Crowley's Yacht Yard v. Pena, 863 F.Supp. 18, 21 (D.C. DC 1994); Delpro Co. v. Brotherhood Railway Carmen, 519 F.Supp. 842, 846 (D.C. Del. 1981); National Nutritional Foods Association v. Weinberger, 512 F.2d 688, 701 (2d Cir. 1975). Accordingly, to ensure compliance with the Act and the APA, the FDA should make it express that any final rule it adopts exempts ephedra herb whether in common food or dietary supplement form.
For the foregoing reasons, the Joint Commenters respectfully request that the FDA exempt ephedra herb from its final rule. A failure to do so would constitute arbitrary and capricious action in violation of the Act and the APA.
Emord & Associates, P.C.
Fifteenth Street, N.W.