![]() |
![]() |
FDA Home Page | Search
FDA Site | FDA A-Z Index | Contact
FDA
JOHN M. TAYLOR
ASSOCIATE COMMISSIONER FOR REGULATORY AFFAIRS
FOOD AND DRUG ADMINISTRATION
BEFORE THE
COMMITTEE ON COMMERCE
UNITED STATES SENATE
OCTOBER 28, 2003
INTRODUCTION
Thank you Mr. Chairman, for this opportunity to testify at this hearing on dietary supplements and the
current regulations to protect American consumers from the potential adverse health risks associated
with the use of certain supplements. I am John M. Taylor, Associate Commissioner for Regulatory Affairs
at the Food and Drug Administration (FDA or the Agency). In my statement today, I will address FDA actions
to implement DSHEA, especially our regulations development, adverse event monitoring, and enforcement
posture. I will also address FDA actions on two major types of dietary supplements that are of current
concern, ephedra and steroid precursors. But first, let me provide you a short background on dietary
supplements.
BACKGROUND ON REGULATION OF DIETARY SUPPLEMENTS
Nearly half of the population of the United States uses “dietary supplements.”1
The Dietary Supplement Health and Education Act of 1994 (DSHEA) establish a unique regulatory framework
in an attempt to strike the right balance between providing consumers access to dietary supplements
that they choose to use to help maintain and improve their health, and giving the FDA the necessary
regulatory authority to take action against supplements or supplement ingredients that present safety
problems, make false or misleading claims, or are otherwise adulterated or misbranded. Although dietary
supplements are generally regulated as foods, there are special statutory provisions and implementing
regulations for dietary supplements that differ in some respects from those covering conventional foods.
Moreover, the regulatory requirements for dietary supplements also differ from those that apply to prescription
and over-the-counter (OTC) drug products.
Congress defined the term dietary supplement as a product that, among other things, is ingested, is intended to supplement the diet, is labeled as a dietary supplement, is not represented as a conventional food or as a sole item of a meal or the diet, and that contains at least one dietary ingredient. The dietary ingredients in these products may include vitamins, minerals, herbs or other botanicals, amino acids, and dietary substances such as enzymes. Dietary ingredients also can be metabolites, constituents, extracts, concentrates, or combinations of the preceding types of ingredients. Dietary supplements may be found in many forms, such as tablets, capsules, liquids, or bars. DSHEA placed dietary supplements in a special sub-category under the general umbrella of foods, but products that meet the drug definition are subject to regulation as drugs.
LABELING OF DIETARY SUPPLEMENTS
Under the Federal Food, Drug, and Cosmetic (FD&C) Act and FDA’s implementing regulations,
the label of a dietary supplement must include:
In addition, if the labeling includes a claim that the product affects the structure or function of the body, a claim of general well-being, or a claim of a benefit related to a classical nutrient deficiency disease, the product must also bear a disclaimer stating that FDA has not evaluated the claim and that the product is not intended to diagnose, treat, cure, or prevent any disease. If a product that is marketed as a dietary supplement includes claims that the product is intended for the use in the diagnosis, cure, mitigation, treatment, or prevention of a disease, it is considered a drug within the meaning of the Act.
DIETARY SUPPLEMENTS CONTAINING STEROID PRECURSORS
Because of the Committee’s interest in steroid precursors, let me discuss them now. FDA is aware
of a wide variety of products that contain steroid precursors. Some consumers ingest steroid precursors
because they believe these products boost testosterone levels and speed muscle growth.
Use of these products has grown dramatically in popularity in the United States. We have heard from athletic organizations, health care professionals and health organizations, and anti-drug abuse authorities about potential health risks that may be associated with their use. However, the scientific evidence about the benefits or adverse consequences of steroid precursors appears to be inconclusive at this time. These products are generally marketed as dietary supplements and targeted to athletes and body builders as performance enhancers. Some of these products are marketed for weight loss or as anti-aging products. While the majority of products containing steroid precursors are not promoted for disease treatment or prevention purposes, a minority of products may be promoted for therapeutic purposes and therefore are subject to regulation as drugs.
In addition, some steroid precursors are clearly outside the scope of the dietary supplement definition and are subject to regulation as drugs because they are intended to affect the structure or function of the body. For example, FDA considers tetrahydrogestrinone, or THG, the subject of what is rapidly becoming a major sports controversy, a new drug under FD&C. Our analysis demonstrates that this is a purely synthetic, non-naturally occurring, highly potent anabolic steroid. It is a designer steroid in the truest sense. It is directly derived, by simple chemical modification, from an anabolic drug that is explicitly banned by the U.S. Anti- Doping Agency. That drug, gestrinone, a synthetic product, is approved in Europe for the treatment of endometriosis, a painful condition of pre-menopausal women. Furthermore, THG is closely related, structurally, to trenbolone, a strong veterinary anabolic steroid approved in the U.S. to increase rate of weight gain and/or improved feed efficiency in beef cattle. Trenbolone is a controlled substance.
Steroid precursors marketed as dietary supplements present complex regulatory issues for FDA regarding the scope of the dietary supplement and drug definitions. FDA is still examining these issues and has not reached any formal conclusion about the status of steroid precursors as dietary supplements under the FD&C Act. Nevertheless, we understand that this is a public health issue that warrants our close attention. FDA is currently pursuing an evaluation of the legal and scientific uses that bear on the status of these kinds of substances and we hope to be able to address this matter more authoritatively in the future.
ADVERSE EVENT REPORTING
Now, let me turn to our discussion of dietary supplements. DSHEA’s regulatory framework is primarily
a post-market program, like much of food regulation. There is no pre-market approval requirement for
dietary supplements. Further, there is no requirement for manufacturers to provide evidence of product
safety to FDA prior to marketing a dietary supplement, unless the supplement contains a “new dietary
ingredient” (a dietary ingredient that was not marketed in the United States before October 15,
1994) that has not been “present in the food supply as an article used for food in a form in which
the food has not been chemically altered” (21 U.S.C. 350b(a)). In contrast, drug regulation involves
an extensive premarket evaluation of safety and effectiveness with explicit standards of evidence. This
evidence provides a basis to guide not only approval decisions but also conditions of use to manage
benefits and risks. In addition, there are post-market reporting requirements for drugs to support product
safety monitoring. These requirements do not exist for dietary supplements.
As a result, voluntary adverse event reports (AERs) are the primary means FDA has for identifying potential safety problems with dietary supplements. Under DSHEA, FDA must rely on AERs as a major component of its post-market regulatory surveillance efforts. Also, unlike drug regulation, FDA cannot compel reporting of adverse events by dietary supplement manufacturers.
In June 2003, FDA’s Center for Food Safety and Applied Nutrition (CFSAN) put in place the CFSAN Adverse Event Reporting System (CAERS) to monitor adverse event reports for foods, cosmetics, and dietary supplements. This state-of-the-art system compiles and analyzes any reports of consumer complaints and adverse events related to CFSAN-regulated products presented to FDA. Health care professionals and consumers voluntarily send submissions to CAERS. While voluntary reporting systems are estimated to capture only one percent of adverse events, they provide valuable signals of potential problems.
ENFORCEMENT
Protecting the public health has always been the Agency’s first responsibility. Consumers need
to have confidence in the safety and effectiveness of the products they use. Therefore, unsafe, ineffective,
or fraudulent products are a threat to the public health.
FDA is serious about its responsibility of ensuring that there is access to effective, safe, scientifically-based health products for our nation’s citizens. U. S. citizens must have access to truthfully labeled, safe, effective, and non-misleading health products.
At the core of FDA’s enforcement efforts is our commitment to enhance the legitimate manufacture, sale, and use of dietary supplements while protecting consumers against unsafe products, fraudulent labeling claims, and other illegal practices. Achieving these goals utilizes a number of strategies, including cooperation and coordination with other state, Federal, and international law enforcement agencies in protecting consumers against unapproved and potentially harmful products offered by Internet outlets, some of which are based abroad.
On December 18, 2002, FDA announced its “Better Health Information for Better Nutrition” initiative. The purpose of the initiative is to improve the health of consumers by providing them with scientifically accurate, FDA-approved information about the health effects of foods and dietary supplements. In undertaking this initiative, FDA recognized that false claims that mislead Americans both endanger the public health and undermine the goals of the FDA. Because FDA recognizes that efficient, effective enforcement is an essential component to ensure that such false and misleading claims do not take root in commercial distribution channels, FDA is prepared to take aggressive enforcement action to ensure that consumers have access to truthful and non-misleading information about products related to their health.
FDA’s commitment to continue its efforts to ensure that there is access to safe, scientifically sound medical products is demonstrated by the Agency’s enforcement actions to combat fraudulent, misbranded, and misleading dietary supplements. For example, over the last 15 months, FDA has witnessed the voluntary destruction of approximately $7.7 million of dietary supplements that were determined to be non-compliant with the FD&C Act and has monitored two voluntary recalls of dietary supplement products.
FDA also sent numerous Warning Letters to marketers of products represented as dietary supplements but whose products did not qualify as such because claims on them caused them to be misbranded and/or unapproved drugs. At least two of these Warning Letters were sent to firms whose products were marketed in lieu of approved drugs that were available to the public. For example, one made claims that its products were alternatives to vaccinations/immunizations against anthrax, measles, smallpox, and encephalitis; the other promoted its product as a natural alternative to Ritalin for ADHD. This calendar year, FDA also issued Warning Letters to 18 firms marketing coral calcium products as effective treatments or cures for a variety of disease conditions. In addition, FDA and the FTC warned website operators, manufacturers, and distributors who were making misleading or deceptive claims on the Internet regarding their products ability to prevent, treat, or cure SARS that they must cease making these impermissible claims. FDA also issued Warning Letters to 8 firms marketing “dietary supplements” as street drug alternatives and warned 26 firms to stop making unproven claims that ephedrine-containing dietary supplements could enhance athletic performance.
Lastly, over the course of the course of the last 15 months FDA utilized its judicial and administrative enforcement tools to take one injunction action and 8 seizure actions against marketers of, and/or fraudulent dietary supplements. Six of the seizure actions occurred in FY 2003 alone, including 3 that were undertaken in cooperation with FTC.
Health Fraud
Traditionally, FDA has taken action against violative dietary supplements as part of its health fraud
efforts. Generally, FDA defines health fraud as the deceptive promotion, advertising, distribution,
or sale of articles that are represented as being effective to diagnose, prevent, cure, treat, or mitigate
an illness or condition, or provide a beneficial effect on health where the product has not been scientifically
proven safe and effective for such purposes.
The Internet is one avenue by which fraudulent products have been promoted. The use of the Internet by our nation's citizens, from school age children to seniors, has opened up vast new opportunities for the exchange of information and for enhancing commerce in all types of consumer products. The Internet is rapidly transforming the way we live, work, and shop in all sectors of the economy. In the health sector, tele-medicine allows people in remote areas to access the expertise of doctors in the nation's finest academic health centers. The Internet also permits an increasing number of individuals to obtaining meaningful medical information that helps them understand health issues and treatment options. As beneficial as this technology can be, it also creates a new marketplace for activity that is illegal, such as the sale of unapproved new drugs, prescription drugs dispensed without a prescription, and products marketed with fraudulent claims about health benefits. Also, because the Internet is a worldwide communications system, U.S. citizens are now more directly susceptible to fraud from sources both foreign and domestic.
Consumers respond to these promotions by spending billions of dollars a year on fraudulent health products. They hope to find a cure for their illness or improve their well-being or appearance. Yet, consumers often fall victim to products and devices that do nothing more than cheat them out of their money, steer them away from useful proven treatments, and possibly do more harm than good.
FDA Web Site Triage Process
In June 1999, FDA established a case assessment or “triage” team with representatives from
the Offices of Criminal Investigation within the Office of Regulatory Affairs, the Center for Drug Evaluation
and Research, the Office of Chief Counsel, and the Office of Policy. The scope of this group has been
expanded to cover all FDA Centers and regulated products including the CFSAN’s Office of Nutritional
Products, Labeling and Dietary Supplements.
Under the triage process, FDA identifies web sites that potentially violate the FD&C Act from the Agency’s Internet monitoring activity, other Federal or foreign law enforcement agencies including our joint partnership with the Federal Trade Commission (FTC), and from states and the public. The triage team evaluates each case to determine whether or not it should be pursued through a civil or criminal investigation. Using this information, we give priority to cases involving unapproved new drugs, health fraud, prescription drugs sold without a valid prescription, and products with the potential for causing serious or life-threatening reactions.
This triage process results in improved coordination of criminal and civil enforcement actions within the Agency, reduces overlapping efforts, and helps the Agency appropriately achieve a maximum deterrent effect when taking action to remove harmful products from the market.
Oversight of Dietary Supplements
FDA shares Federal oversight of dietary supplements with the Federal Trade Commission (FTC). FDA regulates
the safety, manufacturing, and labeling of dietary supplements, while FTC has primary responsibility
for regulating the advertising of these products. Over the last few years, the FDA and the FTC have
worked well together to ensure that there is a seamless assertion of our jurisdiction over these products.
As with all of FDA's activities, priorities are established based on benefit/risk to public health.
The Agency's enforcement of fraudulent health products is based on a priority
system that is often driven by whether a fraudulent product poses a direct or indirect risk to public
health. The susceptibility of the population is also an element that we consider when determining risk.
For example, cancer patients are considered a highly susceptible population, as many have exhausted
conventional or standard care treatments, and may be desperate to try anything that offers hope of a
cure.
Products that present a direct health hazard to consumers are the Agency’s highest priority. These are products that have a reasonable potential for causing direct serious adverse effects, or for which there is documentation of injury or death. When the Agency encounters such products, FDA will use all available civil and administrative remedies to assure that the product is quickly removed from the market. We also aggressively publicize our actions to warn consumers and health professionals about such products. In some cases, the Agency may initiate a criminal prosecution.
Products that are not themselves hazardous can still present an indirect health hazard in that the consumer may delay or forego proven medical treatments or drug therapies, or rely on these products for benefits that simply are never going to materialize. Examples include unproven products promoted for the treatment of cancer, Alzheimer's disease, arthritis, heart disease, and high blood pressure.
In addition to these direct and indirect health risks, we also give priority to products that undermine the integrity of the new drug application (NDA) and Over-the-Counter (OTC) drug review processes. The NDA and OTC drug review procedures provide consumers with assurance that prescription and OTC drugs are both safe and effective. To avoid undermining these procedures, it is essential for FDA to maintain vigorous surveillance, provide prompt industry guidance and outreach, and take enforcement action regarding fraudulent products. Such actions help ensure that manufacturers comply with the requirement to submit an NDA to the Agency for their product and that the playing field is fair and equitable for those who do.
Initiation of Enforcement Activity
When a problem arises with a product, or the Agency receives information that a product may violate
the FD&C Act or regulations, FDA can take a number of enforcement actions to protect the public.
For example, FDA may initially work with a product’s manufacturer or marketer to correct the problem
voluntarily. If that fails, the Agency may bring a lawsuit to seize the product and/or enjoin the firm
marketing or distributing the product. When warranted, FDA may also seek criminal penalties, including
prison sentences, against parties who break the law.
In the appendix attached to my testimony, I describe some of FDA’s recent dietary supplement enforcement activities. As you will see, our enforcement actions are wide-ranging and diverse and take full advantage of the entire breadth of enforcement tools that are available to FDA. You will also see that the type of cases that we have brought have evolved over time. We hope that they also illustrate to the public and the industry that we will take action when warranted, and that FDA also remains committed to consumer and industry education about the proper labeling and use of dietary supplements.
Outreach and Education
FDA recognizes that traditional enforcement actions and coordinated efforts with other agencies are
necessary, but these steps are not the only components of a thoughtful enforcement strategy. We fully
appreciate that the dietary supplement industry has a vested interest in curbing fraudulent operators
and practices and that most of FDA’s regulated industries are interested in complying with the
Act – and do so. For this reason, FDA will continue in its efforts to complement these measures
with industry and consumer education and will continue to assist the industry by issuing regulations
and guidance documents addressing the manufacture, labeling, and sale of dietary supplements.
Examples of prominent FDA outreach activities in this area include:
Partnership with Federal Trade Commission (FTC)
As discussed earlier, FTC and FDA have a long-standing history of working together to combat health
fraud. This partnership was formed out a recognition that although protection of the public health may
be FDA’s primary goal, other can contribute to achieving this goal. To further their mutual interest
in consumer protection, FDA and FTC formed a Dietary Supplement Enforcement Group to closely coordinate
their enforcement efforts against health care fraud. A major activity includes Operation
Cure-All, which is aimed at halting the Internet promotion of products, including dietary supplements,
that make false or misleading disease claims In addition, FDA and FTC chair an Interagency Health Fraud
Steering Committee that meets regularly to coordinate activity on these issues. The workgroup includes
Federal agencies in the U.S. and Canada, and Mexico also has been invited to join the group. As part
of its effort to curb Internet health fraud, FDA has conducted several “surfs” to identify
fraudulent marketing of health care products over the Internet. These actions were carried out in partnership
with the FTC and other law enforcement and public health authorities in the U.S. and abroad. These efforts
have led to many successful actions that have protected the public health. Together, we have succeeded
in accomplishing goals that neither one of our agencies could accomplish individually.
DIETARY SUPPLEMENTS CONTAINING EPHEDRINE ALKALOIDS
A number of plant genera, including ephedra, are known to contain ephedrine alkaloids. Ma huang is a
common name given to Chinese Ephedra, which is used in traditional Chinese medicine. Ephedra has been
shown to contain various chemical stimulants, including the alkaloids ephedrine, pseudoephedrine, phenylpropanolamine
and norpseudoephedrine, as well as various tannins and related chemicals. The concentrations of these
alkaloids depend upon many factors, such as the species, parts of the plant used, time of harvest, growing
location, and production methods. Ephedrine and pseudoephedrine are used in some OTC and prescription
drugs, where they have been demonstrated to be safe and effective for the labeled use.
Dietary supplements containing ephedrine alkaloids have known, and potentially serious, side effects. While ephedra has been used in herbal medicine preparations for thousands of years, in recent years ephedra has been sold primarily in dietary supplement products for weight control, as well as in products promoted to boost energy levels or to enhance athletic performance. Some ephedra-containing products have been marketed as herbal alternatives to illicit street drugs. Ephedra-containing products often contain other stimulants, such as caffeine, that may have synergistic effects and increase the potential for adverse effects.
A number of adverse effects associated with ephedrine alkaloid-containing dietary supplements have been reported to FDA. These include elevated blood pressure, rapid heartbeat, nerve damage, muscle injury, psychosis, and memory loss. More serious effects have also been reported, including heart attack, stroke, seizure, and death.
As the tragic deaths of the Baltimore Orioles’ pitching prospect Steve Bechler and of Sean Riggins, the sixteen year-old from Illinois have reminded us that use of ephedra, particularly in sports, raises serious concerns about safety and has long posed difficult issues for health care professionals, regulators, and consumers. These concerns stem from both the mechanism of action of ephedrine alkaloids on the sympathetic nervous system, and accumulating evidence of potentially serious adverse events after use of ephedra-containing products.
While there has been considerable debate about the safety and effectiveness of dietary supplements like ephedra, as well as the most effective approach to regulating them, one thing is clear: although dietary supplements are regulated as foods and not drugs, the consumer should not assume they are always safe to use. “Natural” does not necessarily mean safe. In particular, botanical and herbal products may have active ingredients with pharmacologic properties similar to, or in the case of ephedra identical to, drug products. They have the potential to cause adverse effects, as well as interactions with prescription and OTC drugs and with ingredients in other dietary supplements.
USE OF EPHEDRA BY ATHLETES
Although FDA is reviewing ephedrine alkaloids under DSHEA to assess the safety concerns, FDA has particular
concerns about the use of ephedra by persons engaged in strenuous exercise. A recent study by RAND,
discussed in more detail below, concluded that ephedra has minimal if any proven benefit for enhancing
sports performance. Yet ephedra acts like an adrenaline boost, stressing the heart, raising blood pressure,
and increasing metabolism. Moreover, the stimulating effects of ephedra may mask the signs of fatigue,
causing even the most well conditioned athletes to push beyond their physical limits.2
Thus, ephedra’s risks are potentially much more serious for competitive athletes than for the
general population. As FDA has said before, ephedra should not be used by people who engage in strenuous
activity.
Because of the special risks of ephedra use in athletes, sports leagues that have acted to restrict ephedra use are making a prudent decision. Even as the Agency evaluates the safety of ephedra use in the population more generally, including its use for weight loss, we see that ephedra poses special risks in the context of sports performance with little or no identified benefit for athletes.
FDA’s ACTIONS ON EPHEDRINE ALKALOIDS
The Agency’s professional, scientific and legal staffs are currently working hard to address the
extraordinary challenges presented by these products. Earlier this year, the Agency published a Federal
Register 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. Our Federal Register 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.
We are currently in the process of analyzing the over 30,000 public comments we received earlier this summer as well as adverse event information and the best available scientific evidence of ephedra's pharmacology and mechanism of action. We are in the final stages of our deliberative review, so I cannot discuss the specifics of that process or the anticipated outcome. However, I want to emphasize that we are committed to moving forward expeditiously to make a determination that is well grounded in all available scientific evidence and that is protective of the public health in accordance with DSHEA.
While we are undertaking these reviews, the Agency has dramatically increased its enforcement actions against ephedrine alkaloids and other dietary supplement products making false or misleading claims. These actions, many of which have been undertaken in collaboration with the FTC, are having an impact on the marketing of dietary supplements in general and ephedra in particular.
Sports Uses of Ephedra
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.3
The actions were primarily a result of the Agency’s surveillance of the firms’ web sites.
Fourteen of the firms responded to the warning letters by discontinuing the product or the claim. The
remaining twelve firms were inspected by FDA. Of those twelve inspected firms, all but one either discontinued
the product or the objectionable claims. Investigation for consideration of regulatory action against
the remaining firm is ongoing. 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. FDA continues to
monitor the compliance of products on the Internet.
DIETARY SUPPLEMENT CURRENT GOOD MANUFACTURING PRACTICES
Another important aspect of FDA’s regulatory and surveillance programs is to help ensure that
dietary supplements are manufactured in a manner that will not result in adulteration. DSHEA gave FDA
the authority to promulgate regulations for dietary supplement current good manufacturing practices
(CGMPs).
On March 13, 2003, FDA published a proposed rule to establish CGMPs for dietary supplements. FDA's proposed rule, if finalized as proposed, will give consumers greater confidence that the dietary supplements they choose to use will have the identity, strength, purity, quality or composition claimed on the label. The CGMPs will help prevent product quality problems such as superpotency, subpotency, contamination, improper packaging, and mislabeling.
The proposed rule would:
The public comment period on this proposed rule closed on August 11, 2003. The Agency is carefully reviewing all of the comments.
Mr. Chairman, thank you for this opportunity to testify. I am happy to answer your questions.
FOOTNOTES:
1 Bennett, J. and CM Brown. 2000. “Use of Herbal Remedies by Patients in a Health Maintenance Organization.” Journal of the American Pharmaceutical Association. Volume 40, Number 3: 353-358.
2Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. File Inventory, Evidence Report/Technology Assessment Number 76. AHRQ Publication No. 03-E022, March 2003. Agency for Healthcare Research and Quality, Rockville, Maryland.
3Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. File Inventory, Evidence Report/Technology Assessment Number 76. AHRQ Publication No. 03-E022, March 2003. Agency for Healthcare Research and Quality, Rockville, Maryland.
Enforcement Strategies Used to Enforce DSHEA
Inspections That Resulted in Voluntary Compliance
Voluntary Recalls
Warning Letters
Seizures and Injunctions
Criminal Enforcement
Joint Enforcement Actions
FDA sent Warning Letters to eight firms promoting dietary supplement products as treatment or preventative remedies for SARS over the Internet. FTC also notified violative firms that they were subject to possible civil or criminal actions under the Federal Trade Commission Act. FDA has conducted appropriate follow-up to ensure that the firms have taken appropriate corrective action.