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FDA published a final rule concluding that dietary supplements containing ephedrine alkaloids (ephedra) present an unreasonable risk of illness or injury under conditions of use suggested or recommended in the labeling, or if the labeling is silent, under ordinary conditions of use, and are therefore adulterated under Section 402(f)(l)(A) of the Federal Food, Drug, and Cosmetic Act.
On December 30, 2003, FDA issued a consumer alert on dietary supplements containing ephedrine alkaloids. The purpose of the consumer alert was to let consumers know as quickly as possible about FDA's determination. In addition, FDA sent letters to manufacturers who market such supplements, stating that FDA was preparing to issue a final rule declaring that such products present unreasonable risks. The purpose of the letters was to advise such manufacturers and distributors that when the rule becomes effective (60 days after publication), FDA may take enforcement action against them or the products if they do not cease distribution of the products.
Today, FDA is issuing a final regulation declaring that dietary supplements containing ephedrine alkaloids are adulterated because they present an unreasonable risk.
They have to take steps to ensure that they will be in compliance with the regulation once it becomes effective. We hope that many responsible firms will stop marketing dietary supplements containing ephedrine alkaloids right away, as a number of companies have done already. We want to be clear, however, that all firms will have to comply with the new regulation upon its effective date in 60 days. Firms that fail to cease distribution of their products by the effective date of the rule will face the possibility of FDA enforcement action without further notice.
That is, essentially, what the rule will do. The rule concludes that dietary supplements containing ephedrine alkaloids present an unreasonable risk to the public health and are adulterated under Section 402(f)(1)(A) of the FD&C Act.
The law that governs how FDA can regulate dietary supplements, the Dietary Supplement Health and Education Act (DSHEA), requires FDA to bear the burden in determining that a lawfully marketed dietary supplement presents a significant or unreasonable risk and should be removed from the market. In contrast to drugs, which must be proven safe and effective to be marketed, DSHEA requires FDA to develop evidence after the supplements are already on the market that a dietary supplement presents an "unreasonable risk of illness or injury." FDA has no authority to require any studies of safety or effectiveness for dietary supplements. FDA first proposed regulating ephedra in 1997, but commenters including the U.S. General Accounting Office generally believed that FDA had not developed sufficient evidence for certain actions proposed. We were determined to make our current decisions based upon the best available scientific evidence. In large part this came from the recent RAND analysis and a careful review of the Boozer et al. 6-month clinical study [which were not available to us until the last several months]. Earlier this year, the Agency published a Federal Register (FR) notice reopening the comment period on its 1997 proposed rule on dietary supplements containing ephedrine alkaloids to seek comment on new scientific evidence about the risks of these products and on a proposed warning statement for the labels of these products. The FR announcement also sought comments on whether, in light of current information, FDA should determine that dietary supplements containing ephedrine alkaloids present a significant or unreasonable risk of illness or injury under the conditions of use recommended or suggested in labeling, or under ordinary conditions of use if the labeling is silent. In order to make the determination regarding unreasonable risk, FDA had to examine the best available scientific evidence and take it into account in assessing whether the product's known or reasonably likely risks outweigh its known or reasonably likely benefits.
We sought comment from health professionals, the supplement industry, and the general public on any additional data on ephedra's safety, so that FDA could acquire the most complete picture possible of the product's potential risks, as a basis for appropriate regulatory action.
FDA has gone to great lengths to obtain and review all of the relevant scientific evidence on ephedra, as well as adverse event information, even though FDA's legal authorities to obtain this information are limited. FDA's analysis of the scientific evidence includes: a comprehensive evaluation of the scientific literature through 2002 conducted by the RAND Corporation; and evaluation of adverse event reports. FDA also reopened the 1997 proposed rule (see above Q&A) for comment in March 2003, soon after the release of an agency "white paper" outlining the types of evidence and the legal standards that the agency was considering as a basis for further action. FDA has since received and reviewed tens of thousands of comments, and will include its formal evaluation of all relevant comments in the final rule. Completing a major new rule on a never-before used legal standard with limited agency authorities and a significant burden of proof is difficult and time-consuming. FDA has worked as quickly as possible to complete the rule in a way that will stand up in court and thus will provide lasting protection for the public health.
While we have been preparing our forthcoming rule, we have been very active in protecting the public health through a series of high profile enforcement actions aimed at addressing a real public health danger. In conjunction with FDA's enforcement actions and other public activities involving ephedra, entire categories of ephedra products have been withdrawn from the market, and many manufacturers have withdrawn as well. Enforcement actions include inspections that resulted in voluntary compliance, voluntary recalls, warning letters, seizures and injunctions, and joint enforcement actions with FTC and DOJ. (More detail on these actions can be found at http://www.fda.gov/ola/2003/dietarysupplements1028.html.
Examples of prominent FDA enforcement and outreach activities in this area include:
In addition to the above enforcement actions:
Other examples of FDA's continued outreach efforts to promote the safe use of dietary supplements include:
In conjunction with all of these actions, ephedra use by consumers has declined significantly, and many firms have reduced their marketing of ephedra-containing products.
The agency chose to do a rule in this case because it the most efficient and powerful way to achieve successful enforcement of this provision against numerous companies. It will apply to all types of currently-marketed dietary supplements containing ephedrine alkaloids, not individual products.
FDA has a variety of enforcement possibilities including seizure of the product, injunction against the manufacturers and distributors of such products, and criminal prosecution of violators.
The rule as published will be a final rule. In accordance with 5 U.S.C.801-808, the rule will become effective 60 days after publication so as to allow for congressional review.
FDA is confident that it has a clear legal basis for taking effective action to protect consumers under the "unreasonable risk" standard. FDA does not believe that it is necessary to look to other authorities to take the action that it has taken today.
Through a series of actions. In 1997, FDA first proposed a rule on dietary supplements containing ephedra including a warning statement on these products. It was modified in 2000. Since publication of this proposal, new scientific evidence has come to light. To solicit comments on this new evidence as well as on a proposed warning statement, in February 2003 FDA published a Federal Register notice outlining FDA's concerns and reopening the comment period. The final rule comes as a result of public comments, literature review, adverse event reports, scientific studies and information sent to the docket.
The rule applies to all dietary supplements that contain a source of ephedrine alkaloids, such as ephedra, Ma huang, Sida cordifolia and pinellia.
Essentially all currently marketed dietary supplements that contain ephedrine alkaloids will be affected by the rule. The scope of the rule does not pertain to traditional Chinese herbal remedies. It generally doesn't apply to products like herbal teas that are regulated as conventional foods. Ephedra is not Generally Recognized as Safe (GRAS) for foods and not approved for use as a food additive.
The FDA is aware of dietary supplements that are marketed as substitutes for dietary supplements containing ephedrine alkaloids. It is not clear how widely they are available. To the extent that these products are brought to our attention, we will evaluate them in the same manner as all other dietary supplements.