Dietary Supplements, Infant Formulas, Cosmetics

• Dietary supplements
  
  
  • More than 115 million Americans consume dietary supplements. Millions of others buy these products for their friends or family. Supplement sales exceeded $17 billion in 2000, according to the FDA.
  
  
  
  • According to CFSAN, "[a] dietary supplement is a product taken by mouth that contains a "dietary ingredient" intended to supplement the diet." Amino acids, botanical products (herbs), minerals, and vitamins as well as extracts and concentrates are some examples of "dietary ingredients" cited by CFSAN.
  
  
  
  • Supplements may come in a variety of forms but "whatever their form may be, the Dietary Supplements Health and Education Act (DSHEA) places dietary supplements in a special category under the general umbrella of "foods," not drugs, and requires that every supplement be labeled a dietary supplement" so that they are not confused with "conventional food[s]" (CFSAN, Overview of Dietary Supplements, 2001).
    
    
    • Before DSHEA, supplements were regulated as foods or drugs depending on how they were labeled. With DSHEA, supplements became a distinct category of product, no longer subject to the premarket approval requirements pertaining to drugs or food additives. The line between supplements, foods, and drugs remains unclear, and the FDA is "engaged in the difficult task of delineating boundaries" between these products. Another challenge facing the FDA is clarifying when a disease-related statement is an appropriate health claim for a dietary supplement, and when a disease claim for a product is necessarily a drug claim. Since drugs and dietary supplements are overseen by FDA in a very different fashion, clarification of this distinction is quite important in how the product will be regulated.
    
    
    
    • Although premarket approval for supplements is not required, manufacturers must inform the FDA when they use "new dietary ingredients" that are "vitamin[s], mineral[s], herb[s], or other botanical, amino acid, or dietary substance[s] for use by man to supplement the diet." "New" means that the product is not historically part of the diet or that the ingredient is not in its natural form. In addition, manufacturers must have some evidence to substantiate their labeling claims.
    
    
    
    • As a general rule, the manufacturers do not register with FDA.
    
    
    
    • Presently, the manufacturer bears the sole responsibility for ensuring that its products "contain the ingredients listed on the label" and that the product is "safe for use in a dietary supplement." Dietary supplement manufacturers are not inspected by the FDA nor are they under any current obligation to conform to good manufacturing practices. Indeed, DSHEA "places the burden on FDA to prove that a product presents a significant or unreasonable risk of illness or injury under the label’s conditions of use before it can be removed form the marketplace."
    
    
    
    • To address safety issues and ensure consumers can rely on the quality of supplements, the FDA has indicated that it plans to issue good manufacturing practice regulations "that will focus on practices that ensure the identity, purity, quality, strength and composition of dietary supplements." This should give a higher confidence level in the products to the consuming public. Although these GMPs have been long-delayed, FDA Deputy Commissioner Lester Crawford said at a June 17, 2002, session of the Association of Food and Drug Officials that the GMPs should be completed by the end of the summer or early fall and the strategic plan for dietary supplements states that issuing such guidance is a high priority.
    
    
    
    • The FDA has worked with the Federal Trade Commission, which regulates fraudulent advertising for non-prescription medical products such as dietary supplements. Through Operation Cure-All, the FDA, FTC, and various state regulatory agencies have sent "cyber letters" to web sites making improper health claims for dietary supplements, in particular, as well as other products that have not been approved by the FDA or medically validated.
    
    
    
    • As part of its Consumer Health Information for Better Nutrition initiative the FDA published a "Dietary Supplement Enforcement Report" summarizing its recent activity in this area, which includes seizures, injunctions, and criminal prosecution of those selling products that make claims that the product treats such diseases or conditions as cancer and obesity. The report also states that "certain products that are clearly problematic and which warrant close scrutiny." Such products include dietary supplements marketed as treatments for autism, behavioral disorders, mental retardation and Down’s syndrome; supplements advertised as cures for cancer; colloidal silver products which some supplement manufacturers claim can cure Alzheimer disease and cancer; supplements advertised as cures for such "life-threatening diseases" as cancer, lupus, and human immunodeficiency virus (HIV); and supplements that promise to help users reduce health problems associated with drinking or smoking. As part of itsenforcement effort, the agency not only will take action against supplement manufacturers that break the law but also will help manufacturers understand their legal obligations by providing additional guidance and educating consumers and health care professionals. (See the FDA’s kava have spurred some to call for additional regulation of the industry. According to a recent Department of Health and Human Services press release, the FDA has sent 6 Warning Letters to companies selling "synthetic ephedra alkaloid products," and the Department of Health and Human Services is funding a study by the RAND Corporation on the health effects of ephedra. Although ephedra derived from herbal sources is considered a supplement, synthetic forms of ephedrine are considered drugs. In 2002, following an FDA seizure of several of its products, a Utah-based supplement company signed a consent decree agreeing to stop manufacturing synthetic ephedrine-containing products. The Department of Health and Human Services has sponsored a scientific review of the risks of using ephedra-containing products,solicited public input about a proposed warning label for these products, and issued Warning Letters to companies implying that ephedra may enhance "athletic performance" (FDA, HHS Acts to Reduce Potential Risks, 2003).
    
    
    
    • Adverse events involving dietary supplements can be reported to the Special Nutritionals Adverse Event Monitoring System. But because the FDA has limited information about manufacturers and supplement products, manufacturers are not required to report adverse events, and because consumers may not report adverse events or fail to identify problems caused by dietary supplements, the OIG suggests that many events are undetected. DSHEA has placed the burden of proving supplements unsafe on the FDA rather than on the manufacturer. The FDA has tested a new voluntary adverse event reporting system for cosmetics, dietary supplements, and foods.
    
    
    
    • The Center for Food Safety and Applied Nutrition’s Adverse Event Reporting System (CAERS) began accepting adverse event reports in June 2003. CAERS is intended to "replace the patchwork of existing adverse event systems that were maintained by individual offices within CFSAN," according to an August 29, 2002, Center letter to stakeholders. Companies will receive letters from the Center notifying them that one of their products has been the subject of a report.
  
  
  • Labeling of supplements: Like foods, dietary supplements must list ingredients, including nutrients that have established daily values. Supplements also must be identified as such and, if botanical products, identify the part(s) of the plant from which the product is derived.
    
    
    • Supplement labels also provide the number of tablets, capsules or gels, the name and address of the manufacturer. Directions for how and how often to use the product must be provided, and the label should tell consumers the composition of the product using the following format: name of the vitamin/mineral; where the ingredient is derived from; the quantity per capsule or tablet and percentage of recommended daily allowance that the quantity represents. For instance, one author cites the following example: Calcium, as calcium carbonate, 1,000 mg per tablet, 100 percent of the US RDA.
    
    
    
    • Manufacturers must notify the FDA when they intend to market a supplement with a label that contains a statement that the supplement contributes to health, affects the body’s structure or function or relieves a certain nutrient deficiency, and must attest that the statement is "truthful and not misleading" (nutritional support statement). A disclaimer is required stating: "This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease."
    
    
    
    • As with foods, supplement manufacturers are permitted to make different types of labeling claims:
      
      
      • Nutrient content claims: As with foods, dietary supplements can make nutrient content claims (such as low or high), in accordance with FDA regulations. For nutrients for which no daily value is established, supplement manufacturers also can inform consumers of the absolute percentage of a nutrient in the product (such as 40% omega-3-fatty acids) or compare the amount of nutrient in the product to another product. Examples of such claims include the relationship between calcium and reduced risk of osteoporosis or plant sterol/stanol esters and risk of coronary heart disease.
      
      
      
      • Qualified health claims: Following a 1999 U.S. Court of Appeals for the District of Columbia decision, Pearson v. Shalala, even when substantial scientific agreement may be lacking, supplement manufacturers (but not food manufacturers) are permitted to make statements supported by the "weight of the scientific evidence" if these statements are accompanied by a disclaimer or qualification indicating that the evidence is not definitive; that the scientific evidence "in support of the claim outweighs the scientific evidence against the claim" and that the claim is consistent with "consumer health and safety."
      
      
      
      • The Pearson case started after manufacturers rejected the FDA’s approach toward claims regarding consumption of folic acid and the risk of spinal chord (neural tube) birth defects; fiber and the risk of colorectal cancer; omega-3 fatty acids and the risk of coronary heart disease, and antioxidant vitamins and the risk of some types of cancer. After the Pearson decision, supplement manufacturers were permitted to make the following qualified claim with respect to supplements containing folic acid and the risk of neural tube defects: "0;.8 mg folic acid in a dietary supplement is more effective in reducing the risk of neural tube defects than a lower amount in foods in common form. FDA does not endorse this claim. Public health authorities recommend that women consume 0.4 mg folic acid daily from fortified foods or dietary supplements or both to reduce the risk of neural tube defects."
      
      
      
      • Supplement manufacturers also may make the following claim about the effect of consumption of omega-3 fatty acids and coronary heart disease: "Consumption of omega-3 fatty acids may reduce the risk of coronary heart disease. FDA evaluated the data and determined that, although there is scientific evidence supporting the claim, the evidence is not conclusive."
      
      
      
      • Qualified health claims also are permitted for folic acid, vitamin B6 and vitamin B12 and vascular disease.
      
      
      
      • The FDA has rejected certain qualified health claims proposed by manufacturers. In a May 2001 letter, the FDA rejected a claim for antioxidant vitamins (for example, vitamin C and vitamin E) and reduced risk of certain cancers because the "scientific evidence demonstrates a lack of significant scientific agreement" establishing such a relationship. In February 2001, the FDA rejected a proposed claim regarding consumption of vitamin E and reduced risk of cardiovascular disease. In 2000, the FDA rejected a proposed claim concerning dietary fiber in supplements and reduced risk of colorectal cancer after the agency’s review of the scientific evidence failed to demonstrate "significant scientific agreement." Indeed, the agency asserted in a letter that the scientific evidence "provides strong evidence that such a relationship does not exist."
      
      
      
      • Qualified health claims continue to be the subject of heated controversy and litigation. These types of health claims currently are permitted for dietary supplements but not for foods. However, a former FDA chief counsel submitting comments to the FDA on behalf of the Grocery Manufacturers of America recently suggested that food manufacturers, like dietary supplement manufacturers, should be permitted to make such claims because "neither Pearson nor the First Amendment permits the FDA to treat the speech of dietary supplement manufacturers differently from the speech of conventional food manufacturers" (Hutt, "The D.C. Circuit’s Opinion in Pearson v. Shalala and the First Amendment to the U.S. Constitution Require FDA To Permit in Conventional Food Labeling the same Qualified Disease Claims That It Permits in Dietary Supplement Labeling," White Paper submitted to FDA Docket No. 02N-0209 (First Amendment Issues) on behalf of the Grocery Manufacturers of America, June 21, 2002).
    
    
    • In December 2002, the FDA announced that as part of its new "Consumer Health Information for Better Nutrition" initiative it would provide additional guidance for food manufacturers wishing to make qualified health claims. The FDA published "Guidance for Industry: Qualified Health Claims in the Labeling of Conventional Foods and Dietary Supplements" was published in the Federal Register December 20, 2002 (FDA, FDA announces initiative to provide better health information, 2002). Manufacturers believing that the "weight of the scientific evidence" supports the benefits of a food product can petition the agency to allow a qualified health claim. The agency hopes that the new policy will "enable consumers to make informed dietary choices yielding potentially significant health benefits." For instance, at a Dec. 18, 2002, press conference, FDA and Federal Trade Commission officials who will work with the FDA in implementing the new initiative (the FTC regulates food advertising) suggested that foodmanufacturers might be able to make claims about possible health benefits of omega-3 fatty acids. A task force of senior FDA officials will help the FDA develop a strategy to review proposed health claims.
    
    
    
    • While food and dietary supplement trade associations - such as the National Food Processors Association, Grocery Manufacturers of America, and Council for Responsible Nutrition - were enthusiastic about the agency's plan to allow qualified health claims for foods as part of its consumer outreach initiative, the Center for Science in the Public Interest pointed to the abundance of misleading dietary supplement claims and expressed concern that the FDA’s initiative would "lower the standard for health claims for foods to that which has been followed for dietary supplements" (CSPI, Statement of CSPI Legal Director, 2002; Guide to US Food Labeling Law, 2003).
    
    
    
    • Structure/function claims: These claims describe how the supplement affects the body’s structure and function (structure/function claim) and or how the supplement can alleviate a common nutritional deficiency. An example of a structure/function claim is "antioxidants maintain cell integrity." But the labeling also must note that "This statement has not been evaluated by the Food and Drug Administration," and manufacturers must notify the FDA of the claim.
    
    
    
    • The FDA has issued a rule describing acceptable structure/function claims such as "supports the immune system" or "helps promote digestion." Also, manufacturers cannot claim that the product treats or cures a disease (cures cancer) because the supplement then would be considered a drug and must have evidence to substantiate their structure/function claims. It should be noted that because the FDA considers obesity to be a disease a claim that a supplement "aids in combating obesity" would constitute a prohibited claim that the supplement can be used to "diagnose, mitigate, treat, cure or prevent a specific disease or class of diseases."
    
    
    
    • Supplement manufacturers cannot currently make health claims based on authoritative statements as permitted for foods, but the FDA has proposed a rule that would allow supplement manufacturers to make these types of statements.

• Infant Formulas
  
  
  • Infant formulas are defined in section 201 (z) of the Act as a food that "purports to be or is represented for special dietary solely as a food for infants by reason of its simulation of human milk or its suitability as a complete or partial substitute for human milk." Under section 412 of the Act, manufacturers must conform to good manufacturing practice, register with the FDA, test the product to ensure there are certain levels of vitamins and that the product is not contaminated by bacteria, retain certain records, recall products that do not conform to these requirements. Adverse events involving infant formula products should be reported to the FDA’s Botulinum Toxin Type A), manufactured by Allergen, which was approved in April 2002 to "temporarily improve the appearance of moderate to severe frown lines between the eyebrows (glabellar lines), a medical condition that is not serious." BOTOX® is available only by prescription. Because BOTOX® is a protein produced by a microbe, it is a biologic "drug" product and falls under the jurisdiction of the Center for Biologics Evaluation and Research.