Dietary Supplements: FDA Should Take Further Actions to Improve Oversight and Consumer Understanding
Published: 2009-01-29T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: Dietary supplements and foods with added dietary ingredients, such as vitamins and herbs, constitute multibillion dollar industries. Past reports on the Food and Drug Administration's (FDA) regulation of these products raised concerns about product safety and the availability of reliable information. Since then, FDA published draft guidance on requirements for reporting adverse events--which are harmful effects or illnesses--and Current Good Manufacturing Practice regulations for dietary supplements. GAO was asked to examine FDA's (1) actions to respond to the new serious adverse event reporting requirements, (2) ability to identify and act on concerns about the safety of dietary supplements, (3) ability to identify and act on concerns about the safety of foods with added dietary ingredients, and (4) actions to ensure that consumers have useful information about the safety and efficacy of supplements.
section_title: What GAO Found
paragraphs: FDA has made several changes in response to the new serious adverse event reporting requirements and has subsequently received an increased number of reports. For example, FDA has modified its data system, issued draft guidance, and conducted outreach to industry. Since mandatory reporting went into effect on December 22, 2007, FDA has seen a threefold increase in the number of all adverse event reports received by the agency compared with the previous year. For example, from January through October 2008, FDA received 948 adverse event reports--596 of which were mandatory reports submitted by industry--compared with 298 received over the same time period in 2007. Although FDA has received a greater number of reports since the requirements went into effect, underreporting remains a concern, and the agency has further actions planned to facilitate adverse event reporting. FDA has taken some steps to identify and act upon safety concerns related to dietary supplements; however, several factors limit the agency's ability to detect concerns and remove products from the market. For example, FDA has limited information on the number and location of dietary supplement firms, the types of products currently available in the marketplace, and information about moderate and mild adverse events reported to industry. Additionally, FDA dedicates relatively few resources to oversight activities, such as providing guidance to industry regarding notification requirements for products containing new dietary ingredients. Also, once FDA has identified a safety concern, the agency's ability to remove a product from the market is hindered by a lack of mandatory recall authority and the difficult process of demonstrating significant or unreasonable risk for specific ingredients. Although FDA has taken some actions when foods contain unsafe dietary ingredients, certain factors may allow potentially unsafe products to reach consumers. FDA may not know when a company has made an unsupported or incorrect determination about whether an added dietary ingredient in a product is generally recognized as safe until after the product becomes available to consumers because companies are not required to notify FDA of their self-determinations. In addition, the boundary between dietary supplements and conventional foods containing dietary ingredients is not always clear, and some food products could be marketed as dietary supplements to circumvent the safety standard required for food additives. FDA has taken limited steps to educate consumers about dietary supplements, and studies and experts indicate that consumer understanding is lacking. While FDA has conducted some outreach, these initiatives have reached a relatively small proportion of dietary supplement consumers. Additionally, surveys and experts indicate that consumers are not well-informed about the safety and efficacy of dietary supplements and have difficulty interpreting labels on these products. Without a clear understanding of the safety, efficacy, and labeling of dietary supplements, consumers may be exposed to greater health risks associated with the uninformed use of these products.

section_title: Letter
paragraphs: Dietary supplements and foods containing added dietary ingredients, such  Dietary supplements and foods containing added dietary ingredients, such  as vitamins and herbs, constitute growing multibillion dollar industries.  as vitamins and herbs, constitute growing multibillion dollar industries.  Sales of dietary supplements alone reached approximately $23.7 billion in  Sales of dietary supplements alone reached approximately $23.7 billion in  2007, and data from the 2007 National Health Interview Survey show that  2007, and data from the 2007 National Health Interview Survey show that  over half of all U.S. adults consume dietary supplements. In 1994, there  over half of all U.S. adults consume dietary supplements. In 1994, there  were approximately 4,000 dietary supplement products on the market,  were approximately 4,000 dietary supplement products on the market,  whereas an industry source estimated that, in 2008, about 75,000 dietary  whereas an industry source estimated that, in 2008, about 75,000 dietary  supplement products were available to consumers. Similarly, food  supplement products were available to consumers. Similarly, food  products—such as fortified cereals and energy drinks—that contain added  products—such as fortified cereals and energy drinks—that contain added  dietary ingredients are in the marketplace in unprecedented numbers, and  dietary ingredients are in the marketplace in unprecedented numbers, and  consumers are expected to spend increasing amounts on these products  consumers are expected to spend increasing amounts on these products  over the next several years.  over the next several years.
The Food and Drug Administration (FDA) regulates dietary supplements  The Food and Drug Administration (FDA) regulates dietary supplements  under provisions of the Federal Food, Drug, and Cosmetic Act, as  under provisions of the Federal Food, Drug, and Cosmetic Act, as  amended by the Dietary Supplement Health and Education Act of 1994  amended by the Dietary Supplement Health and Education Act of 1994  (DSHEA). DSHEA defines dietary supplements as products that, among  (DSHEA). DSHEA defines dietary supplements as products that, among  other things, are intended for ingestion to supplement the diet, labeled as a  other things, are intended for ingestion to supplement the diet, labeled as a  dietary supplement, and not represented as a conventional food or as a  dietary supplement, and not represented as a conventional food or as a  sole item of a meal or diet. They must also contain one or more dietary  sole item of a meal or diet. They must also contain one or more dietary  ingredients. DSHEA does not require manufacturers to register with FDA  ingredients. DSHEA does not require manufacturers to register with FDA  or identify the products they manufacture or the ingredients of those  or identify the products they manufacture or the ingredients of those  products. However, all food facilities, including manufacturers and  products. However, all food facilities, including manufacturers and  distributors of dietary supplements, were required to register with FDA no  distributors of dietary supplements, were required to register with FDA no  later than December 12, 2003, under the Public Health Security and  Bioterrorism Preparedness and Response Act of 2002 and implementing  regulations. This includes an initial registration with FDA and updates  within 60 days of any changes in information. Registration must include  the name and address of the facility and an emergency contact, and  facilities that manufacture or sell certain types of products, such as  vitamins, must self-identify as such.
Under DSHEA, dietary supplements are broadly presumed safe, and FDA  does not have the authority to require them to be approved for safety and  efficacy before they enter the market, as it does for drugs. However, a  dietary supplement manufacturer or distributor of a supplement with a  “new dietary ingredient”—an ingredient that was not marketed in the  United States before October 15, 1994—may be required to notify FDA at  least 75 days before marketing the product, depending on the history of  use of the ingredient. For the most part, FDA relies on post-market  surveillance efforts—such as monitoring adverse event reports it receives  from companies, health care practitioners, and individuals; reviewing  consumer complaints; and conducting facility inspections—to identify  potential safety concerns related to dietary supplements. Once a safety  concern is identified, FDA must demonstrate that the dietary supplement  presents a significant or unreasonable risk, or is otherwise adulterated,  before it can be removed from the market. According to several experts  we spoke with, this regulatory approach has fallen short in protecting U.S.  consumers in the past. For example, while FDA was successful, in 2004, in  banning ephedrine alkaloids (ephedra)—a dietary ingredient used for  weight loss and bodybuilding, among other things—the ban became  effective only after FDA had received thousands of reports of adverse  events, including a number of deaths, and 10 years after the agency issued  its first advisory.
Since ephedra was banned, several changes have occurred in the  regulation of dietary supplements. For example, the Federal Food, Drug,  and Cosmetic Act, as amended by the Dietary Supplement and  Nonprescription Drug Consumer Protection Act, requires companies that  receive a serious adverse event report to submit information about the  event to FDA, beginning in December 2007. As defined in the act, serious  adverse events include any health-related events that result in, for  example, a death, life-threatening experience, inpatient hospitalization,  birth defect, or which require, based on reasonable medical judgment, a  medical or surgical intervention to prevent these serious outcomes. While  the act does not require companies to report moderate or mild adverse  events, such as gastrointestinal distress or headaches, companies may do  so voluntarily. In addition, health care practitioners and consumers can  submit voluntary reports of serious, moderate, and mild adverse events.  Additionally, in an effort to improve the consistency and safety of dietary  supplements, in June 2007, FDA established its Current Good  Manufacturing Practice regulations describing the conditions under which  supplements must be manufactured, packed, and held. These requirements  are being implemented in phases, based on company size, and will be fully  in effect by 2010.
In addition to regulating the safety and labeling of dietary supplements,  FDA also conducts outreach to consumers about these products. While the  Federal Food, Drug, and Cosmetic Act does not explicitly require FDA to  conduct consumer education, according to the agency, it has some  responsibility for doing so.
FDA also regulates foods with added dietary ingredients under provisions  set out in the Federal Food, Drug, and Cosmetic Act. The act generally  requires that when a company adds an ingredient to a food product, that  ingredient must either be generally recognized as safe (GRAS) or go  through FDA’s review and approval process as a food additive. With some  exceptions, the company is responsible for determining that the ingredient  meets the GRAS standard or, failing this, for having it approved as a food  additive. The GRAS standard is defined as a general recognition among  qualified experts that the substance is reasonably certain to not be harmful  under its intended conditions of use; such recognition can come through  scientific procedures, or for substances in use prior to 1958, through  experience based on common use in food. If the added ingredient is GRAS,  the company may add the ingredient to a food product without notifying  FDA, although some do so voluntarily. In most instances, if the ingredient  does not meet the GRAS standard, the company must petition FDA for  approval of the ingredient as a food additive, which also requires  companies to demonstrate a reasonable certainty that the ingredient is not  harmful under the intended conditions of use. According to FDA, meeting  the safety standard for a food additive requires the same quantity and  quality of scientific evidence as is needed to satisfy the GRAS standard.
In July 2000, we reported concerns about the safety of dietary supplements  and foods with added dietary ingredients, as well as about the accuracy of  health-related claims on product labels and in advertising. More  specifically, we reported that consumers faced health risks because  federal laws and agencies’ efforts did not effectively and consistently  ensure that products were safe. Furthermore, we found that consumers  did not consistently receive clear, scientifically supported information  concerning products’ health benefits so they could make informed dietary  choices. To help ensure that dietary supplements and related products are  safe and that consumers receive accurate information about the products,  we made six recommendations to FDA. FDA has implemented two of  these recommendations but has not fully implemented the remaining four,  which deal largely with providing regulations or other information  clarifying industry responsibilities.
At your request, this report examines FDA’s (1) actions to respond to the  new serious adverse event reporting requirements; (2) ability to identify  and act on concerns about the safety of dietary supplements; (3) ability to  identify and act on concerns about the safety of foods with added dietary  ingredients; and (4) actions to educate consumers about the safety,  efficacy, and labeling of dietary supplements.
For this report, dietary supplement means a product intended for human  consumption and does not include products for veterinary use.  Additionally, for this report, dietary ingredient means an ingredient that is  included in the dietary supplement definition in DSHEA, such as vitamins,  minerals, and herbs or other botanicals. To identify FDA’s actions to  respond to the new serious adverse event reporting requirements, we  reviewed FDA’s guidance on reporting requirements for industry and  internal procedures for compiling and tracking adverse event reports;  analyzed the number of reports received before and after the requirements  went into effect; and reviewed plans for improving adverse event  reporting. To examine FDA’s ability to identify and act on safety concerns  associated with dietary supplements, we assessed FDA’s laws and  regulations; analyzed data on FDA’s oversight actions, such as inspections,  import screenings and enforcement activities; and reviewed FDA  resources dedicated to dietary supplements. To examine FDA’s ability to  identify and act on concerns about the safety of foods with added dietary  ingredients, we reviewed laws and regulations regarding food additives, as  well as FDA’s procedures for identifying and acting on concerns about the  safety of foods with added dietary ingredients. To determine what FDA  has done to educate consumers about the safety, efficacy, and labeling of  dietary supplements, we reviewed FDA’s consumer outreach initiatives  and analyzed FDA’s and others’ data on consumer understanding of  dietary supplements. In addition, to address all of our objectives, we  interviewed a wide range of stakeholders, including officials from federal  and state agencies, industry and trade organizations, consumer advocacy  groups, academia, poison control centers, and foreign governments. To  assess the reliability of the data from FDA’s databases used in this report,  we reviewed related documentation, examined the data to identify obvious  errors or inconsistencies, and worked with agency officials to identify any  data problems. We determined the data to be sufficiently reliable for the  purposes of this report. A more detailed description of our objectives,  scope, and methodology is presented in appendix I.
We conducted this performance audit from December 2007 to January  2009, in accordance with generally accepted government auditing  standards. Those standards require that we plan and perform the audit to  obtain sufficient, appropriate evidence to provide a reasonable basis for  our findings and conclusions based on our audit objectives. We believe  that the evidence obtained provides a reasonable basis for our findings  and conclusions based on our audit objectives.
subsections: section_title: Background
paragraphs: According to the Nutrition Business Journal, the dietary supplement  industry is growing, and total sales were about $23.7 billion in 2007, as  shown in figure 1. Top selling supplements in 2007 included multivitamins,  sports nutrition powders and formulas, and calcium, according to the  Nutrition Business Journal. In addition, one of the areas of greatest  growth in supplements within the United States in 2007 was among weight  loss products. Projections through 2011 show that growth in the industry  is expected to continue, in large part because of the aging population and  an increasing interest in personal health and wellness.
Over time, several key events have shaped the regulation of dietary  supplements, as shown in table 1. Significantly, Congress passed DSHEA,  which amended the Federal Food, Drug, and Cosmetic Act and created a  new regulatory category, safety standard, and other requirements for  supplements. Under DSHEA, dietary supplements are generally presumed  safe. With the exception of the banned dietary ingredient, ephedra,  companies may sell otherwise lawful products containing any dietary  ingredient that was marketed in the United States prior to October 15,  1994—referred to as “grandfathered ingredients”—without notifying FDA.  Ingredients that were not marketed before this date are considered new  dietary ingredients. A dietary supplement containing a new dietary  ingredient must meet one of the two following requirements: (1) it  contains only dietary ingredients that have been “present in the food  supply as an article used for food in a form in which the food has not been  chemically altered” or (2) there is evidence that the dietary ingredient is  reasonably expected to be safe under the conditions of use recommended  or suggested in the product’s labeling. In addition, companies planning to  market a dietary supplement with a new dietary ingredient that only meets  the second requirement must notify FDA of the evidence that is the basis  of the determination at least 75 days before marketing the supplement.
As of December 22, 2007, dietary supplement companies are required to  submit any report received about a serious adverse event to FDA, as  mandated by the Dietary Supplement and Nonprescription Drug Consumer  Protection Act. In addition, companies can voluntarily submit reports  about moderate and mild adverse events. Others, such as consumers and  health care practitioners, can submit reports of serious, moderate, and  mild adverse events on a voluntary basis to FDA. Prior to implementing  the mandatory reporting requirements, FDA’s Center for Food Safety and  Applied Nutrition—which, in part, is responsible for promoting and  protecting the public’s health by ensuring that the nation’s food supply is  safe, sanitary, wholesome, and honestly labeled—had a system in place to  receive voluntary reports of adverse events involving dietary supplements  from all parties.
As stated in the Federal Food, Drug, and Cosmetic Act, FDA is also  responsible for protecting the public health by ensuring that the labels of  dietary supplements are not false or misleading. As noted in table 1, the  Nutrition Labeling and Education Act of 1990 amended the Federal Food,  Drug, and Cosmetic Act to require that most foods, including dietary  supplements, bear nutrition labeling. In addition, DSHEA amended the  Federal Food, Drug, and Cosmetic Act to add specific labeling  requirements for dietary supplements and provided for optional labeling  statements. Federal regulations require the following information on the  labels of dietary supplements: (1) product identity (name of the dietary  supplement), (2) net quantity of contents statement (amount of the dietary  supplement in the package), (3) nutrition labeling, (4) ingredient list  (when appropriate), and (5) name and place of business of the  manufacturer, packer, or distributor. In addition, DSHEA specifies that  supplements with labeling that makes disease or health-related claims  must contain a disclaimer that FDA has not evaluated the claim and the  product is not intended to diagnose, treat, cure, or prevent any disease.
Similar to dietary supplements, the market for foods with added dietary  ingredients has been growing, and this trend is expected to continue.  Foods with added dietary ingredients vary greatly, including such products  as orange juice with added calcium, pasta with Omega 3, and sunflower  seeds with guarana. Terms such as “functional foods” and “nutraceuticals”  are sometimes used to describe foods with added dietary ingredients.  However, there are no regulatory definitions for these terms, and some of  these terms include foods with naturally beneficial properties beyond  nutrition, such as pomegranate juice.
section_title: FDA Has Made Changes in Response to the New Serious Adverse Event Reporting Requirements and Has Received an Increased Number of Reports
paragraphs: FDA has made several changes in response to the new serious adverse  event reporting requirements established by law in 2006 and has  subsequently received an increased number of reports. FDA has modified  its existing data system and internal procedures for compiling, tracking,  and reviewing adverse event reports to incorporate mandatory reporting  by industry. Additionally, FDA has issued draft guidance and conducted  outreach to industry regarding the new requirements. Since mandatory  reporting went into effect on December 22, 2007, FDA has seen a threefold  increase in the number of all adverse event reports received by the agency  compared with the previous year. Although FDA received more reports  overall since the reporting requirements went into effect, underreporting  of adverse events remains a concern, and the agency has further actions  planned to facilitate adverse event reporting by consumers, health care  practitioners, and industry.
subsections: section_title: FDA Has Taken Several Actions in Response to the New Serious Adverse Event Reporting Requirements
paragraphs: In 2007, FDA took several actions in response to the new serious adverse  event reporting requirements for dietary supplements. Specifically, FDA  modified its existing database for compiling, tracking, and reviewing  adverse event reports—the CFSAN Adverse Event Reporting System  (CAERS)—to include data fields and instructions specifically for  compiling and tracking mandatory reports. In addition, CFSAN established  procedures for reviewing mandatory serious adverse event reports to  determine if they meet the minimum data requirements for mandatory  reports outlined in guidance to the industry.
FDA has also issued draft guidance and conducted outreach to industry  regarding the new reporting requirements. In October 2007, FDA provided  companies with a form and instructions for submitting mandatory serious  adverse event reports and issued draft guidance describing statutory  requirements and agency recommendations for reporting, recordkeeping,  and records access. Additionally, in December 2007, FDA issued draft  guidance on labeling requirements.
Statutory requirements outlined in draft guidance include the following:    The manufacturer, packer, or distributor whose name appears on the  dietary supplement label (responsible party) must report all serious  adverse events to FDA, as well as follow up medical information received  within 1 year after the initial report, within 15 business days of receipt.
Mandatory serious adverse event reports must be submitted to FDA using  the MedWatch 3500A form and should contain the following minimum  data elements: an identifiable injured person, name of the person who first  notified the responsible party, identity and contact information for the  responsible party, a suspect dietary supplement, and a serious adverse  event or fatal outcome.
The responsible party must include a copy of the dietary supplement label  related to the serious adverse event.
The responsible party must maintain records of all adverse events  reported for 6 years and must provide FDA officials with access to the  records upon request during an inspection.
Labels for dietary supplements marketed in the United States must provide  a complete domestic mailing address or phone number where the  responsible party may receive adverse event reports.
In addition to these requirements, FDA recommended that firms include  an introductory statement on dietary supplement labels to inform  consumers that the contact information provided may be used to report a  serious adverse event. According to comments submitted to FDA by the  three major dietary supplement industry associations, although the  industry broadly supports the new mandatory reporting requirements, it  disagrees with the recommended labeling changes. These industry  associations cite the following three key reasons for their opposition to  FDA’s recommendation: (1) in their view, the changes are unnecessary and  beyond Congress’ intent; (2) the introductory statement may draw undue  attention to the possibility of an adverse event and confuse consumers;  and (3) redesigning and replacing product labels is a substantial added  expense for dietary supplement companies and should have been  proposed through a formal rulemaking process rather than guidance.  According to an FDA official, the draft guidance regarding reporting,  recordkeeping, and records access requirements is close to being finalized.  In December 2008, FDA issued a revision of the draft guidance regarding  labeling changes. According to FDA, before this guidance is finalized, it  will need to be reviewed by the Office of Management and Budget because  of its potential economic impact on industry.
FDA has also worked with industry associations to increase awareness of  the new reporting requirements. For instance, FDA officials have spoken  at industry-sponsored conferences and seminars to increase awareness  and answer questions about the new reporting requirements.  Representatives from two of the leading industry associations we spoke  with stated that they were generally satisfied with FDA’s outreach efforts  regarding mandatory reporting.
section_title: FDA Has Received an Increased Number of Adverse Event Reports Since Mandatory Reporting Went into Effect
paragraphs: Since mandatory reporting requirements went into effect, the agency has  seen a threefold increase in the number of all adverse events reported  compared with the previous year. For example, from January through  October 2008, FDA received 948 adverse event reports, compared with 298  received over the same time period in 2007. Of the 948 adverse event  reports, 596 were mandatory reports of serious adverse events submitted  by industry; the remaining 352 were voluntary reports, which include all  moderate and mild adverse events reported and any serious adverse  events reported by health care practitioners and consumers directly to  FDA. As shown in figure 2, FDA received more serious adverse event  reports between January 1, 2008, and October 31, 2008, than previous  years, including 2003 and 2004, when FDA was receiving adverse event  reports related to ephedra. Adverse event reports from January 1, 2008,  through October 31, 2008, include 596 serious adverse event reports  submitted by industry, 163 serious adverse events reported by others on a  voluntary basis, and 189 moderate and mild adverse event reports.
Since mandatory reporting went into effect, FDA had received 596  mandatory reports of adverse events, such as serious cardiac, respiratory,  and gastrointestinal disorders, as of October 31, 2008. Among other  results, these events involved 9 deaths, 64 life-threatening illnesses, and  234 patient hospitalizations. As shown in table 2, 66 percent of serious  adverse event reports were associated with dietary supplements that  either contained a combination of types of products, such as a product  containing both vitamins and herbals, or could not be categorized under  one of FDA’s other product classifications, and 40 percent were associated  with vitamins. However, according to FDA, because of variability in the  quality and detail of information in reports and the lack of a control group,  the agency cannot necessarily determine a causal relationship between an  adverse event and the dietary supplement associated with the event.  Appendix II provides further detail on adverse event reports related to  dietary supplements received by FDA from January 1, 2003 through   August 6, 2008.
Although FDA has received a greater number of reports since mandatory  reporting requirements went into effect, FDA recently estimated that the  actual number of total adverse events—including serious, moderate, and  mild—related to dietary supplements per year is over 50,000. This  estimate suggests that underreporting of adverse events limits the amount  of information that FDA receives regarding safety concerns related to  dietary supplements or their ingredients and, according to FDA, this can  negatively impact the agency’s ability to identify safety concerns.
Experts have cited several possible reasons for underreporting related to  dietary supplements, including reduced attribution of adverse effects to  supplements due to the assumption that all dietary supplements are safe,  the reluctance of consumers to report dietary supplement use to  physicians, the failure to recognize chronic or cumulative toxic effects  from their use, and a cumbersome reporting process. To facilitate adverse  event reporting for any FDA-regulated products, FDA is currently  developing MedWatchPlus, an interactive Web-based portal intended to  simplify the reporting process and reduce the time and cost associated  with reviewing paper reports. For example, according to FDA planning  documents, MedWatchPlus would simplify the reporting process by  providing a single Internet portal for consumers, health care providers,  and industry to report an adverse event. Furthermore, the proposed  interactive format will prompt reporters to provide relevant information  based on the type of products involved in the adverse event—thereby  facilitating reporting and improving the quality of information FDA  receives. Once an event is reported, the information would be  automatically routed to the relevant FDA centers based on the type of  product involved. Testing and release of the interactive questionnaire  phase of the project is currently expected in 2009.
section_title: Although FDA Has Taken Some Steps to Identify and Act on Concerns about the Safety of Dietary Supplements, Several Factors Limit Its Oversight
paragraphs: FDA has taken some steps—such as analyzing adverse event reports and  detaining certain potentially unsafe imported products—to identify and  act upon safety concerns related to dietary supplements. However, several  factors limit the agency’s ability to detect concerns and efficiently and  effectively remove products from the market. For example, FDA has  limited information on the number and location of dietary supplement  firms, the identity and ingredients of products currently available in the  marketplace, and mild and moderate adverse events reported to industry.  Additionally, FDA dedicates relatively few resources to dietary  supplement oversight activities compared with other FDA-regulated  products. Moreover, once the agency has identified a safety concern, the  agency’s ability to efficiently and effectively remove a product from the  market is hindered by a lack of mandatory recall authority and the  difficulty of establishing adulteration for dietary supplement products  under the significant or unreasonable risk standard. Although FDA has  taken some steps, such as drafting guidance for industry on reporting  serious adverse events and establishing its Current Good Manufacturing  Practice regulations, to improve the oversight of dietary supplements over  the past several years, consumers remain vulnerable to risks posed by  potentially unsafe products.
subsections: section_title: FDA Has Taken Some Actions to Identify and Act on Concerns about the Safety of Dietary Supplements
paragraphs: FDA uses a variety of approaches to identify potential safety concerns  related to dietary supplements. For example, FDA may identify concerns  through surveillance actions such as monitoring adverse event reports and  consumer complaints, screening imports, and conducting inspections. For  instance, during almost half of the 909 inspections conducted at dietary  supplement firms from fiscal year 2002 through May 6, 2008, FDA and its  partners at the state level identified potential problems, such as a lack of  quality control and unsanitary conditions. Table 3 provides examples of  FDA surveillance related to dietary supplements. For more detailed  information on FDA’s actions to identify potential safety concerns, see  appendix II.
In addition, FDA monitors the Internet to identify products that purport to  be dietary supplements but may be fraudulently promoted for treating  diseases. According to FDA, such products pose a threat to public health  because the disease prevention and treatment claims often persuade  consumers to delay or forgo medical diagnosis and treatment. FDA  officials also told us they identify safety concerns by obtaining information  from other agencies at the state, federal, and international level; reviewing  scientific literature; sponsoring safety-related research; and targeting  safety-related investigations on particular classes of products. For  instance, according to FDA, the agency used adverse event information  from the Florida Department of Health to issue a consumer warning about  the product “Total Body Formula.” FDA officials also described current  safety-related investigations it initiated targeting specific classes of  products, such as ephedra substitutes; male potency enhancers that  contain undeclared active pharmaceutical ingredients; and products  making misleading health claims to prevent or cure serious illnesses such  as diabetes, sudden acute respiratory syndrome, and influenza. For  example, officials said they are currently contracting with the University  of California at Los Angeles to monitor adverse event reporting related to  ephedra substitutes. In addition, FDA is conducting animal testing through  the National Center for Toxicological Research to examine interactions  among weight loss supplement ingredients, according to agency officials.
Once FDA has identified a potential safety concern, the agency has several  options available for taking action. According to FDA officials, products or  ingredients of greatest concern for public health generally will be subject  to either administrative or judicial enforcement actions, whereas FDA will  take advisory actions against products of lower public health risk. FDA  officials also noted that, if a firm does not correct violations in response to  an advisory action, FDA may pursue an enforcement action against the  firm. Table 4 provides examples of FDA administrative and enforcement  actions related to dietary supplements. For more detailed information on  FDA’s actions in response to identified safety concerns, see appendix II.
In addition to taking enforcement action on its own, FDA may pursue  enforcement action in conjunction with another federal agency, such as  the Federal Trade Commission, which has enforcement responsibility with  regard to dietary supplement advertising. For example, as part of the  FDA’s Consumer Health Information for Better Nutrition initiative  launched in 2002, FDA and the Federal Trade Commission took joint  enforcement actions against several marketers of dietary supplement  products making unsubstantiated treatment claims for diseases such as  emphysema, diabetes, Alzheimer’s disease, cancer, and multiple sclerosis.  In addition, industry has also initiated some measures to address  unsubstantiated claims. For example, based on monitoring efforts and  company referrals, the National Advertising Division of the Council of  Better Business Bureaus reviews advertising claims for accuracy and then  recommends changes to companies as necessary. This program is  currently funded through a series of multiyear grants from the Council for  Responsible Nutrition.
FDA officials also noted that the agency plans to expand dietary  supplement oversight in the near term. In particular, FDA will add dietary  supplement inspections as an option for its formal state contract  agreements in 2009, which should increase the number of dietary  supplement inspections performed by state officials on FDA’s behalf,  according to FDA officials. To further increase the number of inspections,  FDA is also exploring third-party certification as part of its Food  Protection Plan: An Integrated Strategy for Protecting the Nation’s Food  Supply. To improve the agency’s Internet surveillance, FDA has plans to  implement a sophisticated computer program that will search the Web for  unauthorized disease treatment claims, potentially searching hundreds of  thousands of Web sites per minute compared with a manual search by  FDA staff, according to an FDA official. Moreover, although agency  officials stated it was too early to determine the effectiveness of the newly  established Current Good Manufacturing Practice regulations and serious  adverse event reporting requirements, these new tools could improve the  agency’s ability to oversee the dietary supplement industry. While several  stakeholders generally agreed that the new regulations could improve  FDA’s ability to oversee the dietary supplement industry, some  stakeholders raised concerns about FDA’s ability to enforce the new  requirements given its limited resources.
section_title: Several Factors Limit FDA’s Ability to Identify and Act on Safety Concerns Related to Dietary Supplements
paragraphs: Although FDA has taken some steps to identify and act on safety concerns,  limited information hinders FDA’s oversight of the dietary supplement  industry. In addition, FDA dedicates relatively few resources to dietary  supplement oversight. Furthermore, FDA is limited by a lack of authority  to efficiently and effectively remove products from the market.
subsections: section_title: FDA’s Ability to Identify Safety Concerns Is Hindered by a Lack of Information
paragraphs: FDA’s ability to identify safety concerns is hindered by a lack of  information in three key areas: the identity and location of dietary  supplement firms; the types and contents of products on the market; and  product safety information, such as adverse event data. First, FDA lacks  complete information on the names and location of dietary supplement  firms within the agency’s jurisdiction. Although all dietary supplement  firms must register with FDA as food facilities to provide information on  their name and location, firms specializing in certain product categories,  such as herbal products, are not required to self-identify as dietary  supplement firms under current law. For example, a firm manufacturing  products containing only herbs, such as echinacea and ginseng, would not  be required to identify itself as a dietary supplement firm during the  registration process. Consequently, FDA may not be aware of all dietary  supplement firms that are currently operating. In addition, there is little  assurance that FDA’s existing inventory of dietary supplement firms is  accurate because this information is not updated in a systematic fashion.  As one FDA official explained, a thorough review of FDA’s firm inventory  would probably require dedicating 10 to 15 staff within each field office to  the task for a year—which is unlikely given FDA’s current workload.  However, FDA officials did indicate that modifying the existing  registration categories to better reflect FDA’s inspection responsibilities  could provide the agency with more complete information on the number  and location of dietary supplement firms within its regulatory jurisdiction,  provided industry complies with the new requirements. In FDA’s Food  Protection Plan, the agency requested statutory changes to allow  modifying existing registration categories and require biannual renewals  for food facilities, stating that such changes would ensure FDA has  accurate, up-to-date information and would help the agency assess and  respond to potential threats to the food supply.
Second, FDA does not have comprehensive information on the types and  contents of dietary supplement products that are on the market or their  ingredients. In addition, FDA officials noted that, if a dietary supplement  firm reformulates a product to include different ingredients and/or  changes the amounts of the ingredients without renaming the product,  FDA may not be aware of the changes. Although drug manufacturers are  required by law, with some exceptions, to register the identity and active  ingredients of their products with FDA, the agency lacks the authority to  require similar product information from dietary supplement  manufacturers. Detailed product information could help the agency more  efficiently and effectively analyze the adverse event reports it receives. For  example, according to FDA, voluntary reports often contain inaccurate or  incomplete information on product ingredients. Complete information on  product ingredients could help the agency establish links between  mandatory and voluntary reports on products containing the same  ingredient. Furthermore, a database of marketed products and their  ingredients could help the agency respond more quickly to safety  concerns. For instance, if FDA identified a particular ingredient of  concern, officials could quickly determine which products on the market  contained the ingredient and tailor the agency’s response accordingly.
Third, FDA’s ability to identify safety concerns is undermined by a lack of  information on product safety, such as data on the frequency and  characteristics of adverse events related to dietary supplements. As we  noted earlier in this report, although dietary supplement firms are required  to report all serious adverse event reports they have received to FDA, they  are not required to report mild or moderate adverse events. Additional  information on adverse events could be particularly beneficial because  there is a limited amount of scientific data available on the safety of  dietary supplements compared with other regulated products such as  drugs, which require premarket approval. For instance, FDA officials  noted that mandatory reporting of mild and moderate events could assist  the agency by increasing the amount of data available for signal detection,  as well as provide additional support for safety-related conclusions  regarding particular products or ingredients. Although some stakeholders  have pointed out that mandatory manufacturer reporting of mild and  moderate events won’t fully address the issue of underreporting— particularly for consumers and health care providers—most medical  researchers we interviewed agreed that mandatory reporting of all adverse  events would be beneficial to the agency.
section_title: FDA Dedicates Relatively Few Resources to Dietary Supplement Oversight
paragraphs: FDA dedicates relatively few resources to dietary supplement oversight  activities, including conducting inspections and developing guidance for  industry on key safety-related aspects of DSHEA. Our analysis of FDA  expenditure data found that FDA dedicated approximately 4 percent of  CFSAN resources and 1 percent of its field resources—which are  dedicated to FDA’s Office of Regulatory Affairs—to dietary supplement  programs from fiscal years 2006 through 2007. FDA uses its field  resources to, for example, monitor industry compliance by conducting  surveillance actions such as inspections and import screenings. As FDA  officials explained, limited inspection resources are prioritized according  to public health risk, and dietary supplements are generally considered to  be a lesser risk than, for example, foods that could be contaminated with  foodborne pathogens. Consequently, although FDA conducted 973  inspections of foreign food firms from fiscal year 2002 through fiscal year  2008, FDA conducted no foreign inspections of dietary supplement firms  during this time period. Similarly, although FDA increased the number of  domestic inspections of dietary supplement firms in fiscal years 2004 and  2005, overall, these inspections represented less than 1 percent of total  food establishment inspections conducted by FDA and its state partners  from fiscal years 2002 through 2008. With few resources dedicated to  dietary supplement inspections, FDA’s ability to identify potential safety  concerns through this key surveillance activity is limited.
Furthermore, despite identifying the need to provide industry with  guidance on key aspects of DSHEA, FDA has not done so in a timely  manner. For example, DSHEA authorized FDA to establish Current Good  Manufacturing Practices specific to dietary supplements in 1994; however,  the agency did not publish a proposed rule until 2003 and did not finalize  the rule until 2007. FDA officials noted that it first issued an advance  notice of proposed rulemaking in 1997 and went through a number of  steps, such as conducting public meetings, to develop an overall strategy  for regulating dietary supplements and then submitted its rule to the Office  of Management and Budget for clearance before finalizing the rule.  Because these Current Good Manufacturing Practices are phased in over  time, they will not fully be in effect until 2010—16 years after FDA was  authorized to establish them.
In addition, although FDA recognized the need to develop guidance on the  new dietary ingredient provisions of DSHEA, FDA has yet to issue this  guidance—an omission previously highlighted in our 2000 report. As an  FDA official explained, new dietary ingredient guidance is critical for  dietary supplement safety because, without formal guidance, firms may  not notify FDA before marketing products that have drastically different  safety profiles than their historical use. For example, this official was  concerned that a firm could use bitter orange’s historical use as a flavoring  in marmalade as justification for not submitting a new dietary ingredient  notification to FDA when it uses bitter orange to create a product that is  95 percent synephrine—a powerful stimulant. Similarly, a firm might  choose to market dietary supplement products that contain nano-sized  particles of grandfathered ingredients without notifying FDA in advance.  According to the FDA official, this raises concerns because potential  health risks associated with nano-sized particles are unknown. According  to this official, FDA has started to develop draft guidance for new dietary  ingredients that would clarify what factors FDA will use when determining  if a substance is a new dietary ingredient. More specifically, the guidance  would clarify what changes to grandfathered ingredients would require a  new dietary ingredient notification to FDA and what information should  be included in the notification, among other items. However, this draft  guidance has been under legal review for over a year, and FDA did not  provide us with a time frame for its issuance.
section_title: FDA’s Lack of Authority Limits Its Ability to Remove Products from the Market
paragraphs: Once FDA has identified a safety concern, the agency’s ability to efficiently  and effectively remove a product from the market is hindered by a lack of  mandatory recall authority. For instance, FDA officials commented that  FDA’s ability to protect consumers through its voluntary recall authority is  limited because it relies on industry exercising its responsibility rather  than enforceable requirements. As FDA noted in its Food Protection Plan,  mandatory recall authority would allow the agency to ensure the prompt  and complete removal of unsafe products from distribution channels in  cases where a firm was unwilling to cooperate voluntarily.
Additionally, agency officials and other stakeholders have acknowledged  the difficulty of banning a dietary supplement because FDA must establish  adulteration under the significant or unreasonable risk standard. For  example, it took FDA almost 10 years after issuing its first advisory about  ephedra to gather sufficient data to meet the statutory burden of proof for  banning ephedra from the market. The difficulty of establishing significant  or unreasonable risk is compounded by limited scientific research on the  safety of dietary supplements—which are generally presumed safe under  the law, and firms are not required to provide FDA with evidence of  product safety for ingredients marketed prior to October 15, 1994, such as  ephedra. Underreporting of adverse events also limits FDA’s ability to  meet its burden of proof. In the case of ephedra, one firm withheld  information from FDA on thousands of serious adverse event reports  related to its product—which hindered FDA’s investigation, and prompted  support for establishing mandatory reporting requirements. As previously  mentioned in this report, although mandatory serious adverse event  reporting requirements for industry are now in effect, underreporting of all  adverse events from consumers, health care providers, and industry  remains a concern. According to an agency official, given these data  limitations and the agency’s difficult and costly experience with ephedra,  banning an ingredient is not a very viable option. However, according to  some experts, the difficult process of establishing significant or  unreasonable risk for dietary supplement ingredients with known safety  concerns has raised doubts about FDA’s ability to adequately protect the  public. For example, table 5 summarizes FDA actions for certain dietary  supplement ingredients that have been banned in other countries.
section_title: While FDA Has Taken Some Actions When Foods Contain Unsafe Dietary Ingredients, Certain Factors May Allow Unsafe Products to Reach Consumers
paragraphs: Although FDA has taken some actions, such as issuing warnings, when  foods contain unsafe dietary ingredients, certain factors may allow unsafe  products to reach consumers. FDA may not know when a company has  made an unsupported or incorrect GRAS determination about an added  dietary ingredient in a product until after the product becomes available to  consumers because companies are not required to notify FDA of their self- determinations. In addition, the boundary between dietary supplements  and foods containing added dietary ingredients is not always clear, and  some food products could be marketed as dietary supplements to  circumvent the safety standard required for food additives. Finally,  according to FDA officials, the agency conducts a limited amount of  monitoring for safety concerns associated with foods containing added  dietary ingredients.
subsections: section_title: Companies Are Not Required to Notify FDA When They Make a Self- Determination That an Added Ingredient Is GRAS
paragraphs: The Federal Food, Drug, and Cosmetic Act allows companies to market a  conventional food product with added dietary ingredients if the company  determines that the added dietary ingredient meets the GRAS standard.  These companies do not have to notify FDA before selling the product to  consumers, although some may do so voluntarily. If a company makes an  unsupported or incorrect GRAS determination about an added dietary  ingredient in a product, FDA may not know about the product until after it  becomes available to consumers. This was the case, for example, for  several food products containing such herbs as kava, ginkgo, and  echinacea. Specific examples are as follows:  In 2004, during a food inspection of a juice company, FDA found that the  company was marketing a product that contained kava. According to FDA,  it is not aware of a basis for concluding that kava is GRAS, and it has not  approved kava as a food additive. In addition, kava was the subject of a  public health advisory issued by FDA in March 2002, which warned  consumers of the potential risk of severe liver injury associated with the  use of kava.
In 2001, FDA identified a company marketing cereals with ginkgo biloba  and Siberian ginseng. According to FDA, it is not aware of a basis for  concluding that these ingredients are GRAS, and it has not approved them  as food additives. FDA sent a warning letter to the company, and the  product was subsequently removed from the market.
Also in 2001, FDA identified a company marketing juices with added  echinacea. FDA sent a warning to the company noting that it has not  approved echinacea as a food additive and is not aware of a basis for  concluding that echinacea is GRAS.
FDA learned of these products after they were available to consumers. If  FDA wanted to remove these products from the market, and the  companies did not do so voluntarily, FDA would have to initiate  enforcement actions.
section_title: The Boundary between Dietary Supplements and Foods with Added Dietary Ingredients Is Not Always Clear
paragraphs: The boundary between dietary supplements and foods containing added  dietary ingredients is not always clear. FDA officials have noted, for  example, that a tea with an identical mix of herbal ingredients could be  considered either a dietary supplement or a food product. FDA determines  how to classify the tea based on the product labeling. More specifically,  according to FDA, if the tea is labeled as a dietary supplement and is not  represented as a conventional food, FDA would consider the tea to be a  dietary supplement and regulate it as such. On the other hand, if the tea is  labeled as a food or is represented as a conventional food with terms such  as “drink” or “beverage,” FDA officials noted that they would consider the  tea to be a food.
The way FDA classifies a product is important because the safety standard  that applies to the product varies based on that classification. If the  product is classified as a conventional food, the added dietary ingredient  must meet the GRAS standard or be approved by FDA as a food additive,  except in certain circumstances as authorized in law. If the product is  classified as a dietary supplement, the added dietary ingredient is  presumed safe if it was marketed in the United States before October 15,  1994; otherwise, it is considered a new dietary ingredient, and the  manufacturer or distributor may be required to notify FDA 75 days before  the product with the added dietary ingredient enters the market and  provide some basis for concluding that the ingredient is reasonably  expected to be safe. According to FDA and industry officials, this is a less  stringent standard than that for food additives. However, FDA does not  have the authority to require that the safety of dietary supplements be  approved before entering the market.
These differences in how products are regulated may lead to  circumstances when an ingredient would not be allowed to be added to a  product if it was labeled as a conventional food but would be allowed in  the identical product if it was labeled as a dietary supplement. This was  the case, for example, in August 2007, when FDA identified a company  marketing an iced tea mix containing stevia—an herb that had not been  approved as a food additive because of potential safety concerns,  including reproductive and cardiovascular effects. FDA issued a warning  to the company; however, rather than discontinue using stevia in its  product, the company changed the label to classify the product as a  dietary supplement rather than a food, and the product remains on the  market. We identified other products that also fall within the gray area  between dietary supplements and foods with added dietary ingredients  that are being marketed as dietary supplements. For example, we  identified several nutrition bars, teas, and energy drinks, some produced  by large companies with national distribution, which contain herbs such as  kava, St. John’s wort, and echinacea. If these ingredients are added to  conventional foods and are not GRAS and have not been approved as food  additives, then they would violate the Federal Food, Drug, and Cosmetic  Act. An FDA official told us that FDA is unaware of a basis for concluding  that these ingredients are GRAS, and they have not been approved as food  additives. However, these products may remain on the market because  they are labeled as dietary supplements. Such a process might allow  companies to circumvent the safety standard required for food additives.
In FDA’s 10-year plan to implement DSHEA, issued in January 2000, the  agency identified the need to clarify the boundary between conventional  foods and dietary supplements but did not indicate when or how the  agency planned to address this issue. Moreover, we highlighted this  particular issue in our July 2000 report and recommended FDA take action  to clarify the boundary between conventional foods and dietary  supplements. As of November 2008, the agency had not issued regulations  or guidance to clarify this boundary.
section_title: FDA Conducts Limited Monitoring of Foods with Added Dietary Ingredients
paragraphs: According to FDA officials, the agency conducts limited monitoring for  safety concerns associated with food products that contain added dietary  ingredients. These officials explained that FDA does not track these  products separately from foods, and the agency generally relies on trade  complaints and adverse event reports to identify concerns about these  types of products. FDA officials told us that the current regulatory  framework is sufficient to identify and act on safety concerns regarding  foods with added dietary ingredients. FDA held a public meeting in 2006  regarding these products and, according to FDA officials, the agency is  currently evaluating the comments made during that meeting.
Some stakeholders told us that safety risks associated with foods  containing added dietary ingredients that meet the GRAS standard or have  been approved as food additives are generally low. For example,  stakeholders were generally not concerned about vitamin-fortified  products, such as cereal, unless individuals consume these products in  high doses. However, some stakeholders we spoke with raised concerns  about certain products—such as energy drinks that contain stimulants and  have the potential to cause adverse cardiac effects. In addition, some  stakeholders expressed concern about adding botanicals to foods due, in  part, to the potential for an adverse physiological response. In contrast, an  industry official noted that companies sometimes add dietary ingredients  to foods for labeling or marketing purposes—not to elicit a physiological  effect—and, therefore, the amounts included are low.
section_title: FDA Has Taken Limited Steps to Educate Consumers about Dietary Supplements, and Consumers Remain Largely Uninformed
paragraphs: While FDA has conducted some consumer outreach, these initiatives have  reached a relatively small proportion of consumers using dietary  supplements. Additionally, surveys and experts indicate that consumers  are not well-informed about the safety and efficacy of dietary supplements  and have difficulty interpreting labels on these products. Without a clear  understanding of the safety, efficacy, and labeling of dietary supplements,  consumers may be exposed to greater health risks associated with the  uninformed use of these products.
subsections: section_title: FDA Has Conducted Some Consumer Education about Dietary Supplements, but these Efforts Have Been Limited
paragraphs: FDA has taken some steps to educate consumers about the safety,  efficacy, and labeling of dietary supplements. According to FDA officials,  the agency primarily educates the public about dietary supplements  through publications such as brochures and articles, as well as the  agency’s Web site. For example, agency officials highlighted the following  efforts:    FDA and the NIH’s Office of Dietary Supplements jointly published a  brochure in 2004 to educate consumers about the importance of disclosing  their dietary supplement usage to doctors.
In March 2006, FDA developed a document entitled, “Food Facts: Dietary  Supplements—What You Need to Know” with general information about  dietary supplements.
In August 2008, FDA distributed an article via e-mail and its Web site  entitled “FDA 101: Dietary Supplements” that contained information on  the regulation of dietary supplements, as well as information on the safety,  efficacy, and labeling of these products.
FDA’s Web site provides warnings about certain ingredients and products,  how to report an adverse event, and general consumer information about  dietary supplements, including descriptions of the types of label claims  permitted on dietary supplement products. FDA’s Web site also links  consumers to the NIH, Federal Trade Commission, United States  Department of Agriculture, and National Academies’ Institute of Medicine  Web pages that contain information about the safety and efficacy of  certain dietary supplement ingredients and how to interpret dietary  supplement labels.
FDA has worked jointly with industry, consumer groups, and other federal  agencies to provide consumers with information about label claims.
However, these outreach efforts can only be as effective as the number of  dietary supplement users they reach. While data from the 2007 National  Health Interview Survey show that over half of the U.S. adult population— or at least 114 million individuals—consume dietary supplements, we  found that FDA’s outreach efforts have limited potential to reach the  majority of U.S. adults using dietary supplements. For example, according  to FDA and NIH officials, since 2004, the brochure regarding disclosure of  supplement use to doctors had a distribution of 40,000 paper copies and  received about 171,000 total visits on the FDA and NIH Web sites—which  represent less than 1 percent of estimated dietary supplement users. Other  FDA publications on dietary supplements have also reached a relatively  small proportion of dietary supplement consumers. For example,  according to FDA officials, it distributed about 61,000 English copies and  approximately 35,000 Spanish copies of its document entitled “Food Facts:  Dietary Supplements—What You Need to Know.” In addition, according to  FDA officials, its consumer article on dietary supplements called “FDA  101: Dietary Supplements” was sent via e-mail to almost 32,500 subscribers  to FDA’s “Consumer Health Information” and, as of October 21, 2008,  FDA’s Web site had logged about 3,800 page views of the HTML version  and approximately 2,100 page views of the printer-friendly PDF of the  article.
While agency officials stated that FDA does not evaluate the effectiveness  of its outreach efforts, officials also noted that the agency must continually  market its desired messages to effectively educate consumers.
Additionally, consumer education was highlighted as an important part of  the agency’s 10-year plan for dietary supplements, published in 2000. In the  November 2004 update to this plan, FDA identified the need to provide  consumers with access to reliable scientific information about the safety  of ingredients and supplements so that consumers may make more  informed choices. Currently, according to FDA, CFSAN has no ongoing or  new consumer education initiatives being planned for dietary  supplements. FDA recently announced a partnership with WebMD to  expand consumer access to timely and reliable health information;  however, it is not clear to what extent FDA will use this partnership to  increase consumer understanding about dietary supplements. When asked  about plans for consumer education initiatives, FDA officials explained  that the agency has been directing its limited resources toward activities  that can have the greatest public health impact, such as responding to  foodborne illness outbreaks.
section_title: Consumers Are Not Well- Informed about the Safety, Efficacy, and Labeling of Dietary Supplements
paragraphs: Several studies indicate that consumers are not well-informed about the  safety, efficacy, and labeling of dietary supplements. For example, a 2002  Harris Poll indicated that a majority of adults are misinformed about the  extent to which government regulates the safety of vitamins, minerals, and  food supplements. According to the poll, over half of respondents believed  that dietary supplements are approved by a government agency. A 2002  FDA-sponsored health and diet survey also estimated that a majority of  respondents who used vitamin or mineral supplements believed that the  government approves dietary supplement products before they are  marketed to consumers. However, FDA does not have the authority to  require that supplements be approved for safety and effectiveness prior to  marketing, and, unless a product contains a new dietary ingredient, FDA  does not need to be notified by the manufacturer prior to marketing a  dietary supplement. Additionally, the 2002 Harris Poll estimated that about  two-thirds of respondents believe that the government requires dietary  supplement labels to contain warnings about potential side effects, or  dangers, similar to drugs. However, unlike drug manufacturers, who are  required to include warnings related to adverse effects and  contraindications on their product labels, dietary supplement  manufacturers are required to include few such warnings on their product  labels. Consequently, dietary supplement manufacturers may not  necessarily include warnings about potential adverse effects on the labels  of their products. For example, in the course of our review, we identified  several dietary supplements that contained ingredients with known or  suspected adverse effects, such as kava and black cohosh, that did not  include warnings on their labels. In addition, in 2003, an analysis of 100  dietary supplement labels by the Department of Health and Human  Services’ Office of Inspector General found that the dietary supplement  labels were limited in their ability to guide the informed and appropriate  use of dietary supplements among consumers and often did not present  information in a manner that facilitates consumer understanding.
Furthermore, during the course of our review, most experts we spoke with  noted that, generally, consumers are not well-informed about the safety  and efficacy of dietary supplements. These experts explained that many  consumers believe various myths about dietary supplements. For example,  consumers may believe that if a product is natural, it must be safe; if a  little is good, then more must be better; and if a product does not have a  warning label, it must be safe. Without a clear understanding of the safety,  efficacy, and labeling of dietary supplements, consumers are exposed to  potential health risks associated with the uninformed use of these  products. For example, several experts stated that misconceptions about  dietary supplements could cause consumers to incorrectly assess the risks  and benefits of these products and, in some cases, substitute supplements  for prescribed medicine. In addition, several experts noted that consumers  may not be aware that taking combinations of some supplements or using  certain products in conjunction with prescription drugs could lead to  harmful and potentially life-threatening results. In particular, some  supplements—such as garlic, ginkgo biloba, ginseng, and vitamin E—may  cause blood thinning and lead to life-threatening complications during  surgical procedures. Therefore, consumer education is critical to mitigate  the potential risks associated with the uninformed use of dietary  supplements.
section_title: Conclusions
paragraphs: Americans are widely interested in maintaining health and wellness and,  with an aging population, we expect that consumers’ interest in dietary  supplements will continue to grow. These consumers confront an  extensive variety of dietary supplements available in the marketplace, but  little is known about the safety and efficacy of these products. Yet, most  dietary supplements are presumed safe under current law, and companies  do not need premarket approval for any dietary supplement. If FDA has  concerns about a particular dietary supplement product or ingredient, the  agency bears the burden of proof to require removal of the product from  the market. In the case of ephedra—which was implicated in thousands of  adverse events and a number of deaths—FDA faced a long and arduous  process before finally banning the product in 2004.
At the same time, while more and more products are entering the market  each year, FDA is dedicating a small percentage of its resources to  regulating the dietary supplement industry and educating consumers  about dietary supplements. FDA does not have comprehensive knowledge  of dietary supplement manufacturers or the products on the market and  has little information about potential side effects of various products. In  addition, consumers are not well-informed about dietary supplements,  may not be aware of potential side effects of supplements, and might not  consider a dietary supplement as a factor if experiencing an adverse  reaction. Weaknesses in the regulatory system may increase the likelihood  of unsafe products reaching the market, and a lack of consumer  knowledge increases the potential health risks associated with uninformed  consumption.
section_title: Recommendations for Executive Action
paragraphs: Overall, we are making four recommendations to enhance FDA’s oversight  of dietary supplements and foods with added dietary ingredients.  1.  To improve the information available to FDA for identifying safety  concerns and better enable FDA to meet its responsibility to protect  the public health, we recommend that the Secretary of the Department  of Health and Human Services direct the Commissioner of FDA to  request authority to require dietary supplement companies to identify themselves as a dietary supplement company as part of the  existing registration requirements and update this information  annually,    provide a list of all dietary supplement products they sell and a  copy of the labels and update this information annually, and  report all adverse events related to dietary supplements.  2.  To better enable FDA to meet its responsibility to regulate dietary  supplements that contain new dietary ingredients, we recommend that  the Secretary of the Department of Health and Human Services direct  the Commissioner of FDA to issue guidance to clarify when an  ingredient is considered a new dietary ingredient, the evidence needed  to document the safety of new dietary ingredients, and appropriate  methods for establishing ingredient identity. 3.  To help ensure that companies follow the appropriate laws and  regulations and to renew a recommendation we made in July 2000, we  recommend that the Secretary of the Department of Health and Human  Services direct the Commissioner of FDA to provide guidance to  industry to clarify when products should be marketed as either dietary  supplements or conventional foods formulated with added dietary  ingredients.  4.  To improve consumer understanding about dietary supplements and  better leverage existing resources, we recommend that the Secretary  of the Department of Health and Human Services direct the  Commissioner of FDA to coordinate with stakeholder groups involved  in consumer outreach to (1) identify additional mechanisms—such as  the recent WebMD partnership—for educating consumers about the  safety, efficacy, and labeling of dietary supplements; (2) implement  these mechanisms; and (3) assess their effectiveness.
section_title: Agency Comments and Our Evaluation
paragraphs: We provided a draft copy of this report to the Department of Health and  Human Services for review and comment. We received a written response  from the Acting Assistant Secretary for Legislation that included  comments from FDA. FDA generally agreed with each of the report’s  recommendations and welcomed the report as a means of calling attention  to the challenges FDA faces with respect to regulating dietary supplements  and conventional foods formulated with added dietary ingredients. FDA  noted that although receiving information on all adverse events related to  dietary supplements could enhance FDA’s ability to detect signals of  potential toxicity over time, FDA raised concerns about its ability to  efficiently and effectively analyze the information to identify unsafe  dietary supplements. However, FDA stated that it is working on  methodologies to mitigate this concern and improve data mining for  safety-related signals if FDA were to receive all adverse event reports. In  addition, FDA recognized the need for guidance to industry clarifying  when products should be marketed as conventional foods or dietary  supplements and stated that the agency will consider this recommendation  and its implementation in light of FDA’s limited resources and competing  priorities.  Furthermore, FDA noted that the agency’s resources for  consumer education are extremely limited and that it may not be able to  effectively conduct consumer education on its own. FDA commented that  collaborating with NIH’s Office of Dietary Supplements may be an efficient  and cost-effective way to expand FDA’s current outreach activities.  FDA  also stated that the agency is identifying appropriate content for the  recently announced FDA/WebMD partnership referenced in the report and  anticipates that information on dietary supplements will be included.   FDA’s comments are presented in appendix IV of this report. FDA also  provided technical comments on the draft report, which we incorporated  as appropriate.
As agreed with your offices, unless you publicly announce the contents of  this report earlier, we plan no further distribution until 30 days from the  report date. At that time, we will send copies to the appropriate  congressional committees; the Secretary of the Department of Health and  Human Services; the Commissioner of FDA; the Director of the Office of  Management and Budget; and other interested parties. The report also will  be available at no charge on the GAO Web site at http://www.gao.gov.
If you or your staffs have any questions about this report, please contact  me at (202) 512-3841 or shamesl@gao.gov. Contact points for our Offices  of Congressional Relations and Public Affairs may be found on the last  page of this report. GAO staff who made major contributions to this report  are listed in appendix V.
section_title: Appendix I: Objectives, Scope, and Methodology
paragraphs: We were asked to examine the Food and Drug Administration’s (FDA)  oversight of dietary supplements and foods that contain added dietary  ingredients. Specifically, we were asked to examine FDA’s (1) actions to  respond to the new serious adverse event reporting requirements; (2)  ability to identify and act on concerns about the safety of dietary  supplements; (3) ability to identify and act on concerns about the safety of  foods with added dietary ingredients; and (4) actions to educate  consumers about the safety, efficacy, and labeling of dietary supplements.  Our work included dietary supplements for human use only. We did not  assess FDA’s regulation of dietary supplements for animal use.
To identify FDA’s actions to respond to the new serious adverse event  reporting requirements, we reviewed FDA’s guidance on reporting  requirements for industry and internal procedures for compiling and  tracking adverse event reports. In addition, we obtained and analyzed data  on the number and type of reports received before and after the  requirements went into effect. We verified our methodology for analyzing  these data with FDA officials, and FDA verified our results. We also  reviewed FDA’s plans for improving adverse event reporting.
To examine FDA’s ability to identify and act on safety concerns associated  with dietary supplements, we assessed FDA’s laws, rules, regulations,  planning documents and guidance, such as the Dietary Supplement Health  and Education Act of 1994, Current Good Manufacturing Practice  regulations, and guidance on reporting adverse events. In addition, we  obtained and analyzed data on FDA’s internal procedures and activities to  identify safety concerns, such as conducting inspections and import  screenings and receiving consumer complaints. We also obtained and  analyzed FDA’s internal procedures and data on the agency’s actions once  a safety concern is identified, including issuing warning letters, seizing  products, and banning ingredients. We analyzed these data to determine  the range and extent of actions FDA has taken to identify and act on safety  concerns associated with dietary supplements. We verified our  methodology for analyzing these data with FDA officials, and FDA verified  our results. Furthermore, we reviewed data on FDA resources dedicated  to dietary supplements.
To examine FDA’s ability to identify and act on concerns about the safety  of foods with added dietary ingredients, we reviewed laws and regulations  regarding food additives. In addition, we reviewed FDA’s procedures for  identifying and acting on safety concerns of foods with added dietary  ingredients. We also identified and analyzed instances of actions taken by  FDA to act on safety concerns associated with the addition of dietary  ingredients to foods.
To determine FDA’s actions to educate consumers about the safety,  efficacy, and labeling of dietary supplements, we reviewed FDA’s  consumer outreach initiatives. We also obtained and analyzed data on the  extent to which these outreach initiatives were distributed. In addition, we  analyzed data from FDA and others on consumer understanding of dietary  supplements.
To compare FDA’s regulation of dietary supplements with select other  countries’ regulation of these products, we spoke with representatives  from the governments of Canada, Japan, and the United Kingdom. In  addition, we reviewed documents about the regulation of dietary  supplements in these countries. We did not independently verify  descriptions of foreign laws. We selected these countries because they had  been identified in prior GAO work as having comparable food safety  systems and covered a relatively diverse geographic area (Europe, North  America, and Asia.)
To assess the reliability of the data from FDA’s databases used in this  report, we reviewed related documentation, examined the data to identify  obvious errors or inconsistencies, and worked with agency officials to  identify any data problems. We determined the data to be sufficiently  reliable for the purposes of this report.
To obtain insights on all four objectives, we met with a wide range of  experts, including officials from federal and state agencies, industry and  trade organizations, consumer advocacy groups, academia, and poison  control centers. Through these efforts, we obtained documents and  information related to all four objectives. At the federal level, we met with  officials from FDA, including headquarters and regional and district level  officials, to discuss the agency’s regulatory authorities, actions taken to  implement the mandatory adverse event reporting system, steps taken to  regulate the safety of dietary supplements and foods with added dietary  ingredients, and consumer education responsibilities and actions. In  addition, we met with officials from the National Institutes of Health,  Federal Trade Commission, and Department of Agriculture. At the state  level, we met with officials from the California Department of Public  Health’s Food and Drug Branch and Environmental Protection Agency and  the New York State Task Force on Life and the Law. To obtain insights  from the dietary supplement and food industries, we met with officials  from the American Beverage Association, American Herbal Products  Association, Consumer Healthcare Products Association, Council for  Responsible Nutrition, Grocery Manufacturers Association, National  Advertising Division of the Council of Better Business Bureaus, and  Natural Products Association. In addition, we met with officials from a  large dietary supplement manufacturer in Maryland, a multinational food  and consumer products firm, and two small, herbal products  manufacturers in California. To obtain insights from consumer advocacy  groups, we met with officials from the Center for Science in the Public  Interest, Consumers Union, and Public Citizen. To obtain insights from  public health organizations, the health care community, and academia, we  met with officials from the American Association of Poison Control  Centers; American Medical Association; California Poison Control System;  New York City Poison Control Center; U.S. Pharmacopoeia; Baylor College  of Medicine; Critical Path Institute; Center for Advanced Food  Technology, Rutgers University; Stony Brook University; Center for  Consumer Self Care, Department of Clinical Pharmacy, and Osher Center  for Integrative Medicine, University of California, San Francisco; and the  University of California, Berkeley.
We conducted this performance audit from December 2007 through  January 2009, in accordance with generally accepted government auditing  standards. Those standards require that we plan and perform the audit to  obtain sufficient, appropriate evidence to provide a reasonable basis for  our findings and conclusions based on our audit objectives. We believe  that the evidence obtained provides a reasonable basis for our findings  and conclusions based on our audit objectives.
section_title: Appendix II: Data on FDA’s Actions to Identify and Respond to Safety Concerns Related to Dietary Supplements
paragraphs: This appendix provides additional detail on FDA’s actions to identify and  respond to safety concerns related to dietary supplements.
subsections: section_title: Data on FDA’s Actions to Identify Safety Concerns Related to Dietary Supplements
paragraphs: FDA actions to identify safety concerns related to dietary supplements  include receiving and analyzing adverse event reports and consumer  complaints and conducting inspections.
subsections: section_title: Data on Adverse Events Related to Dietary Supplements
paragraphs: Table 6 compares the number of adverse event reports received and  entered into FDA’s databases for review related to dietary supplements  and drugs and biologics from January 1, 2003, through December 31, 2007.
Table 7 compares the number of dietary supplement-related adverse event  cases characterized as serious from January 1, 2003, through October 31,  2008, and the total number of dietary supplement-related adverse event  cases.
Table 8 shows the number and types of outcomes for all dietary  supplement-related adverse event cases received by FDA from   January 1, 2003, through October 31, 2008.
Table 9 shows the number of dietary supplement-related adverse event  cases by product type from January 1, 2003, through October 31, 2008.
Table 10 shows the number of dietary supplement-related consumer  complaints by adverse event result for fiscal year 2001 through July 3,  2008.
Table 11 shows the number of dietary supplement-related consumer  complaints with adverse symptoms present by adverse event result and  FDA product class from fiscal year 2001 through July 3, 2008.
Table 12 shows the number of foreign and domestic inspections of dietary  supplement facilities compared with food inspections and total  inspections conducted by FDA and states from fiscal years 2000 through  2008.
Table 13 shows the percentage of dietary supplement inspections where  investigators identified problems, from fiscal year 2002 through May 6,  2008.
section_title: Data on FDA’s Actions to Respond to Safety Concerns Related to Dietary Supplements
paragraphs: FDA actions to respond to safety concerns related to dietary supplements  include issuing warning letters to dietary supplement firms, requesting  recalls, and detaining and refusing imports.
subsections: section_title: Data on Dietary Supplement- Related Warning Letters
paragraphs: Table 14 shows the number of Federal Food, Drug, and Cosmetic Act  violations cited in 293 dietary supplement-related warning letters issued  from fiscal years 2002 through 2007.
Table 15 shows the number of dietary supplement-related warning letters  compared with total warning letters issued by FDA from fiscal years 2002  through 2007.
Table 16 provides information on examples of Class I recalls related to  dietary supplement products from fiscal years 2003 through 2008.  According to FDA, Class I recalls are related to products that are  dangerous and defective and pose a serious health concern. A firm may  initiate a recall independently of FDA, or FDA may request a firm recall a  product upon identifying a problem with a product.
Table 17 shows the number of detentions without physical examination of  imported dietary supplement products by general violation categories  from fiscal year 2002 through March 24, 2008.
Table 18 shows the number of detentions without physical examination of  imported dietary supplement products by product classification from  fiscal year 2002 through March 24, 2008.
Table 19 shows the number of Federal Food, Drug, and Cosmetic Act  violations cited in 3,605 dietary supplement-related import refusals from  fiscal year 2002 through March 24, 2008.
Table 20 shows the number of refused imports of dietary supplement  products by product classification from fiscal year 2002 through March 24,  2008.
section_title: Data on FDA Enforcement Actions Related to Dietary Supplements
paragraphs: FDA’s enforcement actions related to dietary supplements include  seizures, injunctions, and criminal investigations. Table 21 shows  information about dietary supplement-related seizure and injunction  actions taken from fiscal year 2002 through July 18, 2008.
Table 22 summarizes dietary supplement-related criminal investigations  resulting in at least one conviction or with charges filed from 2002 through  July 31, 2008.
section_title: Appendix III: Comparison of Select Foreign Countries’ Regulation of Dietary Supplements with the United States
paragraphs: In comparison with the United States, Canada and Japan have more  regulatory requirements in place for dietary supplements and related  products. On the other hand, the United States has developed specific  good manufacturing practices for dietary supplements while the United  Kingdom has not. Table 23 compares the regulatory framework for dietary  supplement products in these foreign countries with the U.S. regulatory  system.
In Canada, companies are required to obtain a product license to market  natural health products, which include a range of products, such as  vitamin and mineral supplements, herbal remedies, and other products,  based upon their medicinal ingredients and intended uses. The product  licensing application must include detailed information about the product,  ingredients, potency, intended use, and evidence supporting the product’s  safety and efficacy. Approved products are assigned a license number that  is displayed on the product label. Manufacturers, packagers, labelers, and  importers of natural health products must obtain a site license to perform  these activities. To obtain a site license, a firm must provide evidence of  quality control procedures that meet government standards for good  manufacturing practices. Firms are required to report any serious adverse  reactions associated with their products within 15 days and must provide  information summarizing all adverse reactions, including mild or moderate  events, on an annual basis.
In the United Kingdom (U.K.), dietary supplements are legally termed  “food supplements” and are regulated under food law—most of which is  European Community (E.C.) legislation implemented at the national level,  according to a U.K. official.  Food supplements are generally not subject to  premarket approval. For example, any supplement that either meets the  guidelines established under E.U. law for specific vitamins and minerals,  or does not include a new or genetically modified ingredient, does not  require approval prior to marketing. According to a U.K. official, most  direct oversight of the dietary supplement industry in the United Kingdom  occurs at the local level of government. For example, all investigations,  enforcement actions, and monitoring activities such as inspections are  undertaken at the local level. Food supplement firms are required to  register with local authorities and should detail the specific activities  undertaken at each establishment as part of this process. However,  centralized information on registered firms is not collected or maintained  at a national level. Additionally, there is no centralized registry of food  supplement products in the U.K. Although government standards for food  good manufacturing practices apply to food supplement manufacturing,  there are no good manufacturing practice guidelines specific for food  supplements. Under E.C. law, firms are required to report any problems  with food products to the local and national authorities and, if the product  is injurious to health, the firm must remove it from the market.
In Japan, products are regulated based on their product claims. There are  two types of claims: Food with Nutrient Function Claims (FNFC), which  are standardized, preapproved claim statements for certain vitamins and  minerals with established benefits, and Food for Specified Health Uses  (FOSHU) claims, which require government approval for safety and  efficacy prior to marketing a product advertised as having a physiological  effect on the body. Since FNFC claims are standardized and preapproved,  firms do not need to notify the government prior to marketing a product  using an approved FNFC claim, provided the product meets established  ingredient content specifications. To use a FOSHU claim on a product, a  firm is required to provide the government with evidence supporting the  product’s physiological effect and safety prior to marketing. Additionally, a  firm must provide information on the firm and its product to the  government, as well as evidence of quality control processes.
section_title: Appendix IV: Comments from the Department of Health and Human Services
section_title: Appendix V: GAO Contact and Staff Acknowledgments
subsections: section_title: Staff Acknowledgments
paragraphs: In addition to the individual named above, José Alfredo Gómez, Assistant  Director; Kevin Bray; Nancy Crothers; Michele Fejfar; Alison Gerry  Grantham; Barbara Patterson; Minette Richardson; Lisa Van Arsdale; and  Chloe Wardropper made key contributions to this report.