03.01.04
On December 30, 2003, FDA announced that within weeks it would publish a final rule regarding a ban on dietary supplements containing ephedrine alkaloids (ephedra). At the same time, FDA issued a Consumer Alert in which it recommended consumers stop buying and using these products immediately. In addition, letters were sent to over 60 companies that sell dietary supplements containing ephedra to give them advance notice of the final rule in order to facilitate their earliest compliance, indicating that FDA would begin strictly enforcing the rule once it was final.
Just over one month later, on February 6, 2004, FDA issued the final rule stating that supplements containing ephedra present an unreasonable risk of illness or injury to those taking them. Under the Dietary Supplement Health & Education Act (DSHEA), FDA said it has the power to remove a dietary supplement from the market if it presents a significant or unreasonable risk of illness or injury when used according to its labeling or under ordinary conditions of use. FDA’s final regulation presents a framework for applying this unique statutory standard and represents the first time a supplement has been removed from the market under DSHEA.
FDA said it came to this conclusion after reviewing evidence about ephedra’s pharmacology; peer-reviewed scientific literature on ephedra’s safety and effectiveness; adverse event reports and a report by the RAND Corporation. In addition, the agency reviewed tens of thousands of public comments on the agency’s request in March 2003 for information about ephedra-associated health risks.
According to FDA, the rule will become effective April 12th, after which any companies caught distributing or manufacturing ephedra-containing dietary supplements will be subject to seizure, injunction or criminal prosecution. In effect, the rule will prohibit the sale of ephedra either alone or in combination with other ingredients in supplements. However, the scope of the rule does not pertain to traditional Chinese herbal remedies or products like herbal teas.
Following the announcement made on December 30th, both Health & Human Services (HHS) Secretary Tommy Thompson and FDA Commissioner Mark McClellan fielded questions, many of which were directed at the possibility of reworking DSHEA. To this issue, Commissioner McClellan commented, “We have done all we can to fulfill the requirements of the dietary supplement law. We’ve gone the whole nine yards to collect and evaluate all the possible evidence to reach a conclusion about an unreasonable risk to the public health. So I do think that when FDA reaches a conclusion like this, we ought to be able to carry it out to provide the protection that Americans need. And we will be doing our best to defend this in court. And if that’s not sufficient, it may be time to reexamine [DSHEA].” Similarly, Secretary Thompson said, “This is the first time that a supplement like this has been taken off the market. It’s a long and extensive process, but we followed it and we did everything necessary. We crossed the t’s and dotted the i’s and we will defend it vigorously in court if need be.” (At press time it was unclear whether or not the ephedra ban would be challenged in court. A New York Times article released the day the final rule was announced suggested only that one company—Metabolife—was reviewing the rule and assessing its options.)
In mid-January Commissioner McClellan revisited dietary supplement issues during a presentation he gave at the University of Mississippi. According to the American Herbal Products Association (AHPA), Silver Spring, MD, the main part of the Commissioner’s presentation included clarifications of numerous issues regarding supplements. Specifically, AHPA said, the Commissioner highlighted the importance of supplements, specifically vitamins and minerals, to human health. He also explained that the dietary supplement law functions differently from U.S. drug law in that manufacturers of dietary supplements are not required to perform safety and efficacy studies of their products prior to marketing them. “There are some good reasons for this,” he said. “Long experience suggests that many dietary supplements appear to be very safe, and because these products occur naturally, it is harder to provide the kind of patent exclusivity that can make for very costly investment in proving the safety and effectiveness of a new synthetic drug.”
As a result of the ban on ephedra, there has also been speculation that FDA, when finished with ephedra, will pursue other dietary ingredients being used in weight loss products as “ephedra substitutes.” At the FDA press conference announcing the impending ephedra ban, Commissioner McClellan commented, “It will definitely be something we’ll be watching.” Later, at the University of Mississippi presentation, he singled out bitter orange (citrus aurantium), aristolochic acid and usinic acid as ingredients, which FDA would more closely examine in the near future. In its final rule announcement on February 6th, however, FDA said it is aware of dietary supplements marketed as substitutes for those containing ephedrine alkaloids but was 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,” the agency said.
As we went to press, NNFA, Newport Beach, CA, released information regarding some of the major implications of the ban. “All dietary supplements, not just ephedra, will be subject to a risk/benefit safety analysis for the first time—in the past, only risk of injury was relevant,” the association said. “Industry can expect further rulemaking instead of waiting for case-by-case enforcement when a widely publicized ingredient safety issue arises. FDA added a new section to the Code of Federal Regulations for ‘Dietary Supplements that Present a Significant or Unreasonable Risk.’ FDA chose this route to cast a wider net over all purveyors.” NNFA noted further that FDA’s lengthy scientific discussion raises the bar on safety substantiation.
Just over one month later, on February 6, 2004, FDA issued the final rule stating that supplements containing ephedra present an unreasonable risk of illness or injury to those taking them. Under the Dietary Supplement Health & Education Act (DSHEA), FDA said it has the power to remove a dietary supplement from the market if it presents a significant or unreasonable risk of illness or injury when used according to its labeling or under ordinary conditions of use. FDA’s final regulation presents a framework for applying this unique statutory standard and represents the first time a supplement has been removed from the market under DSHEA.
FDA said it came to this conclusion after reviewing evidence about ephedra’s pharmacology; peer-reviewed scientific literature on ephedra’s safety and effectiveness; adverse event reports and a report by the RAND Corporation. In addition, the agency reviewed tens of thousands of public comments on the agency’s request in March 2003 for information about ephedra-associated health risks.
According to FDA, the rule will become effective April 12th, after which any companies caught distributing or manufacturing ephedra-containing dietary supplements will be subject to seizure, injunction or criminal prosecution. In effect, the rule will prohibit the sale of ephedra either alone or in combination with other ingredients in supplements. However, the scope of the rule does not pertain to traditional Chinese herbal remedies or products like herbal teas.
Following the announcement made on December 30th, both Health & Human Services (HHS) Secretary Tommy Thompson and FDA Commissioner Mark McClellan fielded questions, many of which were directed at the possibility of reworking DSHEA. To this issue, Commissioner McClellan commented, “We have done all we can to fulfill the requirements of the dietary supplement law. We’ve gone the whole nine yards to collect and evaluate all the possible evidence to reach a conclusion about an unreasonable risk to the public health. So I do think that when FDA reaches a conclusion like this, we ought to be able to carry it out to provide the protection that Americans need. And we will be doing our best to defend this in court. And if that’s not sufficient, it may be time to reexamine [DSHEA].” Similarly, Secretary Thompson said, “This is the first time that a supplement like this has been taken off the market. It’s a long and extensive process, but we followed it and we did everything necessary. We crossed the t’s and dotted the i’s and we will defend it vigorously in court if need be.” (At press time it was unclear whether or not the ephedra ban would be challenged in court. A New York Times article released the day the final rule was announced suggested only that one company—Metabolife—was reviewing the rule and assessing its options.)
In mid-January Commissioner McClellan revisited dietary supplement issues during a presentation he gave at the University of Mississippi. According to the American Herbal Products Association (AHPA), Silver Spring, MD, the main part of the Commissioner’s presentation included clarifications of numerous issues regarding supplements. Specifically, AHPA said, the Commissioner highlighted the importance of supplements, specifically vitamins and minerals, to human health. He also explained that the dietary supplement law functions differently from U.S. drug law in that manufacturers of dietary supplements are not required to perform safety and efficacy studies of their products prior to marketing them. “There are some good reasons for this,” he said. “Long experience suggests that many dietary supplements appear to be very safe, and because these products occur naturally, it is harder to provide the kind of patent exclusivity that can make for very costly investment in proving the safety and effectiveness of a new synthetic drug.”
As a result of the ban on ephedra, there has also been speculation that FDA, when finished with ephedra, will pursue other dietary ingredients being used in weight loss products as “ephedra substitutes.” At the FDA press conference announcing the impending ephedra ban, Commissioner McClellan commented, “It will definitely be something we’ll be watching.” Later, at the University of Mississippi presentation, he singled out bitter orange (citrus aurantium), aristolochic acid and usinic acid as ingredients, which FDA would more closely examine in the near future. In its final rule announcement on February 6th, however, FDA said it is aware of dietary supplements marketed as substitutes for those containing ephedrine alkaloids but was 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,” the agency said.
As we went to press, NNFA, Newport Beach, CA, released information regarding some of the major implications of the ban. “All dietary supplements, not just ephedra, will be subject to a risk/benefit safety analysis for the first time—in the past, only risk of injury was relevant,” the association said. “Industry can expect further rulemaking instead of waiting for case-by-case enforcement when a widely publicized ingredient safety issue arises. FDA added a new section to the Code of Federal Regulations for ‘Dietary Supplements that Present a Significant or Unreasonable Risk.’ FDA chose this route to cast a wider net over all purveyors.” NNFA noted further that FDA’s lengthy scientific discussion raises the bar on safety substantiation.