November 1999 Blog with Durk and Sandy
by Life Enhancement Products Admin on Nov 25, 1999
Index of Files and Description of Contents
CODEX: Public Comments submitted by Durk Pearson & Sandy Shaw to the FDA on Sept. 30, 1997 on Docket 97N-0218, whether FDA should harmonize U.S. standards on dietary supplements to those of the Codex Alimentarius, an international body. We discuss constitutional, as well as scientific and cultural, reasons for not doing so.
GMPCOM: Comments submitted by Durk Pearson & Sandy Shaw to the FDA in response to FDA's request for comments in the Nov. 20, 1995 Federal Registerconcerning consideration of the Natural Nutritional Foods Association's proposed Good Manufacturing Practices (GMPs) for dietary supplements. We discuss reasons we oppose compulsory GMPs for dietary supplements.
EPHCOMAL: Docket No. 95N-0304. Comments submitted by Durk Pearson & Sandy Shaw in response to a number of FDA's requests for comment on FDA's proposed regulations on the sale of ephedra-herb containing dietary supplements. Includes detailed analysis of the comments and conclusions of an expert committee organized by the FDA to discuss this very issue.
EPHWHO: cover letter to EPHCOMAL. Docket 98N-0148, FDA Public Comments on abuse potential of ephedra, medical usefulness, as dietary supplement, trafficking in ephedrine, regulation under WHO rules.
EPHWHO2: Docket 98N-0148, continuation of Public Comments described in EPHWHO.
STRCFUNC: Public Comments submitted by Durk Pearson & Sandy Shaw to the FDA on proposed FDA rules on allowable structure-function claims for dietary supplements, Docket No. 98N-0044, submitted Sept. 23, 1998. We consider serious constitutional (First Amendment) and other defects in the proposed rules. The rules would reduce rather than increase truthful information available to consumers about dietary supplements, precisely the opposite of the intent of Congress in the DSHEA.
FOODSFTY: Pearson & Shaw compare the safety of dietary supplements to ordinary whole foods. We conclude that dietary supplements should not be required to meet higher safety standards than foods, since the historical evidence shows that foods in common form are far more hazardous than dietary supplements. For example, 9,000 Americans die of food poisoning every year.
D&SLTR9: The Durk Pearson & Sandy Shaw LetterTM of March 1999 discusses the Jan. 15, 1999 Appeals Court victory of Pearson & Shaw et al vs. Shalala, FDA, and United States, in which court rules that FDA's process for approving "health claims" is unconstitutional and throws out its undefined "significant scientific agreement" standard.
TREATIES: Sandy Shaw writes on the constitutional limits of what the federal government can do via treaty, which includes international "agreements" on dietary supplements.
FDICREG: Pearson & Shaw submit comments to the Federal Deposit Insurance Corporation (a federal agency that "insures" bank deposits at many banks) on their proposed "Know Your Customer" program (should be called "Spy on Your Customers and Report to Big Brother" program), 12 CFR Part 325, RIN 3064-AC19. We identify constitutional barriers to and statutory problems with the proposed program and ask that it be scrapped. As of the end of the Public Comment period, some 85,000 comments (mostly critical) had been received by the FDIC and Congress was considering bills that would prohibit the proposed rules.
HACCPGMP: Pearson & Shaw comments of 5 June 1997 submitted to FDA concerns the FDA's proposed creation of Hazard Analysis of Critical Control Points (HACCP) as part of Good Manufacturing Practices. We point out that quality control of dietary supplements differs significantly from that of foods and that use of the same analytical framework would be inappropriate.
CODEX
Before the
Department of Health and Human Services
Public Health Service
Food and Drug Administration
Docket No. 97N-0218
RIN 0910-ZA01
Consideration of Codex Alimentarius Standards
ACTION: Advance notice of proposed rulemaking.
62 FR 36243, July 7, 1997
COMMENTS OF
DURK PEARSON AND SANDY SHAW
COMMENTERS Pearson and Shaw are scientists, maintaining residences in Nevada and California, who design dietary supplement formulations and license them to small manufacturing and retailing companies. They are authors of four books on aging and age-related diseases including the million plus copy #1 bestseller Life Extension, a Practical Scientific Approach (Warner Books, 1982). They have also published three other health books, two of which were bestsellers. Their fourth book, Freedom of Informed Choice: FDA vs. Nutrient Supplements, explained First Amendment free speech issues in relation to FDA regulation (prior restraints) of truthful, nonmisleading health claims for dietary supplements (for example, low dose aspirin and the reduction of risk of heart attack), focusing on the costs to the public health of such regulations and on alternative regulatory approaches.
1. In "IA, FDA's Policy Regarding International Standards," FDA says "...the agency's primary goal in participation in such standard-setting activities and use of resultant standards is to preserve and enhance its ability to accomplish FDA's public health mission, with the aim of enhancing regulatory effectiveness, providing more consumer protection with increasingly scarce government resources, and increasing worldwide consumer access to safe, effective, and high quality products."
COMMENT: Providing more consumer protection with increasingly scarce government resources cannot be interpreted to mean that the least expensive regulatory scheme to the FDA (eg., adopting the standards set by others) provides more consumer protection. The FDA is dealing with an increasingly information-rich environment. Attempting to reduce the complexity of this information by massive data deletion, eliminating of human variation by averaging, and oversimplification of current scientific understanding may be easy, it may be cheap, but it is not likely to enhance the public health. If the FDA does not have the resources to set standards itself, a quick and dirty "review" of internationally decreed standards by collecting public comments and "averaging" them (or, more likely, giving them arbitrary and capricious political weightings) is not a substitute. Such a process will result in a great public backlash against the FDA.
The FDA's most valuable, scarce, and fragile resource is legitimacy and public trust. If the FDA continues to lose this, large appropriations will not save the day. When the public looks upon the FDA's actions as politically motivated, arbitrary and capricious, and contrary to fact, FDA's health pronouncements will be widely ignored and scorned, and the FDA's credibility as a reliable source of health information lost.1
Also, in "IA, FDA's Policy Regarding International Standards," FDA notes that, in its Federal Register notice of Oct. 11, 1995 (60 FR 53078), FDA specified three considerations in the FDA's policy. Conspicuously absent from these considerations was FDA encouragement of the provision of more truthful and nonmisleading information so that consumers can make informed choices. This is part of the Congressional mandate on the FDA under NLEA and DSHEA and must be taken into consideration as part of FDA's overall response to Codex.
2. In IB, International Agreements, FDA says "The U.S. Government is a party to a number of international trade agreements. FDA has participated in a number of recent international trade negotiations to ensure that under such agreements, FDA regulatory practices can remain focused on fulfilling the agency's mission to protect the public health while being supportive of emerging, broader U.S. Government trade obligations and policies."
COMMENT: If U.S. companies wish to meet internationally set standards so as to be able to market such "standardized" products in countries other than the United States, they ought to be free to do so. But the products sold within the borders of the United States, as part of U.S. domestic trade, should not be required to meet international "standards." Any products meeting Codex standards should, however, be allowed freely to enter the United States to be offered for sale in the U.S. and ought also to be legal to manufacture in the United States.
Harmonization of regulations is worthwhile in an economic sense until the opportunity costs of foregone choices are greater than the savings due to diminished regulatory costs. In a rapidly growing information-rich field, such as the relation between nutrition and disease, one must carefully consider the regulatory costs of foregone choices. The consumer will ultimately make this decision; the FDA can attempt to interfere, but in the long run the consumer - not the U.S. government and not the FDA - is sovereign in a market driven constitutional republic.
3. In the last paragraph under IB, FDA says: "Thus, FDA's stated policy on international standards and the nation's obligations under the WTO provide compelling impetus for FDA to consider whether to revise its existing system for review and evaluation of international food standards, and if so, how such a revised system might be designed."
COMMENT: We believe that the FDA should not use its scarce resources to evaluate standards set by international bodies for the world at large which are not specific to the concerns of Americans and, which, at least in the case of dietary supplements, will result in even greater hostility toward the FDA and more legal actions taken against it. There are serious constitutional questions about the acceptance of standards set by an agency not a part of the U.S. government or employed by the U.S. government. This can be considered an unconstitutional redelegation of the authority delegated to the agency by Congress to set standards.2 At the very least, for each standard the FDA will have to conduct its own full investigation, not just accept the conclusions of "expert" international committees, which is likely to be very costly. Moreover, the international committees, unlike U.S. government rulemaking bodies, are not required to conform to, for example, the First Amendment, the Commerce Clause, open meeting laws (Federal Advisory Committee Act), and the Administrative Procedure Act, which are other reasons to challenge any purported authority they have to establish standards for the commerce of United States citizens.
4. COMMENT: In order to accept Codex standards, it would be necessary to change DSHEA. While Codex defines dietary supplements narrowly as vitamins and minerals, the DSHEA defines dietary supplements much more broadly to include, in addition to vitamins and minerals, botanicals, amino acids, metabolites, food constituents, and others. Some substances that are regulated as dietary supplements in the U.S. under DSHEA are regulated as drugs in some Codex countries (for example, DHEA, a natural cholesterol metabolite found in the human body). In the United States, it is also possible for a substance to be regulated as either a dietary supplement or a drug, depending upon whether it is intended to treat a disease (for example, beta carotene, when it is intended to treat xeroderma pigmentosum, is regulated as a drug). These are definitions and rules resulting from long political struggles in the United States to meet the desires of Americans. Neither the Codex nor the FDA can change the definition of dietary supplements in the DSHEA without Congressional passage of new authorizing legislation. As we (and, we believe, the majority of Supreme Court Justices) see it, a treaty cannot trump the United States Constitution, from which the federal government derives all of its authority. The federal government cannot legitimately give away the Constitutional rights of its citizens by treaty.
Major changes in DSHEA are not likely to pass this Congress; most current Members voted for DSHEA in the first place.
We propose, therefore, that companies wishing to export to countries requiring that their dietary supplements meet some international standard be free to meet that standard, but companies wishing to sell their dietary supplements within the United States not be required to meet these totally irrelevant (within the U.S.) standards.
5. COMMENT: "Under "IIB Role of Codex Standards Under the SPS and TBT Agreements of the WTO," FDA states that "The Conference also recommended that standards adopted include only those provisions necessary for consumer protection, particularly those related to health and food safety." As we and others have pointed out in other public comments to the FDA, there is a presumption of safety for foods and, under DSHEA, the FDA may not regulate dietary supplements more stringently than foods in common form. In fact, an analysis of risks shows that foods in common form are far more hazardous than dietary supplements. Food poisoning alone kills over 9,000 people every year in the U.S. This consideration should direct the allocation of FDA's scarce resources.
6. COMMENT: Under "IV. Request for Information. Part A," FDA requests responses to various questions. Part of the explanation of question #11 states that "...FDA believes that it will be faced with the following four situations with regard to standards that the agency believes to be suitable for FDA acceptance:" Situation #4 was given as: "(4) or the standard is not identical to or similar to any FDA regulation, and the adoption of the Codex standard is not subject to rulemaking under the act." We request FDA clarification as to how the FDA proposes to accept Codex standards without a rulemaking. We do not see how the FDA can avoid complying with the requirements of the Administrative Procedure Act, which provides the only way the general public can provide feedback to the agency concerning the regulations they must live with.
7. COMMENT: The last question given in this section ("IV. Request for Information. Part A") is: What goals, in addition to those listed previously, should be considered by the agency in developing any new regulations governing consideration of Codex standards? We believe that, in addition to the five other considerations FDA listed just before this question, there should be an additional consideration: (6) To ensure that the Codex standards do not conflict with the NLEA or DSHEA or the United States Constitution, including but not limited to the First Amendment protection of speech and press. We note here, for FDA consideration, that Justice Sandra Day O'Connor said, in an aside during a talk she gave that was televised on C-SPAN ("America and the Courts") on Sept. 27, 1997, that international agreements cannot take away property rights under the United States Constitution. We believe that the matter of the Constitutional limits on what the federal government can do through international agreements (eg. in expanding its powers under the Constitution or depriving its citizens of Constitutional rights) is about to become a major and highly contentious issue that will surely reach the Supreme Court.
8. COMMENT: Under "IV. Request for Information. Part B1," FDA proposes that, within an FDA notice of newly adopted Codex standards that FDA would publish in the Federal Register, FDA would describe the nature of the Codex standard, provide FDA's preliminary views on the standard, describe information the agency would need to evaluate the standard, invite public comment, and state the agency's preliminary plans to perform substantive review of the standard. We propose that FDA add the following to that information to be published in the Federal Register: (6) Identify conflicts with the NLEA, DSHEA, and the United States Constitution, including but not limited to the First Amendment protection of speech and press.
9. COMMENT: FDA asks, under "IV. Request for Information. Part B2, Enlisting Assistance of Expertise Outside of the FDA," what limitations there might be to the use by FDA of outside experts as part of an agency process established to review and evaluate Codex standards. One limitation would be that meetings of expert bodies working for the FDA would have to meet open meeting laws (the Federal Advisory Committee Act, FACA) and be open to the public. Some scientific experts may oppose this on the grounds that it will prevent "objectivity," that is, it would make transparent the wheeling and dealing and political tradeoffs that are an inherent and unavoidable part of any process, whether scientific or not, that is a part of political decisionmaking. However, since these decisions will affect hundreds of millions of people, there is simply no justification in an open society for making them behind closed doors. Indeed, FACA is the law, and legitimacy demands it.
10. COMMENT: FDA asks, under "IV. Request for Information. Part B3. Assessing Impact on Small Business," What issues, if any, would have a disproportionately large impact on small entities or would place small entities at a disadvantage relative to large entities? Regulations, in general, impose a greater impact upon small companies, simply because the cost of regulation must be paid out of a much smaller financial base. Thus, the FDA should consider the impact of enforced Codex standards upon the dietary supplement industry, which is comprised of (mostly) small businesses. This problem would be entirely avoided if the FDA follows our proposal given above, that American companies wishing to offer products in other countries would have to meet whatever standards exist in those countries, but that Codex standards would not be mandatory within the borders of the United States.
11. COMMENT: Under "IV. Request for Information. Part C. Maintenance of Public File of FDA Determinations Regarding Codex Standards," FDA asks for suggestions. We request that FDA put all such information on the Internet.
1 In the May 1995 FMI (Food Marketing Institute) survey, 45% of consumers trust no one and rely on themselves for assuring the nutritional value of the food they eat, up from 6% in 1994. Manufacturers followed at 23%, government 13%, food stores 5% and consumer groups 3%. A major shift has occurred at the expense of government, which led the list in 1990. In the 1995 survey, twice as many consumers reported looking to industry for assuring nutritious foods as the government. (as reported in Sloan and Stiedemann, "Guaranteed Success: How to Make Products Consumers Really Want," J. of Nutraceuticals, Functional & Medical Foods 1(1):69 (1997)
2 See AFL-CIO v. Occupational Safety and Health Administration, 965 F.2d 962, 984 (11th Cir. 1992), as discussed in Martin et al, "Environmental Law: Determination on Silica May Expose Flaw in Rule," The Nat'l Law Journal pp. B12-B14 (March 17, 1997). This article is attached as Exhibit 1.
Submitted by,
Durk Pearson
Sandy Shaw
Public Comments to FDA
on Proposed Good Manufacturing Practices
for the Dietary Supplement Industry
Submitted by Durk Pearson & Sandy Shaw
31 March 1997
"Background. On Nov. 20, 1995, representatives of the dietary supplement industry submitted to FDA a suggested outline for the development of CGMP regulations for dietary supplements."
COMMENT: The organization that submitted the suggested outline for CGMP regulations for dietary supplements, the Natural Nutritional Foods Association, represents only their members, a small part of the dietary supplement industry. We, therefore, appreciate this opportunity to provide our comments on the NNFA's proposed CGMP regulations.
"Based on the submission and the comments that the agency receives in response to this notice, FDA will consider whether to develop a proposed rule that is designed to establish CGMP that will ensure that dietary supplements are produced under conditions that will result in a safe and properly labeled product but that does not impose any unnecessary burden on the industry."
COMMENT: We believe that any CGMP standards should be developed by the industry itself and be voluntary. Good manufacturing practices do not necessarily have to be the same for every company, as the level of quality assurance will inevitably reach a point of diminishing returns as more and more money, personnel, and technology are invested in it. Larger firms may wish to invest larger amounts of money for the ever diminishing amounts of additional safety and quality, while smaller firms may not. A reasonable standard would include a range of practices, rather than a single set of procedures that all must follow.
"The objectives of the CGMP, as stated by the industry representatives [NNFA], are to ensure that consumers are provided with dietary supplement products that : (1) Are safe and not adulterated or misbranded; (2) have the identity and provide the quantity of dietary ingredients declared in labeling; and (3) meet the quality specifications that the supplement is represented to meet. The industry [NNFA] submission was patterned after the CGMP for food regulation contained in part 110, but also contained requirements beyond those in part 110 that the industry representatives [NNFA] stated that they 'consider essential to the manufacture of safe and properly labeled dietary supplements.'"
COMMENT: Any CGMP for dietary supplements should be no stricter than for foods in common form, since the record shows that foods in common form are actually far more hazardous than dietary supplements. For example, in 1989, the worst public health problem resulting from the use of dietary supplements, eosinophilia-myalgia syndrome resulting from contaminated tryptophan, took place. About 38 people died and some 1,500 people became seriously ill. Yet, despite the unfortunate results of this tragedy, it was more risky for the consumers of soft cheese to eat soft cheese that year or any year than it was for the consumers of tryptophan to take tryptophan that year. About 9,000 people die each year from contaminated foods. The record for safety for dietary supplements is more favorable than that for foods in common form and, hence, the standards for CGMP for dietary supplements should not be stricter than for foods in common form.
"Personnel (c). Education and training. Each person engaged in the manufacture of a dietary product should have the proper education, training, and experience (or any combination thereof) needed to perform the assigned functions. Training should be in the particular operation(s) that the employee performs as they relate to the employee's functions. Appropriate documentation of training shall be retained by the manufacturer."
COMMENT: It is remarkable to believe it necessary to inform a manufacturer of the need for a employee to have education, training, and experience so as to be able to perform his/her function. A person running a shoeshine shop or a hot dog concession would know this, let alone a dietary supplement manufacturing operation. The requirement for "appropriate documentation of training" is potentially burdensome, since many persons may have training that was obtained through supervised work experience, for which there may be no specific "documentation."
"Sanitation of Buildings and Facilities. (b)(1) Cleaning and sanitizing agents used in cleaning and sanitizing procedures shall be free from undesirable microorganisms and shall be safe and adequate under conditions of use. Compliance with this requirement may be verified by any effective means including purchase of these substances under a supplier's guarantee or certification, or examination of these substances for contamination."
COMMENT: The FDA has approved a wide variety of cleaning and sanitizing compounds for the food industry. Why not just publish the list and make it available to the dietary supplement industry? That would certainly simplify matters.
"Production and Process Controls. (2)(ii). An accurate statement of the weight or measure of each raw material used in the manufacture of a dietary product. Each batch shall be formulated with the intent to provide not less than 100 percent of each claimed dietary ingredient."
COMMENT: FDA well knows that, though one may adjust one's production equipment to provide 100% of each claimed dietary ingredient, there will be a statistical range of fills around a mean value. One would have to way overfill to have, say, a 95% statistical probability of having all fills at least at 100% of the claimed dietary ingredient.
"Warehousing, Distribution and Post-Distribution Procedures. (4)(g)(3). The manufacturer, distributor, and holder of a dietary product shall at all times utilize quality control operations that reduce natural or unavoidable defects to the lowest level currently feasible." (emphasis added)
COMMENT: This is entirely unnecessary and a burden to small operations. The urgency to reduce natural or unavoidable defects depends upon the risks posed by these defects. The reduction of no risk or low risk defects to the "lowest level currently feasible" will require expensive equipment that will not increase public safety, but may drive small manufacturing operations out of business that cannot afford this equipment. One has to wonder why the NNFA has proposed such a stringent, expensive, and unnecessary rule which is reasonable for a pharmaceutical drug, but not for dietary supplements.
"Warehousing, Distribution and Post-Distribution Procedures. (4)(g)(4). The mixing of a dietary ingredient or dietary supplement containing defects above the current defect action level with another lot of dietary ingredient or dietary supplement is not permitted and renders the final product adulterated within the meaning of the act, regardless of the defect level of the final product. (emphasis added)
COMMENT: Again, the need for such a rule would be reasonable for a pharmaceutical drug which contains small amounts of powerful active ingredients, but is not reasonable for most dietary supplements. For example, suppose a lot of a powdered multi-vitamin had too little vitamin C. One could mix it with another lot of powdered multi-vitamin with extra vitamin C so that the entire mixed lot had the correct level of vitamin C. This is in no way an "adulteration" of anything. If the final lot is below the action level for the product, it should be as acceptable as a lot that "just happened" to end up with that way.
Actually, the mixing of dietary ingredients takes place during manufacturing, not warehousing, distribution, and post-distribution. All the warehouse needs to do is follow the product label instructions for storage and shelf life.
"The agency asks for comments on whether there should be new CGMP regulations, whether the regulations should be mandatory or voluntary, and, if mandatory, how long it would take establishments to come into compliance."
COMMENT: As we noted above, we do not think there should be mandatory CGMP regulations for the reasons stated before. Such regulations tend to freeze manufacturing practices into concrete, discouraging the institution of new, more cost-effective techniques. The added burden of keeping records for the government and for dealing with pop inspections (eg., warrantless searches of dubious constitutionality) is particularly great for smaller companies. Larger companies may see detailed and voluminous recordkeeping requirements as a way to get rid of smaller competitors, which is unlikely to be in the public interest.
"IV. Summary and Request for Comments, 1. Is there a need to develop specific defect action levels (DAL's) for dietary ingredients?"
COMMENT: There are thousands of dietary ingredients. To develop a specific defect action level for each of these ingredients would be an exceedingly expensive, time-consuming, and thankless project for FDA. Yet, ingredients are different and it wouldn't be possible to just lump them together. Furthermore, in most cases one could not say that at this defect action level everything is OK, but slightly beyond this point, it isn't OK. The defect action levels for most dietary supplements involve manufacturing defects far less serious than, say, bacterial contamination. In a powdered dietary supplement, for example, the usual effect of excess moisture is a clumping and hardening of the product, undesirable of course but unlikely to be hazardous. In a food, under certain conditions, moisture will foster the growth of bacteria. Dietary supplement manufacturers, guided by consumer acceptance, will know what the limits of moisture content should be.
"IV. Summary and Request for Comments, 4. The agency asks for comments on whether there is a need for CGMP to include requirements for manufacturers to establish procedures to document that the procedures prescribed for the manufacture of a dietary supplement are followed on a continuing or day-to-day basis.
FDA is aware that no provision of part 110 deals with the establishment of documentation that a manufacturer is following established procedures prescribed for the manufacture of a dietary supplement, and that section 402(g) of the act states that any CGMP regulations for dietary supplements are to be modeled after the CGMP regulations for food. However, FDA's tentative judgment is that section 402(g) of the act does not preclude FDA from adopting CGMP regulations for dietary supplements that have no counterpart in part 110 if there is an appropriate basis for so doing. FDA requests comments on this issue."
COMMENT: As we noted above, the safety record for dietary supplements has been better than that for foods in common form. Therefore, there is no appropriate basis for including stricter recordkeeping by manufacturers of dietary supplements and such adoption would be arbitrary, capricious, without rational basis, in violation of statute law and in violation of the APA.
"IV. Summary and Request for Comments, 5. The agency asks for comments on whether dietary supplement CGMP should require that reports of injuries or illnesses to a firm be evaluated by competent medical authorities to determine whether followup action is necessary to protect the public health."
COMMENT: There is no requirement that food manufacturers have reports of injuries or illnesses evaluated by competent medical authorities to determine whether followup action is necessary to protect the public health. Hence, there should be no such requirement for the manufacturers of dietary supplements. Such a requirement would not only prove to have no measurable effect on the public health, but it would be a very expensive burden for small companies, which would have to have medical followup for every instance of ordinary falls or catching a cold.
"IV. Summary and Request for Comments, 5. The presence of pharmacologically active substances in these products distinguishes them from most other foods."
COMMENT: That may be the way dietary supplements and foods were viewed decades ago, but it is not how scientists view them today. Dietary supplements that are derived from foods contain pharmacologically active substances found in the foods. The reason people eat foods at all is because of the pharmacological effects they experience as a result of eating them, which include a complex variety of physiological and psychobiochemical changes. For example, the polyphenols found in chocolate, tea, coffee, and fruits and vegetables, have a diverse array of effects including psychopharmacological effects.
"IV. Summary and Request for Comments, 5. It may be appropriate to provide that CGMP requires that a manufacturer critically evaluate the available scientific information on the safety of the dietary ingredients that it intends to use in its products to assure itself that those products will be safe. FDA asks for comments on whether such an evaluation is necessary and, if so, what elements need to be included in such an evaluation and their relative importance (eg., the presence and potency of pharmacologically active substances, the presence of different microorganisms, the presence of different contaminants and impurities). In addition, the agency asks for comments on whether it should require that such an evaluation be documented in a firm's records, and, if so, what type of records would be adequate to document that such an evaluation had occurred."
COMMENT: Many of the ingredients in dietary supplements have been evaluated for quality and safety and health effects by the large manufacturers that offer them for sale. One of the assurances that a dietary supplement manufacturer has for the quality of the ingredients he uses is the manufacturer for those ingredients. There is no reason that a dietary supplement manufacturer should be required to duplicate an evaluation already performed by a much larger company with far more resources. Including requirements for the evaluation of all pharmacologically active substances creates an unnecessary burden. There are many thousands of substances contained naturally in a fruit or a vegetable or an extract of these. Most of the pharmacologically active substances have not even been identified yet. The potencies will depend upon the quantity, concentration, and interactions with many other substances, as well as upon the particular physiology of each individual consumer. A simple mixture of vitamins and minerals would require a very expensive analysis in order to attempt the impossible, to determine all possible interactions. Yet, where is the safety concern that requires the spending of such large sums? Drug manufacturers must control closely such matters as the exact quantities of pharmacologically active ingredients, as well as interactions with other drugs or foods and of possible contaminants. This is a reasonable expectation for drug manufacturers, but not for dietary supplement or food manufacturers. Nutrient supplements are foods, not drugs.
Before the Food and Drug Administration, Rockville, MD
RE:Docket No.95N-0304;Dietary Supplements Containing Ephedrine Alkaloids
DURK PEARSON & SANDY SHAW
PEOPLE FOR THE CONSTITUTION
PO Box 3666
Tonopah, NV 89049
TO: Dockets Management Branch (HFA-305)
Food and Drug Administration
12410 Parklawn Dr., Rm. 1-23
Rockville, MD 20857
Comments for Docket No. 95N-0304
Before the
FOOD AND DRUG ADMINISTRATION
Rockville, MD
In re: Proposed rule: )
Dietary Supplements Containing )
Ephedrine Alkaloids ) Docket No. 95N-0304
Fed. Reg. 62(107): 30678-30724 )
June 4, 1997 )
18 August, 1997
INTRODUCTION TO COMMENTS OF DURK PEARSON & SANDY SHAW
Durk Pearson and Sandy Shaw are scientists and authors, maintaining residences in Nevada and California. Their three best-selling books include the million copy #1 best-seller Life Extension, a Practical Scientific Approach (Warner Books, 1982).
Their fourth book, Freedom of Informed Choice: FDA v. Nutrient Supplements argues that truthful, non-misleading speech on labels and in labeling is protected by the First Amendment against FDA censorship and discusses the cost to public health of such censorship.
Pearson and Shaw design dietary supplement formulations and license them to small marketing and manufacturing companies. The formulations designed by Pearson and Shaw include dietary supplements containing ephedra herb. Pearson and Shaw and their licensed marketers and manufacturers (all are small businesses) would suffer substantial economic harm if the Proposed Rules regarding the use of ephedra herb in dietary supplements were adopted. Furthermore, Pearson & Shaw believe that consumers of ephedra herb dietary supplements would actually be endangered by the Proposed Rule.
Pearson & Shaw do not believe that the FDA has met their burden of proof under DSHEA that ephedra herb dietary supplements are unreasonably unsafe when used as directed; on the contrary, the evidence presented by the FDA shows that extant ephedra herb supplements with extant labeling are generally safer than food in common form. FDA's labeling proposals, moreover, are an impermissible prior restraint that violate the First Amendment of the U.S. Constitution. Pearson & Shaw request that FDA withdraw this Proposed Rule, attempt gather evidence that meets their DSHEA burden of proof, and if successful, reconvene the Committee, and develop a new Proposed Rule that, unlike the current Proposed Rule, is not arbitrary, capricious, contrary to fact, and does not violate the First Amendment. Please see Pearson & Shaw's 107 pages of Comments (attached).
Sincerely,
Durk Pearson
Sandy Shaw
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Pearson & Shaw's Comments to the FDA on Ephedra Alkaloid Containing Dietary Supplements
All quotes, with page numbers given, are taken from the transcript of the August 27-28 1996 Food Advisory Committee meeting on ephedrine-alkaloid containing dietary supplements.
1. The FDA believes that ephedra contains ephedrine, a pharmacological agent, and is therefore a drug, not a food. As the FDA's Dr. Elizabeth Yetley said (Vol. I pg. 37): "Foods would be used for non-therapeutic purposes."
This is a very narrow view of foods. Many foods are used for therapeutic purposes, that is to treat or prevent disease, including garlic, fish oils, prunes, cranberry juice, low fat foods, yogurt, and vegetables and fruits. The FDA allows a health claim (may reduce the risk of cancer) for fruits and vegetables, as is also true for oat bran and wheat bran.
Dr. Hui: "It's very difficult to distinguish between what is a food and what is a drug. Think about glucose. Glucose is a drug when somebody is hypoglycemic and glucose is a deadly poison for someone who is very hyperglycemic." (Vol. I pg. 122)
Dr. Jasinski: "...I was curious in your definition of lack of pharmacologic effect as being a defining factor [of a food]. I have been drinking coffee, and I've got a tachycardia from drinking the coffee right now. So by your definition, coffee beans would not be allowed to be marketed because you can get a pharmacologic effect from coffee beans." (Vol. I pg. 124)
The notion that foods can be separated from drugs on the basis that drugs have a pharmacological effect and foods do not is false. At the most basic level, foods have a psychoactive effect by providing a sense of well being and energy following eating and the cascade of profound biochemical effects that result from eating, such as increase in blood glucose levels and alterations in release of neurotransmitters and hormones in various areas of the brain and body. Carbohydrates, for example, have been shown to increase the passage of the amino acid tryptophan across the blood-brain barrier into the brain, where it is used by the brain in the manufacture of serotonin, a natural calming and sedating agent. Some people crave carbohydrates when anxious, thus using food as a tranquilizer, a pharmacological effect. It is well known that a few drops of sugar in water on the tongue of a crying infant often calms it; here sugar water is used as a medicine. This traditional infant tranquilizer is called a "sugar tit."
Many components of foods are known to have psychoactive effects and are consumed largely for those psychoactive effects, including coffee, tea, chocolate, and caffeine containing soft drinks. Recently, in fact, it has been discovered that anandamide (believed to be the natural ligand for brain cannabinoid receptors) and oleylethylamide, an inhibitor of anandamide hydrolase (the enzyme that breaks down anandamide) are found in chocolate, which may account for chocolate's production of a temporary sense of well being in many chocoholics. The expression "chocoholic" itself implies an intense craving and chocoholics often vie with each other over who has the most extreme chocolate craving. Paul Rozin of the University of Pennsylvania and his coworkers have found that 23% of premenopausal women crave chocolate in the perimenstruum, the days just before and after the start of menses. Those women also rate chocolate as being more pleasurable than other people do. These are pharmacological effects.
Tea (Camellia sinensis) is one of the most commonly consumed beverages in the world. In traditional Chinese medicine, tea is recognized to have various health and medicinal effects and is used as a treatment to help digestion, eliminate phlegm, diuresis, reduce sleeping time, improve eyesight, for detoxification, and to eliminate body heat (Han et al, "The Screening of Anticarcinogenic Ingredients in Tea-Polyphenols," Journal of Nutraceuticals, Functional & Medical Foods Vol. 1 No. 2, 1997, pg. 8). The health effects of tea are becoming known to growing numbers of Westerners as a result of the publication of papers in peer-reviewed scientific journals, which effects include antimicrobial, diuretic, antipyretic and immune function regulation, as well as possible preventive effects in cardiovascular disease and cancer. Traditional Western use of tea was based on tea's tonic and diuretic effects. Indeed, the British craving for tea's stimulating effects was so strong that it led to a severe balance of trade deficit with China, which in turn resulted in the British opium war against China. Thus, tea is both a food and a medicine and has pharmacological effects.
Other foods consumed for psychoactive and pharmacological effects include beer and wine. Certainly some of the effects of these beverages are due to their alcohol content, but the same amount of alcohol ingested in the form of different alcoholic beverages provides a significantly different experience due to other active ingredients, such as the hops (an herb with stimulant/sedative effects) in beer and polyphenols in wines.
The distinction between foods and drugs cannot be made on the basis of the presence or absence of a pharmacological effect, particularly these days when the effects of individual components of foods are being isolated and foods created (for example, by genetic engineering) that contains larger or smaller amounts of selected components (for example, high oleic sunflower oil). We suggest that the only reasonable way to judge all foods and all drugs is on the basis of the ratio of risks to benefits of their use for individual users, not on the arbitrary and capricious basis of whether there is or is not a pharmacological effect.
Furthermore, there is an identifiable market of consumers who seek foods that enhance health, based upon such studies in the public domain as Wrick, Gilbert's HealthFocus study, Childs and Poryzees' survey, annual FMI consumer inquiries, and recent Yankelovich research (Childs, "Functional Foods and the Food Industry: Consumer, Economic and Product Development Issues," Journal of Nutraceutical, Functional & Medical Foods, Vol. 1 No. 2 1997, pg. 30). These individuals are comfortable with self-selection of products for health and subscribe to a health maintenance credo. Functional foods interests include disease prevention, disease therapy, performance enhancement, and (especially in the U.S.), weight loss. Wellness is in fact something of a personal philosophy or spiritual element to these consumers. Hence, the FDA must consider how FDA censorial or prohibitive policies is going to be perceived by these consumers and, thus, the likelihood of such policies being effective for the intended purpose. It is exceedingly likely that the FDA's attempts to define foods as those substances that are only nutritive and not therapeutic is doomed to failure. Indeed, this was the message of the DSHEA. Because of this, FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that fits within the ambit of Congress's will, and re-propose a new Rule.
2. Individuals having heart attacks or strokes while using ephedra herb or ephedrine-containing products is not evidence that the ephedra herb or ephedrine-containing products caused the heart attacks or strokes. One thing we need to know is how many heart attacks and strokes would be expected in the user population during the period in question.
Mr. Ford: "...the figure that we have used is about a million and a half doses per day [of ephedra products], and that's just from the health food stores." (Vol. I pg. 250) Dennis Jones: "...the enormous number of users of this herb. My estimate is 5 to 8 million Americans each year for 10 to 12 weeks, but other people have four times that estimate." (Vol. I pg. 277) Dr. Bruce M. Chassy: I just wanted to make the point that if millions of people are taking products that contain ephedra alkaloids and we are seeing a very low incidence of these kinds of serious effects, we need to know whether that incidence is any greater than spontaneously occurs." (Vol. II pg. 118, emphasis added) Dr. E. Wayne Askew (Acting Chairman of the Committee): "And I don't think that we can give you an answer to that." (Vol. II pg. 119)
But information is available from a number of sources, including public agencies such as the Public Health Service and the Centers for Disease Control, for the heart attack incidence by age. The FDA did not provide this essential information to the Committee during their two day meeting in which they were evaluating the risks of ephedra alkaloid-containing products. How, then, could the FDA or the Committee members know whether the incidence of the adverse events were greater for the user population than would have been expected of the general population in the users' age range?
Scientists at the FDA's Center for Drug Evaluation and Research make the same point in a letter to The Lancet (Vol. 350, July 5, 1997, pg. 69). In commenting on a study of the possible dangers of using non-sedating adrenergic agonist antihistamines, the scientists state: "...this type of analysis contains inherent flaws and may be subject to biases that could lead to misinterpretation of the data. First, this study does not account for the spontaneous rates of background cardiac events in the untreated population." These FDA scientists also caution that there may be a bias in reporting when there is heightened awareness of potential adverse events. The FDA has publicized its concerns about ephedra (see statement by Dr. Lori Love of the FDA, Vol. I pg. 198: "...we have publicized our safety concerns on ephedra-containing products a number of times."), thus creating a potential atmosphere of heightened concern and, hence, a possible reporting bias. They conclude their letter by noting: "...the FDA has been carefully monitoring spontaneous adverse drug reactions reported in association with the use of these antihistamines. This monitoring is not limited to analysis of crude reporting rates, but includes careful review of individual reports and follow up." We think that the evidence we present in these comments will show that the FDA has done nothing approaching a "careful review" and "follow up" in the case of adverse reports on ephedra alkaloid containing dietary supplements. This neglect supports the view of many that FDA has had a long-standing bias in favor of prescription and OTC drugs and against dietary supplements. Because of this, FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this error, and re-propose a new Rule.
3. FDA's treatment of the ephedra supplement adverse reaction reports exhibits FDA's infamous bias against dietary supplements. There have been thousands of complaints received by the FDA from users of aspartame (and MSG) claiming aspartame (or MSG) caused adverse events, including seizures and strokes.
Strokes and seizures are "consistent" with the known effects of excess excitotoxic amino acid (e.g. aspartic and glutamic acids) activity, but that doesn't mean that aspartame (or MSG) caused them. FDA has consistently refused to reconsider the wide use of aspartame (and MSG) in foods (and in fact has increased the categories of foods that may contain aspartame) despite the large number of complaints because it is convinced by the scientific studies of aspartame (and MSG) that aspartame (and MSG) use is safe. However, safety trials of aspartame (and MSG) were done largely on normal people (some aspartame safety studies included individuals with phenylketonuria or non-insulin-dependent diabetes); none of the safety trials on normal individuals would be expected to include individuals with known cardiovascular disease, just as such individuals were excluded in the weight loss clinical trials with ephedrine. Hence, evidence for aspartame (and MSG) safety may be of no better quality than that for ephedrine, despite thousands of complaints to the FDA of adverse events, some of them serious. (For information on aspartame safety trials, see, for example, Stegink and Filer, Aspartame Physiology and Biochemistry, Marcel Dekker, 1984)
The association of the consumption of a substance and the occurrence of an adverse event is not the same as cause and effect. Dr. Cynthia T. Culmo, of the Texas Department of Health, discussed the state of Texas' recent experience with adverse event reports from users of ephedra-alkaloid containing products. The FDA has relied heavily on this evidence. However, note the exchange on Vol. I pp. 81-82 between Dr. Culmo and Dr. Jasinski:
Dr. Jasinski (Vol. I pg. 81): "But that's associated, and being causal and associated is different." "A certain percentage of young people are going to die from strokes or some unexplained cardiac event, and it's associated." "...have you done some sort of analysis on this data?"
Dr. Culmo (Vol. I pg. 82): "It's tabulated. It hasn't actually been broken down. But, again, we keep saying associated. I don't believe we've ever gone on record and said caused. (emphasis added) Here, Dr. Culmo backs down under the pressure of tough comments and admits that these associations are just that, associations, and that, to her knowledge, the Texas Department of Health has never publicly called these associations a cause and effect relationship. Because of bias, FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this error, and re-propose a new Rule.
4. The FDA argues that even a clear warning will not protect all those in the sensitive population that should not use ephedra-alkaloid containing products because many of them may not know they have the medical conditions in the warning. However, this is a problem for all those sensitive to food components -- that they may not know they are sensitive.
Some food sensitivities, such as to peanut protein, can be fatal, while others can cause severe allergic reactions requiring hospitalization. People generally find out by eating the food and having a reaction. Most such food sensitivity discoveries probably occur in childhood. But this shows that warning labels only protects those who already know they are sensitive to a food, the same situation as exists with the ephedra herb warnings. FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this error, and re-propose a new Rule.
5. FDA instructed the Committee members not to consider any benefits of ephedra herb use. In the absence of benefits of use, this makes any risks totally unacceptable. However, there are benefits described by many users, benefits which consumers are capable of assessing, such as weight loss or energy. A number of peer-reviewed double-blind placebo controlled scientific studies have been published (and some of these cited during the Committee meeting) showing that ephedrine is thermogenic and can be used successfully to help in weight loss. This was one benefit that the FDA decreed could not be considered. Several committee members (1996) complained of the problem of considering safety when they were forbidden to consider benefits.
The FDA describes the Committee's conclusions on determining a safe level (in the rulemaking proposal, pg. 29), "FDA notes that many members of the Food Advisory Committee stated that they were unaware of a basis for determining a safe level."
Dr. George Ricaurte (Vol. II pg. 222): "With the issue of a margin of safety, I'm left at somewhat of a loss because for a margin of safety you really have to have some indication and what I've heard this afternoon is that all purported purposes of use are being taken off the table [by the FDA] and it leaves you with, well, what the heck are we going to use this for. If there's no clear answer to that, then the margin of safety, quite frankly, has to go to infinity because you can't do a risk/benefit when we don't have a perceived benefit." (emphasis added)
Dr. Inchiosa (Vol. II pg. 227): "...I could imagine this is going to be very confusing for the consumer, who look at a product that claims nothing, yet has a tremendous list of warnings because the warnings are going to be increased. And, so, really, in an age where we're trying to increase information it's disinformation or no information only a condition of more confusion." "So, therefore, I agree with Dr. Ricaurte that since you have no claimed benefit, there's no margin of safety that can be calculated." (emphasis added)
Dr. Croom (Vol I pg. 149) (comments directed to Dr. Yetley)
"...as a scientist, when someone says no risk, I can imagine a spill of this water on this microphone, and when I come to one serious event and I get electrocuted." "Because no sounds more like why I go to church than a scientific analysis, okay?"
Because of FDA's incorrect charge to the Committee (that benefits could not be considered) the Committee's risk/benefit analysis could only consider risk, thereby resulting in arbitrary and capricious very low dose recommendations that are not in accord with the scientific evidence. Because of this, FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this error, and re-propose a new Rule.
6. Ephedra dietary supplements are already less dangerous than foods in common form. If you consider food poisoning as a result of bacterial contamination alone, there are 9,000 deaths a year. This does not include the deaths, serious illnesses, and disabilities occurring in many more people from heart attacks and strokes resulting from food-derived excess calories, fat, and cholesterol. It is not uncommon for a heavy meal to trigger a heart attack in those at risk. The fat and the noradrenaline released in response to the food increase platelet aggregability, thus increasing the risk of an abnormal blood clot that can cause a heart attack or stroke.
People think food is much safer than it is and need to be educated so as to be more careful in using and preparing foods. This is education the FDA could be doing that would be a far better use of limited public funds than attacking the use of ephedra herb products on the basis of poor data.
John J. Guzewich (Vol. II pg. 238): "...if the CDC has a figure, you know, for infectious disease, which is my area, food-borne disease, that 20 to 30 percent of our population today is at risk for food-borne disease from infectious sources for high-risk population, I don't know if that is a fair number to say for these kinds of compounds [the ephedra alkaloids]."
Indeed, the CDC estimates that approximately 60,000,000 to 80,000,000 Americans suffer from food poisoning each year -- about one quarter to one third of all food consumers. How does the incidence of fatalities caused by bacterial food poisoning compare to the incidence of fatalities associated with ephedra dietary supplements? Nine thousand fatalities per year from bacterial food poisoning in the U.S. is equal to about one food poisoning fatality per 30,000 food consumers.
The FDA has found 21 deaths associated over three years with the use of ephedra supplements, or about 7 deaths per year. This is the associated-but-not-necessarily-causal numerator. What is the denominator, the number of people using ephedra supplements on any given day?
The members of the committee were very concerned that the FDA had not even attempted to supply the essential denominator information. The transcript of the 1996 Food Advisory Committee expressed grave concern about the FDA's lack of a denominator:
Dr. Hui, Vol. II pg. 61 "...what you have put together is very useful for us but these are literature written for professionals by scientists and it's used to treat diseases. There's nothing that's really safe. I think it's all risk-benefit ratio."
Right. That's why the denominator information is very important.
Mr. Appler, Vol. II pg. 81 "Your device center of FDA is having a conference on the 21st of September on a topic called Denominator Data. Since reports of injuries have to be filed under the statute for medical devices, the center is concerned that it can't evaluate the meaning of enumerator ... without knowing what the denominators are."
Dr. Ricaurte, Vol. II pg. 132 "I don't see Dr. Kessler organizing a meeting to address ephedrine OTC and convening an advisory group seeking advice as to what to do with regard to safety of these compounds, and yet here we are."
"Now the issue then is what is the denominator for--I mean, that's the only way I can try to get at that issue of safety as the agency seeks advice."
Dr. Jasinski, Vol. I pg. 161 "...yes, we have some serious events, but--I mean, we have a numerator but no denominator in any of this, and coming back to predict safety data, they're asking us to predict safety data without telling people to go out and do a clinical trial to validate the predictions."
Dr. Kessler, Vol. I pg. 161 "...I ask you to consider [giving] us your best judgment in light of what [data] exists."
The FDA expects magic, that scientists can make a scientific judgment affecting millions of Americans on the basis of very little and poor quality information provided by the FDA. The FDA has failed in its duty to provide necessary information, such as the essential denominator data, to the Committee, and should withdraw its proposed Rule until such time that it can hold a properly informed Committee meeting, which can then render an informed decision on which the FDA can base an informed Rule.
Dr. Marangell, Vol. II pg. 276 "We've been talking about the numerator and denominator, and in my assessment of this I agree the data is very poor..."
Dickinson, Vol. I pg. 284 "Industry needs more information, needs to be able to come forward with more information on the denominators, as has been mentioned by several speakers here today."
Some denominator information was provided by industry during the committee meeting:
Mr. Betz, Vol. II pg. 27 "Over the past five years, Omnitrition has sold approximately 100 million servings of ephedra-based products. We believe that our position in the market is relatively small, probably around 5 percent of the market share. If you assume it's 10 percent, if you move out on a limb and assume it's 10 percent, that's over the last five years, one billion servings of ephedra-based products."
Dr. Ziment, Vol. II pg. 29 "Although you say one billion servings have been sold over five years, that means 200 million a year and I would guess that the average consumer takes what, 50 to 100 servings, which may mean one or two million people are taking this drug. Now, the real question for me is what percentage of one million people who take a drug should be allowed to have adverse reactions before control is taken?"
Mr. Betz, Vol. II pg. 30 "...our estimates, our understanding of the estimates with respect to the number of people in the United States who are actually using ephedra-based dietary supplements is ... more on the order of perhaps 10 to 20 million people, who have used at some point in the last five years ephedra-based supplements."
Mr. Ford, Vol. I pg 250: "...the figure that we have used is about a million and a half doses per day [of ephedra products], and that's just from the health food stores."
Dennis Jones, Vol. II pg. 277: "...the enormous number of users of this herb. My estimate is 5 to 8 million Americans each year for 10 to 12 weeks, but other people have four times that estimate."
Commenters Pearson and Shaw license a dietary supplement containing whole ground ephedra herb (about 1.8 gram of herb per serving, adjusted to contain 20 mg. total of ephedra alkaloids per serving). Their experience in the market has led them to conclude that the number of consumers of ephedra alkaloid containing dietary supplements is similar to those given at the Committee meeting by representatives of the industry: 1,000,000 to 8,000,000 Americans consume these supplements on any day.
If as few as 212,000 people are using ephedra supplements and if the 21 deaths were actually a result of ingestion of ephedra alkaloid containing dietary supplements and if food poisoning were the only cause of deaths from consuming foods in common form, then there would be about the same incidence of deaths from consuming foods in common form as of ephedra alkaloid containing dietary supplements. In actuality, the number of people using these supplements is probably closer to ten times as high, there is no compelling evidence that the 21 deaths were all caused by the ingestion of ephedra alkaloid containing dietary supplements and, of course, there are many other causes (besides bacterial food poisoning) of deaths from consuming foods in common form.
Let us take the lowest industry estimate, 1,000,000 users on any given day, which would result in a worse case incidence estimate: 7 ephedra associated deaths per year per million ephedra users.
Compare this to 33 bacterial food poisoning caused deaths per year per million food users.
Even if all the deaths associated with ephedra were definitely caused by ephedra when used according to the label instructions (which the FDA certainly does not contend), the extant dietary supplements (some of which contain up to 110 mg. ephedrine and most of which also contain caffeine) with the extant labels (15 percent of which provide no warnings) are already 4 to 5 times safer than food in common form.
Moreover, remember that the food death incidence figure refers to bacterial food poisoning, not anaphylactic reactions, not cardiovascular deaths from excessive doses of calories, fat, and cholesterol, and not other causes.
Congress has not delegated authority to FDA under DSHEA to require dietary supplements to be safer than food in common form. In this rulemaking, the FDA exceeds its Congressionally delegated authority by requiring a much higher standard of safety for dietary supplements than for food in common form. FDA's rulemaking is a clear expression of FDA's bias against dietary supplements. FDA must withdraw this proposed rulemaking because it is ultra vires and violates the APA.
The safest way to establish dose when using an ephedra alkaloid containing dietary supplement (or virtually any other kind of supplement) is to begin with a low dose (perhaps 1/4 to 1/2 of the suggested single serving size) and gradually increase the dose to the suggested level of use. As Adam Gissen noted on Vol. II pg. 38: "If you try to limit its [ephedra alkaloid containing dietary supplements] use, people are certainly not going to take something that you want to build up to the full dose over 10 days to two weeks, that's not possible to do in one week." FDA's proposed label statement limiting the dose and the use to one week will discourage consumers from building up the dose slowly. FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this error, and re-propose a new Rule.
7. Under DSHEA, FDA cannot regulate dietary supplements more stringently than foods in common form. FDA has done precisely this, hence it must withdraw the Rule, and re-convene the Committee with instructions to use a standard that does not fly in the face of the will of Congress.
8. FDA has not met its burden of proof, to show that ephedra is a significant and unreasonable risk when used according to label instructions, and not misused or abused. For example, FDA assumed consumers reporting adverse reactions were using the products according to label instructions. They must provide evidence for this, but did not attempt to do so. The FDA also admitted that it had obtained very few samples of what the consumer was using at the time of the incident in order to analyze them. Hence, they had no way to know whether those consumers for which adverse reports were made were following label instructions or were abusing the supplements or even whether they were taking drugs such as cocaine at the same time. Dr. Lori Love (FDA), Vol. II pg. 149 "...we cannot verify in many cases what a consumer used."
Mr. Israelson, Vol. II pg. 119: "...on the formulas, which cause these serious adverse reactions at low dosage, 1-to-5 milligrams [of ephedra alkaloids], do you have the formulas themselves, so we could identify what else is in there?"
Dr. Lori Love, Vol. II pg. 119: "I do not have that in hand and we actually were just analyzing that data over the weekend."
Dr. Love, Vol. II pg. 107: "...we have only a relatively few samples where we've been able to collect the sample that the consumer was using at the time of the injury and be able to analyze that."
Dr. Georgitis, Vol. II pg. 107: "Dr. Love, I have a question for you, in terms of the serious adverse events below the median value of 20 milligrams per serving of the ephedrine alkaloids, do you have a percentage as to how many of those out of the total adverse events:
Dr. Love, Vol. II pg. 107: We haven't expressed our data in that form because, of course, we have only relatively few samples where we've been able to collect the sample that the consumer was using at the time of the injury and be able to analyze that." Because of this failure to meet the Congressionally mandated standard of proof, FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this error, and re-propose a new Rule.
9. People who don't know they have one of the conditions given on ephedra herb labels as contraindications, conditions such as cardiovascular disease, hypertension, diabetes, etc., may still use ephedra herb. Some misuse due to ignorance, however, is unavoidable no matter what regulations you put in place and the same problem applies to many other common and widely available products. For example, people who are at risk of heart attack may buy a shovel and shovel snow, eat a high fat meal or engage in an intense exercise regimen, and drop dead. People who don't know they have diabetes may chronically eat high sugar foods and damage themselves via hyperglycemic glycosylation and other mechanisms. People with one of the medical conditions as those given on a label for which an OTC should not be used (including ephedrine containing OTCs) may not realize they have one of those medical conditions. Perhaps a warning could be added: "If you are not sure whether you have one or more of these conditions, see a physician before using this product." However, the list of warnings can be made only so long without type so small you need a magnifying glass to read it.
There has to be some room for personal responsibility in the sale and use of any product. That is why we favor education rather than the FDA representing that they shield consumers from the need to consider risks. It is dangerous for consumers to believe that the FDA has done all their thinking for them, thus excusing them from taking responsibility for their actions.
10. The FDA at several points during the 1996 meeting of the Drug Advisory Committee told the participants to ignore the issue of adverse reactions associated with the use of ephedrine alkaloids in OTC drug products, which includes phenylpropanolamine (in OTC products for weight loss), pseudoephedrine, and ephedrine.
Dr. Harry H.S. Fong (Vol. I pg. 47): "Currently, pseudoephedrine and phenylpropanolamine are used in OTC. So, what would happen if ephedrine is banned from the OTC market? Would pseudoephedrine and phenylpropanolamine follow up in also being removed from the market? They are, after all, similar alkaloids, and they are also derived from ephedra?"
Dr. Elizabeth Yetley (Vol. I pg. 47): "I think that what we're really focusing on today is not the drug issues, but the dietary supplement issues."
This response of Dr. Yetley of the FDA evades the important fact that anyone can walk into a supermarket or drug store and buy these OTC products containing ephedra alkaloids. If the FDA is going to restrict the dose or length of use of ephedrine containing products on the basis of safety, it is a reasonable question why these others, with similar effects, would not also be restricted. (Note, too, that some OTC products contain 24 mg. of ephedrine plus 120 mg. of theophylline, a caffeine like drug. Moreover, the OTC pseudoephedrine and phenylpropanolamine containing products contain about 3 to 6 times as much of pseudoephedrine or phenylpropanolamine alkaloids as the total ephedra alkaloid content of a typical ephedra dietary supplement.) This again brings up the question of bias on the part of the FDA. Moreover, if ephedrine containing dietary supplements used for weight loss or energy have FDA set doses that do not provide the benefits sought by consumers, many such consumers may turn to available OTC products containing pseudoephedrine or phenylpropanolamine or ephedrine plus theophylline at higher dosages, with the perverse result that some consumers may end up using higher doses of ephedrine alkaloids than they did in the dietary supplements.
Dr. Irwin Ziment, Vol. II pg. 115: "...I feel that there is a disconnect in that we are hearing a lot about the dangers of ma huang and ephedrine without knowing the dangers of comparable orthodox drugs." Dr. Ziment, Vol. II pg. 116: "...Dr. Love, perhaps can give us a little bit more information on the side effects that are actually recorded, even on a year-to-year basis in adverse drug reports on the legitimate ephedrine products."
Dr. Lori Love (FDA), Vol. II pg. 116 "I don't have that data and I will defer to people from Drugs [FDA] on that." Unfortunately, there were no data on this essential subject supplied by Drugs (Branch of FDA) at the meeting.
There are political issues in whether the FDA regulates the OTC ephedra alkaloids or the ephedra alkaloid containing dietary supplements.
Dr. Jasinski (Vol. I pg. 99): "What I don't understand is if you look at the DAWN data that you quoted, pseudoephedrine was much greater a public health problem, two to three times by my estimate, as ephedrine, yet you control, you exempted pseudoephedrine when the DAWN data which was used for the basis shows it's two or three times the incidents and emergency rooms and deaths. Could you go through that?"
Frank Wickham (Texas Department of Health)(Vol. I pg. 99): "Yes, Dr. Jasinski, that was a result of a political decision and based upon pressure brought upon the sponsor of the original legislation." (emphasis added)
(Such political pressure can and will be brought to bear upon the FDA. Placing different standards upon the safety of ephedra alkaloids in OTC products and in DSHEA dietary supplement products would be arbitrary and capricious.)
Then, Dr. Jasinski said (Vol. I pg. 99): "...the health food stores make money selling ephedrine-containing products. The drug stores with the pharmacists make their money by selling pseudoephedrine-containing cold products, if you want to look at this cynically. Is this politics?"
Mr. Wickham, Vol. I pg. 100: "...I think that is part of the politics as far as the market is concerned, yes."
Here we see a clear conflict of interest between the marketers of ephedra alkaloid containing dietary supplements and the drug stores offering an ephedra alkaloid in OTC pseudoephedrine-containing cold products. We must carefully examine FDA policies to be sure that there is no FDA bias toward the OTC trade of ephedra alkaloid containing products. In the recent past the FDA has stated explicitly its concerns that the sale of dietary supplements might impinge upon the sales of pharmaceutical drugs.
FDA must withdraw the Rule and re-convene the Committee without suppressing extremely relevant information, make a new decision which considers this essential data, and issue a new rule.
11. Reducing the dose below an effective level (for weight loss or energy) will result in increased risks for those people who will take more to try to get the results they seek (not knowing how much they should take as one serving or the daily limits they should respect) and, perceiving the use instructions as "fake" or government propaganda, may also ignore the safety warnings, perceiving them to be equally "fake" or not useful as well.
Many consumers already using ephedra herb products will be familiar with doses above the dose suggested by FDA and may consider the entire label a misleading government message, with potentially lethal consequences, especially if the contraindications are perceived to be, like the dose and maximum use period disinformation, something to be ignored.
Setting dosages to arbitrarily low levels will not "fool" consumers and is not the answer to ignorance among consumers about safety considerations. Better education and more information is the best answer. It is not a perfect answer but, in a free society, it is far better than the alternative of FDA attempting to impose choices on millions of people. The FDA's credibility to dietary supplement consumers rests on whether consumers consider them a reliable source of information. If not, the FDA's "advice" will surely fall on deaf ears. Because of this, FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this error, and re-propose a new Rule.
12. Caffeine toxicity: Oral doses of greater than 1 gram of caffeine may be toxic in adults. That is about the same as is found in ten cups of coffee or in 10 No-Doz tablets. (Pentel, "Toxicity of Over-the-Counter Stimulants," JAMA 252:pg. 1902, 1984) The theophylline in OTC ephedrine products (120 mg. per tablet) is even more toxic in overdose than is caffeine. Because of this, FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that is free from arbitrary and capricious bias against dietary supplements and in favor of OTC drugs, and re-propose a new Rule.
13. We have examined published reports of adverse events with ephedrine, phenylpropanolamine, and pseudoephedrine that are exhibits to the FDA's proposed rulemaking, including 56, 60, 62, 63, 67, 68, 69, 70, 71, 73, 100, and 128.
We concluded that most of the adverse events were associated with abuse:
Reference 68 concerns a 28 year old woman with a three week history of progressing shortness of breath, dry cough, fatigue, and orthopnea. She admitted to taking 25 mg. ephedrine tablets for 8 years to try to lose weight. One week before the onset of symptoms she reduced her daily intake from 80 tablets to 3 tablets, after which her symptoms rapidly worsened. 80 tablets of 25 mg. of ephedrine is 2000 mg. (!) a day. This is an immense overdose; it is possible that the tolerance experienced by users of ephedrine explains at least in part why this woman didn't die from taking so much.
Reference 67 concerns a 32 year old housewife who developed congestive heart failure after ten years of taking large quantities of ephedrine containing compounds for energy. It is not clear exactly what dose she was using but it appears to have been an immense overdose, as she was taking three bottles of an ephedrine containing cough medicine daily at the time of psychiatric referral.
Reference 66 concerns a 36 year old insurance agent who was taking a cough medication containing ephedrine. He had progressively increased his ephedrine intake until he was drinking more than a bottle a day, each of which contained 400 mg. of ephedrine.
Reference 69 concerned a 20 year old man who suffered an intracerebral hemorrhage after taking an unknown quantity of "speed," containing ephedrine. It was clearly used as a substitute for illicit drugs, such as amphetamine. The patient had used "speed" in the past but did not know the exact composition of the pills, though urine drug screen on admission revealed no amphetamine, methamphetamine, phenylpropanolamine, or caffeine.
Reference 70 concerned three case reports. Cases one and two had both used large quantities of the same ephedrine containing pills (each pill contained 15.3 mg. of ephedrine). Case 1 consumed 10 of the pills (150 mg. of ephedrine) all at once and Case 2 had consumed 10-20 of the pills (153 to 306 mg.) daily for 23 years! Case 3 suffered a ruptured berry aneurysm which, unfortunately for its victims, can result from many commonplace events, including exercise and emotional excitement.
Reference 86 concerned a 54 year old Polish woman who had become psychotic. She admitted under questioning to have taken increasing quantities of ephedrine over the past 20 years, to her most recent dosage of up to 15 tablets, each containing 30 mg. of ephedrine (450 mg. of ephedrine) five times a day (a total of 2,250 mg. of ephedrine!) during exacerbations of her asthma.
Reference 82 concerned a 26 year old man who developed psychosis. Three days before admission to the hospital, he started taking ephedrine (30 mg. five tablets twice a night) to keep awake while holding a job in a bakery. The total amount of ephedrine he had ingested in the three days before admission was 750 mg.
Reference 100 concerned a 45 year old man who had been taking a daily herbal diet supplement for weight loss. After several weeks of using "greater amounts," he began to get restless and couldn't sleep. At that time, he experienced personality changes and mania. The amount of ephedrine he was using is not clear, but the "greater amounts" suggests that it may have been an excessive amount and substantially greater than that recommended in the label instructions.
Reference 128 concerns a 33 year old woman who developed acute hepatitis in association with the use of ma huang. Unfortunately, this is not a problem uniquely associated with ma huang or even herbs in general. Any plant matter may have the problem. Ma huang from Asia may be grown in fields fertilized with fresh human feces. Commenters Pearson and Shaw (and many other dietary supplement formulators) require that the raw herb be sterilized with heat, ethylene oxide, or ionizing radiation before used in the manufacture of their licensed products. Most reputable herb suppliers do this before sale, even if it is not specified in the purchase order.
A number of Americans were recently reported in national newspapers as having developed hepatitis as a result of eating imported strawberries, causing something of a public relations problem at the FDA, since the public blamed the FDA for the problem.
Reference 56 concerns a 14 year old girl who took 15 to 18 capsules of a product containing (per tablet) 25 mg. of ephedrine, 200 mg. of caffeine, and 50 mg. of phenylpropanolamine, in a suicide gesture. She developed cardiac arrhythmias as a result, from which she recovered. If she took 15 capsules, her total dose was 375 mg. of ephedrine, 3000 mg. of caffeine (doses of caffeine alone of 1000 mg. or more may be toxic), and 750 mg. of phenylpropanolamine.
Reference 122 concerns potential risks to medically controlled hypertensive patients taking sustained-release pseudoephedrine for nasal congestion. The authors found that "pseudoephedrine administration did not result in statistically significant changes in any cardiovascular parameter. Mild disturbances in sleeping pattern and urinary retention in some male subjects were the only significant symptoms detected. The authors concluded that "while sustained release pseudoephedrine appears safe for the majority of medically controlled hypertensive patients without statistically significant effects on blood pressure or heart rates, our studies did show an upward trend in these parameters which, in a larger population of hypertensive patients, may prove to be clinically significant."
Reference 71 concerns a 17 year old girl who had made an attempt at self-poisoning 12 months previously but was said not to be a drug abuser. She was admitted to hospital after taking 20 tablets containing pseudoephedrine 60 mg. (a total of 1200 mg. of pseudoephedrine) and was diagnosed with an intracranial hemorrhage. The authors note at the end of the letter that "Pseudoephedrine has only rarely produced neurological complications. Because it is a very weak sympathomimetic amine, which has not achieved status as a drug of abuse or addiction. The present case, however, serves to illustrate its potential dangers." If ephedrine becomes available only in low dosages, pseudoephedrine might be abused more frequently.
Reference 62 concerns three patients that developed clinical evidence of heart injury after acute ingestion of phenylpropanolamine. The first case, a 24 year old woman had chest pains three hours after ingesting a single capsule containing 50 mg. of phenylpropanolamine, 4 mg. of chlorpheniramine, and 0.2 mg. of belladonna alkaloids. It ought to be considered that the combination of these substances, rather than the phenylpropanolamine, was responsible for her injuries. Cases two and three were clearly cases of abuse. Patient two had taken eight capsules each containing 50 mg. of phenylpropanolamine, 8 mg. of chlorpheniramine, and 2.5 mg. of isopropamide. Patient three was a 31 year old schizophrenic woman who ingested approximately 40 tablets, each containing 50 mg. of phenylpropanolamine and 200 mg. of caffeine. This is clearly abuse.
Reference 63 concerns a 43 year old black woman who was brought to the hospital after two episodes of palpitations associated with shortness of breath, tinnitus, dizziness, diaphoresis, and inability to stand. She had no prior history of heart disease, but had a history of hypertension, which was controlled without medication. She was taking capsules that contained 75 mg. of phenylpropanolamine and 200 mg. of caffeine. The total amount she was taking was not specified. This woman should not have been taking a sympathomimetic with her history of hypertension.
Reference 65 concerns three patients. One, an 18 year old obese woman, was admitted to the hospital with neurological symptoms after taking two tablets of ComtrexR for "congestion." The patient experienced a grand mal seizure at the hospital. No drug scan was done, so we do not know whether she might have been using any drugs along with the Comtrex. The second patient, a 26 year old man, drank three to six ounces of whiskey eight hours prior to admission. He had taken two black capsules three to four hours prior to admission. Each capsule contained 200 mg. of caffeine, 25 mg. of ephedrine, and 50 mg. of phenylpropanolamine. His blood alcohol was 5 mg% (5 times the legally drunk level). This man eventually died in the hospital. This combination of high dose alcohol, along with high doses of caffeine, ephedrine, and phenylpropanolamine is clearly drug abuse. The third patient was a 17 year old man who ingested two black capsules, later identified as "pick-me-up" capsules containing 200 mg. of caffeine, 200 mg. of ephedrine, and 50 mg. of phenylpropanolamine. This man had a large stroke and died.
Reference 73 is a 1990 review of reported adverse drug reactions (ADRs) for phenylpropanolamine since 1965. "Since 1965, 142 ADRs have been reported in 85 studies, 69% of these in North America. Many such cases may go unrecognized. Of ADRs attributed to legitimately [OTC or prescription] sold PPA products, 85% occurred after consumption of OTC products versus only 15% after prescription drugs. The PPA product often contained combination ingredients, or PPA was consumed along with additional drugs. An overdose of PPA was taken in about a third of the cases. After ingestion of non-overdose amounts, 82% of the [reported] ADRs were severe. The most frequent side effects involved symptoms compatible with acute hypertension, with severe headache the most common complaint. Twenty-four intracranial hemorrhages, eight seizures, and eight deaths (mostly due to stroke) were associated with PPA ingestion." While the discussed adverse reactions are serious, 142 ADRs (though possibly underreported) should be compared to the tens of millions of consumers using PPA products during this 25 year period. In fact, this paper mentions that in 1981, a marketing research company reported that 9.5 million adults were using OTC diet aids, making PPA the fifth most used drug in the U.S. At the time of the publication of this paper (1990), three FDA advisory panels had judged PPA to be safe. In another study cited here, a review of over 200,000 prescriptions for PPA-containing products found no increased incidence of hospitalization for hypertension, arrhythmias, or stroke.
Reference 60 concerns a 28 year old man with no known cardiac risk factors and no history of smoking, drinking alcohol, or using reacreational drugs, or family history of heart disease, who had a heart attack after taking 60 mg. of pseudoephedrine. Subsequent examination showed that he had normal coronary arteries. The authors suggest that "pseudoephedrine, a sympathomimetic agent, may be implicated in the initiation of coronary spasm..." FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this lack of consideration for the information in the adverse reaction cases that FDA claims to depend upon, and re-propose a new Rule.
14. We have considered the data presented by the FDA in light of the paper on how to evaluate adverse drug reactions in Reference 43 (Jones, "Approaches to Evaluating Causation of Suspected Drug Reactions" in Strom, Velo (eds): Drug Epidemiology and Post-Marketing Surveillance, New York: Plenum Press, 1992, pp. 103-113:
The limitations of the FDA data make it very difficult to assess the degree of cause and effect versus mere association. For example, Table 3, the Naranjo Algorithm and Types of Data Requiring Judgement provides a series of 10 questions about the adverse event that can be used to assess cause and effect versus association. Question 5 is: "Are there alternative causes which could have caused event?" This question refers to confounders. For example, there is a background incidence of such events as heart attacks and strokes in the population of probably millions of individuals using the ephedra alkaloid containing products. The FDA did not provide information to the Food Advisory Committee on this background level of these types of events, making it virtually impossible to know whether the incidence of adverse events reported was higher or lower or about the same as the background incidence. As Dr. Bruce M. Chassy noted at the Food Advisory Committee meeting (Vol. II pg. 119): "...we need to know whether that incidence is any greater than spontaneously occurs." (Such data exist. For example, G. Michael Vincent, a cardiologist at the University of Utah School of Medicine in Salt Lake City says that there are 8,000 sudden, unexplained deaths among children and adults each year.)
The FDA has admitted that it has little information on what the consumer actually took. A consumer who is abusing a substance (by, for example, taking inappropriately large doses) may not be perfectly truthful about this stupid behavior when asked what they took. The FDA simply assumed that the consumer used the product according to the label instructions. For example, Dr. Love (Vol. I pg. 210) said "And the adverse events are reported when the product was apparently used according to label instructions, which appears to be in the majority of the individuals where we have evaluable data." (emphasis added) Then on Vol. II pg. 120, Dr. Love says "Are you asking if we can verify that or any other information that our patients give us? I mean that's a very difficult question. If the patient told you that they took an over-the-counter product at X value [dosage], you would believe them."
There is a need to verify the dose the consumer claimed to take. However, Dr. Lori Love of the FDA noted (Vol. II pg. 149): "...we cannot verify in many cases what a consumer used." Then on pg. Vol. II 107, Dr. Love says "...we have only a relatively few samples where we've been able to collect the sample that the consumer was using at the time of the injury and be able to analyze that." Dr. Love admitted (Vol. II pg. 107) that the FDA could not provide information on the dose-response relationship (as, for example, how many of the adverse events took place at dosages below the median value of 20 milligrams per serving). This is important for answering question 8 of the Naranjo Algorithm: "Was reaction dose-related?" A median amount does not provide any information on the distribution of doses, eg., do the doses fall in a narrow range about the average or do they have a very broad range or is there a bimodal distribution. A small percentage of very high dosages could have had a large effect on the median. This is particularly important with respect to the deaths. Did they occur at especially high dose levels? It would have been much more useful if the FDA had supplied the average dose and the standard deviation.
Moreover, Dennis Jones reported to the committee (Vol. I pg. 275) that "...a fixed ephedrine/caffeine combination based mainly on the work by Astrup and his colleagues has been approved for weight loss indications in Europe and is being touted by many as the safest and most effective treatment available. Danish data indicated only 86 reportable adverse reactions, which were defined as reactions which necessitate stopping the therapy, out of 9.6 million daily doses during a two-year period..." The FDA should have followed up on this information before issuing their proposed new rules. We suspect that the FDA was in a big rush to get their rules out because of political, not scientific or public health, considerations.
The FDA did not prepare a ma huang tea in the usual manner (heated in a pot) to determine how much of the ephedra alkaloids are extracted so as to know how much the consumer might have actually ingested in the case of ma huang products used as a traditional tea. Instead, the FDA put the ma huang into a pot and added methanol and water, boiled it, evaporated it, and put it on a carrier. That is not how a tea is prepared for human consumption! Plus you get much faster absorption when in the form of a concentrated extract on a carrier as compared to the absorption when a person swallows ground whole ephedra herb.
Question #4 of the Naranjo Algorithm asks: "Did reaction reappear when drug re-administered?" But Dr. Love (Vol. I pg. 202) stated at the Food Advisory Committee meeting that the FDA has reports on rechallenges in only 4 percent of the reported adverse events. FDA has done an extremely poor job of discriminating between causality and mere association without proof of causality, hence FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that corrects this error, and re-propose a new Rule.
15. The FDA seems to be in an awful rush to get these proposed rules issued, when the poor quality of the data available at the Drug Advisory Committee meeting would strongly suggest the collection of additional information, as we have suggested in these comments.
For example, on Vol. II pg. 158 Dr. Jasinski asks Dr. Love: "...have you prepared a report on your data, how you collected it, how you interpreted it and what conclusions you've made, and have you submitted this to internal review within the agency or outside the agency? And, similarly, have you taken the report from this ad hoc committee and submitted it to a peer review?" Dr. Love answered (Vol. II pg. 158): "We, of course, intend to do that, but we were analyzing this data even over the weekend to supply the information to you at this committee meeting here." Then on Vol. II pg. 196, Dr. Kessler says "I have promised a number of people that the agency will work hard to get to a decision soon after this advisory committee." (emphasis added)
What about the report and the peer review that Dr. Love said the FDA "intend[s]" to do? That report and peer review were not a part of the record for public comment. Apparently, the FDA does not "intend" to do it. One suspects that at least some of the rush here is due to political considerations. FDA has behaved in a grossly arbitrary and capricious manner, using the Committee as little more than a fig leaf to cover their politically influenced decision. Perhaps now that David Kessler is no longer FDA Commissioner, FDA can take whatever amount of time is required to do the job correctly. FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that is based on science, not political considerations, and re-propose a new Rule. Congress, not FDA, is supposed to be the judge of political considerations.
Michael Davidson, M.D.
Analysis of Adverse Events Reports
16. There was inadequate time at the meeting to consider the report of Michael Davidson, M.D., a physician and fellow of the American College of Cardiology, assistant professor of medicine at Rush Presbyterian-St. Luke's Medical Center, and medical director of the Chicago Center for Clinical Research.
Dr. Davidson was commissioned by the NNFA to review the case files underlying 191 adverse event summaries (see Adverse Event Clinical Summaries at Tab F). He gave detailed analyses of all these events at the Food Advisory Committee meeting. Of the 191 events, he categorized 84 as serious. Of the 84 serious events, he determined that 13 were not related to ephedra, 8 were unknown for lack of information, 34 were remotely related, 22 were possibly related, and 7 were probably related. Dr. Davidson's report to the Committee is on Vol. I pp. 59-69 of the meeting transcripts.
ARBITRARY AND CAPRICIOUS FDA CONCEALMENT OF ADVERSE EFFECT DATA ON OTC PRODUCTS CONTAINING EPHEDRINE, PSEUDOEPHEDRINE, AND PHENYLPROPANOLAMINE, ALKALOIDS FOUND IN EPHEDRA HERB
Vol. I pg. 226 FDA's Dr. Love:
"Texas and Ohio's data includes OTC drug products. This database does not. Where we identify a product afterwards as an OTC drug, we get a label, we find out that it's a drug, it's taken out of our database..." (Emphasis added.)
So it is not possible to compare the rate of adverse reactions reported for the ephedrine, pseudoephedrine, and phenylpropanolamine (which are the principal active ingredients in ephedra herb) containing OTCs as compared to the reports for ephedra herb containing dietary supplements. FDA has wilfully removed OTC adverse reaction information from their database that is just as relevant to the Committee's charge as is the adverse reaction information on the ephedra supplements. In some respects, this OTC information that the FDA concealed from the Committee is better for determining safe dosage because it is less noisy; amounts per dose, instructions, and warnings are all specified in FDA OTC monographs. FDA did not supply this important data on many ephedra dietary supplement adverse reaction reports. One concludes that FDA is exhibiting its infamous bias against dietary supplements and in favor of more tightly regulated drugs. FDA must withdraw its Rule and convene a new Committee that has access to all relevant information.
ADMISSION THAT FDA PROVIDED NO DATA ON NUMBER OF EPHEDRA SUPPLEMENT USERS AND THAT FDA ACCEPTS INDUSTRY FIGURES
Vol. I pg. 240 Dr. Ziment:
"...I've got a report here of a "PrimeTime Live" television interview in which the CEO of the Los Angeles company that manufactures Herbal Ecstasy said that his firm alone sold 15 million units of this product. The amount sold in this country must be absolutely enormous. Is there any further details or extrapolation from this type of information to guess what the market is?"
Vol. I pg. 240 FDA's Dr. Love:
"I think generally FDA do not have this data and will have to defer to industry."
FDA'S NARROW VIEW OF TRADITIONAL USES OF EPHEDRA
Vol. I pg. 75 Dr. Culmo:
"The most common traditional use for ma huang is to treat respiratory disorders. There is no evidence to show that it was prescribed or promoted for weight loss, athletic performance enhancement, stimulation, or euphoria, as is commonly practiced today."
This is incorrect. A Chinese law (over 2,000 years old) prohibits horse riders who are under the stimulating/euphoric influence of ephedra herb tea from galloping their steeds through villages. This early DUI (driving under the influence) law shows that the Chinese have traditionally used (and sometimes misused) ephedra for more purposes than FDA and Dr. Culmo are aware of.
COMMITTEE MEETING AFFECTED BY POLITICS MORE THAN SCIENCE
Vol. II pg. 68 Dr. McCausland:
"What changes is compromise. The facts don't change."
Dr. McCausland is referring to the fact that the Committee's recommendations have changed drastically since the 1995 meeting without any significant changes in the scientific data. This is science filtered through political considerations, which is not science at all.
Vol. II pg. 221 Dr. Ricaurte:
"I think it's telling that just from October '95 until here we are 8, 9, 10 months later, we've already gone from an estimated safety level down 10-fold and I'm not quite sure on what basis we're doing that."
FDA ADOPTION OF CANADIAN STANDARDS VIOLATES APA, FACA, AND DELEGATION OF CONGRESSIONAL AUTHORITY DOCTRINE
The FDA proposes that a dietary supplement is adulterated if it contains 8 milligrams (mg.) or more of ephedrine alkaloids per serving or if its labeling suggests or recommends conditions of use that would result in intake of 8 mg. or more in a 6-hour period or a total daily intake of 24 mg. or more of ephedrine alkaloids and requires a label warning not to use the product for more than 7 days. The transcript records of the 1996 Food Advisory Committee meeting showed no consensus for a limit on the daily dose of ephedrine alkaloid containing dietary supplements, which ranged from 0 mg. to 60 mg. of the alkaloids a day.
The limit FDA now proposes is virtually the same limitation on the dose and length of use of ephedrine containing ephedra dietary supplements as Canada has recently done for OTC nasal decongestants containing ephedrine: 6 to 8 mg. of ephedrine per single dose repeated three to four times daily, used for no longer than 7 days.
Dr. Micheline Ho, Chief of the Product Regulation Division, Bureau of Pharmaceutical Assessment, Vol. I pp. 106-122, appeared at the Food Advisory Committee meeting, but provided none of the data that led the Canadian government to decide on that dose. Her presentation, however, may have influenced the final determination by FDA of the dosage limitation proposed in the rulemaking. It also influenced some of the Committee members. For example:
Dr. Wang, Vol. II pg. 189, "...since in the OTC drugs ephedrine is allowed to consume, what, 150 milligrams per day on the sustained release product, maybe a 10-fold safety factor, following the Canadian way, is 15 milligrams per day for food, but again I am just pulling that as a figure." (emphasis added)
Mr. Israelson, Vol. II pg. 223, "So, with that reservation that we're making decisions based on crucial cases without adequate evidence, I would repeat that the Canadian proposal as it's being used there is a reasonable model to follow. And my understanding of that proposal is that it would be based on 6 to 8 milligrams of total alkaloids. That would give a daily value of 28 to 32 total alkaloids." (emphasis added)
Dr. Fukagawa, Vol. II pg. 198, "...I would concur with the Canadian experience in that the safe level in dietary supplements would be anywhere between zero to 3.1 milligrams per day of the ephedra alkaloids, and then one can make the calculations after that with respect to ephedrine in terms of per-serving and per-day recommendations." (emphasis added)
Mr. Israelson, Vol. II pg. 191, "...if we look at the Canadian levels, which were 6 to 8 milligrams 4 times daily, or 24 to 32 milligrams, without the addition of other stimulant materials and with good manufacturing practices, I think that that's something that the industry would be able and willing to support and comply with." (emphasis added)
Mr. Israelson, Vol. II pg. 193, "Under DSHEA, we're able to have a lot of labeling that would essentially follow what the Canadian labeling would say, if that would be helpful to solve your concern." (emphasis added)
The data used by the Canadian government to determine the dose and length of use were not presented at the Food Advisory Committee meetings of 1995 or 1996, nor were these data available for American public examination and comment. The data that were presented at the 1995 and 1996 Food Advisory Committee meetings provided no or very weak evidence to support the Canadian dose and length of use limits. There was no Committee consensus on the dosage or duration of use limitations, yet the Canadian standard was chosen, perhaps because it was (relatively) politically safe and because Mr. Israelson, representing certain industry interests, urged the FDA to accept those limitations.
Per the APA (Administrative Procedures Act), the Canadian standard cannot be adopted without examining the data used to establish this standard, putting these data into the public record, and permitting public comment on the data, the basis for how the standard was established.
Under the APA, the ultimate regulation may remain controversial but at least the procedure ensures public access to the debate and identification of important issues and scientific evidence used in the agency's decisionmaking process. If the FDA accepts the Canadian government's conclusion without further examination and critical analysis, the FDA will have bypassed the salutary purposes of notice-and-comment rulemaking.
The adoption of another government's determination that is made without meetings open to the American public for examining the data underlying the determination are a violation of FACA (Federal Advisory Committee Act).
Moreover, the Congress has delegated to the FDA the authority to make determinations on safety issues concerning dietary supplements. It did not and cannot delegate this authority to the Canadian government. The FDA does not have the constitutional authority to redelegate the rulemaking authority given them by Congress to the Canadian or any other extragovernmental entity. Hence, the use of the Canadian standard is unconstitutional. This same issue was part of a 1992 decision by the 11th U.S. Circuit Court of Appeals in which the court considered the propriety of OSHA's incorporation of the standards and findings of outside organizations (e.g., not part of OSHA, not part of the United States government and not subject to U.S. law concerning open meetings, etc.). In that case, the court vacated a "generic" OSHA rulemaking to set permissible exposure limits for 428 substances identified by the agency as air contaminants. The court found that while OSHA may "rely on the recommendations and documentation" of outside organizations (such as the 'threshold limit values' established by the American Conference of Governmental Industrial Hygienists), the outside body's findings "did not relieve OSHA of the responsibility for making detailed findings, with adequate explanations, for all statutory criteria. (See AFL-CIO v. Occupational Safety and Health Administration. 965 F.2d 962, 984 (11th Cir. 1992)
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LABELING OF EPHEDRA DIETARY SUPPLEMENTS
FDA's Labeling Power Is Limited
"[N]o one disputes the proposition that [t]he Constitution created a Federal Government of limited powers") (New York v. United States, 505 U.S. ___,___(1992) (slip op., at 7) quoting [several citations deleted]. The powers granted under the Constitution to the federal government are outlined in the Constitution (the enumerated powers) and interpreted by the U.S. Supreme Court. The Bill of Rights describes further limits to the powers of the federal government.
The First Amendment of the US Constitution absolutely prohibits the FDA from banning labeling that is neither misleading nor deceptive. Indeed, Pearson & Shaw, et. al, have a First Amendment lawsuit against the FDA Commissioner before the U.S. District Court for the District of D.C. at this very moment. (Civil Action No. 95-1865 (EGS), District Court for the District of Columbia) If the FDA proceeds with its proposed Rule, it is asking for another lawsuit.
The Commissioner of the U.S. Food and Drug Administration promises, in his oath of office, to "protect, defend, and uphold" the U.S. Constitution. Unless we are to suppose that the oath of office is simply a ritual devoid of meaning and that the taking of the oath incurs no obligations, then the FDA Commissioner is obligated to seriously consider the constitutionality of his rules before it proposes them. There can be no excuse that it is somebody else's responsibility.
The U.S. Supreme Court has made it clear that the First Amendment does not permit government to keep information from the public in order to manipulate public choices. That includes, for example, information on the published peer reviewed clinical trials of ephedrine as a weight loss aid. It also includes information on the adverse effects reports received by the FDA from consumers using OTC products containing the same alkaloids as in ephedra: ephedrine, pseudoephedrine, and phenylpropanolamine (which is racemic norephedrine, the principal metabolite of ephedrine in humans.)
If there are political factors involved in the FDA's decisionmaking, then the public has a right to know what they are. Though the disclosure of this information may be deemed an embarrassment or inconvenient to the agency, the Constitution trumps the agency's embarrassment or inconvenience.
Quotes from the U.S. Supreme Court decision in 44 Liquormart v. Rhode Island (1996 WL 241709 (U.S.))
"...a State's paternalistic assumption that the public will use truthful, nonmisleading commercial information unwisely cannot justify a decision to suppress it." (at 8)
"It is precisely this kind of choice, between the dangers of suppressing information, and the dangers of its misuse if it is freely available, that the First Amendment makes for us." (quoting from Pittsburgh Press Co. v. Pittsburgh Comm'n on Human Relations, 413 U.S. 376, 93 S.Ct. 2553, 37 L.Ed.2d. 770 (1973)
"In case after case following Virginia Pharmacy Bd., the Court, and individual Members of the Court, have continued to stress the importance of ... the impropriety of manipulating consumer choices or public opinion through the suppression of accurate 'commercial' information..." (J. Thomas, concurring, at 21)
QUOTES FROM COMMITTEE TRANSCRIPTS
AND COMMENTS
Food Advisory Committee Meeting
August 27-28, 1996
Vol. II pg. 12 James Prochnow, an attorney with Patton Boggs
"...a dietary supplement manufacturer is able to inform each consumer of how a supplement or one of its ingredients affects the function and structure of the human body as long as it is not promoted to prevent, diagnose, mitigate or treat or cure a disease. As a result, a statement that a particular dietary supplement is effective for weight loss, mental alertness or clarity or for just plain energy does not make that related product a drug as defined by the Federal Food, Drug and Cosmetic Act."
Vol. II pg. 262 Dr. Ricaurte
"...I'm surprised at the fact that a number of potential uses and why these compounds, products, have been distributed have been taken off the table..."
It's no surprise. The FDA has instructed the Committee members that no use benefits may be considered in evaluating the risk/benefit of ephedra use, which requires that any mention of uses be eliminated. Prohibiting label mention of uses is unconstitutional as well as being a gross disservice to the customer. Note that the most common uses are ones where the consumer is able to judge whether they are receiving the promised benefits: satisfaction or reduction of appetite, weight loss, mental alertness and energy. Note further, DSHEA does not give authority to FDA to exclude benefits of a supplement from their Committee considerations.
Double blind placebo controlled peer reviewed published studies of the safety and effectiveness of 20 mg. ephedrine three times per day (e.g., Astrup, et al) were referred to several times during the meeting. FDA is not ignorant of this. FDA even officially admits "Other actions of ephedrine include stimulation of oxygen uptake and thermogenesis (heat or energy production)." (page 15 of the proposed Rule notice.) FDA's prohibition on the consideration of any benefits from ephedra dietary supplements is yet another example of FDA's bias against nutrient supplements, and is arbitrary, capricious, and contrary to fact. FDA must withdraw the proposed Rule, re-convene the Committee, refrain from forbidding the members from considering all relevant facts, and develop a new rule.
Vol. I pg. 153 Dr. Ziment
"...the patients who are taking herbal medicines rather than the standard drug produced by an ethical pharmaceutical firm, that individual is looking for magic. And if somebody's looking for magic, they're not going to be bound down by scientific recommendations. So even if we limit the amount of ephedra alkaloids in the drug, a person who's looking for a particular effect is simply going to take enough of the drug to give them that effect." "I think we're really expecting some sort of scientific control over the way people exercise free behavior, and that's not going to be easy."
And its not constitutional, either.
Vol. II pg. 245 Dr. Benedict
"And the cat, frankly, is already out of the bag. We can remove all of the labels regarding weight loss and all of the other things and people are still going to know that this is something that they think will work."
The FDA has required this committee to disregard any evidence for efficacy of ephedra in weight loss and anything else, but they cannot prevent that information from reaching the public. When the public has information which they think the government (FDA) is trying to keep from them, their respect for the FDA as a source of information plummets until it is all but ignored.
"In the May 1995 FMI [Food Marketing Institute] survey, 45% of consumers trust no one and rely on themselves for assuring the nutritional value of the food they eat, up 6% from last year [1994]. Manufacturers followed at 23%, government 13%, food stores 5% and consumer groups fell dead last at 3%. A major shift has occurred at the expense of government, which led the list five years ago [1990]. Today, twice as many look to industry as government for assuring nutritious foods." (data from Food Marketing Institute, 1995. Trends in the United States Consumer Attitudes and the Supermarket 1995, Washington, DC, p. 57, as quoted from pg. 69 of Sloan and Stiedemann, "Guaranteed Success: How to Make Products Consumers Really Want" in J. of Nutraceuticals, Functional & Medical Foods (Haworth Press) Vol. 1 No. 1, 1997.) (emphasis added)
The authors report in the same article that they have recently conducted proprietary research to determine what motivates consumers to purchase products in health food stores. They found (pg. 72) that 62% purchase supplements to prevent disease; 54% for increased energy; 40% to improve fitness; 31% to increase alertness; 27% to reduce stress; 25% to treat medical problems; and 21% to fight depression. As the authors note, "...the diet and disease connection with supplements has come a long way in just a few short years."
It is clear, from the above, that the government has suffered a decline in the extent to which the public relies upon it for nutritional information. If the FDA continues its practice of attempting to mold consumer dietary supplement choices by limiting information (such as prohibiting uses on labels) or by providing disinformation (such as mandating bogus time limits for use), the government's public credibility will decline further until it will cease to be of any relevance whatever in the area of nutritional information. The FDA's proposed Rule will cause great consumer harm because it will cause loss of credibility in all label warnings, not just FDA mandated bogus ones. All this is in addition to the insurmountable constitutional problems posed by the FDA's proposed Rule.
Vol. II pg. 37 Adam Gissen
"...one of the most telling things has been the desire to limit the use of products like this to some duration of time. This is in spite of a complete lack of scientific information indicating that this makes the product safer or more effective."
"In fact, ...all of the studies that have been done on ephedra have been done over a duration significantly longer than one week."
Millions of people have used ephedra dietary supplements for periods of time far in excess of one week. FDA's proposed Rule requiring the label to state a one week limit on duration of use will backfire in a very serious manner. A warning that 99% of the customers know is false or misleading will reduce the credibility of the real pharmacologically justified warnings (e.g., contraindications such as cardiac arrhythmias and hypertension) thereby making the FDA directly responsible for an increase in adverse reactions and deaths.
Vol. I pg. 42 Dr. Larsen
The working group "agreed that the ephedrine alkaloid limit should be below that for currently marketed OTC drugs, and label instructions should advise consumers that more frequent use or using more than instructed does not increase effectiveness." This is patently false and will reduce consumer confidence in label warnings. Instructions ought to advise consumers that more frequent use or using more than instructed increases risk of adverse reactions, not the obviously bogus statement that it does not increase effectiveness. FDA seems to believe that dietary supplement consumers are all idiots. This is untrue; market surveys have repeatedly shown that dietary supplement customers average considerably above the general population in formal education and intelligence. The FDA's Rule mandates label disinformation, and serious adverse consequences will inevitably occur unless the proposed Rule is withdrawn, new Committee meetings held, and a modified scrupulously honest Rule subsequently re-issued.
Vol. 1 pg. 280 Dr. Jones
"Finally, if the above is not sufficient, one extra line on the label will certainly kill the herbal street drug look-alike market: Warning -- exceeding the maximum permitted intake may result in temporary impotence."
"Those who understand the roles of the catecholamines in mammalian physiology will appreciate the scientific rationale for this cautionary statement."
Dr. Jones is entirely correct. His statement is not a bogus warning; it is truthful, not misleading, useful, and likely to be very effective.
The FDA does have a constitutionally legitimate role in assuring that dietary supplements sold in interstate commerce have adequate warnings. No warnings or inadequate warnings were found on a disproportionate number of products associated with adverse reactions:
Vol. I pg. 31 Ms. Binzer
(From 1995 working group meeting): Approximately 15 percent of all the dietary supplements collected in the review did not bear warning statements of any kind; 85 percent of the dietary supplements bore warning statements ranging from very general states, such as "consult your physician before beginning any nutritional or exercise program" to more specific warning statements, which tended to include recommendations not to use the product if consumers suffers from various medical conditions, experiences certain adverse effects, is taking certain medications, or is under a certain age.
Vol. I pg. 91 Frank Wickham
"...we've had this death of this young man due to a toxic level of ephedrine, taking it, of course, not having any idea that the product was dangerous..." (emphasis added)
Apparently there were no warnings on the label. This is certainly a legitimate and useful area for FDA action -- so long as the FDA mandated warnings are truthful and not misleading, rather than the proposed disinformation which will reduce credibility of all label warnings to the consumer.
Vol. I pg. 121 Ms. Ho (Canadian official)
"Subsequently, perhaps due to misuse or the fact that as a food the product did not contain any of the warning statements present in drug labeling, and because consumers may have exceeded recommended usage directions, two serious adverse reactions were reported in 1993" "Although as in most cases of adverse event reporting cause-and-effect relationship are not firmly established..." (emphasis added)
On the basis of misuse and/or a lack of important warnings, Canada now disallows the inclusion of ephedra as a non-medicinal ingredient in traditional herbal remedies and its use as food is no longer permitted rather than mandating appropriate warning labels. Canada does not have a U.S. Constitution, DSHEA (Dietary Supplement Health and Education Act), a FACA (Federal Advisory Committee Act), nor an APA (Administrative Procedure Act) and hence can not be used as a model for FDA action.
Vol. I pg. 133 Dr. Chassy
"You seem to have set national policy in Canada, if I heard you correctly, on the basis of two serious cases, and this committee is being asked to address itself to the issue of association versus scientific evidence of causality that the ephedrine alkaloids cause serious consequences. Could you share with us those serious cases and how you reached the determination, which you obviously did, that there was a causal relationship?"
Vol. I pg. 133 Ms. Ho (Canadian government representative)
"I don't have a lot of details about the two cases. I know that one was related to cardiovascular effects in a middle-aged male, I think, with a predisposing heart condition. The other one was a teenager who abused the drug product." "People were being told ignore label directions and, yes, do take ten tablets instead of two tablets today if you want the product to be effective or if you want to lose weight faster." (emphasis added)
If the FDA limits dosage to the Canadian rule of 8 mg. ephedra alkaloids three times per day for a maximum of one week instead of the usual informal industry standard dose of 20 mg. ephedra alkaloids three times per day without time limit, the above is exactly what will happen in the U.S. The FDA's ill designed proposed Rule is about to destroy the integrity and credibility of the ephedra dietary supplement warning and instruction labels and thereby increase the incidence of adverse reactions. This is not a theory; it has already happened in Canada and FDA cannot plead ignorance of the consequences.
Vol. I pg. 157 Dr. David Kessler
"We have two very real cases that the medical examiners have at least associated with the use of the products, the compounds under discussion. We need to reduce those risks. You're never going to reduce it to zero. You're never going to have somebody not do something very stupid that you can't predict. You can't safeguard against everything in this world. But I am convinced that those two individuals died needlessly because the information wasn't communicated to them about the hazards associated with these products." (emphasis added)
Dr. Kessler is correct. However, he did not state here what the labels on these products actually say about doses and about warnings. Were there no or inadequate warnings on the labels or did the individuals misuse the products?
Vol. I pg. 169 Constance Hardy (referring to FDA's second market review in April 1966, which identified 125 different dietary supplement products containing ephedrine alkaloids, some being duplicates (not necessarily the same formulation) of products collected in the first market review)
"Product labels, however, did not necessarily specify the form of the botanical source of ephedrine alkaloids, that is, whether it was an extract, a concentrate, or raw herb." "In some cases where the ingredient was listed as ma huang or ephedra without any further clarifying terms such as an extract or a concentrate, the ephedrine analytical values found on the products were higher than could be expected for the range of ephedrine alkaloids known to be present in the natural herb."
Vol. I pg. 174 Hardy
"...26 products had no warning statements at all; a general statement was noted on 14; disease or condition states were on 86 products; drug interaction statements were on 37; adverse effects noted were on 25 products; maximum daily use imperative--that's something to the effect 'Do not exceed'--you know, it specifically has the word 'exceed.' That was on 35 of the products, and age restrictions was 35."
Vol. I pg. 205 Dr. Love
Death of a 20 year old male college student who took eight tablets of an ephedra-containing "street drug alternative" although the label instructions were to take four and not to exceed four in a 24 hour period. The coroner's report stated (pg. 206) that the cause of death was "cardiac arrhythmia due to the synergistic effects of ephedrine, pseudoephedrine, phenylpropanolamine, and caffeine."
Dosage information was not given by Dr. Love; however, this is clearly a case of drug abuse, not use in accord with the label. We agree with FDA that labeling that promotes an ephedra dietary supplement as a street drug look-alike (e.g., Herbal Ecstasy) is false and misleading and can and should be prohibited in interstate commerce.
Vol. I pg. 275 Jones
"In the United States, our market surveillance covers over 300,000 users of ephedra herb with a particular range of products and has failed to reveal any serious adverse effects. We have had occasional minor complaints, but these were generally associated with failure to follow label instructions -- in other words, failing to start with a low intake and building up to a comfortable level...taking it too late and being kept awake at night--and these complaints did not occur in those who followed label instructions." "...the products concerned are manufactured under GMP conditions to a strict specification, and we analyzed both incoming raw materials and the finished product for ephedrine alkaloids and alkaloid pattern."
Vol. II pg. 37 Adam Gissen
"...these products have negative tolerance when looking at their effects on the central nervous system."
"And that's one of the things that makes something like ephedra a real poor alternative to speed. People develop tolerance, very very rapidly to the effects of ephedra on the central nervous system, especially used responsibly, in other words, starting at a low dose and slowly building up to some recommended level."
Tolerance develops very rapidly to the cardiovascular effects of ephedrine, too. Several members of the Committee agreed that slowly increasing the dose over a few days would reduce the risks of adverse reactions. We agree with this, and believe that it should be part of the label instructions. Unfortunately, FDA's proposed rule requiring labeling to state a maximum use period of seven days makes that impossible, and hence this labeling requirement should be withdrawn. Instructions recommending a slow build-up to a full dose over a period of a few days to several days will reduce the adverse reactions far more effectively than a seven day limit which will be almost universally ignored.
Commenters Pearson & Shaw license formulations containing approximately 1.8 grams per dose of ground ephedra herb (the amount being adjusted on the basis of lot analyses to contain a total of 20 mg. of ephedra alkaloids). No ephedra extracts are used in this product, there is no caffeine or other methylxanthines, and it contains no synthetic ephedrine, pseudoephedrine, or phenylpropanolamine. Here are the label instructions:
"DIRECTIONS: Add 4 ounces of hot or cold water to one heaping tablespoon of mix. Stir briskly. Allow the mixed tea to stand for a couple of minutes. DO NOT EXCEED THREE SERVINGS A DAY! Keep in a cool, dry place. Keep lid tightly closed when not in use."
"SUGGESTED USAGE: For first three days, drink one serving in the morning as soon as you wake up. For the next three days, drink a second serving before lunch. From then on, drink a third serving one hour before dinner."
"CAUTION: KEEP OUT OF REACH OF CHILDREN. Not for use by children, pregnant or lactating women. May cause insomnia in sensitive individuals, especially if taken too soon before bedtime. Consult your physician if you are taking asthma medications, anorectic (appetite suppressing) drugs, antidepressants, or cardiovascular medications. Do not consume this tea if you are pregnant or lactating or have high blood pressure, cardiovascular disease (especially cardiac arrhythmia), diabetes, prostatic hypertrophy, glaucoma (angle closure), hyperthyroidism, psychosis, thyroid disease, or Wilson's disease. Do not drink this tea within 14 days after taking MAO (monoamine oxidase) inhibitor drugs. If symptoms of allergy develop, discontinue use. Avoid the use of antacids containing aluminum with this product."
The label also discloses that the ingredients include ephedra herb powder. We wanted to put "contains 20 mg. ephedra alkaloids (primarily ephedrine)" on the label but were advised by one of our attorneys (who worked for the FDA for many years) that we should not do it because the FDA might use this statement as the basis for declaring our formulation to be a new unapproved drug. We believe that all ephedra herb containing products should disclose that information on the labels, stating the total amount per dose of ephedra alkaloids.
Note that these instructions increase the dose from the initial dose of 20. mg. ephedra alkaloids once per day to the final 20 mg. three times per day over a period of seven days. This very conservative rate of daily dose increase will be made unfeasible by the FDA's proposed rule mandating a labeled maximum use period of seven days; only one day of full dose and full effect would be allowed, hence rendering a product with these instructions ineffective and uncompetitive. For all practical purposes, the FDA may as well prohibit all labeling that instructs the customer to slowly increase their dose over a period of several days.
FDA has not met DSHEA's burden of proof for their requirement that the labeling limit use to seven days. A number of comments by Committee members and consultants also expressed doubts about the basis for such a limit. FDA's primary interest in the seven day limit appears to be their use of it to prohibit any labeling which would suggest uses which would require longer than seven days. (See pg. 36 of the Proposed Rule notice, "a. Claims that promote long-term use.") FDA thereby attempts an end run around the First Amendment, believing that their seven day rule may receive more judicial leniency than the strict scrutiny that would apply to a prior restraint on such truthful non-misleading speech as labeling suggesting weight loss benefits when used for longer periods of time (eg. longer than a week).
In order to keep the label information-free regarding possible weight loss benefits, FDA ignores the increased risk to consumer safety. FDA is well aware that the development of tolerance to both the CNS and cardiovascular effects of ephedra alkaloids reduces the risk of these adverse reactions. They even admit this when they say on pg. 48 of the proposed Rule Notice, "FDA requests comments on whether the warning statement should disclose the possibility of increasing the risk of adverse events by a pattern of stopping and starting use." This is another iatrogenic risk created by the FDA's proposed 7 day use limit, which will cause those consumers who heed it to repeatedly start and stop taking the supplement.
FDA proposes to require that labels say "Taking more than the recommended serving may cause heart attack, stroke, seizure, or death." While it is true that taking too much of anything (including oxygen and water) can cause death, FDA has not met its DSHEA burden of proof that a warning of this severity is appropriate for their proposed label Rule specifying less than 8 mg. ephedra alkaloids three times a day for a week maximum. With such a low permitted dose, most consumers will continue to take more than 8 mg. TID, just as consumers have been doing for many years. Unfortunately, consumers won't get any information from labels on how much more it is reasonable to take. Those who take 2 to 3 times the label dose will be receiving about the same amount of ephedra alkaloids per dose that consumers have been taking for years. Those who know that the FDA has drastically reduced the dose -- but not by exactly how much -- may take much more, thereby being subject to an increased risk of adverse reactions or even death.
The application of the FDA's above Rule warning to such a low dose (8 mg. TID) will be considered bogus by essentially all consumers who have previous experience with ephedra supplements, thereby casting unwarranted doubt on real and truly justified warnings such as "Don't take this product if you have hypertension or a cardiac arrhythmia." The FDA's above proposed warning would make much more sense if applied to a product containing 20 mg. of ephedra alkaloids or more, that is, if it applied to doses of the size of those that have been widely used for many years. There will be a serious cost involved if FDA requires the arbitrary and capricious use of inappropriately severe warnings -- a cost in increased adverse reactions and death due to loss of consumer confidence in fully justified warnings.
On page 47 of the 100 page proposed Rule notice, FDA proposes to require the statement "Larger quantities may not be more effective." As we have commented above, this is not only misleading (since larger quantities may also be more effective), it is so obviously deceptive (particularly with respect to the most common use, weight loss) that the credibility of all warnings on the label will be seriously reduced.
FDA then disinforms both the people of the United States and the Congress by saying "The agency is not aware of any data or other information that establishes that there are benefits from the use of dietary supplements containing ephedra alkaloids." (See pg. 47 of the proposed Rule Notice.) This is a lie. Ephedrine is the principal ephedra alkaloid. The transcripts of the meetings show that the FDA Committee is well aware of reputable peer reviewed published double blind placebo controlled clinical trials with ephedrine (though not necessarily on the same amount of the same compound when contained in the herb) that show that it can be effective for weight loss. Indeed, (inconsistently) these studies are even discussed on pg. 17-19 of the proposed Rule Notice. An advertisement that was equally misleading would be illegal.
In any case, FDA's attempt to require more severe warnings on ephedra dietary supplement labels than on OTC (over the counter, no prescription required) drugs containing larger doses of the same alkaloids contained in ephedra supplements is arbitrary, capricious, contrary to reason, and is a further indication of FDA's bias against dietary supplements and in favor of more heavily regulated OTC drugs.
On pg. 51 of the proposed Rule Notice, FDA says:
"The agency considered the applicability of OTC drug data and tentatively concluded that these data, which involve use in a restricted population (physician-diagnosed mild asthmatics) under limited directions for use (i.e., not to exceed 12.5 to 25 mg. every 4 hours, not to exceed 150 mg. in 24 hours) and with warnings and contraindications for use, has no application here. The determination of safety for drugs is based on a weighing of the proven benefits of the use of the product against the risks. This approach may not be used with foods under section 402(a) of the act. The only question for food use under this section is whether it will cause harm or not. While the concept of "unreasonable risk" as stated in section 402(f)(1)(A) of the act, may imply that some evaluation of effects, including risks and benefits, is appropriate for dietary supplements, it is not necessary to reach that question here, because, as stated above, there are no demonstrated benefits for ephedrine alkaloids. Moreover, the risks attendant on consuming dietary supplements containing levels of ephedrine permitted in oral bronchodilator drugs (12.5 to 25 mg. ephedrine per dose) are manifest."
COMMENT: The FTC concludes "tentatively" that the OTC drug data on ephedra alkaloid containing products has no application here. The FDA argues that the OTC data apply to a restricted population with directions for limited use and with warnings and contraindications. However, OTC drugs may be purchased freely by anyone (not just a restricted population) and used for any length of time and at any dosage their purchasers may choose. Adverse events resulting from abuse and improper use of the OTC drugs may provide valuable data for evaluating the adverse events resulting from the abuse and misuse of the dietary supplements containing ephedra alkaloids. We reviewed published reports of adverse events of individuals taking ephedrine, phenylpropanolamine, and pseudoephedrine containing products that are exhibits to the FDA's proposed rulemaking (exhibits 56, 60, 62, 63, 67, 68, 69, 70, 71, 73, 100, and 128). Our review indicates that most of the adverse events were a result of abuse or misuse of the products.
The FDA argues that the safety for drugs is based on a weighing of the proven benefits of the use of the product against the risks and that benefits may not be considered for foods, only whether they will cause harm or not. The FDA admits that the concept of "unreasonable risk" (as stated in section 402(f)(1)(A) of the act) may imply that "some evaluation of effects, including risks and benefits, is appropriate for dietary supplements, it is not necessary to reach that question here because...there are no demonstrated benefits for ephedrine alkaloids." There are a number of published peer-reviewed studies indicating that ephedrine has a thermogenic effect that helps with weight loss. But, in the final analysis, it is consumers using these dietary supplements who are the judge of whether they are getting benefits or not. In the case of weight loss or energy, a consumer is quite capable of evaluating whether he or she has lost weight or gained energy. If the FDA is going to assume that nothing has a "demonstrated" benefit other than those very few dietary supplements for which it has approved "health claims," then nearly all dietary supplements will be denied a risk/benefit analysis. This is unreasonable, arbitrary, and capricious.
The FDA then states that "the risks attendant on consuming dietary supplements containing levels of ephedrine permitted in oral bronchodilator drugs (12.5 to 25 mg. ephedrine per dose) are manifest." A number of comments during the Food Advisory Committee meeting by consultants and Committee members who were experienced in their practices with the use of ephedrine for bronchodilation indicated that when used according to label instructions, these risks are not great. The real problem, with both OTC and dietary supplements containing ephedra alkaloids, is abuse and misuse by careless consumers.
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AMOUNT OF EPHEDRA ALKALOIDS PER DOSE
AND TOTAL DOSE PER DAY
QUOTES FROM 1996 FOOD ADVISORY COMITTEE TRANSCRIPTS
AND COMMENTS
Although we have already made several comments as to why the FDA should not limit ephedra alkaloid to 8 mg. per dose with a total dose of 24 mg. per day, but instead should set the limit at 20 mg. per dose, 60 mg. per day, we hereby provide further reasons for this conclusion.
The most fundamental reason that the FDA has not met the DSHEA burden of proof on their dose limits is that ephedra dietary supplements are already much safer than food in common form. This is true even though the doses found in current products are given by the FDA as having a median of 17 mg. per dose with a mean of 30 mg. per dose (standard deviation = +-31 mg.). Unless FDA is allowed to set far higher standards of safety for dietary supplements than for food in common form (which is not allowed by DSHEA), a 20 mg. dose cannot be considered unreasonably unsafe when used as directed. We believe that a dose limit is needed (we consider a 110 mg. dose to be grossly irresponsible), and that 20 mg. total ephedra alkaloids per dose is reasonable as demonstrated by the current safety record. A 20 mg. per dose limit with a total dose of 60 mg. per day is realistic and will be accepted by consumers; the FDA's proposed limits will be generally ignored by consumers, thereby reducing the credibility of the other label warnings and instructions, and causing consumers to take multiple doses -- sometimes too many multiples -- thereby causing avoidable adverse reactions and harm.
Vol. I pg. 206 Dr. Love
In a summary of the FDA analyses on products associated with adverse event reports "where we had information on how the consumer used the product so that we could calculate the milligrams per consumer use," the products range from one product at 0 all the way up to over 50. The mean dosage was approximately 30 mg. plus or minus 31. (!!) One of the supposedly ephedra-containing products associated with an adverse event had zero ephedra alkaloids in it. What were the rest of the ingredients?? FDA doesn't say.
Vol. II pg. 234 Dr. Askew
"From the information that has been presented to me, I've been impressed by the amount of people that are actually consuming this product without having adverse reactions, and I draw more my conclusions as to its relative safety from that than from the adverse incidence reports which are very difficult to deal with because of the nature of the reports."
Vol. I pg. 153 Dr. Ziment
"...the patients who are taking herbal medicines rather than the standard drug produced by an ethical pharmaceutical firm, that individual is looking for magic. And if somebody's looking for magic, they're not going to be bound down by scientific recommendations. So even if we limit the amount of ephedra alkaloids in the drug, a person who's looking for a particular effect is simply going to take enough of the drug to give them that effect." "I think we're really expecting some sort of scientific control over the way people exercise free behavior, and that's not going to be easy."
A second major reason why FDA cannot set their dose limits at 8 mg. per dose and 24 mg. per day is that OTC drugs are readily available to anyone for any purpose at any supermarket that contain 24 mg. of ephedrine and 120 mg. of theophylline, a caffeine like stimulant methylxanthine, with a 150 mg. per day of ephedrine label limit. FDA's Rule dose is not only arbitrarily and capriciously far lower, but it lacks reason; no increase in safety will occure if current ephedra supplement customers switch to an OTC product with higher doses of ephedrine and methylxanthenes than the typical ephedra herb dietary supplement.
Vol. II pg. 104 Dr. Ziment
"If we say ma huang and ephedra products in dietary supplements are unacceptable does this create the concept that people who want to take these drugs have to buy orthodox ephedrine over-the-counter or would it give the message that we think people should go to MDs and have them evaluate the patient and then prescribe the ephedra products?" (emphasis added)
A third major reason that the FDA cannot impose the Rule doses is that it is far lower than the doses traditionally used in ephedra herb teas. FDA is legally required to allow the marketing of grandfathered products in traditional doses provided the labels are unchanged. It would be regrettable if FDA forced the industry to take this route because the original labels had few if any warnings and no drug interaction precautions. If this occurred, it would be harm caused by the FDA's proposed Rule, not harm inherent in the herb.
Vol. II pg. 105 Dr. Croom
"If you take the Chinese pharmacopeia the range of ma huang or ephedra that you can use is 1.5 to 9 grams. Actually most of the formulas used by practitioners that I've seen range around 6 grams but there is a ma huang tong that is based on a 9-gram dose." "If you take the more moderate, 5 to 6 grams, and you say the Japanese pharmacopeia is the only official source that sets a minimum, which is .6 percent, if you take in commerce, no matter what these range of values you've seen, the average is probably 1.2 percent. Then you will find that if you took 5 grams, which is approximately two tablespoons -- I have cut it and weighed it myself -- that you will find that at a .6 to a 1.2 that you are getting 15 to 30 milligrams per tablespoon in ma huang tea for the minimum concentration of .6 to an average of 1.2 If you take the two tablespoons, therefore, you are at the same dose that we found most physicians using, between 25 and 50 for the pure compounds." (emphasis added)
The USP standard for ephedra herb is at least 1.2% ephedra alkaloids. Our own extensive experience is that most of the herb available on the US market is between 1.2 and 1.8%, in agreement with the observations of Dr. Croom.
Vol. II pg. 172 Dr. Croom
"The Chinese herb itself has between generally 1 and 2 percent [ephedrine alkaloids]. An average dose of the herb is 6 grams. That means you have between 6 and 12 milligrams of alkaloids there. So I'm taking traditional long-term use, what do we know from others, not to justify the use, but to say for safety where are the numbers..."
Incorrect math. The 6 grams of herb contains between 60 and 120 milligrams of alkaloids.
Vol. II pg. 219 Dr. Fong
Here, Dr. Fong states that the German Commission E dosage [no prescription required] is 1 to 6 grams per dose and that the "Japanese and the Chinese pharmacopeia of ephedrine alkaloid content in ephedra of 0.7 and 0.8 percent, not less than."
This calculates to a range of 7 milligrams to 48 milligrams a serving, though Dr. Fong refers only to the 7 milligrams. With a more likely ephedrine content, it calculates to 12 mg. to 72 mg. per dose.
Vol. I pg. 44 Ms. Bowen
"...we published a proposal in 1995 to remove ephedrine-containing products for bronchodilator use from the marketplace due to three events, one being diversion and difficulty containing that by the DEA under their current rulemakings, and also some evidence [emphasis added] in our adverse event reporting system of misuse of the products" Removal was not proposed because after 50 years or so of use these products were suddenly found to be unreasonable unsafe when used as directed. What evidence of misuse of products is in the adverse event reporting system? FDA deleted all OTC data from their database and refused to supply it to Committee members even though Committee members asked for it. Note, too, that while the FDA mentions this previously proposed (and failed) removal of the ephedrine alkaloid containing bronchodilators in the Rule Notice, FDA deceptively leaves the false impression that this previous proposed removal was for safety reasons, not because ephedrine was being diverted for use as a precursor of illicit blackmarket methamphetamine.
Vol. I pg. 45 Ms. Bowen
"over the counter bronchodilators has single dose of 12.5 to 25 mg. of ephedrine, not to exceed 150 mg. a day."
Primatene tablets, containing 24 mg. ephedrine plus 120 mg. theophylline, are still on the market. So are products containing pseudoephedrine (the second major ephedra alkaloid) and phenylpropanolamine (a racemic version of norephedrine, the principal human metaabolite of ephedrine. The maximum dose of OTC pseudoephedrine is 60 mg., and the maximum OTC dose of phenylpropanolamine is 120 mg.
Vol. I pg. 46 Dr. Jasinski (the drug abuse expert)
"Most of the concern of the DEA is not with ephedrine at a retail level."
Vol. I pg. 72 Dr. Askew
"Now, also the question has been raised as to whether or not the OTC drugs are experiencing the same incidence of adverse reaction reports as the food products are, and I think this is probably a fair question."
Vol. I pg. 73 Dr. Culmo
"TDH [Texas Dept. of Health] provided oral and written comments in October 1995 to the committee's working group on ma huang. At that time, we indicated that TDH had collected 900 reports of adverse reactions to ephedrine-containing products for Texas citizens; that was 400 from over-the-counter or OTC drug products and 500 from food products. We now have substantially more than a thousand reports of injuries or adverse events." (emphasis added)
Vol. I pg. 162 Dr. Ziment (expert on the use of ephedrine in asthma and other respiratory diseases)
"As somebody who has been treating asthma for a long time, I regard ephedrine as an asthma drug. And I think I know that the dose is something between 50 and 60 mg. three or four times a day. And I rarely have changed those dosages in treating patients, whatever their underlying or secondary condition may be. So I think we should use those dosages as a starting dose of what is safe and reasonable, and make the equivalent dose of ma huang equated to those dosages of pure ephedrine." (emphasis added)
Vol. II pg. 165 Dr. Ziment
"...this implication that more than seven days could be hazardous, as opposed to less than seven days in some sort of long-term fashion. I just don't see the evidence for that."
Vol. II pg. 240 Dr. Katz
"When I looked at this question, I had to divorce my experience as a physician with ephedrine since as a practicing pediatric pulmonologist back in the late '70s and early '80s we used a lot of ephedrine for children with asthma. It has been supplanted by obviously much better drugs, but we saw very few serious adverse effects."
Vol. II pg. 105 Dr. Croom
"One of the things that we discussed in the committee [1995 working group] was certainly that when you set the level at 25 total ephedrine alkaloids, but ephedrine being seen as the most cardioactive and potentially the largest side effect being lower at 20, was one of the things that was discussed." "...there was also consensus certainly between Dr. Tyler and I and this was also forwarded to the charman, that if things were used in combination with things like caffeine that we were both in agreement that ratio--this is individual dose--should be a 10/15 level, not a 20/25, because of what was unknown we felt like in the lack of data, even though there is some data." (emphasis added)
We agree with Dr. Croom and Dr. Tyler: 20 mg. ephedrine in 25 mg. total ephedra alkaloids per dose if there is no caffeine or other methylxanthines, 10/15 mg. per dose if the product contains caffeine or other methylxanthines, with a maximum of three doses per day.
Vol. II pg. 57 Gordon Peterson
"And I then decided I would look at what is considered the pharmacological bible, Goodman's and Gilman's, in their book, Pharmacological Basis of Therapeutics, and found ephedrine listed as follows and I quote: 'The usual oral dose is 25 to 50 milligrams repeated every three to four hours for a 150 to 300 milligrams per day dose.' "I then ... looked in the American Hospital Association's Hospital Formulary which recommends the following: 'The usual adult dosage is 25 to 50 milligrams every three to four hours.'" "Another quote from this American Hospital Association's Formulary is... 'For self medication in children 12 years old and older, the usual dosage is 12.5 to 25 milligrams every four hours.'" "It goes on....'For children 6 to 12 years of age, ephedrine is safe at 6.25 to 12.5 milligrams every four hours.'"
Vol. II pg. 58 Mr. Peterson
"Another study. This one comes from the International Journal of Obesity 1993, and I quote: 'We conclude that the ephedrine/caffeine combination is safe and effective in long-term treatment in improving and maintaining weight loss.'" "'The side effects are minor and transient and no clinically relevant withdrawal symptoms have been observed.'"
Vol. II pg. 75 Mr. Appler
"I find it difficult to believe on any scientific or toxicological basis that my ingestion by inhalation [sic, this should be per oral] in a health compromised population, 25 milligrams single dose, 150 a day, is safe as declared by FDA and its experts. But that oral ingestion at the levels you recommended last October [1995 working group] 20 milligrams of ephedrine alkaloids, 25 total alkaloids, AD/100 per day, is possibly the hazard that FDA has tried to present it as."
"If that were so, we would be seeing literally thousands of injuries among the tens of millions of daily users of bronchodilator products. Needless to say, despite the far more sophisticated system FDA has for capturing drug reactions, no such substantial reports for bronchodilator use have appeared."
Not only that, but Primatene tablets containing ephedrine are available OTC, meaning that anyone can walk into a supermarket or drug store and buy them and then use or misuse them any way they wish. If significant adverse reactions were occuring in users (rather than high dose abusers) of Primatene tablets, the lawsuits alone would have driven Primatene tablets off the market long ago.
Vol. II pg. 16 Mr. Prochnow
This testimony concerns an approved protocol for a clinical study of ephedrine: "The Institutional Review Boards of Harvard and Vanderbilt on a preliminary test they go through would not probably have approved the protocol for these studies unless they felt that there was a good possibility or probability that the levels of ephedrine that were going to be tested, about 25 milligrams per dosage... was an appropriate safe level. ... the parameters of the protocol included at least 30 milligrams of caffeine per serving size and at least 25 milligrams of ephedrine alkaloids per serving size."
Vol. II pg. 111 Dr. Ricaurte
"What I'm puzzled by is the apparent disconnect between the data on the products we've been discussing the last day and a half and what several members of the committee has said is our 50-year long experience with OTC ephedrine-containing products." "...the issues of some of the adverse effects, certainly they haven't loomed as major concerns with OTC products contained in the ephedra alkaloids. Is it the reporting system? ...if we are going to use, as was suggested by the Special Working Group before [1995], as a benchmark or a starting point on dosage issues, prior experience with OTC products containing the ephedra alkaloids, then I think the issue of why the apparent disconnect exists is critical."
Vol. II pg. 111 Dr. Love
"Of course, the reporting systems are different and the products are very different."
The FDA is focusing on ephedrine and other ephedra alkaloids. Thus, it is reasonable to compare adverse reactions with other products containing ephedrine and other ephedra alkaloids. The admission by Dr. Love that the reporting systems are different may be pertinent in that there has been no FDA publicity concerning alleged dangers of the use of the OTC ephedrine, pseudoephedrine, and phenylpropanolamine products during the period when FDA has been publicizing the alleged dangers of dietary supplements containing those alkaloids.
Vol. II pg. 112 Dr. Love
"The product from one manufacturer containing ephedrine plus these other ingredients cannot be compared necessarily to a product from another manufacturer that may be listed as containing the same ingredients. You don't know what their source is, you don't know what their potency or anything else is. And because there can be natural variations, even the products from a single manufacturer can have lot-to-lot and batch-to-batch variability that may well affect their safety profile."
This is a good reason for doing a competent followup on reports of adverse reactions, to find out what the consumer actually ingested. The FDA cannot just say "we don't know anything so let's just ban all products containing ingredients that may have (but we don't know) been involved."
Vol. II pg. 115 Dr. Ziment
"I want to follow-up what Dr. Ricaurte was referring to. I still don't feel that I understand what the reported and recognized dangers are of taking either over-the-counter ephedrine or even pseudoephedrine or phenylpropanolamine. And I certainly have prescribed agents of this nature. And I feel there is a disconnect in that we are hearing a lot about the dangers of ma huang and ephedrine without knowing the dangers of comparable orthodox drugs." (emphasis added)
Vol. II pg. 116 Dr. Ziment
"Well, Dr. Love, perhaps can give us a little bit more information on the side effects that are actually recorded, even on a year-to-year basis in adverse drug reports on the legitimate ephedrine products."
Vol. II pg. 116 Dr. Love
"I don't have that data and I will defer to people from Drugs on that." (emphasis added)
However, no people from Drugs appeared at this meeting to inform the committee members on these data. It is appalling that the FDA did not provide this clearly very relevant, very important information that is indispensable to making a scientific judgment on the risks in using products containing ephedrine alkaloids, particularly when this data was identified as important and requested by Committee members.
Vol. II pg. 116 Dr. Weintraub
"...there are no serious adverse effects within the dose range that is printed on the label. There are some adverse effects that occur due to taking of products with different names which may mislead the public or be sort of fanciful names that would indicate a different indication other than bronchial dilation. So, but, as bronchial dilator, used as a bronchodilator there are no major adverse effects." (emphasis added)
Specific Proposal for a Constitutional Acceptable Label
Vol. II pg. 190 Dr. Blackburn
"I want to see whether if we vote for any of these levels, recommended levels that have come down 10-fold in 2 days, or in 10 months [since the 1995 working group meeting], down to 2 milligrams, what we're really doing, and I think only the people from the industry can tell us. Then if we know what we're doing, then we go ahead and do it. If we reduced it to those kind of doses with these kind of restrictions and this sort of quality control, is there going to be any market and are we banning the drug for use as a good supplement, in which case we might as well go and vote that way?"
But, the banning of ephedra herb products is not possible under DSHEA because the FDA has only very poor quality and unconvincing evidence that using ephedra herb products per label instructions poses a substantial and unreasonable risk to those using it. It cannot meet its burden to prove these alleged risks. Hence, the FDA now wants to reduce the permitted label single dose and permitted label total daily dose and permitted label number of days of use so that none of the benefits of using ephedra will be obtainable by consumers, thereby causing these troublesome (to the FDA) products to dissappear from the market. This is a ban by the back door.
Vol. II pg. 209 Dr. Jasinski
"...my view is that you're probably going to wind up with a dose of no more than 40 to 60 milligrams of total ephedrine alkaloids per day. The reason for this, just doing this and coming back again, from being a pharmacologist and a clinical psychopharmacologist and looking at this in terms of what we know about ephedrine, we know that from studies which have been done over the last couple of years that you can take anhydrous caffeine and give it to people and get amphetamine-, cocaine-like effects, maximizing at about 200 milligrams, between 100 and 200 milligrams."
Right. Note that the FDA approved dose of caffeine in OTCs like NoDoz is 100 mg. to 200 mg. An unwanted overstimulating effect would be particularly noticeable to an adult who had not experienced coffee before, just as most adults in the U.S. probably have not experienced ephedra herb before. However, in the U.S., most adults already have tried coffee and, if they had an unpleasant reaction, avoid it.
Vol. II pg. 210 Dr. Jasinski
"...somewhere about 2.5 milligrams of amphetamine...is equivalent to about 10 to 15 milligrams, 12.5 milligrams, of ephedrine. So one would look at this to keep it in this dose range of what people are using as the average or maximum sort of caffeine dose."
Vol. II pg. 221 Dr. Ricaurte
"I think it's telling that just from October '95 until here we are 8, 9, 10 months later, we've already gone from an estimated safety level down 10-fold, and I'm not quite sure on what basis we're doing this."
Vol. II pg. 222 Dr. Ricaurte
"With the issue of a margin of safety, I'm left at somewhat of a loss because for a margin of safety you really have to have some indication and what I've heard this afternoon is that all purported purposes of use are being taken off the table and it leaves you with, well, what the heck are we going to use this for. If there's no clear answer to that, then the margin of safety, quite frankly, has to go to infinity because you can't do a risk/benefit when we don't have a perceived benefit." (emphasis added)
The FDA has made this conclusion inevitable by requiring that the committee disregard any evidence concerning the efficacy of ephedra for those purposes for which it is being most widely sold: weight loss and energy. When you cannot consider any benefit, then of course even small risks will seem unacceptable.
Vol. II pg. 222 Dr. Ricaurte
"Question number 3 [the possibility 'of significant harm' and 'serious adverse effect in at least one individual']--I'm not sure that there's many compounds that can satisfy that requirement, so the answer is, no, I can't, but I'm not sure that it's entirely a fair question with regard to the ephedra alkaloid per se."
And it is not the definition of harm mandated in DSHEA, either.
Vol. I pg. 145 Mr. Israelson
"... the standard you are asking us to look at is significant harm, which has two sub-definitions, I'm just curious how you arrived at that definition, specifically in its two subparts, which is different from the statutory definition within the law." (emphasis added)
Because FDA has chosen to charge the Committee with a definition of harm contrary to that intended by Congress, FDA must withdraw the Rule, re-convene the Committee, reach a new conclusion that fits within the ambit of Congress's will, and re-propose a new Rule.
Vol. II pg. 231 Dr. Ziment
"So my recommendation is that ephedrine, as such, has always been prescribed by orthodox physicians in a dose of about--a minimal dose of 15 milligrams 3 times a day for adults and proportionately less for children. That should be the baseline dose for the orthodox, and I believe it's safe even if used for a prolonged period of time because I certainly used it that way. I've looked at the literature and I don't see much evidence that that dosage is harmful."
Vol. II pg. 236 Dr. Wang
"What margin of safety? What I did is just took a 10-fold safety factor from the OTC maximum level per day basis for, again, ephedrine alkaloid."
It would be interesting to consider what would be left on the market if all products had to be taken on the basis of a 10-fold safety factor. Oxygen, water, sugar, and total daily caloric intake all fail the tenfold safety test. DSHEA does not authorize the FDA to impose a 10X safety margin, either.
Vol. II pg. 249 Dr. Jasinski
"Thirdly, I think there is a telling point which was made that you have to be very cautious. I have been both historically and been involved in people that have made decisions that have driven things underground. I think what amazed me is watching the anabolic steroids of people passing laws because they got concerned about athletes using these. We have now a whole underground economy with anabolic steroids being imported which are being used which are less pure than those which were manufactured as pharmaceuticals coming in, and that's creating public health problems and uncertainties."
Remember that Dr. Jasinski is an expert on drug abuse. Heed his warning.
Vol. II pg. 249 Dr. Jasinski
"And I would think it would be better to encourage industry to come in with a position which they can defend on what they're going to do voluntarily and that this would be legitimate to set the standards. It would be much better than trying to impose a policy."
Far better, and far more effective. The FDA seems to think that if it makes a rule and points enough guns at enough people, any rule will work. This one won't. It will cause far more harm than it prevents, an all too common result at the FDA.
Vol. II pg. 250 Dr. Croom
"We've got to find a better way, I would say, to come together and talk about how do we impact the public health because there are benefits coming here and not just risk..."
Vol. II pg. 255 Dr. Dentali
"When I came here, I understood that my mission is the common-sense one, is to reduce the risk with these products. So when I got the updated version of the adverse events, I wanted to do a rigorous analysis of those, particularly with respect to the October [1995] recommendations. For me, that would be to look at the adverse reactions that are consistent with ephedrine use and to eliminate the ones that are not, to look at ones that are consistent with the levels of ephedrine that were recommended in October or that were proposed by a few members and eliminate those that were not, to look at the ones that were combined with other known stimulants and eliminate those reports, to look at the ones that were resulting from clear abuse and to eliminate those, to look at the ones that were made with only the herb and the herb extract and to include those and exclude all the others, and to exclude the ones that were resulting from chronic use. And I feel that that wasn't done and I feel that that was very important for me to be able to have a handle on beginning to look at the risk as it was presented to me regarding the adverse effects for us to determine for traditional use and traditional forms what is the danger of using this botanical."
A very cogent objection.
Vol. II pg. 262 Dr. Ricaurte
"So the pendulum has swung from one extreme of being very cynical to trying to regard this as a product, a dietary ingredient that should be used by consumers and not be over-regulated, not be in a position where the FDA or the medical profession or the scientific advisory group is put into a position of over-regulating something that adult Americans may wish to use under safe conditions. Those have not been defined."
Vol. II pg. 262 Dr. Ricaurte
"I think as long as the concern for some of the use is misuse and abuse, I find it somewhat, again, disingenuous to make recommendations, well, we're going to limit the dose from 20 down to 10 or down to 5. As a consumer, I don't have to be particularly adept in mathematics to realize that if now the tablet or capsule or a spoonful contains only 5 milligrams, I take 2 or I take 3 or I take 4. So the dose considerations and frequency of use suggestions, while I recognize that they're well-intended and I appreciate what the efforts are in terms of looking at the reality of the use of the product by a population of individuals who may be predisposed to misusing or abusing the product, I don't think those are particularly effective safeguards."
They are worse than ineffective; they will substantially increase the risk of harm by destroying the integrity and credibility of all the label instructions and warnings on ephedra dietary supplements.
Vol. II pg. 265 Mr. Israelson
"...I share the view that has been expressed that if you ban this product, you'll drive it underground and create a bigger problem."
Vol. II pg. 270 Dr. Woosley
"...as I think you pointed out, Dr. Ricaurte, there is no risk/benefit ratio you can establish when you don't have a known benefit..."
There are benefits known to the Committee; the FDA just refuses to allow the Committee to consider them, thereby guaranteeing a proposed Rule that is not based on reason or evidence.
Vol. II pg. 274 Dr. Inchiosa
"...in the experiences in Ohio, the Canadian study, even the information collected was that young people who are abusing the drug largely get it from ephedrine hydrochloride from over-the-counter preparations. I heard that statement made that a large number of the use by young and abuse by young was from over-the-counter preparations, not the difficult process of extracting something from a nutritive supplement."
Vol. II pg. 197 Dr. Kessler
"It's [the judgment on a safe level of ephedrine] based on the record before individuals. We have alot of different individuals with a lot of different expertise. We'll take that into account. For some, it'll be the information that has been presented over the last two days. For some, it'll be information that has been presented both in the working group and over the last two days. For others, they certainly can draw upon the literature that they're familiar with and their own expertise, but it's the record before them as has been presented. I think that the starting base is over the last two days, certainly."
But the data supplied over the last two days is of very poor quality and, as admitted by Dr. Love, has not yet been peer reviewed. Moreover, vital OTC adverse event safety data has been expressly removed by the FDA.
Vol. II pg. 204 Dr. Chassy
"We are talking about a dietary supplement which I as a consumer, when I walk into a store that sells these products, have every reason to believe are at least as safe as the foods in my diet that I mean to supplement and so I would hold them up to a very high standard of expected safety."
As we have shown, ephedra herb dietary supplements are already much safer than foods in common form. The bottom line is that consumers have unrealistic beliefs about the presumed safety of foods and need badly to be educated about that. Educating consumers about the risks of foods is of far greater importance than that of dietary supplements, on the basis of the record, yet the FDA has done a very poor job of providing needed information on food risks to consumers.
Vol. II pg. 157 Dr. Jasinski
"...the critical question has been the relationships of these deaths and your data and the particular interpretation versus the interpretations we've heard, and there has been a conflict."
"...and the essence of the scientific culture is we have peer review." (emphasis added)
Vol. II pg. 158 Dr. Jasinski
"My question is have you prepared a report on your data, how you collected it, how you interpreted it and what conclusions you've made, and have you submitted this to internal review within the agency or outside the agency? And, similarly, have you taken the report from this ad hoc committee and submitted it to a peer review?" (emphasis added)
Vol. II pg. 158 Dr. Love
"We, of course, intend to do that, but we were analyzing this data even over the weekend to supply the information to you at this committee meeting here." (emphasis added)
They were in such a tight schedule that they didn't have time to do the internal review or submit the data and their conclusions to peer review. So they just rushed into the meeting without that. Where is that peer review that they intended to do?
Vol. II pg. 248 Dr. Jasinski
"...I have been disturbed to some extent by what is really the lack of either scientific scholarship or scientific quality through all of this. ...it's like the question I asked Dr. Love in terms of did she write a report, was it reviewed, was it peer reviewed, making this available before you start getting these discussions." (emphasis added)
Vol. II pg. 26 Mr. Betz
"...although I pointed out last time [meeting in 1995] that these three products contain absolutely no ephedrine alkaloids, they're still in the report as part of this larger report."
The report that the FDA provided to the Committee was carefully purged of data pertaining to OTC drugs containing the same ephedra alkaloids as the dietary supplements, but apparently little or no care was taken to remove adverse reaction reports for dietary supplements that contained no ephedra alkaloids whatsoever. The FDA's report would never pass peer review. It must be noted that the FDA report as given to the Committee would not meet the Supreme Court's Daubert criteria for weeding out junk science.
Vol. II pg. 53 Mr. Shapiro
"...it has also been widely reported that the individual [college student who died in Florida] ignored clear warnings on the product and took at least twice the daily dose all at once. Those same reports indicate that his companions all took three times the daily dose without incident. In addition, according to the police report, cannabis and another product, Nexus, consisting of the herb kava-kava were found in the hotel room." "It is noteworthy that the autopsy report contains no findings at all relating to the presence of other substances such as cannabis, cocaine, amphetamines or barbiturates. It appears that no tests were performed for the presence of these and other substances which is most certainly very strange." "Yesterday, Dr. Love said that the tests were performed. If so, the results were not made a part of the autopsy report." (emphasis added)
"The Ad Hoc Committee on the Safety of Ma Huang submitted to you as part of their package the declaration of Dr. Joseph Brazelica, a toxicologist, which sets forthe many deficiencies in the autopsy report and concludes: 'That it is not possible to determine from the report of autopsy to a reasonable degree scientific certainty that the cause of death was the ingestion of some quantity of a product containing ephedrine.'" (emphasis added)
Vol. II pg. 110 Dr. Askew
"Clarification of the autopsy." (This refers to the autopsy mentioned earlier in which there was some question as to what the coroner found in the consumer's bloodstream.)
Vol. II pg. 110 Dr. Love
"The clarification of the autopsy report is that information on the consumer's negative ethanol and cannabis levels are in the record."
Vol. II pg. 147 Dr. Love
Dr. Love clarifies the Florida autopsy report, which found ephedrine alkaloids and caffeine positive, while a long list of others tested for were negative, including cocaine, amphetamines, strychnine, cardioregulatory drugs, and others.
Vol. I pg. 229 Dr. Fukagawa
"...in letters that we've received from Mr. Appler from the Ad Hoc Committee on the Safety of Ma Huang and from Mr. Shapiro at Bass and Ulman, who also referred to the 20 year old from Florida, suggest that his situation was perhaps not as clear-cut with the presence of other compounds in his hotel rooms etc., and the lack of toxicological reports or analyses." (emphasis added)
Vol. I pg. 229 Dr. Love
"Actually all of his blood levels for anything else were negative, and the coroner directly attributed it to the use of this product." "Now, where is the exception is this is the highest level of ephedrine alkaloids that we have analyzed in any product." (emphasis added)
Why didn't the FDA show the autopsy report? Mr. Prochnow said that this data was not in the autopsy report.
Vol. II pg. 65 Dr. Calvin McCausland from Enrich International, Orem, Utah
"...if you look at the 20-year old in Florida and the autopsy report, you will find reasonable doubt. That reasonable doubt has been spelled out by Dr. Borzelica, from the Medical College of Virginia and it's in those three volumes that you have before you." "There are other deaths that have been listed that have reasonable doubt. They took ephedrine a week before, reportedly. There is none in the tissues of the autopsy. Reasonable doubt."(emphasis added)
Vol. I pg. 59 Michael Davidson, M.D.
Dr. Davidson's qualifications and his review of the adverse event reports on behalf of the NNFA. See Adverse Event Clinical Summaries at Tab F referred to by Dr. Davidson. He reviewed the case files underlying 191 of these adverse event summaries. Of these 191 case files, he categorized 84 of the events to be serious and 107 not to be serious. "Of the 84 serious events, I found that 13 were not related to ephedra. I classified eight as unknown for lack of information. Thirty-four were remotely related; 22 were possibly related, and seven were probably related."
pg. 61 "Six deaths were possibly associated with ephedra. In two cases, not enough information was provided to consider an assessment. Two deaths were related to consumption of toxic doses of ephedra." "Of the six deaths possibly associated with ephedra, three were due to sudden death and cardiac abnormalities were present on autopsy in all three individuals. Two of the possibly associated deaths were due to strokes. One of these deaths was due to a strong [stroke?] that occurred in an obese individual male who was using multiple other supplements and who had basilar artery atherosclerosis on autopsy. Another was a fatal stroke that occurred in a 44 year old female due to a left internal carotid artery occlusion. She had a very strong family history of strokes. The sixth possibly associated individual whose death was from a seizure was also on phenteramine, Apidex, a prescription drug for weight loss. All of these six possibly associated deaths occurred on the high dose ephedra products." [How high?]
"There were ten cases of non-fatal myocardial infarction. Of these ten cases, four, in my judgement, were not related to ephedra. In another three reports, there was not enough information provided to make an assessment. In three cases of myocardial infarction, a possible association with ephedra exists. In all three of these reports, post-myocardial infarction angiograms revealed normal coronary arteries. All three individuals were consuming high-dose ephedra in combination with caffeine.
There were 17 reports of non-fatal strokes. Three cases were unrelated or remotely related to ephedra-containing products. In four additional cases, not enough information was available for me to make an evaluation. In the remaining ten cases, a possible association with ephedra products exists.
In four of the ten possibly associated cases, these individuals had significant hypertension of hyperlipidemia diagnosed prior to the stroke. One case involved a male with a dilated left ventricle as a possible source of emboli. The remaining five cases involve premenopausal women. At least two of these women were on oral contraceptives. One of these was noted to be a cigarette smoker and the other was diagnosed as having a positive lupus inhibitor. In the three remaining possibly associated cases, oral contraceptive use is unknown and one was a cigarette smoker, and one of these women was on the product for over a year before she suffered as intracerebral hemorrhage. All but one of these stroke patients--the exception being the woman with a positive lupus inhibitor--were on the high-dose ephedra containing products.
There were 16 reports of seizures. Of these cases, the majority of seizures occurred in individuals with either a history of seizures or an abnormal EEG on follow-up. As I am not a neurologist, I made only a limited evaluation of these cases.
In summary, with the exception of two cases of toxic exposure to ephedrine, there appears to be only infrequent possible associations of ephedra-containing products with severe adverse reactions. These infrequent possible associations are characterized by coronary or cerebral thrombosis and seizures.
Of the 105 non-serious adverse events that I reviewed, these are characterized by increases in blood pressure, tachycardia, nervousness, and dizziness. These symptoms are expected potential side effects of ephedra-containing products. These side effects appear to be dose-related, occurring in greater frequency in the high-dose ephedra-containing products.
To test the hypothesis that low-dose ephedra products below 15 mg. per dose, which is the recommended dose of the working panel, do not have a significant rate of adverse events, I reviewed the adverse events associated with the ephedra product containing less than 15 mg. per dose. These products account for over one-third of all the ephedra-containing products, but only approximately 7% of the adverse events. Of these 42 adverse events on low-dose products, there were only two serious events that were possibly related to the product. I mentioned one was the young woman who had a stroke who also had a positive lupus inhibitor, and the other was a 55 year old female who had a seizure.
Based on my medical review of the ephedra adverse event reports, I have the following opinions:
Number one, last year's [1995] recommendation of the ephedra working group and those of the dietary supplement trade associations are appropriate. The two main issues that appear to affect adverse reactions are the dose of the ephedra and the quality assurance of the product.
The proposal to lower the ephedra alkaloid content to 60 mg. per day with 15 mg. of ephedra per dose, expressed as ephedrine equivalents, provides a margin of safety based on the fact that the vast majority of both serious and non-serious adverse reactions occurred with products that exceeded these dosage thresholds.
Improved good manufacturing practices and quality assurance will provide dosing consistency within product batches. Because dosing consistency is important, I would add to the recommendation that products that can be easily mis-dosed not be permitted. (emphasis added)
The ephedra working group also recommended very appropriate warnings and labeling instructions. I would also include on the label cautions against the use by smokers, those taking oral contraceptives, and those with a history of cardiovascular or seizure disorders.
Vol. II pg. 107 Dr. Georgitis
"Dr. Love, I have a question for you, in terms of the serious aadverse events below the median value of 20 milligrams per serving of the ephedrine alkaloids, do you have a percentage as to how many of those out of the total adverse events?
Vol. II pg. 107 Dr. Love
"We haven't expressed our data in that form because, of course, we have only a relatively few samples where we've been able to collect the sample that the consumer was using at the time of the injury and be able to analyze that." (emphasis added)
This is clearly a very important question concerning how the numbers of reports of adverse events related to the amount of ephedrine actually consumed. Here, the FDA admits that it doesn't know that. This is a very poor reflection on the follow-up of the FDA after receiving such reports.
Vol. II pg. 108 Dr. Kessler (to Dr. Love)
"...you asked for relatively clean cases that didn't have a lot of confounding factors--where you have a medical examiner, where you have a sample--could you just go through those cases and at what levels you saw significant adverse reactions?
Vol. II pg. 108 Dr. Love
"Well, unfortunately, I don't have all the data in hand here, but there are a number including very recent cases for which we yet don't have all information on how the consumer used the product but a more recent death, again, it appears to be a cardiomyopathy case. The total alkaloids in that case are 10 milligrams, total alkaloid. As I stated a death from what appears to be long-term use of a product containing 10 milligrams of total ephedrine alkaloids."
The FDA here mentions a single case of what "appears" to be long-term use of a product containing 10 milligrams of total ephedrine alkaloids. No information is provided on what else the individual was taking or how the FDA knows how much of the product the individual was using, or how often.
Vol. II pg. 109 Dr. Kessler (to Dr. Love)
"And just go through that case. I mean just so we have some--I mean the best data that we have."
Vol. II pg. 109 Dr. Love
"Well, as I stated I don't have all those details."
This is a shockingly small amount of total information on what is supposed to be their best or one of the best cases providing evidence concerning adverse reactions versus dose.
Vol. I pg. 228 Dr. Chassy
"I'm trying to get at something that gives us some feel for where we begin to see a dose-response correlation, because as it stands now, you have effects all across the board. But you do have fewer products with very high amounts of ephedrine alkaloids in them, and where you have fewer of those products on the market, you seem to have around the same number of cases of adverse effects reported, which suggests that there is a dose-response relationship."
Vol. I pg. 234 Dr. Jasinski
"...you're showing this increase [in relative incidence], and how much of this increase is actually an increasing showing that we're getting a growing public health problem that's going to project, or how much of this increase is related to the change in the way you've done things in publicizing this and asking people to report in?"
Indeed, the FDA's publicity concerning the adverse events reports they received in which injuries were associated with (but not necessarily caused by) the use of ephedra alkaloid containing dietary supplements has resulted in reports on CNN and a recommendation not to use ma huang in the July 1997 Reader's Digest (pg. 85). The FDA's warnings have also appeared repeatedly on network TV. There has been no similar FDA publicity during this period concerning adverse events reports the FDA has received for ephedra alkaloid (ephedrine, pseudoephedrine, or phenylpropanolamine) containing OTC products.
Vol. II pg. 277 Mr. Guzewich
"...I want compliment Dr. Love on what she's trying to do in running a surveillance program. I've been doing that for 16 years for food-borne disease. It's not an easy task and she has a very difficult and often thankless job, and you're reporting for poor quality data and when it's the only data you can get ahold of and you're trying to make decisions on that kind of data..."
Yes, the data are poor quality, and the FDA cannot improve the quality of these data by dumping them into the lap of a hapless committee, which is then told to ignore any benefits of the products. Moreover, the FDA failed to present the committee with other available and important information. The FDA could have prepared a report on the adverse events and had the data peer-reviewed, but it did not. The FDA should have had data available on the spontaneous occurrence of MIs and strokes and seizures in the population using the ephedra products, but did not. The FDA should have had data available on the occurence of adverse side effects in the OTC ephedrine containing drugs for comparison, but they did not.
Vol. II pg. 282 Mr. Guzewich
"...sophisticated choices about products that might be at risk to them, I think, is more than we can reasonably expect consumers to have to assess when they choose between different bottles on the shelf. Therefore, consumers should be able to purchase a product in the market and find it safe at normal use, and even at abused levels..." (emphasis added)
More and better information on labels and in labeling and other methods of education for consumers so that they can make choices is a far better and safer choice, in our opinions, than to treat consumers as unmitigated idiots that must have decisions made for them by committees assembled by the FDA and given by the FDA poor quality data and unreasonable limitations (eg., do not consider any benefits) to make decisions for them. The final point made by Mr. Guzewich, that a product in the market should be safe at virtually any dose is impractical and ridiculous. Consumers must be expected to assume some personal responsibility for their use of products, at least extending to their compliance with label instructions. Moreover, DSHEA requires that dietary supplement products not be unreasonably unsafe when used as directed, not to be safe no matter how badly abused.
Vol. II pg. 285 Dr. Chassy
"Several [committee members] have noted the quality of the data, and without blaming the FDA staff in any way because they are to be commended, they need to build a cause-and-effect relationship, however hard that may be. I think they especially need to do it because DSHEA sets us in a situation where they [FDA] may find themselves in court being asked to bear the burden of proof that the ephedra alkaloids have done damage in a specific case, and they may find themselves doing that again and again and again."
The above comment speaks for itself. FDA data from this Committee meeting would never meet the Supreme Court's Daubert criteria for weeding out junk science. Because of this, FDA must withdraw the Rule, re-convene the Committee, provide sound peer reviewed data to the Committee members in advance, reach a new conclusion that fits within the ambit of Congress's will, and re-propose a new Rule.
It doesn't seem that the thousands of pages of materials that the FDA presumably distributed to each of the committee members before the meeting were actually read by most of them, judging by the questions asked of the FDA during the meeting. These questions included what are the background numbers of cardiac deaths and seizures among the population using ephedrine-containing dietary supplements and what were the levels of adverse reports for OTC products containing similar amounts of ephedrine as ephedrine-containing dietary supplements).
The answers to these questions are key information in interpreting the meaning of the adverse reports. Yet, at the meeting, Dr. Love (FDA) did not have this information. Either the committee members did not do their homework or the FDA did not have key information available either before or at the meeting or both.
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SPECIFIC PROPOSAL FOR A CONSTITUTIONALLY ACCEPTABLE LABEL
The FDA cannot ignore the limits placed on it by the First Amendment of the U.S. Constitution. We have discussed these limitations at some length (often quoting Supreme Court Justices) in a prior section on general labeling considerations. The FDA has no constitutional authority to prohibit statements that are true and not misleading. The FDA does have the authority to prohibit statements that are false or misleading, and to require reasonable disclosure of hazards on the labels and labeling of dietary supplements sold in interstate commerce. This discussion considers the application of these limits and powers to a specific product.
Commenters Pearson & Shaw license formulations containing approximately 1.8 grams of ground ephedra herb per one tablespoon serving (the amount of ephedra herb being adjusted on the basis of herb lot analyses so that one tablespoon of product contains a total of 20 mg. of ephedra alkaloids). No ephedra extracts are used in this product, there is no caffeine or other methylxanthines, and it contains no synthetic ephedrine, pseudoephedrine, or phenylpropanolamine.
Since whole ground herb is used rather than an instantly soluble ephedra alkaloid extract, blood levels of the alkaloids increase much more slowly as the ground herb slowly releases its alkaloids, thereby providing a time-release effect and reducing the risk of adverse effects in sensitive individuals.
Products containing real ephedra herb when ingested are pharmacokinetically substantially different from products containing ephedra alkaloid extracts; regulating them in an identical manner is arbitrary, capricious, and contrary to fact.
With a one tablespoon serving, this product contains approximately 1.8 grams of ephedra herb (adjusted to standardize the amount of ephedra alkaloids) per serving of tea, quite conservative compared to the traditional tea serving of 1.5 to 9 grams (usually 5 to 6 gm.) of ephedra herb referred to on page 20 of the proposed Rule.
On the basis of the FDA's proposed Rule, we propose the following new label for this product:
NOTICE: CONTAINS EPHEDRA HERB WHICH CONTAINS EPHEDRINE ALKALOIDS.
FDA MANDATED SERVING SIZE:: 1 TEASPOON (contains 6.7 mg. total ephedra alkaloids). The FDA believes that a serving size of 8 mg. or more would present an unreasonable risk of injury or illness. Taking more than this recommended serving may cause heart attack, stroke, seizure, or death.
TRADITIONAL SERVING SIZE: 1 TABLESPOON (contains 20 mg. total ephedra alkaloids from approximately 1.8 grams of herb). This serving size is NOT approved by the FDA.
DIRECTIONS: Add 4 ounces of hot or cold water to one serving of mix. Stir briskly and drink. DO NOT EXCEED THREE SERVINGS A DAY! On the first day, drink one-half serving before breakfast. For the next two days, drink one serving before breakfast. For the next three days, drink a second serving before lunch. From then on, drink a third serving one hour before dinner. Do not take more than one serving within a 6 hour period. Keep in a cool, dry place. Keep lid tightly closed when not in use.
FDA MANDATED INSTRUCTIONS: Consult a health care provider before use. Do not use this product for more than 7 days. Risk of adverse reactions increases with duration of use. Starting and stopping use may increase risk of adverse reactions.
WARNING: KEEP OUT OF REACH OF CHILDREN. NOT FOR SALE TO OR USE BY PERSONS UNDER THE AGE OF 18. DO NOT EXCEED RECOMMENDED SERVING SIZE OR FREQUENCY. May cause insomnia in sensitive individuals, especially if taken too soon before bedtime. Consult your physician before use if you are taking asthma medications, decongestants, anorectic (appetite suppressing) drugs, antidepressants, or cardiovascular medications. Use of caffeine containing beverages may increase the stimulating effects of this product. Do not use this tea if you are pregnant or lactating, if you have high blood pressure or cardiovascular disease (especially stroke or cardiac arrhythmia) or a family history of these disorders, diabetes, difficulty in urination due to prostrate enlargement, seizure disorder, glaucoma, hyperthyroidism, or psychiatric disease. Do not drink this tea within 14 days after taking MAO (monoamine oxidase) inhibitor drugs. Stop use and call your health care professional if dizziness, headache, heart palpitations, or tingling sensations occur. Stop use or reduce serving size if sleeplessness, tremors, nausea, or nervousness occurs. Stop use if symptoms of allergy to this product develop.
Note that these instructions increase the serving size from the initial one-half of 6.7/20. mg. ephedra alkaloids once per day to the final 6.7/20 mg. three times per day over a period of seven days. This schedule is designed to reduce the incidence of adverse effects by allowing the development of tolerance to the CNS and cardiovascular effects of the ephedra alkaloids.
The Caution on page 43 of the proposed Rule has been modified in several respects:
1) "Warning" is used rather than "Caution," as is tentatively proposed by the FDA.
2) Rather than "Seek advice from a health care practitioner if you are pregnant or nursing or if you are at risk or are being treated for high blood pressure, heart, heart, thyroid or psychiatric disease, diabetes, seizure disorder, stroke, or difficulty in urination due to prostrate enlargement." these and other conditions are all listed as "Do not use if..." absolutely contraindicated conditions. We do not believe that these conditions should be required as absolute contraindications (rather than checking first with your doctor), as we have expressed it, but the stronger form of warning we have used should not be prohibited. It would be arbitrary, capricious, and not in the public interest for the FDA to standardize the warning in such a way as to prevent the listing of additional contraindications or to prevent contraindications from being listed as absolute rather than relative. FDA should require a minimum list of contraindications but must never prohibit additional or stronger contraindications than their minimum required list. For example, rather than "Consult your health care professional before use if you are taking an MAO inhibitor or any other prescription drug." we believe that we should be permitted a label warning that taking an MAO inhibitor within the last 14 days is an absolute contraindication.
3) "Taking more than the recommended amount will not necessarily increase benefits." has not been used because it is both weak and lacks credibility. Worse yet, this lack of credibility may tend to reduce the credibility of the other warning statements. Instead, we have used the FDA's much stronger warning: "The FDA believes that a serving size of 8 mg. or more would present an unreasonable risk of injury or illness. Taking more than this recommended serving may cause heart attack, stroke, seizure, or death." We do not believe that this stronger warning should be required, but the FDA should not prohibit a stronger warning than the one that is proposed.
4) We have not instructed the user to consult with their health care professional if they are taking any prescription drug. Such consultations may easily cost $50 or more; people will generally ignore this warning. It is unreasonable to expect customers to take this action; they simply won't do it. It is unwise to put a warning on the label that one knows will be generally disregarded, for such warnings promote a general disregard for other far more important warnings. As an alternative to this ineffective warning, we believe that we should be allowed to say "Consult your physician before use if you are taking asthma medications, decongestants, anorectic (appetite suppressing) drugs, antidepressants, or cardiovascular medications." If the FDA Rule requires the label to carry "Consult your health care practitioner before use if you are taking an MAO inhibitor or any other prescription drug," this statement will be prefixed with the truthful non-misleading "FDA mandated Warning:", which is protected speech under the First Amendment.
5) Users of ephedra dietary supplements should not be instructed to call a physician if "sleeplessness, tremors, nausea, or nervousness occur," since these are not likely to be precursor symptoms of a potentially serious or life-threatening adverse reaction. Instead, they should be instructed to "stop use or reduce serving size." If users are instructed to make an expensive call to their doctor because of a minor matter like temporary insomnia, they are less likely to call their doctor when "dizziness, headache, heart palpitations, or tingling sensations occur," which may be symptoms of far more serious problems such as hypertension, stroke, or a potentially serious cardiac arrhythmia. There is a very real cost to diluting major warnings with minor warnings. If the FDA's Rule requires the label to carry their preferred warning, it will be prefixed with the truthful non-misleading "FDA mandated Warning:", which is protected speech under the First Amendment.
6) The split label: This label identifies FDA mandated information as such. This label contains two different serving sizes, one mandated by the FDA and identified as such, and an alternate serving size that provides a traditional amount of ephedra herb per serving.
Identifying FDA mandated information as such is truthful and non-misleading. Indeed, without such identification, the customer would be misled into believing that the product manufacturer voluntarily agreed with this information and had voluntarily placed it on the label. FDA has no constitutional authority to prohibit the truthful identification of the FDA as the source of this information and its mandatory nature.
The FDA mandated serving size is one teaspoon containing 6.7 mg. ephedra alkaloids. This serving size is clearly identified as being recommended by the FDA. Moreover, the FDA's reasons are clearly and forthrightly stated, "The FDA believes that a serving size of 8 mg. or larger would present an unreasonable risk of injury or illness. Taking more than this recommended serving may cause heart attack, stroke, seizure, or death." This is the strongest warning regarding serving size that the FDA has proposed in the Rule. If this were the only serving size described on the label, we believe the FDA would have no objections.
The traditional serving size is one tablespoon containing 20 mg. of ephedra alkaloids. It is in fact at the low end of the traditional ephedra herb dosage range. The statement that this is a traditional serving size is truthful and non-misleading; the FDA has no constitutional authority to prohibit it. An FDA prohibition of this traditional serving size statement would be a content based prior restraint caused by FDA's not wanting people to know this information. The FDA doesn't want people to know this information, because if they learn of it, people may not behave the way the FDA wants; customers may choose to take the larger servings rather than the FDA's preferred smaller ones. The First Amendment prohibits the manipulation of consumer behavior by restricting the communication of truthful, non-misleading information.
Quotes from the U.S. Supreme Court decision in 44 Liquormart v. Rhode Island (1996 WL 241709 (U.S.))
"...a State's paternalistic assumption that the public will use truthful, non-misleading commercial information unwisely cannot justify a decision to suppress it." (at 8)
"It is precisely this kind of choice, between the dangers of suppressing information, and the dangers of its misuse if it is freely available, that the First Amendment makes for us." (quoting from Pittsburgh Press Co. v. Pittsburgh Comm'n on Human Relations, 413 U.S. 376, 93 S.Ct. 2553, 37 L.Ed.2d. 770 (1973)
"In case after case following Virginia Pharmacy Bd., the Court, and individual Members of the Court, have continued to stress the importance of ... the impropriety of manipulating consumer choices or public opinion through the suppression of accurate 'commercial' information..." (J. Thomas, concurring, at 21)
The First Amendment of the US Constitution absolutely prohibits the FDA from banning labeling that is neither misleading nor deceptive. Indeed, Pearson & Shaw, et. al, have a First Amendment lawsuit against the FDA Commissioner before the U.S. District Court for the District of D.C. at this very moment. (Civil Action No. 95-1865 (EGS), District Court for the District of Columbia) If the FDA proceeds with its proposed Rule, it is likely to be sued again.
Note, too, that this product does not describe any non-traditional uses (or indeed, any uses at all) on the label or labeling. Nearly all customers of this product use it before meals to help satisfy appetite (the reason most foods are eaten) as an adjunct to their own personal weight loss or weight maintenance program.
In addition to considering the constitutional issues that an FDA attempt to ban this label would raise, we suggest that the FDA consider the pragmatic public health value of allowing the vendor to provide a maximum serving size that is likely to be heeded. The FDA's serving size is so small that consumers will generally ignore the FDA's dose limitation. This is especially likely for the many millions of people who have had prior experience with ephedra herb products.
Without an alternate serving size that is more likely to be heeded by the consumer, the consumer may take unnecessary risks. The consumer will know that the FDA has radically reduced the dose of the supplement, so they will take more -- perhaps far too much more than needed to compensate for FDA's dosage reduction.
For the sake of both liberty and government legitimacy under the constitution, FDA must not attempt to prohibit ephedra dietary supplement labels from displaying truthful non-misleading traditional dose statements.
For the sake of consumer safety, the manufacturers of existing products must not be prohibited from informing the consumer of both the size of the old dose and the new dose. If FDA prohibits the publication of this information on the labels and in the labeling of existing products, they will not only be violating the First Amendment ban on content based prior restraint in an unconstitutional attempt to manipulate the public's behavior by denying them information, FDA will be dramatically increasing the risks to the public of accidental overdose. Moreover, the FDA's credibility will drop further as its actions are scrutinized in public fora such as health newsletters and the Internet.
The alternate serving size provides 20 mg. of ephedra alkaloids, a little more than the 17 mg. median dose and substantially less than the 30 mg. mean dose of products that FDA identified in its market survey, and with which millions of consumers may be familiar. By providing the customer with an alternate serving size near the low end of the traditional dose range, there is a reduced risk of large accidental overdoses taken by consumers who reject FDA's recommended dose but who otherwise don't know how much to take. If the FDA continues to arrogantly delude itself by believing that it can control people's behavior by enforcing ignorance through their proposed rule, they will succeed only in violating the constitution, discrediting themselves, and causing greater risk and harm through uninformed and unintentional gross overdoses.
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ONE SIZE DOES NOT FIT ALL:
EPHEDRA HERB IS NOT EPHEDRA HERB EXTRACT
EPHEDRA HERB EXTRACT IS NOT SYNTHETIC EPHEDRINE
FDA'S PROPOSED RULE ANALYTICAL METHOD WILL NOT PROVIDE ACCURATE MEASUREMENTS OF THE BIOAVAILABLE EPHEDRA HERB ALKALOIDS IN PRODUCTS MADE WITH ACTUAL EPHEDRA HERB RATHER THAN WITH EXTRACTS
Food Advisory Committee meeting August 27-28, 1996
When actual ephedra herb is ingested rather than an instantly soluble ephedra alkaloid extract, blood levels of the alkaloids increase much more slowly as the ground herb slowly releases its alkaloids, thereby providing a time-release effect and reducing the risk of adverse effects in sensitive individuals.
Products containing actual ephedra herb when ingested are pharmacokinetically substantially different from products containing ephedra alkaloid extracts; regulating them in an identical manner is arbitrary, capricious, and contrary to fact.
Vol. I, pg. 146 Dr. Jasinski
"...we already know if you put medications in a certain sort of matrix that's natural may alter this from -- the pharmacology from the pure medication in terms of absorption and rate of limitation [elimination?]."
Vol. I, pg. 146 Dr. Yetley
"We are not aware of data on the botanicals that would answer the questions you have." "But those are the scientific issues that we're asking this group of experts to discuss and to make some recommendations on."
Vol. I, pg. 147 Dr. Inchiosa
"The herbs themselves might contribute to affecting the alkalinity of the urine, which is going to affect the half-life of the drug, which is going to influence the steady state plasma concentrations."
Vol. I, pg. 157 Dr. Hsieh
"Do you want us to look at the compounds, or do you want us to look at the herb? And the two should not be equated." (emphasis added)
Vol. I, pg. 158 Dr. Yetley
"I understand that the two are not equated, but both could be ingredients in the products that we're seeing. So you need--the botanical is certainly very common, or at least extracts of the botanical, concentrated extracts of the botanical are very common in these products. But it is also possible that some of these products may have synthetic form, so it's really both." (emphasis added)
Didn't the FDA do any analyses of the products in their market review to determine whether there was synthetic ephedrine added, whether there were any ephedra alkaloids other than ephedrine in them (as would be the case with a genuine ephedra herb extract), and what percentage contained the actual herb rather than an ephedra alkaloid extract?
Even though the FDA's Dr. Yetley correctly states, "I understand that the two are not equated,..." FDA's proposed Rule does precisely that; it treats ephedra herb products exactly the same as ephedra herb alkaloid extract products.
Because of this, FDA must withdraw the Rule, re-convene the Committee, reach new conclusions that correct these errors, and re-propose a new Rule.
Vol. I, pg. 180 Dr. Jasinski
"Just a question of Dr. Obermeyer. What is the extraction efficiency? Have you done this? If you take the herb and make a tea, what is the extraction efficacy?" (emphasis added)
Vol. I, pg. 180 Dr. Jasinski
"I'm not talking about your chemical analysis. If somebody makes a tea, what is the extraction efficacy?" (emphasis added)
Vol. I, pg. 180 Dr. Obermeyer
"That depends on brew time. So if you would steep it for one minute versus three minutes versus someone that forgot it in their tea cup for ten minutes, that would be much different." (emphasis added)
Vol. I, pg. 181 Dr. Jasinski
"What's the maximum extraction efficacy you can do if you make a tea and you put it in the pot and you boil it up?" (emphasis added)
Vol. I, pg. 181 Dr. Obermeyer
"We have not worked on that for the maximum. What we would extract it for would be methanol to be the maximum out of an herb..." (emphasis added)
The FDA has no idea how much of the ephedra alkaloids would actually be extracted and ingested from a cup of tea made with actual ephedra herb (rather than ephedra extract or synthetic ephedrine HCl). Furthermore, the FDA has no idea how much of the ephedra alkaloids would be extracted in the human gut from ground ephedra herb consumed as an iced tea which is consumed without brewing.
The numbers the FDA's Dr. Obermeyer is providing are the results of chemical analysis that have very little if anything to do with how a tea containing actual ephedra herb (rather than ephedra alkaloid extract) is used. There is no hot methanol extraction, either in the consumers' tea pots or in the human GI tract.
Vol. I, pg. 181 Dr. Jasinski
"I mean, the question before the group is, you know, in terms of dose and what you're going to get and what the safe dose is going to be. If you don't know what people get out of the herb when they brew it, there's no way to answer this question." (emphasis added)
FDA's proposed Rule treats products containing actual ephedra herb exactly the same as products containing ephedra herb extract which is arbitrary, capricious, and contrary to fact. Because of this, FDA must withdraw the Rule, do its laboratory homework, re-convene the Committee, reach new conclusions that correct these errors, and re-propose a new Rule.
Vol. I, pg. 181 Dr. Obermeyer
"Right. Most of the products really are encapsulated or tablets of the ma huang extract. This is what we are seeing mostly. And very few products are actually the herb root as a tea." (emphasis added)
FDA's Dr. Obermeyer here admits that Dr. Jasinski is correct in his concerns that ephedra herb products are not the same as ephedra alkaloid extract products. Dr. Obermeyer also admits that "very few" of the products that the FDA is considering in this meeting "are actually the herb ... as a tea.".
If the FDA wishes to proceed with their proposed Rule without gathering the needed new data on actual ephedra herb products, holding new Committee meetings, and making major modifications in the Rule and analytical method, FDA should exempt all products from this Rule that contain actual ephedra herb rather than ephedra herb alkaloid extracts or synthetic ephedrine. To apply the proposed Rule to products that contain actual ephedra herb (not ephedra herb alkaloid extracts or synthetic ephedrine) would be arbitrary, capricious, and contrary to fact.
Technical note: Although we have an herbal text which refers to the "twigs and roots" being used in ephedra herb teas, we do not believe that use of the roots is a common commercial practice. Ephedra Sinica (and related species) is a perennial; leaves (which look rather like green twigs or pine needles) and the stems that bear them are harvested, not the roots. By leaving the roots and some of the stems and leaves, the plant's stems and leaves grow back next spring, and can be harvested year after year. This is particularly important since Ephedra Sinica is a slow growing plant. If grown from seeds or cuttings, several years will pass before the plant can be harvested. We have seen a lot of the ephedra herb that is imported into the U.S., but we have seen only the needle-like leaves and the stems that bear them; we have never seen any ephedra roots.
Vol. I, pg. 184 Dr. Fong
".... The data as I sit here running through my mind is when you talking about extraction with methanol, and then people taking the capsule with the total extracts or with the herb in there, and what is the bioavailability? We really don't know what the patient is getting, at least in my mind." (emphasis added)
Vol. I, pg. 184 Dr. Obermeyer
"I believe the literature would probably support your thoughts." (emphasis added)
This is a member of the FDA staff here implying that the FDA has not done a search of the literature on the amount of ephedra alkaloids which are bioavailable from the actual herb (as opposed to a methanolic extract), let alone done the research themselves! Furthermore this is a tacit admission that these are substantive relevant considerations.
Vol. I, pg. 186 Dr. Dentali
"My understanding is that these products that are the industrial supply for what companies are buying and then placing in the capsule mixed with other ingredients are extracts of water and alcohol, not pH manipulated. So you may have high temperature water, alcohol, and that's why the concentrations typically are not higher than 6 percent..."
This refers to the process currently used to produce the commercially available ephedra herb extracts. These ephedra herb extracts are clearly made in a different way - with a hot methanol/water mixture - than how a consumer would brew tea (no methanol), which in turn is different than direct ingestion of the actual ground herb, which would not involve the high temperatures used in brewing. Products made with ephedra herb extract are different from products where the actual herb is brewed in hot water, which in turn are different from products where actual ground ephedra herb is ingested without high temperature brewing.
Vol. I, pg. 186 Dr. Jasinski
"So you just put it into a pot and add alcohol and water and you boil it up?"
Vol. I, pg. 186 Dr. Dentali
"Pretty much."
Vol. I, pg. 186 Dr. Dentali
"Evaporate it off, put it on a carrier."
There is much faster gut absorption of the alkaloids when on a carrier (from an ephedra herb extract) as compared to the rate of gut absorption when a person swallows actual ground herb.
Vol. I, pg. 152 Dr. Dentali
"I did happen to come across two studies, and I can get the reference to you and possibly a copy of it. One was conducted in Japan. They had been seeing--they reported seeing a high incidence of adverse effects recently with products containing ephedrine alkaloids. They realized that their data was based on ephedrine and not the extract, and they conducted an animal trial with equivalent amounts of ephedrine alkaloids and comparing the two--in mice, I believe. ... Generally, they found that absorption levels were about half time-wise and the concentrations in the plasma were about half." (emphasis added)
Ephedra herb extract is not ephedrine, and its pharmacological effects are not the same as ephedrine. Most of the products producing serious adverse reactions were abused ephedrine containing products, some misbranded as ephedra herb extract products. It is very common to analyze a so-called ephedra product and find nothing but ephedrine; these products do NOT contain either ephedra herb extract or ephedra herb.
Vol. I, pg. 276 Jones
"The available data indicates that though ephedra herb shares some of the properties of ephedrine itself, it also possesses beneficial properties in its own right and is furthermore much better tolerated on an alkaloid equivalence basis." (emphasis added)
Vol. II, pg. 80 Mr. Appler
Continues to analyze the Texas reports. He states "...of the 94 reports in the Poison Control Center for North Texas, there were exactly two that were related to herbal and two others related to ma huang. In every one of those cases, as Dr. Patrick points out, there was no permanent injury of any sort and all the results seen there were mild." (emphasis added)
Vol. II, pg. 257 Dr. Dentali
"The other area that I feel that didn't receive adequate scientific attention was the differences between the herb, the herb extract, and ephedrine." (emphasis added)
Ephedra herb extract is not ephedrine. Ephedra herb is not ephedra herb extract; the FDA proposed Rule analytical method LIB No. 4053 may be suited to products containing ephedra alkaloids from ephedra herb extract; we will leave comments on this to those who use ephedra herb extract in their products. We use only ephedra herb (no alkaloid extract, no synthetic alkaloids). FDA's proposed analytical method is incapable of accurately measuring the amount of bioavailable ephedra alkaloids contained in the actual herb.
When a consumer drinks a serving of ephedra herb tea - made with the actual herb, not an alkaloid extract - the extraction of the ephedra alkaloids from the herb in the hot water filled teacup is less than when the herb is extracted in a boiling methanol-water solution in an extract factory or in the FDA's proposed Rule analytical method. No consumer uses a boiling hot methanol-water mixture to make his or her tea.
When a consumer ingests ground ephedra herb in an iced tea that has never been boiled, the extraction of the ephedra alkaloids occurs slowly in the consumer's gut at 37oC, not in a boiling mixture of methanol and water. The FDA's proposed Rule analytical method will greatly exaggerate the real deliverable ephedra alkaloid content of actual ephedra herb products. Remember, the FDA's method was designed to measure the alkaloid content of products made with the alkaloid extract; it has not been validated for products
Before the Food and Drug Administration, Rockville, MD
RE:Docket No.98N-0148;International Drug Scheduling; ... Ephedrine...
DURK PEARSON & SANDY SHAW
People for the Constitution, Box 3666, Tonopah, NV 89049
TO: Dockets Management Branch (HFA-305)
Food and Drug Administration
12410 Parklawn Dr., Rm. 1-23
Rockville, MD 20857
Comments for Docket No. 98N-0148
Before the
FOOD AND DRUG ADMINISTRATION
Rockville, MD
In re: Comments Concerning Abuse)
Potential, Actual Abuse, Medical)
Usefulness, Usefulness as a ) Docket No. 98N-0148
Dietary Supplement Under DSHEA, )
and Trafficking in Ephedrine and)
Ephedra Sinica Herb )
Fed. Reg. 63(52): 13258-13259 )
March 18, 1998 )
3 April, 1998
INTRODUCTION TO COMMENTS OF DURK PEARSON & SANDY SHAW
Note: These comments pertain to ephedrine, ephedra herb, ephedra herb and ephedrine containing dietary supplements, and the family of ephedra alkaloids found in ephedra sinica. No comments are hereby tendered regarding dihydroetorphine or remifentanyl. These comments apply to "isomers of psychotropic substances" only insofar as any FDA recommended WHO rules would apply to the family of ephedra alkaloids found in ephedra sinica.
Durk Pearson and Sandy Shaw are scientists and authors, maintaining residences in Nevada and California. Their three best-selling books include the million plus copy #1 best-seller Life Extension, a Practical Scientific Approach (Warner Books, 1982). Their fourth book, Freedom of Informed Choice: FDA v. Nutrient Supplements argues that truthful, non-misleading speech on labels and in labeling is protected by the First Amendment of the United States Constitution against FDA censorship and discusses the cost to public health of such censorship.
Pearson and Shaw design dietary supplement formulations and license them to small marketing and manufacturing companies. The formulations designed by Pearson and Shaw include dietary supplements containing ground ephedra herb leaves and stems. Pearson and Shaw and their licensed marketers and manufacturers (all are small businesses) would suffer substantial economic harm if the FDA were to recommend, and WHO were to implement, restrictions on the sale of ephedra herb itself or on DSHEA compliant dietary supplements containing ephedra herb. Furthermore, Pearson & Shaw believe that consumers of ephedra herb dietary supplements would actually be endangered by any such restrictions.
DSHEA (Dietary Supplement Health and Education Act) places a substantial statutory burden of proof on FDA to demonstrate that an herbal dietary supplement is unreasonably unsafe when used as directed before FDA is legally permitted to take any action to restrict or prohibit the sales of such a supplement or its ingredients. Under the provisions of DSHEA, FDA has no statutory authority to recommend that WHO restrict ephedra herb, ephedra herb containing dietary supplements, or their constituent ingredients unless FDA has met their DSHEA burden of proof.
Pearson & Shaw do not believe that the FDA has met their statutory burden of proof under DSHEA that ephedra herb and ephedrine containing and ephedra herb containing dietary supplements are unreasonably risky to consumers when used as directed.
On the contrary, the evidence presented by the FDA's own Expert Committee on Ephedrine Alkaloid Containing Dietary Supplements (which we review at length in the attached 107 page public comment document previously filed by Pearson & Shaw with the FDA) shows that extant ephedra herb supplements with extant labeling are generally safer than food in common form. Please see Pearson & Shaw's 107 pages of Comments (attached). We filed these comments on FDA's Docket No.95N-0304: Dietary Supplements Containing Ephedrine Alkaloids, and they address the abuse potential, actual abuse, potential dangers, actual dangers, and usefulness as DSHEA regulated dietary supplements of ephedrine and ephedra herb containing products.
Note that the aforementioned FDA Expert Committee on Ephedrine Alkaloid Containing Dietary Supplements found that millions of Americans were using ephedrine containing dietary supplements. They identified only a few abusers among these many millions of American users, and found no evidence of abuse of either ephedra herb itself or of ephedra herb containing dietary supplements.
Re illicit trafficking:
There is no illicit trafficking in ephedra herb or in dietary supplements containing ephedra herb. Ephedrine itself has already been designated as a listed chemical and is subject to chemical diversion regulations under 21 CFR part 1310 which are enforced by the Drug Enforcement Administration, due to its potential for use as a precursor in illicit methamphetamine manufacturing.
Any recommendation by FDA to WHO (or any other party) that ephedra herb (or ephedra herb containing dietary supplements) be subject to the same restrictions as ephedrine itself would be arbitrary, capricious, contrary to fact, and a violation of the Administrative Procedure Act.
There is no record of ephedra herb ever having been used as a precursor for illicit methamphetamine.
To make one kilogram of illicit methamphetamine would require about 1.5 kg. of ephedrine, and a few kilograms of other chemicals (e.g., red phosphorous) and solvents. The conversion would be performed in reaction vessels of a few liters volume, and the whole operation can be (and often has been) performed in a residential kitchen or bathroom.
To make 1 kg. of illicit methamphetamine from ephedra herb, however, would require that the ephedrine first be extracted from approximately 200 kg. of raw ephedra sinica herb with the use of approximately 2,000 kg. of solvents in an extraction vessel of approximately 3,000 liters volume. Obviously, an operation of this scale cannot be readily hidden, and extraction solvent purchases of this magnitude would be both prohibitively expensive and highly suspicious, to say nothing of the difficulties involved in the illicit disposal of such huge amounts of used solvents. It is obvious, therefore, why ephedra herb has never been used as a source of ephedrine for illicit methamphetamine manufacture. It is also obvious that ephedra herb containing dietary supplements would be an even more difficult and less economic source of ephedrine than ephedra herb itself.
For these reasons, and additional reasons stated in the attached 107 pages of comments, if FDA makes any recommendations to WHO regarding ephedrine, FDA must distinguish between ephedra herb (and DSHEA regulated dietary supplements containing ephedra herb) on the one hand and pure ephedrine on the other.
FDA, in accord with U.S. law, must recommend to WHO that ephedra herb itself and ephedra herb containing dietary supplements NOT be subject to any additional regulation, and under no circumstances be regulated the same as ephedrine; any other recommendation would be a clear violation of the intent of the DSHEA and of the APA.
Sincerely,
Durk Pearson
Sandy Shaw
Before the Food and Drug Administration, Rockville, MD (2)
RE:Docket No.98N-0148;International Drug Scheduling; ... Ephedrine...
.fo Second Comments of Durk Pearson & Sandy Shaw page #
DURK PEARSON & SANDY SHAW
People for the Constitution, Box 3666, Tonopah, NV 89049
TO: Dockets Management Branch (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852
Second Comments for Docket No. 98N-0148
Before the
FOOD AND DRUG ADMINISTRATION
Rockville, MD
In re: International Drug )
Scheduling; Convention On )
Psychotropic Substances; Single )
Convention On Narcotic Drugs; )
World Health Organization )
Scheduling Recommendations for )
Ephedrine; Comments On Abuse )
Potential, Actual Abuse, Medical)
Usefulness, Usefulness as a ) Docket No. 98N-0148
Dietary Supplement Under DSHEA, ) (Second Comments)
and Trafficking in Ephedrine and)
Ephedra Sinica Herb; Limits to )
FDA Authority Under DSHEA; )
Limits to FDA's Authority to )
Accept and Adopt International )
Standards and Recommendations )
Fed. Reg. 64(6): 1629-1634 )
January 11, 1999 )
10 February, 1999
INTRODUCTION TO COMMENTS OF DURK PEARSON & SANDY SHAW
Note: These comments pertain to ephedrine, ephedra herb, ephedra herb and ephedrine containing dietary supplements, the family of ephedra alkaloids found in ephedra sinica, and related isomers such as pseudoephedrine and phenylpropanolamine. No comments are hereby tendered regarding dihydroetorphine or remifentanyl.
Durk Pearson and Sandy Shaw are scientists and authors, maintaining residences in Nevada and California. Their three best-selling books include the million plus copy #1 best-seller Life Extension, a Practical Scientific Approach (Warner Books, 1982). Their fourth book, Freedom of Informed Choice: FDA v. Nutrient Supplements argues that truthful, non-misleading speech on labels and in labeling is protected by the First Amendment of the United States Constitution against FDA censorship and discusses the cost to public health of such censorship.
Commenters' First Amendment and APA (Administrative Procedure Act) arguments were recently vindicated by the 3-0 decision of the US Circuit Court of Appeals for the District of DC against the FDA on January 15, 1999 in Pearson and Shaw et al v. Shalala et al. (Case No. 98-5043)
Pearson and Shaw design dietary supplement formulations and license them to small marketing and manufacturing companies. The formulations designed by Pearson and Shaw include dietary supplements in the form of herbal teas containing ground ephedra herb leaves and stems. Pearson and Shaw and their licensed marketers and manufacturers (all are small businesses) would suffer substantial economic harm if the FDA were to recommend, and WHO were to implement, restrictions on the sale of ephedra herb itself or on DSHEA compliant dietary supplements containing ephedra herb. Furthermore, Pearson & Shaw believe that consumers of ephedra herb dietary supplements would be endangered, rather than helped, by any such restrictions.
COMMENTS OF DURK PEARSON & SANDY SHAW
We hereby include with and incorporate into these Comments our First Comments on 98N-0148 of 1 April 1998, and our very closely related and relevant prior Comments on 95N-0304 of 18 August 1997, and on 97N-0218 of 30 September 1997. (See attached.)
Abuse of Ephedra Herb Containing Dietary Supplement Teas
is Not a Significant or Widespread Problem
FDA states that in the US, ephedrine and ephedrine containing combination products have been abused. To prepare for Commenters' Comments on 95N-0304 (see attached), the Commenters made a FOIA (Freedom Of Information Act) request on the FDA for all documents pertaining to the safety and abuse potential of ephedrine and ephedrine containing products, including OTC drugs and dietary supplements. The Commenters received several thousand pages of documents which clearly and unequivocally demonstrated that abuse of ephedrine and ephedrine containing products was not common, amounting at most to a few tens of cases per year out of several million non-abusing users each year. The reported abuse was almost entirely of OTC drug products, many of which were mislabeled or misbranded. At most, this abuse led to no more than a few deaths per year, and there was no evidence of abuse of ephedra herb containing dietary supplement teas.
This is a far smaller problem than the abuse of non-prescription NSAIDS (Non-Steroidal Anti-Inflammatory Drugs) such as aspirin, ibuprofen, and sodium naproxen which result in approximately 9,000 deaths per year in the US. Moreover, it is widely accepted by experts in the field that caffeine addiction is common among coffee consumers, and that anyone who consumes about 800 milligrams or more of caffeine per day will quickly become addicted, and suffer very severe headache pain for a week or more during caffeine withdrawal. There are at least several hundred thousand caffeine addicts in the US. (See Caffeine and Behavior by B.S. Gupta and U. Gupta, CRC Press, 1999) Ephedrine abuse in the US is a far smaller problem than either the abuse of caffeine or NSAIDS, and abuse of dietary supplement teas containing ground whole ephedra herb is essentially non-existent.
In its request for comments, FDA states, "In addition, in the USA, combination products containing ephedrine in herbal preparations have been abused." The several thousand pages of documents that the Commenters received from the FDA in response to their 1997 FOIA did not contain evidence of abuse of ephedra herb tea. Capsules or tablets containing ephedrine are far more readily abused than the true ephedra herb teas licensed by the Commenters for reasons discussed in Commenters' comments to 95N-0304 and below.
Scientific Differences Between Ephedrine Containing
OTC Drugs and Ephedra Herb Tea Dietary Supplements;
Ephedra Herb Tea is Far Less Likely to be Abused:
It is very easy for a drug abuser to swallow several cheap 50 milligram ephedrine pills or 60 mg. pseudoephedrine pills, and to repeat this foolish act every hour. Because of this, there have been several reported hospitalizations due to overdoses of ephedrine or pseudoephedrine pills, and one overdose death. This frequency of abuse, hospitalizations, and death from misuse of ephedrine or pseudoephedrine 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 ephedra herb containing dietary supplements on the basis of their relatively low level of reported abuse. Finally, while it is quick and easy to take 10 ephedrine or pseudoephedrine tablets, it is not at all quick and easy to take 20 to 30 cups of ephedra herb dietary supplement tea containing the same amount of ephedrine.
Because of these prominent and fundamental scientific differences between ephedra herb tea dietary supplements and ephedrine or pseudoephedrine OTC tablets, there is no rational scientific basis for Scheduling ephedra herb tea dietary supplements.
In addition to the statutory prohibitions mentioned below against FDA's complicity in effectively banning (via supporting the proposed Scheduling) dietary supplement teas containing ephedra herb, there are compelling scientific reasons for distinguishing between ephedrine or pseudoephedrine containing OTC drugs and ephedra herb containing dietary supplement teas. Even if the proposed Scheduling is adopted for OTC drugs, the reasoning on which it is based is inapplicable to dietary supplement teas containing ephedra herb.
Ephedra Herb Containing Dietary Supplement Teas Are Not Subject
to Diversion to Illegal Drug Manufacture.
There are no reported cases in the scientific or forensic literature of ephedra herb containing dietary supplement teas being diverted to the illicit manufacture of methamphetamine or methcathinone, whereas there have indeed been cases where hundreds of thousands of OTC ephedrine and pseudoephedrine pills have been subject to such diversion. The reason for this difference is simple. It is easy and highly profitable to convert OTC ephedrine and pseudoephedrine pills to methamphetamine, whereas it is extremely difficult and utterly unprofitable to perform such an illegal conversion using a dietary supplement tea containing ground ephedra herb as a precursor.
A typical ephedrine tablet may contain 50 milligrams of ephedrine (or 60 mg. pseudoephedrine in common OTCs) and 150 milligrams (180 mg.) of inert tablet filler-binder. The ephedrine or pseudoephedrine content is 25%. The ephedrine and pseudoephedrine 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 containing dietary supplement tea contains 20 milligrams of ephedrine contained in about 2 grams of ground ephedra herb (the amount of which is varied to standardize the ephedrine content per serving of tea) which 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 dietary supplements is typically 0.1% to 0.15%, not the 25% commonly found in ephedrine (or pseudoephedrine) tablets. Because of this, at least 200 times as much solvents would be required to extract the ephedrine from the mixture, and the illicit production equipment would have to be at least 200 times larger than would be required for extracting ephedrine from tablets. Extraction of 10 kilograms of ephedrine from 10,000 kilograms of herbal tea using 100,000 to 200,000 kilograms of solvents is not an operation that can be hidden in a garage or an apartment, completely unlike the case with ephedrine or pseudoephedrine tablets. Moreover, many of the other constituents of the herbal tea would be far more difficult to separate from the ephedrine, unlike simple tablet fillers and binders such as dicalcium phosphate.
In addition, a typical ephedra herbal tea dietary supplement sells for 50 cents to $1.00 per serving, a cost per milligram of contained ephedrine (or pseudoephedrine or phenylpropanolamine) that is about 10 to 100 times higher than ephedrine, pseudoephedrine, or phenylpropanolamine OTC tablets. When one considers the added cost of at least 200 times as much solvents, the difficulty of an illicit operation purchasing so much solvents without arousing suspicion, the cost of processing equipment that is at least 200 times larger, the far greater difficulty, cost, and much lower efficiency of extracting the ephedrine from such a dilute complex mixture, and the difficulty and cost of hiding such large extraction and purification equipment and such large amounts of solvents (to say nothing of disposing of the 100 to 200 tons of used solvents afterward!), it is not surprising that ephedra herb tea dietary supplements have never been diverted to methamphetamine manufacture, and never will be.
Although ephedrine can be used in the illicit manufacture of methamphetamine, bulk sales of this substance are already controlled in the US by the DEA as a "listed chemical" precursor compound under the Controlled Substances Act. There is no record of ephedra herb ever being used as a precursor by illicit drug manufacturers. It would be economically impractical to do so as explained above and in Commenters' First Comments to 98N-0148 and Commenters' Comments to 95N-0304.
The WHO proposed Scheduling is irrational, arbitrary, and capricious because it will be completely ineffective unless pseudoephedrine and phenylpropanolamine are controlled at least as stringently as ephedrine:
Far more widely used than ephedra herb containing dietary supplement teas and ephedrine containing OTC drugs are OTC drugs that contain pseudoephedrine (e.g. Sudafed®) and phenylpropanolamine. The same simple efficient palladium catalyzed hydrogenation (or the illicitly popular iodine-red phosphorus method) 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, too. The amounts of pseudoephedrine and phenylpropanolamine used in the OTC drug industry are far larger than the amounts of ephedra herb used, hence any rule that restricts ephedra herb containing dietary supplement teas but not pseudoephedrine and phenylpropanolamine OTC drugs is irrational, arbitrary, and capricious because it will be completely ineffective in controlling the supply of precursors for the manufacture of illicit methamphetamine, methcathinone, and amphetamine. Since there is very little problem with the abuse of pseudoephedrine and phenylpropanolamine OTC drugs, it is expected that the very large drug companies manufacturing these products will apply for and receive Convention Article 3, paragraph 2 or 3 exemptions to prescription requirements. Recommending that ephedra herb containing dietary supplement teas be Scheduled will therefore have no effect on either abuse or diversion to as precursors to illicit drug manufacture.
Because of these considerations, any FDA recommendations that do not reject the proposed Scheduling violates the Administrative Procedures Act and DSHEA (under which ephedra herb is a dietary supplement), and therefore must be rejected.
Neither the Law Nor the Facts Permits FDA to
Recommend Adoption of the Proposed UN Scheduling
Applicable to Ephedra Herb Containing Dietary Supplement Teas
On the basis of both the law (DSHEA and APA) and the administrative record of the facts, FDA cannot make any recommendation to the UN that would interfere with the manufacture, availability, and sale of properly labeled ephedra herb tea dietary supplements, for to do so would be arbitrary, capricious, not in accord with the facts, and contrary to law. Before FDA could make any recommendation to any international body that would interfere with the manufacture, availability, and sale of ephedra herb teas, FDA must first meet its DSHEA (Dietary Supplement Health and Education Act) burden of proof that properly labeled ephedra herb teas are unreasonably unsafe when used as directed. FDA has not met that burden of proof.
FDA does not have the constitutional legal authority to simply accede to the recommendation of an international organization that ephedrine containing products be Scheduled under international psychotropic convention drug laws in violation of U.S. statutes and the restrictions on federal power under the U.S. Constitution.
The Limits of Federal Authority Under Treaties
One legal argument on treaties is, of course, that a treaty cannot go beyond the bounds of the Constitution by, for example, giving away Constitutionally protected rights. As the U.S. Supreme Court ruled in Geofroy v. Riggs (1890): "The treaty power, as expressed in the Constitution, is in terms unlimited except by those restraints which are found in that instrument against the action of the government or of its departments, and those arising from the nature of the government itself and of that of the States. It would not be contended that it extends so far as to authorize what the Constitution forbids, or a change in the character of the government or in that of one of the States, or a cession of any portion of the territory of the latter, without its consent." In 1957 in Reid v. Covert, the Court ruled that "no agreement with a foreign nation can confer power on the Congress, or on any other branch of Government, which is free from the restraints of the Constitution." Moreover, the Court continued, "this Court has regularly and uniformly recognized the supremacy of the Constitution over a treaty."
An on-point argument as to why FDA cannot simply accede to the recommendations of an international agency can be found in a recent issue of the National Law Journal:
An analysis published in the March 17, 1997 National Law Journal (NLJ), Martin, Farber, Chajet "Determination on Silica May Expose Flaw in Rule," offers a Constitutional argument to oppose standards (such as the UN Scheduling of ephedra herb containing dietary supplement products) supposedly binding upon the United States that are developed under the auspices of the United Nations. These legal arguments are equally applicable to the proposal that is the subject of this Comment.
The case of interest concerns an OSHA rule in which OSHA incorporated certain standards and findings (on silica -- ordinary sand -- as a carcinogen) that were developed by the International Agency for Research on Cancer (IARC). An important constitutional issue was raised in the article concerning the OSHA rule: whether an Executive agency which has received its rulemaking authority as a result of delegation by Congressional statute can re-delegate that authority to a third party. The Constitution states in Article I Section I: "All legislative powers herein granted shall be vested in a Congress of the United States..."
As the NLJ article noted: "...the agency [OSHA] has taken what is concededly a broad delegation of authority and effectively redelegated that authority to an extragovernmental entity." "Though OSHA may well have broad authority to decide issues under the OSH Act, it does not follow that the agency can pass that same authority to another entity."
The issue arose, though indirectly, in the context of a 1992 decision by the 11th U.S. Circuit Court of Appeals (AFL-CIO v. Occupational Safety and Health Administration 965 F.2d 962, 984 (11th Cir. 1992)), in which the Court considered the propriety of OSHA's incorporation into its rules of the standards and findings of an outside organization. In that case, the court vacated a "generic" OSHA rulemaking to set permissible exposure limits for 428 substances identified by the agency as air contaminants. "The court found that while OSHA may 'rely on the recommendations and documentation' of outside organizations (such as the "threshold limit values" established by the American Conference of Governmental Industrial Hygienists), the outside body's findings 'did not relieve OSHA of the responsibility for making detailed findings, with adequate explanations for all statutory criteria.'"
The NLJ article then goes on to say "The inevitable debate over the marriage of OSHA regulations and the IARC silica findings may also spill over into the constitutional realm. Necessarily, Congress must delegate to the executive branch substantial, but not unbridled, authority to implement the policy judgments of the legislative branch. The undelegable essentials of the legislative function are the determination of the legislative policy and its formulation as a defined and binding rule of conduct."
Commenters have argued in their recently filed 108 pages of public comments on an FDA rulemaking concerning ephedra alkaloid containing dietary supplements (95N-0304) that the FDA cannot adopt the standards for ephedra herb dietary supplements set by the Canadian government because Canada is not bound by the U.S. Constitution, the U.S. Congress cannot delegate its Constitutional legislative powers to the Canadian government, the FDA cannot redelegate its rulemaking authority to the Canadian government, and the Canadian government is not bound by (among other things) the procedural requirements of the FACA (open meeting law) or the APA (Administrative Procedures Act). All this applies as well to standards -- such as drug control schedules -- set by the United Nations.
Note that the FDA's proposed rules on ephedra herb containing dietary supplements -- considered a high priority by the FDA -- were to go into effect in February 1998; however, the rules have not yet been issued because the FDA could not meet its burden of proof under DSHEA. FDA cannot legally take ephedra herb dietary supplement products off the market via the back door method of acceding to an international treaty which would effectively accomplish such removal without first meeting the DSHEA burden of proof that such dietary supplements, when properly labeled, are unreasonably unsafe when used as directed.
The Article 3, Paragraphs 2 and 3 Convention Exemption
FDA has stated that the 1971 UN Psychotropic Convention provides that "Under Article 3, paragraphs 2 and 3, a party may exempt from certain controls under the Convention, including the prescription requirement, if the preparation is compounded in such a way that it presents no, or a negligible, risk of abuse." However, This provision is expressly applicable to drugs, not to dietary supplements. No dietary supplement has ever received an exemption under this provision.
Adverse and Disparate Impact on Small Businesses
and FDA Failure to Comply with Statutory Requirements
Regarding Same
FDA has failed to fulfill its statutory obligation to consider the impact of this proposed regulatory action on small businesses. This failure is sufficient to require that the FDA exercise option #3, "reject the recommendations [regarding Scheduling ephedrine containing products] entirely." in its recommendations to WHO and CND (United Nations Commission on Narcotic Drugs).
Non-prescription medications containing pseudoephedrine are the most popular drugs in the US for the symptomatic relief of colds, flu, and allergies. The most popular brands are made by large corporations that may have the financial and legal resources to seek an Article 3, paragraph 2 or 3 exemption. The small businesses producing ephedra herb containing dietary supplements do not have these resources, and the failure of FDA to consider this difference in its Federal Register announcements of January 11, 1999, legally precludes the FDA from making any recommendation other than option #3, "reject the recommendations entirely."
CONCLUSION
DSHEA, APA, the scientific facts, constitutional limits on treaty powers and delegation, and statutes requiring assessment of regulatory impact on small businesses require that FDA adopt option #3; "reject the recommendations entirely."
Submitted 10 February 1999 by Durk Pearson & Sandy Shaw
Comments of Durk Pearson & Sandy Shaw and People for the Constitution
Before the
U.S. FOOD AND DRUG ADMINISTRATION
Rockville, Maryland
In re:
Regulations on Statements Made )
for Dietary Supplements Concerning ) Docket No. 98N-0044
the Effect of the Product on the )
Structure or Function of the Body)
COMMENTS OF
DURK PEARSON & SANDY SHAW
AND
PEOPLE FOR THE CONSTITUTION
Durk Pearson & Sandy Shaw ("Pearson & Shaw") and People for the Constitution ("People") hereby submit their joint comments in response to the call for public comments on the above referenced matter published in the April 29, 1998 Federal Register (Vol. 63 No. 82, pp. 23624-23632.
The Commenters
Durk Pearson & Sandy Shaw are research scientists and authors, specializing in the study of aging, age-related diseases, and free-radical associated disorders. They have spent thirty years studying the biochemistry of aging processes, nutrient-disease relationships, and FDA policies. In 1990, they received the Paul F. Glenn award of the American Aging Association, a professional society, for their educational activities directed to the public via books, articles, radio, and television concerning aging research and its practical implications. They have published four books, including three bestsellers. One, Life Extension, a Practical Scientific Approach (Warner Books, 1982), was on the New York Times Bestseller List for ten months and was #1 on the list for several weeks. They have also published a book on FDA regulatory policies concerning health claims, Freedom of Informed Choice: FDA v. Nutrient Supplements (Common Sense Press, 1993), which discusses the First Amendment implications of FDA's regulations. Pearson & Shaw have created several popular and safely used lines of dietary supplements, which they take themselves, that are marketed worldwide by license. Pearson & Shaw wish to communicate more truthful, nonmisleading scientific information about the health effects of their dietary supplements to consumers who wish to receive such information.
Pearson & Shaw are also plaintiffs in Pearson & Shaw et al v. Food & Drug Administration et al, No. 98-5043, which has been consolidated with case No. 98-5084 and is currently before the United States Court of Appeals for the District of Columbia Circuit. This case challenges certain FDA regulations concerning health claims as a prior restraint and violation of the plaintiffs' First Amendment protected speech rights. The briefs and filings in this case may be downloaded from www.emord.com.
People for the Constitution ("People") is a public interest organization that informs the public about their constitutional rights and the limits the Constitution places upon Federal government regulatory powers, including the regulation of communication of truthful, nonmisleading scientific information. People also commissions legal research on Constitutional issues in preparation for possible litigation against the Federal government in defense of Constitutional rights, including those of the First Amendment.
Members of People wish to communicate more truthful, nonmisleading scientific health information about dietary supplements and to receive such information.
COMMENTS
The FDA's proposed new rules for allowable structure/function claims:
1. Violate the First Amendment by placing a prior restraint on truthful, nonmisleading scientific information about dietary supplements, including that from published peer reviewed scientific papers.
2. Reduce the amount of information that may be communicated on labels and in labeling of dietary supplements, in opposition to the express will of Congress as explained in Public Law 103-417 (DSHEA) that "there is a growing need for emphasis on the dissemination of information linking nutrition and long-term good health," "consumers should be empowered to make choices about preventive health care programs based on data from scientific studies of health benefits related to particular dietary supplements," and that "...the Federal Government should not take any actions to impose unreasonable regulatory barriers limiting or slowing the flow of safe products and accurate information to consumers."
3. Are "arbitrary and capricious and not according to law" under the APA because the FDA's proposed definition of "disease" is so encompassing that nearly all truthful nonmisleading structure/function information about a dietary supplement would provide information directly or indirectly relating to the treatment, cure, diagnosis, or risk reduction of a "disease" and, therefore, be disallowed.
In Section I. Introduction, FDA states "FDA also notes that a dietary supplement for which only structure/function claims are made in the label or labeling in accord with section 403(r) of the act [DSHEA] may nevertheless be subject to regulation as a drug if the agency has other evidence (see 21 CFR201.128) that the intended use of the product is for the diagnosis, cure, mitigation, treatment, or prevention of disease."
COMMENT: There is nothing in the DSHEA authorizing the FDA to treat dietary supplements as drugs when there is no disease claim made for the dietary supplement. In Sec. 3 (DSHEA), it states that "Except for purposes of section 201(g), a dietary supplement shall be deemed to be a food within the meaning of this Act." Moreover, the use of a supplement is not determined by the manufacturer or vendor of a supplement, but by consumers, in which the limit of each individual consumer's knowledge plays a key role.
COMMENT: FDA's proposed rules defining "disease" and acceptable structure/function claims are arbitrary and capricious and are so complex, contradictory, and overlapping that it is impossible to determine just what truthful speech is left that may be communicated after all possible disease references, allusions, inferences, and implications have been ruled out and is, therefore, unconstitutional, being void for vagueness. For example:
IIB(4) "Under proposed 101.93(g)(1), a 'disease' is any deviation from, impairment of, or interruption of the normal structure or function of any part, organ, or system (or combination thereof) of the body that is manifested by a characteristic set of one or more signs or symptoms."
IIC "FDA emphasizes that in determining whether a statement about a product constituted a disease claim under these criteria, FDA would also consider the context in which the statement appeared. A statement that by itself would be considered an acceptable structure/function claim could become a disease claim if, in context, an effect on disease were expressed or implied."
IIC(2): "FDA believes that reference to a characteristic set of signs or symptoms, even in the absence of the name of the disease, can be understood as a reference to the disease itself." "Claims of an effect on symptoms that are not recognizable as characteristic of a specific disease or diseases would not constitute disease claims."
COMMENT: Health is not just the absence of disease, but the absence of disease is certainly a significant and necessary part of health. The only sort of structure/function information that escapes the labryinth of FDA's all-encompassing rules and regulations on disallowed information is information that is so vague that it is very unlikely to help consumers make informed choices for preventive health care. For example, the FDA will allow (it says) a claim that a product "helps maintain a healthy cholesterol level," but would not allow a claim that a product may help reduce cholesterol levels (even if true) because the latter would be a "disease" claim. What, then, does the FDA's acceptable claim mean when it says that the product "helps maintain a healthy cholesterol level?" If the product does help maintain a healthy cholesterol level, it must mean that it lowers cholesterol, at least under some circumstances, to help maintain a healthy cholesterol level. If the product cannot help lower cholesterol levels or (to put it another way) cannot help prevent cholesterol levels from rising, how can it help maintain healthy cholesterol levels? We believe that the FDA approved statement "helps maintain a healthy cholesterol level" is likely to be interpreted by consumers as meaning that it helps lower cholesterol levels. Indeed, niacin and some antioxidant vitamins (including vitamins E and C in certain dose ranges) do appear to help lower LDL cholesterol levels in many people and this is important information for consumers to know, but under FDA's proposed rules is prohibited by a prior restraint.
The FDA says that a claim that a product "helps maintain cardiovascular function and a healthy circulatory system" is OK, but to say that the product "may reduce cholesterol levels" is not OK. The latter contains helpful information for the many consumers who are trying to "maintain cardiovascular function and a healthy circulatory system" by reducing their cholesterol levels, but the vague claim that a product helps "maintain cardiovascular function and a healthy circulatory system" does not tell the consumer anything about what the product actually does (or purports to do). Information about a product's mode of action (its mechanism) is key information as to whether a product is likely to do any particular person any good. When significant scientific evidence supports a particular mechanism of action of a dietary supplement, that information ought to be permitted (indeed, it should be encouraged) to be made available to the public.
FDA does allow that "Claims of an effect on symptoms that are not recognizable as characteristic of a specific disease or diseases would not constitute disease claims." They then state that examples of such claims would be "reduces stress and frustration," "inhibits platelet aggregation," and "improves absentmindedness." Doesn't the first claim suggest that the product could be used as a tranquilizer? A product that "inhibits platelet aggregation" is very likely to reduce the risk of a heart attack or occlusive stroke for many people since platelet aggregation is one of the ongoing processes in most heart attacks and occlusive strokes. It is apparently only because most members of the general public are unaware of this that the FDA considers this claim to be acceptable. Once the general public becomes aware of the disease implications of platelet aggregation, then, presumably, this claim too will become unacceptable since it will clearly be a "disease" claim. Moreover, "absentmindedness" is universally recognized as characteristic of age-related memory loss or even Alzheimer's disease. Why is "improves absentmindedness" allowed but "lowers cholesterol" prohibited? Under the proposed rule, it is impossible for the regulated to determine what is legal and what is illegal. The proposed regulations are arbitrary, capricious, in violation of the express will of Congress, and void for vagueness.
Another example of the inconsistency of the FDA's distinction between allowed and non-allowed structure/function claims: FDA will permit "supports the immune system," but will not permit "supports the body's ability to resist infection." But, since it is the immune system itself that fights infection, supporting the immune system may very possibly support the body's ability to resist infection. Again, though, "supports the immune system" is less useful to consumers because it provides less specific information; it does not explain what particular aspect of immune activity is supposedly supported, eg., the mechanism of the supplement's effects (or purported effects). Again, the FDA doesn't want too much information to be provided, lest the consumer might make the connection between a truthful description of the effect of a dietary supplement and a disease, and purchase the supplement for the prevention or amelioration of that disease. As the U.S. Supreme Court noted in 44 Liquormart, "a State's paternalistic assumption that the public will use truthful, nonmisleading commercial information unwisely cannot justify a decision to suppress it." "It is precisely this kind of choice, between the dangers of suppressing information, and the dangers of its misuse if it is freely available, that the First Amendment makes for us."
We note that the FDA's attempts to severely narrow the limits of acceptable scientific information (structure/function claims) that may relate to the treatment, cure, or prevention of disease will hurt most those who are the least knowledgeable. Some of the well educated and well read are already likely to know about platelet aggregation and its implications for heart attacks and occlusive strokes, for example, whereas the poorly educated are not. About the time the poorly educated start to become aware of the link between platelet aggregation and heart attacks and occlusive strokes, the FDA will (under the new rules proposed here) proclaim this information to be an unacceptable disease claim, thus preventing the poorly educated from benefiting from this information in making dietary supplement choices. Hence, the FDA's policy of restricting the flow of truthful information has a disparate impact on the poor and less well educated.
The FDA says, in IIC(4)(c): "Citation of a title of a publication or other reference, if the title refers to a disease use" would render a product to have a "disease" claim even when otherwise no disease claim is made.
COMMENT: The DSHEA (Sec. 403B) expanded the permissible communication of scientific information on dietary supplement labels and in labeling: "A publication, including an article, a chapter in a book, or an official abstract of a peer-reviewed scientific publication that appears in an article and was prepared by the author or the editors of the publication, which is reprinted in its entirety, shall not be defined as labeling when used in connection with the sale of a dietary supplement to consumers when it is not false or misleading" and meets certain other conditions. Now the FDA attempts to restrict the communication of scientific information made expressly permissible under the DSHEA by banning the citation of scientific papers in which the title contains a reference to a disease use. The DSHEA section on use of citations does not authorize this proposed FDA requirement and it severely strains the imagination that Congress authorized the use of certain published abstracts of scientific papers without intending that the title of the papers be used, as well.
Moreover, Section 403B(c) of this section of DSHEA notes that "Burden of Proof: In any proceeding brought under subsection (a), the burden of proof shall be on the United States to establish that an article or other such matter is false or misleading." FDA proposes a blanket ban on the citation of scientific papers in which the name of a disease appears in the title, but has provided no evidence that all (or even any) such scientific papers would be false or misleading.
We recommend that the FDA reviewers of these comments download the Appellants' Reply Brief (www.emord.com) in Pearson & Shaw et al v. Food and Drug Administration et al (Case No. 98-5043 and Consolidated Case 98-5084) for, among other things, extensive citation of Senate, House, and other Congressional reports on the failure of the FDA to meet the Congressional intent in NLEA and DSHEA to increase the communication of truthful, nonmisleading information to the public on dietary supplements. For example, the FDA was not to require "definitive proof" of a nutrient-disease relationship before authorizing claims, but was to depend upon evidence that a "significant segment of scientists having relevant expertise agree...that consumers are reasonably likely to obtain the claimed health benefit." S.Rep. 103-410 at 34. Also, "The FDA has acted to restrict the information that the public may receive about dietary supplements." S.Rep.103-410 at 16. And again, "FDA has applied [significant scientific agreement] in a way that limits consumer access to important information on diet and health." S.Rep. 103-410 at 23. And again "Despite the fact that the scientific literature increasingly reveals the potential health benefits of dietary supplements, the Food and Drug Administration has pursued a regulatory agenda which discourages their use by citizens seeking to improve their health through dietary supplements." S.Rep. 103-410 at 14.
The FDA's attempt to ban communication of certain truthful and nonmisleading scientific papers when the title has the name of or refers to a disease is in violation of the First Amendment. Scientific speech is fully protected. We note here for the record that we will not be limited by this unconstitutional rule and will cite any and all scientific papers we think relevant, whatever their title may be. If the FDA makes an issue of this, then we will cite these papers with the name of the disease removed and replaced with a bracket: "[word or words removed because of FDA threats, in violation of our First Amendment rights. Sieg heil!]". We do not think that consumers, the scientific community, the Congress, health freedom activists, or the courts will be amused by the FDA's blatantly unconstitutional censorship and blatant violation of the clear written intent of Congress in the official records to increase the flow of health information to the public.
We intend to propose that Congress hold "contempt of Congress" hearings on the FDA's continuing resistance to the clear instructions of the Congress in the NLEA and DSHEA to increase the amount of information flow on the health effects of dietary supplements to consumers. We believe that until there are actual punishments in place for specific FDA rulemaking individuals responsible for wilfully refusing to comply with the statutory instructions of the Congress, we will see this sort of unlawful behavior taking place again and again. (For example, who at FDA is responsible for writing these proposed new rules?) The FDA seems to forget that Congress has the sole Constitutional authority to make Federal law and that the FDA's authority to implement laws passed by the Congress comes from the Congress and may be taken away and given to another agency by the Congress, and agency rulemakers found to be in contempt of Congress may be imprisoned.
Comments submitted by:
_____________________________
Durk Pearson & Sandy Shaw
_____________________________
People for the Constitution
PO Box 3666
Tonopah, NV 89049
Dated: Sept. 23, 1998
Comparison of Food Safety to Nutrient Supplement Safety
(c) 1998 by Durk Pearson & Sandy Shaw
Introduction
There is a statutory presumption of safety for foods. Historically, this presumption of safety has applied to nutrient supplements, which have been regulated as foods. The FDA now proposes to shift the burden of proof on harm from the FDA to nutrient supplement manufacturers in this rulemaking procedure. The FDA's proposal to require nutrient supplements to meet the far stricter safety standards of food additives or drugs reflects the FDA's assumption that nutrient supplements are less safe than foods. However, the evidence indicates otherwise.
The worst public health problem associated with a nutrient supplement involved the development of a serious disorder, eosinophilia-myalgia (EMS), in association with the ingestion of supplements containing the essential amino acid tryptophan. As a result of EMS, 38 Americans died and about 1,500 others became sick. The U.S. Centers for Disease Control (CDC), the government agency whose mission is to identify the causes of epidemics, investigated the cause of EMS and published their final report in which they identified contamination in batches of tryptophan from one manufacturer as the cause of the tryptophan supplement associated EMS.1,2 No other nutrient supplement has been involved in such a disaster. As a result of the EMS incident, the FDA proposes to regulate amino acids and many other nutrient supplements, including high potency vitamins, as unapproved drugs or as unapproved food additives. The tryptophan-associated EMS is the linchpin of the FDA's case for stricter regulation of nutrient supplements. However, the risks of contaminated foods are even greater than that of the contaminated tryptophan.
Risk of Contaminated Tryptophan
The U.S. Centers for Disease Control estimated that 15,000,000 Americans were using tryptophan supplements at the time of the EMS incident which killed 38 people.1 This results in a death rate of 2.5 deaths per million users for 1989, the year in which nearly all of the contamination occurred. (If the deaths are averaged over the 25 years that tryptophan has been used as a nutrient supplement, the death rate per user per year is, of course, far lower.)
Risk of Contaminated Food
There are many types of potentially lethal food contaminants. For the sake of brevity, let us consider only one type, listeriosis, caused by the pathogenic bacterial contaminant Listeria monocytogenes. Listeriosis alone causes about 450 deaths and about 100 fetal deaths every year in America.3 There are about 260,000,000 food users in America, so the death rate among American food users from listeriosis alone is about 2.1 per million per year, and this occurs every year -- not once in a quarter century. Some foods are more likely to be contaminated with this bacterium than others. For example, those who eat soft cheese are about 2.6 times as likely to become infected with listeriosis than those who do not.4 This means that the listeriosis death rate is about 5.4 per million soft cheese eaters each and every year. Compare this to the death rate of 2.5 per million tryptophan supplement users which occurred once during a quarter century period of tryptophan supplement use.
Note, too, that there are many other deaths from other lethal food contaminants each year. For example, the deaths from contaminated undercooked hamburger in the Western U.S. earlier this year were caused by a toxin producing an E. coli bacterial strain. Salmonella, from undercooked eggs and poultry, is also extremely common.
It is not necessary to ban tryptophan supplements to prevent a repetition of the EMS incident, any more than it is necessary to ban soft cheese. It is not even necessary (though it is desirable) to identify which of several contaminants was (or were) responsible for the EMS. L-tryptophan has been manufactured by companies using processes that have been shown to be safe by many years of historical experience. Just as the FDA has developed Good Manufacturing Practices for foods, the FDA should do the same for nutrient supplements. One requirement ought to be that a nutrient manufacturer must provide an HPLC analysis of each batch of a nutrient. Each batch of tryptophan, for example, should be analyzed by HPLC, so that any contaminant peaks in the batch that were not present (or are present in greater amounts than) in historically safe batches can be readily determined. The safety procedures and assurances incorporated into Good Manufacturing Practices would be safeguards against the poor manufacturing practices that led to the production of the contaminated tryptophan that caused EMS.
Conclusion
In 1989, the year of the contaminated tryptophan EMS epidemic, a tryptophan supplement user had a lower risk of death from EMS than a soft cheese user's risk of death from listeriosis from contaminated soft cheese. Even the worst case supplement problem, EMS from contaminated L-tryptophan over a roughly one year period after a quarter century of safe use, caused a lower death rate per million tryptophan supplement users in that year than the annual year after year death rate per million users of soft cheese from listeriosis contamination alone. The FDA's proposal to require nutrient supplements to meet a much stricter safety standard than common foods makes no sense. The Agency is misallocating far too much of its limited resources to the regulation of nutrient supplements, when the risks of common foods are greater.
1) Belongia, et al, "An Investigation of the Cause of the Eosinophilia-Myalgia Syndrome Associated with Tryptophan Use," The New England Journal of Medicine, 323:357-365 (9 August, 1990)
2) Kamb, et al, "Eosinophilia-Myalgia Syndrome or Fibromyalgia with Eosinophilia - A Reply," Journal of the American Medical Association, 269:3108-3109 (23/30 June, 1993)
3) Gellin, et al, "Listeriosis," Journal of the American Medical Association, 261:1313-1321 (3 March, 1989)
4) Schuchat, et al, "Role of Foods in Sporadic Listeriosis: 1: Case-Control Study of Dietary Risk Factors," Journal of the American Medical Association, 267:2041-2045 (1992)
LIFE EXTENSION NEWS
VOLUME II - ISSUE #2 - MARCH 1999
Something very important has happened since our last newsletter. We are very happy to report that:
We Win Our First Amendment Suit Against FDA!!
Freedom of Speech Lives!!
On Jan. 15, 1999, in a landmark decision, a panel of the
U.S. Court of Appeals for the District of Columbia Circuit, ruled
3-0 in favor of plaintiffs (that's us!), deciding that the FDA's
health claim approval process was unconstitutional under the First Amendment and "arbitrary and capricious" under the Administrative Procedure Act. Winners of this case include us, our co-plaintiff the American Preventive Medical Association, and (added to our case from a separate appeal) Citizens for Health. Additional winners (who filed an amicus brief in support of our First Amendment challenge of FDA regulations) were: Direct AIDS Alternative Information Resources, People Against Cancer, and the Foundation for Advancement of Innovative Medicine. In addition to the Department of Health and Human Services, Food & Drug Administration, and the United States, other losers (who filed an amicus brief supporting the FDA information restrictions) were: American Cancer Society, American Heart Association, Center for Science in the Public Interest, Public Citizen, and Consumer Federation of America.
Special Thanks
We met constitutional attorney Jonathan Emord as a result of publishing our 1993 book, Freedom of Informed Choice: FDA vs. Nutrient Supplements (still available from Common Sense Press for $6.95, (800)542-3230) and of our reading his excellent paper, "The Doctrine of Commercial Speech in First Amendment Jurisprudence," Cato Institute Policy Analysis (Sept. 23, 1991). Jonathan has skillfully argued our FDA suit from its initial filing in 1994 through the legal mazes to this long-awaited victory. (The FDA may appeal, but we do not expect they will be able to reverse this decision.) We spent a lot of our own money in this case, but also got major help along the way in paying the legal bills from Julian Whitaker, M.D., and the American Preventive Medical Association. Some additional financial help came from the National Health Federation, Life Enhancement Products, Life Extension Foundation, Greg and Michelle Pryor of Life Priority, Inc., and a few others who wish to remain anonymous. An analysis of the decision, as well as our briefs and oral arguments, may be downloaded from www.emord.com.
Those of you who have followed our work know that we have been publicly critical of the FDA for many years, including a long section (Appendix E) in our #1 bestseller Life Extension, a Practical Scientific Approach. In Freedom of Informed Choice, we specifically focused on the deleterious consequences of FDA's regulations of "health claims" and why we thought these regulations violated the First Amendment's protections of speech and press. If you want to improve human performance and extend human lifespan, it is not enough to do research. You have to be able to turn research findings into practical products people can buy and use, and you have to be able to inform people of what those products do; the FDA has long stood as the major barrier to these ends.
Suiting Up
The suit started for us in 1993, when we began filing Public Comments in response to the FDA's proposed rules regulating what health claims they would permit for dietary supplements.2 As far as we were (and are) concerned, the Constitution's First Amendment makes it clear that the federal government has no authority to regulate truthful speech at all. It seemed to us that the idea that "commercial speech" (what you say when it accompanies a commercial transaction) is somehow less deserving of constitutional protection than other kinds of speech (though the First Amendment says nothing of the kind) makes those of us involved in commercial transactions - either as buyers or sellers - into second class citizens. We had already become aware of this "commercial speech" doctrine by 1986 and realized that it was allowing government agencies, such as the FDA, unprecedented control over the communication of truthful scientific information when it accompanied a product.
FDA Censorship of Truthful Information Kills
In our Freedom of Informed Choice: FDA vs. Nutrient Supplements, we discussed the constitutional and scientific issues of FDA's regulation of the dissemination of scientific information. We explained what a disastrous effect upon the public health the FDA was having by drastically slowing the flow of truthful health information concerning dietary supplements, such as antioxidant vitamins. (We also included several diabolically nasty cartoons aimed at the FDA.) One of our examples was low-dose aspirin. In the "Physician's Health Study" published in 19891, it was reported that in previously healthy men over 50, an aspirin every other day reduced the risk of a first heart attack by about 44%. Ten years later, the FDA still unconstitutionally prohibits aspirin companies from communicating this information to the general public. (It only decided a few months ago to allow the information to be communicated to doctors!) During this period, hundreds of thousands of people have died from heart attacks unnecessarily because they did not know about and were not taking low-dose aspirin (the latest evidence places the most protective dose for most people over 50 in the range of 1/4 to 1/2 aspirin a day - we take 1/4).
"Commercial Speech" in the Courts
We began reading the entire text of U.S. Supreme Court decisions in "commercial speech" cases in 1993 to learn how the Court and how individual Justices viewed the constitutional limits on government regulation of advertisements and of product labels. We found a well developed jurisprudence that provided for an awkward (and, to our minds, unsatisfactory) "balancing test" (of free speech vs. government interests in regulating speech) that attempted to allow yet provide limits to government regulations of truthful speech accompanying the sale of a product. We considered FDA's regulations on truthful health claims to have gone beyond the bounds set by the Court and by Congressional statutes and far beyond the bounds set by the clear language of the First Amendment ("Congress shall make no law . . .abridging the freedom of speech or of the press") and filed suit against the FDA in 1994. We thought, in doing so, we might push the envelope on freedom of speech to help restore constitutional restraints on government regulation of "commercial speech."
The D.C. Appeals Court in our case logically developed the consequences of prior U.S. Supreme Court decisions concerning First Amendment limitations on governmental censorship, with particular focus on the communication of scientific information as part of "commercial speech." As we had hoped, this decision has enlarged the boundaries of freedom of speech recognized by the Courts as being clearly beyond constitutional federal government regulatory power.
Courts Do Not Usually Consider Constitutional Arguments
In fact, the Court did something very unusual. Courts generally examine constitutional challenges to laws after they have considered procedural challenges. If a law can be thrown out on a procedural basis, a Court will almost always do that in preference to taking on a constitutional challenge. Rarely do the constitutional questions get a review. In our case, however, the Court stated, "Normally we would discuss the non-constitutional argument first, particularly because we believe it [that an undefined standard is no standard] has merit. We invert the normal order here to discuss first appellants' most powerful constitutional claim, that the government has violated the First Amendment by declining to employ a less draconian method - the use of disclaimers--to serve the government's interests [of protecting the public from misleading information]" Thus, the Court said, "even if 'significant scientific agreement' were given a more concrete meaning, appellants might be entitled to make health claims that do not meet that standard - with proper disclaimers." (The Court decided this, though it was not one of the issues we raised in this case because we didn't think the courts were ready for it! it looks to us as if they are pointing the way for the FDA -- how, if they take the decision seriously, they can thereby avoid both violating the First Amendment's constitutional prohibitions and the otherwise inevitable next FDA First Amendment suit!)
The Court's discussion of the First Amendment implications of the FDA's not permitting disclaimers was a response to our complaint that the FDA refused to permit four claims that we wished to make. They prohibited all four proposed claims (such as "antioxidant vitamins may reduce the risk of certain cancers" and "omega-3 fatty acids may reduce the risk of cardiovascular disease") by claiming that there was not "significant scientific agreement" (which they would not define) and would not permit us to qualify the claim by including, for example, information about the limits of the current evidence of cancer risk reduction by antioxidant vitamins and what types of evidence exist (cell cultures, animal, clinical studies, epidemiological studies, etc.). The Court established that there is a clear First Amendment preference for more information rather than less, and the use of disclaimers to correct potentially (but not inherently) misleading information must be considered by the agency.
Undefined Standard is No Standard At All
One specific rule the new decision throws out is the FDA's purported "significant scientific agreement" standard for health claims. The Court agreed with our argument that the FDA has established no standard since the FDA has refused to define what "significant scientific agreement" means. This is a statutory violation because Congress required in the DSHEA that the FDA establish a procedure and standard for accepting health claims.3
The FDA will now have to proceed with new rulemakings in which it attempts to decide what "significant scientific agreement" might mean when they cannot define it simply as whatever the FDA says it is on a case by case basis. We think it likely that the FDA will first attempt to propose the same old unconstitutional rules dressed up in new verbiage. You can be sure we will be filing Public Comments!
The Court appears to have found some of the government's arguments a bit ridiculous. For example, on page 10 of the decision, the Court notes, "As best we understand the government, its first argument runs along the following lines: that health claims lacking 'significant scientific agreement' are inherently misleading because they have such an awesome impact on consumers as to make it virtually impossible for them to exercise any judgment at the point of sale. (emphasis in original) It would be as if the consumers were asked to buy something while hypnotized, and therefore they are bound to be misled. We think this contention is almost frivolous." Both of us got a good laugh out of that. See the excerpts from the oral arguments below (ADDENDUM) for even more laughs.
The FDA Does Not Approve This Claim
The Court also said, "The government's general concern that, given the extensiveness of government regulation of the sale of drugs, consumers might assume that a claim or a supplement's label is approved by the government, suggests an obvious answer. The agency could require the label to state that 'The FDA does not approve this claim.'" We had suggested such an approach, which we called a "split label," in our early Public Comments to the FDA, but the FDA rejected it. Perhaps they were concerned that people might see 'The FDA does not approve this claim' everywhere and wonder why they needed the FDA in the first place. In fact, the FDA has approved only two health claims for dietary supplements during the entire eight year period since the Nutrition Labeling and Education Act required the FDA to review and approve health claims for dietary supplements and foods.
Consequences of this Court Decision
This decision has made us feel great (as a friend of ours put it, we feel "like the 'minutemen' did!") It is possible, with enough conviction, careful choices of case, court and attorney, plus time and money, to bind the federal government down with the chains of the Constitution. The result of this decision is going to be immense, though there seems to be almost no notice yet in the mainstream press. Greater freedom of speech is going to dramatically increase the market potential of the dietary supplement industry, with much more information about products being supplied to consumers. As consumers learn more about the effects of dietary supplements, they will become more sophisticated in evaluating available products and far less likely to believe lies (whether from private or government sources). As with any new technology, it will take consumers a while to sort things out and locate and stick with reliable sources of information. Fly by night outfits may do well in the short run but suppliers of truthful and nonmisleading information about dietary supplements, as well as those who receive the information, will come out the long-term winners.
Because of extensive and burdensome government regulations of medicine and medical insurance, alternative medicine (for example, dietary supplements) is one of the few areas of medical practice that is still in a free market in which consumers pay with their own money and get what they pay for. We hope that those alternative medical practitioners and their patients who want to require taxpayer coverage of alternative medicine under Medicare and other government programs are not successful in getting their wish because the result would be to help the government take over and destroy the freedom we currently enjoy in alternative medicine. He who pays the piper calls the tune . . . .
Speaking of Government Takeover of Medical Practice:
The Federal Government Has No Constitutional Authority to Regulate Intrastate Use of Medical Marijuana
We also have a suit filed with the U.S. District Court for the District of Columbia (97CV00462(WBB)) challenging the federal government's authority under the Constitution to take action against the intrastate prescription and use of medical marijuana in states where that is legal, on the basis of the First, Ninth, and Tenth Amendments, and the limits of the Commerce Clause4. This case is not about whether medical marijuana is a good medication or not; it is about whether the federal government has constitutional authority to regulate the intrastate practice of medicine and whether Congress and the "drug czar" can grant the federal government general police powers (which the constitution does not do) over medicine or anything else by the simple expedient of decreeing all commerce to be interstate.
It is, of course, impossible to predict how this will come out. We believe our constitutional arguments are very strong and there has been some movement in recent U.S. Supreme Court and lower court decisions to limit the intrastate reach of the Commerce Clause (eg., U.S. vs. Lopez, 1995; U.S. vs. Pappadopoulos, 1995). Still, there are those in the judiciary who care much more about maintaining the federal government's usurped powers than of restoring constitutional limits to federal actions. (This is called "outcome based" jurisprudence.) It will demand considerably more courage on the part of the courts to decide in our favor than the FDA First Amendment suit did. If we win, it will vastly increase freedom of choice in medical practice by jettisoning the "one size fits all" federal government approach (the whole point of the constitutional design of federalism) to allow 50 different competing intrastate regulatory approaches. We will, however, have to raise more money for the appeal (whether it is the government or ourselves who file it) after the District Court decision on our medical marijuana/federalism suit comes down. You can download the briefs and oral arguments for our medical marijuana suit from www.emord.com.
Is this fun or what? Yes, but only when you win.
References
1 "Final Report on the Aspirin Component of the Ongoing Physicians' Health Study," New England Journal of Medicine321(3):131-135 (July 20, 1989)2 The reason for filing comments during the Public Comment period after an agency has published a proposed rule in the Federal
Register is not because you expect the agency to care what you
have to say, but because it gives you standing to sue. If you do
not file comments on a proposed rule and are later injured by it,
you cannot go directly to the federal courts to challenge the
rule; you have to first "exhaust your Administrative remedies,"
which means spending a lot of money in the agency's internal
Administrative court where you cannot hope to win.
3 It is also unconstitutional because the Constitution authorizes
only one federal institution to make laws, the Congress. See
U.S. Constitution, Article I, Section 1. The federal agencies
can carry out the will of Congress pursuant to Congressionally
created law, but cannot make rules in the absence of statutory
authorization. This is a constitutional principle that is widely
flouted by federal agencies. (For one thing, why limit your
rulemaking to that authorized by Congressional statute when
nobody in a regulatory agency has ever been thrown in jail or
lost their job or even been disciplined by the Congress for
making law that went beyond or even defied the explicit will of
Congress as expressed in statute?) A time is rapidly approaching
when a properly chosen regulatory agency rule or rules should be
challenged on the basis of Article I, Section 1 of the
constitution; however, we didn't judge that this case was the
right one for such a challenge or that the courts were ready for
it.
4 Our co-plaintiffs include Julian M. Whitaker, M.D., Jeffrey A.
Singer, M.D., Richard D. Fisher, M.D., Henry N. Blansfield, M.D.,
William Regelson, M.D., American Preventive Medical Association,
and Life Extension Foundation. Our thanks to these brave people!
ADDENDUM: Oral Arguments in Pearson & Shaw et al v. Shalala et al.
You can learn a lot about a court and its judges by
listening to oral arguments, in which there is usually a lively interaction between each side's attorney and the judges, who interrupt frequently to ask questions and make comments, sometimes pointed and humorous. Unfortunately, we were not able to travel to Washington, D.C. to hear oral arguments, so we did the next best thing by getting and reading the transcript of the
oral arguments. The following short excerpt shows how dubious
the judges were of the FDA's position that unapproved health
claims are inherently misleading.
THE COURT: . . . Do you seriously argue that these statements
are inherently misleading?
MS. KOHL [Christine N. Kohl, representing the FDA]: In the
FDA's judgment, Your Honor, yes, they are. There is such power
over the consumer in the market place at the point of sale . . .
THE COURT: . . . what if the proposed statement were exactly
what your FDA's parent Agency [HHS] said, quote, "Fatty acid
omega-3 is under study because of a possible association with a
reduced risk of heart disease in certain people." That was the
only thing they wanted to put on the label, and it was word for
word what HHS put out. Is your position that is inherently
deceptive?
MS. KOHL: Yes, Your Honor, that's the scientific judgement
of the FDA that there is not -
THE COURT: So HHS, FDA's position is that HHS is making
inherently deceptive statements.
MS. KOHL: . . . These regulations that are being challenged
apply only to labeling on the dietary supplement.
THE COURT: But why does that matter? . . . Why is it
inherently deceptive in the label, and not in the brochure.
THE COURT: Is this [that the statements are inherently misleading in a label] some impression the FDA has? Or maybe they have some study in the back. But I mean, I've got to tell
you, I walk to the grocery store all the time. . . . I just don't
get the impression that people are absolutely terrorized when
they approach a dietary supplement.
THE COURT: It's not like approaching a lawyer.
THE COURT: Yes. Label, as opposed to reading an article in a
magazine. I mean, is this something that you think it really
rises to the, you have to have a qualitatively different standard
when they go into the grocery store?
THE COURT (a few lines later): . . . But I find the argument
that this is inherently misleading is absurd . . . .
MS. KOHL: Well, Your Honor, again, it is the Agency's scientific judgment based on their -
THE COURT: Well, that's not a scientific judgment. That's a
legal judgment, isn't it?
THE COURT: . . . in order to win your case, you have to
establish that this is inherently misleading. That's basically what you are arguing, isn't it?
MS. KOHL: . . . If the Court doesn't agree with the FDA's
conclusion that these claims have so much potential for abuse
that they are inherently misleading --
THE COURT: Potential? Wait a minute counsel. You are
switching between inherent and potential. I'm trying to take out
of the case, obviously, and I think Judge Garland is too, this
inherently misleading notion.
MS. KOHL: And my response to that is, if you --
THE COURT: Is, you hate like hell to give it up, but --
THE COURT: You can't legally. They're in trouble if they
give it up.
THE COURT: I know, because the Agency said inherently misleading.
Too Early to Recommend Vitamin E Supplements
Says American Heart Association
One of the losing amici in the above case was the American Heart Association, which supported the FDA's information-restricting policies. In the Feb. 1, 1999 "Yahoo! News," there was a report on the AHA's view (from Circulation 1999;99) on the possible health benefits of taking antioxidant supplements. The AHA says, according to the report, that, although there is some evidence suggesting that diets rich in antioxidants such as
vitamins A, C, and E can reduce heart disease risk, it is still
too early to recommend the use of antioxidant supplements to the
general public. Moreover, "[a]lthough diets alone may not
provide the levels of vitamin E intake that have been associated
with the lowest risk in a few observational studies," we should
wait for more studies before making public recommendations to
take vitamin E supplements.
Why would the AHA make "wait and see" recommendations about
vitamin E supplements in the face of the astronomically high
medical and human costs of heart disease (the #1 killer in
industrialized countries and already the #2 killer in most Third
World countries), the large and growing body of evidence
supporting the protective effects of vitamin E (including both
large epidemiological and intervention studies, such as CHAOS),
as well as the low potential risk of supplemental vitamin E at
the dose levels found to be protective in prospective and
intervention studies? We don't know, but we have to wonder if someone in the AHA fears that, if people think they can substantially reduce their own risk of heart disease by taking vitamin E, they may be less likely to donate money to the AHA. As Nobel Prize winning James Buchanan's "Public Choice" theory has shown, those running large bureaucratic organizations tend to do whatever will keep money flowing into their organization.
Balloon Payment
Government is the ultimate "fly by night" organization.
Current officeholders benefit from what they do today (such as
lying and spending a lot of other people's money) and then
somebody else has to fix the resulting disaster later. This is
particularly bad for life extenders, as we intend to (or at least we are trying to) be around later.
--Sandy Shaw
Before the Federal Deposit Insurance Corporation
Washington, D.C.
In re:
Minimum Security Devices and ) 12 CFR Part 325
Procedures and Bank Secrecy Act ) RIN 3064-AC19
Compliance )
Federal Deposit Insurance Corporation
Notice of Proposed Rulemaking
COMMENTS OF
DURK PEARSON & SANDY SHAW
AND
PEOPLE FOR THE CONSTITUTION
Durk Pearson and Sandy Shaw ("Pearson & Shaw") and People for the Constitution ("People") hereby submit their joint comments in response to the call for public comments on the above referenced matter published in the December 7, 1998 Federal Register (Vol. 63 No. 234, pp. 67529-67536).
Durk Pearson & Sandy Shaw are scientists and authors. They have written extensively on both scientific and constitutional issues. Their first book, Life Extension, a Practical Scientific Approach (Warner Books, 1982) sold over one million copies and was on the New York Times Bestseller List for ten months. Their most recent book Freedom of Informed Choice: FDA vs. Nutrient Supplements (Common Sense Press, 1993) argues that the FDA's regulation of truthful health information on labels and in ads is dangerous to the public health and a violation of the First Amendment's prohibition on government abridgement of freedom of speech and the press. Pearson & Shaw are plaintiffs in a suit against the FDA for First Amendment violations (see www.emord.com). The suit is currently before the Court of Appeals for the District of Columbia Circuit. Pearson & Shaw have banks accounts in FDIC-insured banks and are opposed to having their banks either collect or report private financial information to the government, which they consider an invasion of their privacy as well as an unconstitutional search and seizure under the Fourth Amendment. They are prepared, if necessary, to bring suit against the FDIC on constitutional grounds to prevent the institution of the proposed rule.
People for the Constitution ("People") is a public interest litigation and education organization that educates the public about their constitutional rights and the limits the constitution places upon Federal government regulatory powers, including the Fourth Amendment right to freedom from unreasonable searches and seizures of their persons, houses, papers, and effects. People also commissions legal research on Constitutional issues in preparation for possible litigation against the Federal government in defense of Constitutional rights, including privacy and freedom from unreasonable searches and seizures.
Members of People object strenuously to the collection and disclosure by FDIC-insured banks at which they have accounts of personal financial information to the government in the absence of probable cause.
The proposed regulation (pg. 67529): "The FDIC is proposing to issue a regulation requiring insured nonmember banks to develop and maintain 'Know Your Customer' programs. As proposed, the regulation would require each nonmember bank to develop a program designed to determine the identity of its customers; determine its customers' sources of funds; determine the normal and expected transactions of its customers; monitor account activity for transactions that are inconsistent with those normal and expected transactions; and report [to the FDIC] any transactions of its customers that are determined to be suspicious."
Stated purposes of the proposed regulation: "...the proposed regulation will reduce the likelihood that insured nonmember banks will become unwitting participants in illicit activities conducted or attempted by their customers." "By identifying and, when appropriate, reporting such transactions in accordance with existing suspicious activity reporting requirements, financial institutions are protecting their integrity and are assisting the efforts of the financial institution regulatory authorities to combat illicit activities at such institutions."
Compliance (Subpart C, 4(f)): "Availability of documentation. For all accounts opened or maintained in the United States, each insured nonmember bank must ensure that all information and documentation sufficient to comply with the requirements of this section are available for examination and inspection, at a location specified by an FDIC representative, within 48 hours of an FDIC representative's request for such information and documentation."
COMMENTS
Violation of the Fourth Amendment:
FDIC nowhere in their proposed rule discuss the Fourth Amendment implications of the rule. The Fourth Amendment states, "The rights of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures, shall not be violated, and no warrants shall issue, but upon probable cause, supported by oath or affirmation, and particularly describing the place to be searched, and the persons or things to be seized." The FDIC's proposed rule establishes processes for compulsory searches of the papers of Americans without following the Fourth Amendment requirement for probable cause and search warrant and is, hence, in violation of the Fourth Amendment. The proposed FDIC procedures establish unconstitutional government fishing expeditions for the papers of large numbers of innocent persons to find evidence of wrongdoing by a few.
Recent Court decisions have begun tightening legal restrictions on government searches and seizures after a period of loosening such limits far beyond that allowed under the clear language of the Fourth Amendment. For example, see a recent Ninth Circuit ruling (opinion written by Judge Kozinski) that a police "profile" of alleged characteristics of those more likely to have committed drug crimes provides no probable cause to search a person or his/her car for evidence of criminal activity. The U.S. Supreme Court ruled 9-0 (Dec. 8, 1998) that police cannot search people and their cars after merely ticketing them for routine traffic violations.
Commerce Clause
The U.S. Supreme Court has consistently supported the view that the constitution does not give the federal government general police powers (U.S. v. Lopez, 115 S. Ct. 1624 (1995); Justice Thomas, concurring). Under the Commerce Clause, the federal government has regulatory powers over interstate commerce, commerce with foreign nations, and commerce with Indian tribes. Federal authority does not extend to intrastate crime of a local nature, such as the possession of a gun within 1,000 feet of a school (U.S. v. Lopez, 1995), "The Act [Gun-Free School Zones Act of 1990] neither regulates a commercial activity nor contains a requirement that the possession be connected in any way to interstate commerce. We hold that the Act exceeds the authority of Congress "[t]o regulate Commerce ... among the several States."). (emphasis added) The proposed FDIC rule does not specify what procedures will be put in place by the FDIC to ensure that the federal government (FDIC) regulates only interstate commerce and does not, thereby, overstep its constitutional authority. If the federal government were allowed to ignore the distinction between interstate and intrastate characters of the transactions they were investigating, it would make a nullity of the constitution's limited delegation of authority to the federal government under the Commerce Clause.
As decided in Printz v. United States (Nos. 95-1478, 95-1503, U.S. Supreme Court), the federal government cannot compel state or local governments to enforce or administer federal law, nor can the federal government circumvent that prohibition by conscripting the state's officers directly. We argue here that, since the federal government was denied constitutional authority to regulate intrastate commerce, that the federal government has no constitutional authority to evade this constitutional limitation by conscripting private entities such as banks into regulating such local commerce.
Customer Privacy
The FDIC states (pg. 67530): Privacy Issues. "The proposed regulation requires insured nonmember banks to gather information about customers that, if misused, could result in an invasion of a customer's privacy. Given the potential for abuse in this area, it is the FDIC's expectation that, in complying with the Know Your Customer regulation, a nonmember bank will obtain only that information that is necessary to comply with the regulation and will limit the use of this information to complying with the regulation."
Comments: FDIC discusses here how the government has high expectations of the banks required to collect and report the valuable private customer information demanded by the FDIC without probable cause or warrant (see Fourth Amendment above). However, despite the high moral tone of the government's stated "expectations," the result is mere hot air since the federal government puts in place no procedural safeguards whatever for actual protection of that information. There are no penalties for bank failure to "obtain only that information that is necessary to comply with the regulation" or to "limit the use of this information to complying with the regulation." Moreover, those undefined limitations are void for vagueness and are arbitrary and capricious, since the FDIC never makes it clear to banks exactly how much of what kind of information is necessary to ascertain (for example) the sources of a person's income or how they would be expected to spend their money or of how a bank is to know when a customer has crossed over a purported line that tells them when somebody's spending pattern is "suspicious." In fact, because it is not at all clear how much information will be "adequate" for the purpose, the banks are likely to collect far too much information, subjecting each and every law-abiding customer to extensive (and unconstitutional under the Fourth Amendment) monitoring.
The Fourth Amendment prohibits federal government searches and seizures of persons, houses, papers, and effects without some evidence of wrongdoing. It is certainly easier for the government to force banks to conduct unreasonable searches and seizures for them than it is for the government to develop credible evidence of wrongdoing with which to obtain a search warrant, but it is still unconstitutional. The Constitution was not put in place for the convenience of the federal government in law enforcement, but to declare the federal government's delegated powers under the constitution and to prohibit the federal government from abridging constitutional rights of Americans.
Classifying Customers into Varying Risk-Based Categories
Page 67531, Paragraph (d) -- "Contents of Know Your Customer Program": "In complying with this section, it may be beneficial for insured nonmember banks to classify customers into varying risk-based categories that the insured nonmember banks use in determining the amount and type of information, documentation and monitoring that is appropriate."
Comments:
A. When credit companies classify customers into varying risk-based categories, they are required to provide customers with copies of their credit reports so that errors can be corrected. Unfortunately, banks can and do make costly errors affecting their customers. (Government agencies have been known to make a few errors, too, and to abuse power to the detriment of those under their control.) Hence, there must be protective safeguards in place so that innocent citizens can become aware of and correct errors in their risk-based classifications. The cost to innocent citizens (who comprise the overwhelming majority of bank customers) of such errors can be very severe, including (for example) detailed monitoring by banks of their private financial transactions and the reporting of these, their private conduct and economic choices, to the government. Such monitoring could be used by government officials, for example, to illegally spy on political "enemies."
B. Another serious problem with such classification is that, in classifying customers into varying risk-based categories (that is, the risk of laundering money), certain groups (such as blacks, hispanics, Asians, and Arab-Americans) are disproportionately more likely to be classified as high risk. For example, it is an undeniable fact that a far higher percentage of blacks are incarcerated for drug crimes (one reason for money laundering) than are whites. Hispanics are more likely to have contacts in Latin America, where much drug traffic money laundering activity takes place. Arab Americans may be suspected of greater likelihood of involvement with Middle Eastern terrorists and Asians in criminal triads. What does the FDIC propose to do about the proportional overrepresentation of blacks, hispanics, and other minorities in the high-risk categories? Is the FDIC prepared for an avalanche of Civil Rights suits based upon its proposed classification? Is the FDIC prepared to reimburse banks that follow the FDIC suggestion to categorize "risky" customers and are then sued by minorities under the Civil Rights Act? Or, as is more likely, is the FDIC prepared to punish banks that have proportional overrepresentation of minorities in the high-risk categories?
No rational basis: The deposit and withdrawal of funds of unknown source (provided the cash is not counterfeit) has no effect upon the soundness or the reputations of FDIC-insured banks and poses no threat to the funds of their customers. FDIC asserts, without supporting evidence, that their new required monitoring and reporting protects the reputation of the bank. But, clearly the proposed rules are intended to promote, not the interests of FDIC-insured banks or their customers, but the ability of the federal government to identify possibly money-laundered funds that the federal government can seize, thus increasing the federal government's revenues from forfeitures. Requiring that banks act as government law-enforcement investigators for determining who among their customers may have committed crimes involving money (and most crimes do) has no rational relation to FDIC overseeing the carrying out of fiduciary responsibility by FDIC-insured banks to bank owners and bank depositors. Under this rationale, the federal government could demand that General Motors monitor all customers' purchasing histories and report anything "suspicious" on the basis that some of the money being used to purchase vehicles is obtained illegally, some vehicles being purchased will be used as getaway cars from robberies at public buildings or for running over IRS agents, and some vehicles will be used to deliver illicit drugs, etc. etc. The FDIC has a low profile, however, so most Americans would not be expected to know about being monitored under this proposed "Know Your Customer" program. However, we intend to use our free speech and free press rights under the First Amendment to inform as many people and civil liberties organizations as possible (a "Know Your Government" program) about this FDIC-proposed outrage.
Agents of the government:
Furthermore, if bank facilities and/or employees are going to be commandeered to provide law-enforcement services for the federal government by actively looking for and investigating supposedly "suspicious" customer transactions, then there is a very serious constitutional question of whether the bank becomes thereby an agent of the government and must meet all constitutional standards. A recent Ninth Circuit court decision (Berger v. Hanlon, 129 F. 3d 505, 13 Nov. 1997) ruled against CNN in a suit for damages, stating that TV news crews who are invited to accompany police on raids are considered governmental agents and must meet constitutional standards. Banks required to perform searches and seizures of customers' private information for the FDIC cannot be allowed to do so without the full protections of the Constitution against invasion of customers' privacy, unreasonable searches and seizures, and other protected rights. At the very least, bank customers have the right to be individually fully informed of the FDIC rules before the institution of federal government required monitoring and reporting and should be fully informed of the procedures to be used by their bank in monitoring their account activities. Just as citizens have the right to refuse searches of their cars requested by police, citizens ought, in logic and in reason, to have the right to refuse searches of their private financial information otherwise unavailable to the government. The government would then be free to seek warrants (as defined by the Fourth Amendment) to obtain such data on the basis of probable cause.
In Kolender v. Lawson, 461 U.S. 944 (1983), the U.S. Supreme Court expressly said that for a government official to demand ID from a law-abiding person is unconstitutional. There is a strong argument, then, that the FDIC's proposal to require that records of a person's ID and private financial transactions be turned over by a bank to an FDIC official within 48 hours of the government's demand is also unconstitutional.
Disparate Impact on Small Banks and Small Businesses
Small businesses, particularly those frequently or usually dealing in cash, such as hardware stores, gas stations, beauty salons, convenience stores, liquor stores, auto repair shops, bail bonds, and pawnshops, would be particularly likely to be investigated under this proposed rule. Yet such businesses (particularly those in inner cities) are more likely to be owned by minorities than are larger businesses. Hence, the proposed rule will have a disparate impact on minority-owned small businesses.
Moreover, it is not as though this bank "service" (eg. detailed monitoring and reporting of customers' financial transactions, sources of funds, etc., as specified in the proposed rule) will have no cost to the bank or its customers. The bank is likely to pass along these not insignificant costs to its owners and customers in the form of lower returns on invested capital for owners and lower interest rates paid or reduced services to customers. Small banks and small depositors will be hurt more than large banks and large depositors by these costs. Because of the particularly high costs likely to be involved in monitoring "high risk" small business customers in inner city areas, this rule will have a severe chilling effect on the opening or maintaining of banks and small businesses in those areas.
EXHIBIT 1 (ATTACHED):
Attached as Exhibit 1 is a photocopy of an article, "Privacy Concerns Spark Criticism of Bank Rule" (The Wall Street Journal, Dec. 10, 1998) in which it was reported that the FDIC has received nearly 3,000 complaints as of December 9, 1998 against the above described proposed FDIC rule. The article describes complaints based upon privacy, searches and seizures in violation of the Fourth Amendment, and the conscription of bankers as government law enforcement agents.
According to the article, "The proposed rule ... was meant to formalize procedures that many institutions have already had in place for years." We ask the FDIC to identify the banks that have already put these unconstitutional procedures in place at the behest or suggestion of the FDIC (or any other governmental agency) and to accept no further transmissions of information obtained from these banks under these unconstitutional "Know Your Customer" programs until such time as constitutionally required due process procedural safeguards have been put in place to, among other things, protect the innocent from unreasonable federal government searches and seizures.
Moreover, if the proposed rule is only "meant to formalize procedures that many institutions have already had in place for years," then the FDIC is in violation of the "due process" requirements of the Constitution, as well as the Administrative Procedure Act, for establishing the "informal" procedures in the absence of proposing the rule in the Federal Register and allowing for Public Comment.
Action: Notice of Proposed Rulemaking
We ask that the FDIC withdraw the proposed rule. We also ask the FDIC to stop unconstitutionally collecting information from any extant "Know Your Customer" programs.
Comments submitted by:
___________________
date
________________________
Durk Pearson
Sandy Shaw
___________________________
People for the Constitution
PO Box 3666
Tonopah, NV 89049
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