FDA Takes Second Shot at Ephedra

FDA Takes Second Shot at Ephedra
by Marc S. Ullman, Esq.

With the publication of the April 3, 2000 Federal Register, the Food and DrugAdministration (FDA) announced it was withdrawing "certain provisions of a proposedrule . . . relating to dietary supplements containing ephedrine alkaloids" (ephedra).Among the provisions of the proposed rule which the FDA stated it was no longer pursuingwere restrictions on the daily dosage of ephedrine alkaloids and the duration for whichephedrine products could be recommended for use. This action made official what hadlargely been seen as inevitable following the Aug. 4, 1999 report issued by the GeneralAccounting Office (GAO). The report critiqued the FDA's proposal for a lack of"transparency"--a failure to adequately explain the basis for the proposedrestrictions on ephedra use. Among the most critical of GAO's cited deficiencies was FDA'sreliance on numerous adverse event reports (AERs) without any critical examination forreliability.

While the initial reaction to FDA's April 3 announcement was that the Agency was infull retreat, the likely explanation is that FDA is undertaking a tactical fallback andreorganizing for a new regulatory initiative. There is evidence that a renewed assault onephedra supplements should be expected. This is noted by the release of several statementsby FDA within the Federal Register announcement itself, a second FederalRegister document published the same day, a "Guidance For Industry" issuedin conjunction with the partial withdrawal, and the release of 140 new AERs related toephedra.

First, the Federal Register notice announcing the withdrawal noted that severalsignificant portions of the initial proposal remain alive. These include the ban oncombining ephedra with any other substance known to have a stimulant effect (e.g.,caffeine and yohimbine). This would effectively ban the plethora of ephedra weight controlproducts currently on the market. The proposal to require a warning statement on the labelof all dietary supplements containing ephedrine alkaloids also remains viable. This wouldadvise consumers that supplements containing ephedrine alkaloids can cause side effectsincluding dizziness or severe headache, which may be early symptoms of more seriousadverse events such as hypertension or stroke.

Second, the April 4 Federal Register also contained an announcement that FDAplanned to release 140 new adverse event reports related to ephedra. As a response to theGAO's critique of the earlier series of reports, FDA also stated it had contracted for acomprehensive review of the new AERs by "outside scientific and clinicalexperts." One week later, the Agency posted a listing of all 1,400 AERs on its Webpage. (The FDA concluded that 22 of the AERs were directly attributable to the use ofephedra and that in 38 cases, the evidence was "supportive" of a link betweenthe AER and the use of an ephedra supplement.)

FDA has made the data underlying these conclusions available through the Freedom ofInformation Act, and announced that it will consider any other information on these AERsthat is submitted to it within the next 45 days.

Industry trade associations have criticized this time frame, arguing that it is notlong enough to allow for serious analysis and review of FDA's conclusions. MichaelMcGuffin, president of the American Herbal Products Association (AHPA), said, "FDAhas had the information on these adverse events since March 31, 1999--over one year. Tonow give the industry 45 days to respond does not seem to allow for a thorough analysis.In addition, FDA has suggested that the next public meeting on ephedra regulations willinvolve the public health service and we are concerned that the Agency may not allow theindustry the time it needs to prepare a position in this very serious matter."

Finally, on March 31, as it announced its intention to publish the April 3 FederalRegister notices, FDA also released a "Guidance for Industry, Street DrugAlternatives," reminding the industry that it is not permissible to sell a dietarysupplement as an alternative to an illegal drug. While this is a legally sound position,FDA's decision to link this document with ephedra supplements is questionable. Whileephedra "street drug knock-offs" may have been a concern several years ago, noneof the recently released AERs appears to be related to this type of product. Thus, theAgency's intent to link the Guidance to its actions on ephedra seems to be part of acampaign to generate momentum in support of an effort to revive the proposed regulations'restrictions on ephedra use.

In the next several months we can expect further FDA action. The Agency's recentdecision to withdraw part of its ephedra proposal, while appearing to be a favorable moveon the surface, is more likely to be just the first step in a renewed effort to restrictthe manner in which this herb can legally be marketed.

Marc Ullman is a partner in New York-based Ullman, Shapiro and Ullman LLP.