Fragen/Antworten zum Thema Ephedra von der FDA

Anarchill · Anmeldedatum: 05.08.2003 Beiträge: 74

Ich denke mal, dass das interessiert. Ist der O-Text von der FDA Page.

Questions and Answers about FDA's
Actions on Ephedra Dietary Supplements
Dec. 30, 2003

What did FDA do today?

FDA issued a consumer alert on dietary Supplements containing Ephedrine alkaloids, as well as letters to manufacturers who market such supplements, that regulatory action to restrict sales of these products is imminent because they pose an unreasonable health risk. FDA intends to publish a final rule on Ephedra in the coming weeks. The rule will provide the basis for FDA's conclusion that dietary Supplements containing Ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use in the labeling (or if no suggested conditions than ordinary use) and are therefore adulterated under Section 402(f)(l)(A) of the Federal Food, Drug, and Cosmetic Act.

What is the purpose of the consumer alert?

To let consumers know as quickly as possible about FDA's regulatory determination, as the agency completes the administrative actions required under the dietary Supplement law.

What is the purpose of the letters?

FDA is notifying manufacturers and distributors of the publication of this rule, which becomes final 60 days after publication, and advising them that, at that time, FDA may take enforcement action against them or the products if they do not cease distribution of the products.

Are you banning Ephedra?

That is, essentially, what the rule will do. The rule will conclude that dietary Supplements containing Ephedrine alkaloids present an unreasonable risk to the public health and are adulterated and unacceptable under Section 402(f)(1)(A) of the FD&C Act.

Why didn't FDA reach this conclusion sooner?

The law that governs how FDA can regulate dietary supplements, the Dietary Supplement Health and Education Act (DSHEA), requires FDA to do a lot of hard work with limited tools in order to determine that a dietary Supplement is too unsafe to be marketed. In contrast to drugs, which must be proven safe and effective to be marketed, DSHEA requires FDA to develop evidence post marketing that a dietary Supplement presents an "unreasonable risk of illness or injury." But FDA has no authority to require any studies of safety or effectiveness, or even to obtain reports of adverse events from manufacturers. 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 action. There is now considerably more evidence available on Ephedra's risks and benefits than when the proposed rule was published. 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 FDA's view, "unreasonable risk" implies a risk-benefit calculus. In order to make such a calculus, the FDA had to examine the best available scientific evidence and take it into account in assessing whether the product's known or suspected risks outweigh its known or suspected 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 further regulatory action.

FDA's actions are to be reviewed under a strict judiciary standard that requires the agency to provide as thorough of a foundation as possible for its regulatory action. This regulation will be the first time ever that the standards in the dietary Supplement law, now ten years old, have been used to impose major restrictions on the sale of a dietary supplement.

What has FDA been doing to meet the requirements to take action under the dietary Supplement law?

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; a review of subsequent studies including evaluation of a major study by independent academic experts; and evaluation of adverse event reports. FDA also reopened the 1997 proposed rule (see above Q&A) for comment in March 2003, in conjunction with 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 of these 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. Given all of this effort, if FDA's action to protect the public health against an unreasonable risk cannot be sustained, then the dietary Supplement law will clearly need to be reconsidered.

What have you been doing in the meantime to protect 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, criminal enforcement, 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 outreach activities in this area include:

* In October 2001, FDA brought a seizure action against $2.8 million worth of finished drug products containing synthetic Ephedrine hydrochloride that were labeled as dietary supplements. United States v. 1009 Cases . . . E'ola International AMP II, No. 2:01CV - 820C (D. Utah filed Oct. 22, 2001). As a result of this seizure, in 2002, the manufacturer signed a consent decree agreeing to the condemnation and destruction of the seized products and prohibiting it from manufacturing or distributing violative Ephedrine hydrochloride products. In other actions, we have sent warning letters to multiple firms that were marketing products containing synthetic Ephedrine alkaloids as dietary supplements, resulting in the removal of the illegal products from the marketplace.
* On February 28, 2003, based on the conclusions of the RAND study, FDA warned 26 firms to cease making unproven claims that Ephedrine-containing dietary Supplements enhance athletic performance. Since performance enhancement was one of the two principal ways in which Ephedra has been marketed, the impact of these warning letters has been substantial. These products have generally complied with our letters. FDA continues to monitor them to ensure they comply with the law, and will take further enforcement actions as necessary.
* On March 31, 2003, FDA also took new enforcement action against firms marketing street drug alternative products, some of which contained Ephedra or other sources of ephedrine. FDA sent warning letters to eight firms. The majority of the firms stopped selling these products or removed the street drug alternative claims for these products.

In addition to the above enforcement actions:

* On March 7, 2003, FDA announced proposed rules to establish manufacturing and labeling standards for all dietary supplements. FDA's proposed rule is intended to reduce risks associated with adulterated or misbranded dietary Supplement products. FDA solicited comments from the public and industry on this proposal. Written comments were received until August 11, 2003, and FDA expects to finalize the rule in the coming year.
* FDA has also taken new steps to educate the public about dietary Supplements containing ephedra. In February 2003, in proposing a warning label and possible further regulatory action for Ephedra products, FDA described adverse events that have been associated with Ephedra and particular risks faced by persons with certain medical conditions. The proposed label warns about an association of Ephedra use with serious adverse events, including heart attack, seizure, stroke, and death; cautions that the risk can increase with the dose, with strenuous exercise, and with other stimulants such as caffeine; specifies certain groups (such as women who are pregnant or breast feeding) who should never use these products; and lists other conditions, such as diseases and the use of certain medications, that rule out the use of Ephedrine alkaloids.

Other examples of FDA's continued outreach efforts to promote the safe use of dietary Supplements include:

* Expanded use of our Web site to communicate critical information and useful strategies about dietary Supplements to industry and consumers. Examples include FDA Talk Papers, articles in the FDA Consumer magazine, Fact sheets, etc. Other examples of these materials include CFSAN's "Overview of Dietary Supplements" and "Tips for the Savvy Supplement User." Industry has access to guidance documents, such as FDA's "Statement of Identity, Nutrition Labeling, and Ingredient Labeling of Dietary Supplements Small Entity Compliance Guide" which discusses compliance with the Agency's regulations implementing DSHEA's labeling provisions.
* FDA continues to work closely with other Federal and state entities including FTC, DEA, Customs, etc. involved in combating health fraud. An example is our joint FDA/FTC project entitled, "Operation Cure-All", which is aimed at halting the Internet promotion of products, including dietary supplements, that make false or misleading disease claims. This year, FDA has issued more than five times as many warning letters for misleading and unsubstantiated claims involving dietary supplements, including misleading claims about Ephedra products.

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.

Why a rule?

Because the FDA intends for Ephedra-containing dietary Supplements to stay off the market. A rule is the most efficient and powerful way to achieve successful enforcement. It will apply to all types of currently-marketed dietary Supplements containing Ephedrine alkaloids, not individual products. It will provide a far stronger foundation for sustaining FDA's regulatory action in court, because it will comprehensively lay out the scientific basis for FDA's action. In addition, this rule will, for the first time, articulate the legal standard by which we can successfully undertake and enforce the agency's actions to protect the public health under the challenging standards of DSHEA.

What types of enforcement actions are possible?

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.

Is this rule final? Why wait 60 days?

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.

By sending out letters right now we're sending a strong and unambiguous signal that responsible retailers should stop selling these products as soon as possible and consumers should stop buying and using Ephedra products right away. The 60 days has to do with the Congressional Review Act.

Why does FDA believe "Imminent Hazard" hasn't been met in this case?

In 21 CFR 2.5, Imminent Hazard is defined, in part, as: "Within the meaning of the Federal Food, Drug, and Cosmetic Act an imminent hazard to the public health is considered to exist when the evidence is sufficient to show that a product or practice, posing a significant threat of danger to health, creates a public health situation (1) that should be corrected immediately to prevent injury and (2) that should not be permitted to continue while a hearing or other formal proceeding is being held."

The "imminent hazard" is a much higher legal threshold than "unreasonable risk." While it is challenging to acquire and evaluate the scientific evidence related to Ephedra under the dietary Supplement act, FDA is confident that it has a clear legal basis for taking effective action to protect consumers under the "unreasonable risk" standard. FDA is much less confident that regulatory action under the "imminent hazard" standard would be successful in keeping Ephedra products off the market.

When will we see publication of this rule?

In the coming weeks. It is now under review. We don't have an exact date.

How did FDA arrive at this final rule?

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.

What types of products are subject to the rule?

Dietary Supplements that contain a source of Ephedrine alkaloids, such as ephedra, Ma huang, Sida cordifolia, and pinellia.

Are all products containing Ephedra affected?

Essentially all currently marketed dietary Supplements will be affected by the rule. 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.

What do the firms that received the letters have to do next?

They have to take steps to ensure that they will be in compliance with the law once it becomes effective. We hope that many responsible firms will stop marketing dietary Supplements containing Ephedra right away, as a number of companies have done already. But we want to be clear that all firms will have to comply with the new regulation. Firms 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.

If FDA has concluded that these products are unsafe, why are they going to remain on the market after the final rule is issued?

Because this is what the dietary Supplement law requires to take effective action against broad classes of products. The law places the burden on the FDA to prove that a dietary Supplement creates an unreasonable risk, without requiring companies that market Ephedra-containing products to provide clear evidence on their safety and effectiveness. To enforce a prohibition on the marketing of dietary Supplements containing Ephedra by any company, the agency can best meet this burden of proof in a way that receives the most legal deference by laying out all of the evidence supporting the regulatory actions and responses to public comment in a formal rule. Otherwise the agency's expert staff would have to justify the scientific basis for the agency's actions in multiple legal proceedings brought by individual manufacturers, having to review the evidence and public comments in each and every one of these cases, making it more likely that Ephedra products would remain on the market. A final regulation permits effective action against entire classes of products, as the agency believes is necessary for Ephedra-containing dietary supplements. In general, major regulations involving issues like Ephedra safety that are not new cannot take effect until a minimum of 60 days after publication.