A Utah federal court has barred FDA from enforcing its ban on ephedra products containing 10 mg or less of ephedrine alkaloids per daily dose.

The ruling allows Nutraceutical Corp. to resume marketing its low-dose ephedra product.

FDA issued its final rule banning the sale of ephedrine-containing products in February 2004. The agency determined the ingredient posed an "unreasonable risk" to users through a risk-benefit analysis (¹ Also see "Ephedra Rule Cites Lack Of Safety Data In Vulnerable Subjects" - Pink Sheet, 16 February, 2004., p. 10).

Nutraceutical Corp. filed suit in May 2004, alleging that FDA's use of a risk-benefit analysis to substantiate a ban of the ingredient violates the Dietary Supplement Health & Education Act (² Also see "Ephedra Ban Makes Food, Supplement Regs “Unworkable” – Lawsuit" - Pink Sheet, 10 May, 2004., p. 21).

If upheld, the final order in favor of Nutraceutical Corp. could make it more difficult for FDA to apply a risk-benefit calculus in future supplement actions.

The decision also could serve as precedent for other litigation targeting the ban.

The court agreed with plaintiffs that the risk-benefit analysis "adds language not intended by Congress and has the effect of shifting the burden of proof from the government to the manufacturers" of ephedra supplements.

Imposition of a risk-benefit analysis would require marketers to "demonstrate a benefit as a pre-condition to sale, and that is contrary to Congress' intent," the court found. Since DSHEA regulates supplements as foods, supplement marketers are not required to prove a product's benefit prior to sale.

In addition to its decision on the agency's risk-benefit method, the court took issue with the data provided by FDA to substantiate its finding that all doses of ephedra pose a health risk.

FDA did not provide "specific data involving the oral ingestion of 10 mg per day" of ephedra-containing supplements, the court noted. The ruling points out that DSHEA requires FDA to demonstrate a product's unreasonable risk by proving that the risk exists "under conditions of use recommended or suggested in labeling."

"To declare all [ephedra supplements] adulterated, as it has done, the FDA must prove that any dose amount, no matter how small, presents a significant or unreasonable risk of illness or injury," the court explained.

The reference provided by FDA on the effects of low-dose ephedra use was a review of a study of intravenous injections of epinephrine, which the author of the review used to derive the potential effects of orally ingested ephedrine.

The author used a "hypothetical mathematical model to perform a pharmacokinetic analysis of the effects of ephedrine alkaloids," the court noted. The review determined that the effects of using 1.5 mg of ephedrine every four hours (9 mg daily) would cause increases in heart rate and systolic blood pressure.

However, the review also noted that epinephrine is more potent that ephedrine, the court pointed out. In addition, the ruling said that acceptance of the review would be "applicable only upon acceptance of [the reviewer's] mathematical model," and noted that the negative health effects in the study would result from "chronic" intake, "which is not the condition of use suggested on the labeling" of Nutraceutical Corp.'s product.

The court further disagreed with statements in FDA's submissions that a safe dosage level of ephedra could not be identified. The agency provided an excerpt of the transcript from a Food Advisory Committee meeting in August 1996 in which several physicians and researchers stated they were unable to reach a conclusion on a safe dose of the botanical.

The court determined that "the statement that a safe level cannot be determined is simply not sufficient to meet the government's burden."

"The statute requires an affirmative demonstration of 'significant or unreasonable' risk at a particular dose level to support a finding of adulteration," the final rule states.

The court decision means that marketers of ephedra-containing supplements with a 10 mg daily dose or lower now are legally permitted to market their products, according to Jonathan Emord of the Washington, D.C. law firm Emord & Associates, which represented Nutraceutical Corp. in the case.

One challenge facing firms will be locating sources for the ingredient, Emord noted. Nutraceutical Corp. said it currently has no plans to sell ephedra..

However, the American Herbal Products Association pointed out that "FDA was not...specifically instructed [by the court] to refrain from acting against other brands that contain less then 10 mg of ephedrine while it reviews its current regulation."

The decision also does not reverse the laws banning ephedra in some states, such as California, Illinois and New York.

Emord contended that firms seeking to market an ephedra product containing more than 10 mg per daily dose technically would be able to do so under the ruling. However, FDA still has the authority to act against those companies on a case-by-case basis, he added.

FDA still is evaluating its options in moving forward with a response to the decision, a spokesperson said.

The agency could file an appeal, or could seek a stay of the court's order. If FDA decided to revise its final rule on the ephedra ban, it would have to publish a notice of proposed rulemaking in the Federal Register soliciting scientific evidence on ephedra, Emord said.

After gathering scientific evidence on the ingredient, FDA then would have to evaluate the evidence to determine the precise dose at which ephedra presents an unreasonable risk, and then re-write the rule according to that dosage.

The ruling "calls into question how the FDA applied the law in the case of ephedra," Sen. Orrin Hatch (R-Utah) commented.

"I do not believe it is a good example of how the government should resolve dietary supplement safety," he said, referring to ephedra's regulatory history.

The Council for Responsible Nutrition agreed that the ruling "demonstrates that DSHEA works, and that FDA will be held to the statutory standards of proof in the law."

The decision also "further underscores that dietary supplements are not to be treated as drugs...and that FDA must acknowledge those distinctions in its administrative and enforcement measures," CRN said.

Utah Court Overturns Ephedra Ban For Low-Dose Products

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