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 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. 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. 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.