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,

NOTICE: The "Durk Pearson & Sandy Shaw Life Extension News" is for informational purposes only. Its contents are not intended as advice for the diagnosis, treatment, or cure of any medical condition. Pearson & Shaw are scientists, not doctors. If you have a medical condition, see a physician. Durk Pearson & Sandy Shaw® do not own any part of any dietary supplement company. They license their formulations and receive royalties on sales. The formulations they design and use are those which contain their names on the label.