Dietary Supplements: FDA Should Take Further Actions to Improve Oversight and Consumer Understanding
Released: 2009-03-02T00:00:00

Letter

Background

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.

FDA Has Made Changes in Response to the New Serious Adverse Event Reporting Requirements and Has Received an Increased Number of Reports

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.

FDA Has Taken Several Actions in Response to the New Serious Adverse Event Reporting Requirements

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.

FDA Has Received an Increased Number of Adverse Event Reports Since Mandatory Reporting Went into Effect

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.

Although FDA Has Taken Some Steps to Identify and Act on Concerns about the Safety of Dietary Supplements, Several Factors Limit Its Oversight

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.

FDA Has Taken Some Actions to Identify and Act on Concerns about the Safety of Dietary Supplements

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.

Several Factors Limit FDA’s Ability to Identify and Act on Safety Concerns Related to Dietary Supplements

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.

FDA’s Ability to Identify Safety Concerns Is Hindered by a Lack of Information

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.

FDA Dedicates Relatively Few Resources to Dietary Supplement Oversight

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.

FDA’s Lack of Authority Limits Its Ability to Remove Products from the Market

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.

While FDA Has Taken Some Actions When Foods Contain Unsafe Dietary Ingredients, Certain Factors May Allow Unsafe Products to Reach Consumers

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.

Companies Are Not Required to Notify FDA When They Make a Self- Determination That an Added Ingredient Is GRAS

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.

The Boundary between Dietary Supplements and Foods with Added Dietary Ingredients Is Not Always Clear

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.

FDA Conducts Limited Monitoring of Foods with Added Dietary Ingredients

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.

FDA Has Taken Limited Steps to Educate Consumers about Dietary Supplements, and Consumers Remain Largely Uninformed

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.

FDA Has Conducted Some Consumer Education about Dietary Supplements, but these Efforts Have Been Limited

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.

Consumers Are Not Well- Informed about the Safety, Efficacy, and Labeling of Dietary Supplements

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.

Conclusions

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.

Recommendations for Executive Action

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.

Agency Comments and Our Evaluation

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.

Appendix I: Objectives, Scope, and Methodology

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.

Appendix II: Data on FDA’s Actions to Identify and Respond to Safety Concerns Related to Dietary Supplements

This appendix provides additional detail on FDA’s actions to identify and respond to safety concerns related to dietary supplements.

Data on FDA’s Actions to Identify Safety Concerns Related to Dietary Supplements

FDA actions to identify safety concerns related to dietary supplements include receiving and analyzing adverse event reports and consumer complaints and conducting inspections.

Data on Adverse Events Related to Dietary Supplements

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.

Data on FDA’s Actions to Respond to Safety Concerns Related to Dietary Supplements

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.

Data on Dietary Supplement- Related Warning Letters

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.

Data on FDA Enforcement Actions Related to Dietary Supplements

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.

Appendix III: Comparison of Select Foreign Countries’ Regulation of Dietary Supplements with the United States

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.

Appendix IV: Comments from the Department of Health and Human Services

Appendix V: GAO Contact and Staff Acknowledgments

Staff Acknowledgments

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.