1 Dietary Supplement Health and Education Act of 1994, Pub. L. No. 103-417, 108 Stat. 4325, 4326 (1994) (codified in scattered sections of 21 U.S.C.) [hereinafter DSHEA].

2 See Kaiser, Iona N., Dietary Supplements: Can the Law Control the Hype?, 37 Hous. L. Rev. 1249, 1250 (2000)Google Scholar (“In 1994, under great pressure from the public and herbal supplement manufacturers, the United States Congress passed the Dietary Supplement Health and Education Act of 1994.”).

3 See DSHEA, supra note 1.

4 Several bills were introduced in the last Congressional session that would amend DSHEA. See, e.g., Dietary Supplement Safety Act of 2003, S. 722, 108th Cong. (2003); Dietary Supplement Information Act, H.R. 724, 108th Cong. (2003). However, there is no current effort to change the “New Dietary Ingredient” section of DSHEA that is the subject of this article.

5 21 U.S.C. § 350b (2000).

6 21 U.S.C. § 350b(c).

7 See 21 U.S.C. §§ 321(ff)(1), 350b.

8 See, e.g., Meeting Notice, FDA, Notice of Dietary Supplement Public Meeting, Pre-Market Notification Program for New Dietary Ingredients, 69 Fed. Reg. 61680 (Oct. 20, 2004), available at http://www.cfsan.fda.gov/∼lrd/fr041020.html (“What should FDA consider to determine whether a substance falls within a particular category of the statutory definition of ``dietary ingredients'’ under sections 201(ff)(1)(A) through (F) of the act?”).

9 21 U.S.C. § 350b(a)(2).

10 21 U.S.C. § 342(f)(1)(C) (2000).

11 21 U.S.C. § 342(f)(1)(A).

12 21 U.S.C. § 321(ff)(3)(A)-(B) (2000).

13 DSHEA § 9. FDA has promised to publish a final dietary supplement GMP rule by December 31, 2004. However, at the time this article was written, no such rule was forthcoming. See Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Dietary Supplements, 62 Fed. Reg. 5700 (proposed Feb. 6, 1997).

14 21 U.S.C. § 350b.

15 See S. REP. NO. 103-410 (1994).

16 Id.

17 Id.

18 21 U.S.C. § 321(ff)(1)-(3).

19 See S. REP. NO. 103-410 (1994).

20 Id.

21 FDA, supra note 8.

22 See DSHEA.

23 FDA, supra note 8.

24 See, e.g., S. REP. NO. 103-410, at §§ 2, 3 (stating that the purpose of DSHEA is to “clarify that dietary supplements are not drugs or food additives” and to clarify that “regulations relating to food additives are not applicable to dietary supplements and their ingredients used for food additive purposes, such as stabilizers, processing agents, or preservatives”).

25 DSHEA § 3(a).

26 DSHEA § 4.

27 DSHEA § 9.

28 DSHEA § 6; A dietary supplement label may describe the supplement's effects on “structure or function” of the body or the “well-being” achieved by consuming the dietary ingredient. To use these claims, there must be substantiation that the statements are truthful and not misleading and the product label must bear the statement, “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.” Nutritional support statements need not be approved by FDA before manufacturers market products bearing the statements; however, the agency must be notified no later than thirty days after a product that bears the claim is first marketed. Id.

29 DSHEA § 7(b).

30 DSHEA § 5.

31 See supra note 13 and accompanying text.

32 21 U.S.C. § 342(f)(1)(C).

33 See 21 C.F.R. § 2.5 (2005).

34 21 U.S.C. § 342(f)(1)(C).

35 Final Rule Declaring Dietary Supplements Containing Ephedrine Alkaloids Adulterated Because They Present An Unreasonable Risk, 69 Fed. Reg. 6788 (Feb. 11, 2004) (codified at 21 C.F.R. pt. 119). In the past year, FDA demonstrated that it can effectively remove unsafe dietary supplements from the market. After years of controversy, FDA banned ephedrine alkaloids from dietary supplements on April 12, 2004. Id. For the first time, FDA determined that a dietary supplement posed an unreasonable risk and removed it from the market. FDA found that ephedrine alkaloid dietary supplements are adulterated under the FFDCA since they present an unreasonable risk of illness or injury if used as labeled or under ordinary conditions. The agency reached its conclusion seven years after proposing restrictions on ephedrine alkaloid dietary supplement products, and after looking at pharmacology studies, scientific literature on ephedrine alkaloid effects, and thousands of adverse event reports. Id.

36 Id.

37 DSHEA § 8; see infra Section C.

38 The new dietary ingredient section does not limit the form of dietary ingredients set forth in § 201(ff)(1)(E).

39 21 U.S.C. § 350b(a)(2).

40 21 U.S.C. § 342(g).

41 Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Dietary Ingredients and Dietary Supplements, 68 Fed. Reg. 12,158 (proposed Mar. 13, 2003). Publication of the final rule is imminent.

42 21 U.S.C. § 350b(c).

43 DSHEA § 8.

44 Id.

45 The § 342(f) adulteration provision would apply if the dietary supplement contains an NDI and failed to meet the § 350b(a)(1) or (2) requirements. Further, the dietary supplement as a whole could be considered adulterated if it did not meet the standard that it not “present a significant unreasonable risk of illness or injury under (i) conditions of use recommended or suggested in labeling, or (ii) if no conditions of use are suggested or recommended in the labeling, under ordinary conditions of use.” 21 U.S.C. § 342(f)(1).

46 Nutrition Labeling of Dietary Supplements, 21 C.F.R. § 101.36 (2005) (“The names of dietary ingredients that are declared under ¶ (b)(2)(i) [requiring declaration when a claim is made about such ingredients] of this section shall be presented in a column aligned on the left side of the nutrition label …”).

47 DSHEA §§ 3, 8; Designation of Ingredients, 21 C.R.R. § 101.4(g) (regulating labels for dietary supplements containing such other ingredients).

48 21 U.S.C. § 350b(c).

49 See FDA, New Dietary Ingredients in Dietary Supplements, at http://www.cfsan.fda.gov/∼dms/ds-ingrd.html (Sept. 10, 2001).

50 See, e.g., NATIONAL NUTRITIONAL FOODS ASSOCIATION, “GRANDFATHERED LIST” (on file with authors) [hereinafter NNFA]; COUNCIL FOR RESPONSIBLE NUTRITION, LIST OF DIETARY INGREDIENTS “GRANDFATHERED” UNDER DSHEA (1998) (on file with authors) [hereinafter CRN].

51 Id.

52 Id.

53 Letter from Felicia B. Satchell, Office of Nutritional Products, Labeling and Dietary Supplements to Holly M. Bayne, Hyman, Phelps & McNamara, P.C., 2 (July 15, 2001), available at http://www.fda.gov/ohrms/dockets/dockets/95s0316/let0004.pdf.

54 Id.

55 See id.

56 Id. at 2-3.

57 21 U.S.C. § 350b(a)(1).

58 Id.

59 140 CONG. REC. H11173 (daily ed. Oct. 6, 1994) (statement of Rep. Waxman).

60 Email from Robert J. Moore, Center for Food Safety and Applied Nutrition to Emily Marden, Sidley Austin Brown & Wood LLP (Apr. 22, 2004) (on file with author).

61 The nature of this exemption may be the subject to further comment by FDA following the current comment period.

62 21 U.S.C. § 350b(a)(2).

63 The regulation that has been issued, 21 C.F.R. 190.6, deals only with the administrative details of filing an NDI notification, containing, for example, indication that the notification must contain the name and address, the name of the NDI, etc.

64 Based on reviews by the authors of FDA responses to NDI notifications over the past five years.

65 See Press Release, FDA, FDA Announces Major Initiatives for Dietary Supplements (Nov. 4, 2004), available at http://www.fda.gov/bbs/topics/news/2004/NEW01130.html.

66 See id.

67 While most of the elements of the initiative confirm the FDA's ongoing enforcement policy for dietary supplements, the agency has announced several significant new positions. These include: (1) a “signal detection” approach to safety issues, indicating that the agency intends to respond more quickly to potential issues; (2) heightened review and enforcement of new dietary ingredient safety submission requirements; and (3) a focus on cautionary information required on dietary supplement labels. Id.

68 Id.

69 Id.

70 See, e.g., Letter from Thomas D. Gardine, District Director, Philadelphia District, FDA to James Vercellotti, President, ATF Fitness Products, Inc. (Nov. 19, 2004), available at http://www.fda.gov/foi/warning_letters/g5134d.htm; Thomas D. Gardine, District Director, Philadelphia District, FDA to Darlene Doble, President, The Sanapac Co., Inc. (Dec. 10, 2004), available at http://www.fda.gov/foi/warning_letters/g5122d.htm [hereinafter Letter to The Sanapac Co., Inc.].

71 Press Release, U.S. Department of Health and Human Services, HHS Launches Crackdown on Products Containing Andro: FDA Warns Manufacturers to Stop Distributing Such Products (Mar. 11, 2004), available at http://www.fda.gov/bbs/topics/news/2004/hhs_031104.html.

72 Meeting Notice, FDA, Notice of Dietary Supplement Public Meeting, Pre-Market Notification Program for New Dietary Ingredients, 69 Fed. Reg. 61680 (Oct. 20, 2004), available at http://www.cfsan.fda.gov/∼lrd/fr041020.html.

73 Id.

74 CFSAN 2005 Priorities: NDI Revised Definitions, Health Claims Rule, HEALTH NEWS DAILY (Dec. 2, 2004).

75 FDA, Dietary Supplement Health and Education Act of 1994, available at http://www.cfsan.fda.gov/∼dms/dietsupp.html (Dec. 1, 1995).

76 See generally 21 U.S.C. § 321.

77 The definition states that: Dietary supplement –

• (1) means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients:

• (A) a vitamin;

• (B) a mineral;

• (C) an herb or other botanical;

• (D) an amino acid;

• (E) a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or

• (F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), or (D).” The dietary supplement definition contains several additional components:

• (2) means a product that—

• (A)(i) is intended for ingestion in a form described in section 411(c)(1)(B)(i); or (ii) complies with section 411(c)(1)(B)(ii);

• (B) is not represented for use as a conventional food or as a sole item of a meal or the diet; And (C) is labeled as a dietary supplement; and

• (3) does—

• (A) include an article that is approved as a new drug under section 505, certified as an antibiotic under section 507, or licensed as a biologic under section 351 of the Public Health Service Act (42 U.S.C. § 262) and was, prior to such approval, certification, or license, marketed as a dietary supplement or as a food unless the Secretary has issued a regulation, after notice and comment, finding that the article, when used as or in a dietary supplement under the conditions of use and dosages set forth in the labeling for such dietary supplement, is unlawful under section 402(f); and

• (B) not include -- (i) an article that is approved as a new drug under section 505, certified as an antibiotic under section 507, or licensed as a biologic under section 351 of the Public Health Service Act (42 U.S.C. § 262), or (ii) an article authorized for investigation as a new drug, antibiotic, or biological for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public, which was not before such approval, certification, licensing, or authorization marketed as a dietary supplement or as a food unless the Secretary, in the Secretary's discretion, has issued a regulation, after notice and comment, finding that the article would be lawful under this Act. 21 U.S.C. § 321(ff)(2)-(3).

78 FDA has also not objected to a premarket notification filed for Muifulvate, a byproduct of Hungarian peat. See FDA, New Dietary Ingredients in Dietary Supplements, Docket No. 95S-0316, available at http://www.cfsan.fda.gov/∼dms/ds-ingrd.html (Sept. 10, 2001).

79 See S. REP. NO. 103-410 (1994).

80 S. REP. NO. 103-410, at 8-9 (2004).

81 See NNFA, supra note 50; CRN, supra note 50.

82 Requirements for Nutrient Content Claims; Health Claims, and Statements of Nutritional Support for Dietary Supplements, 62 Fed. Reg. 49,859, 49,860 (Sept. 23, 1997) (codified at 21 C.F.R. 101).

83 Requirements for Nutrient Content Claims; Health Claims, and Statements of Nutritional Support for Dietary Supplements, 62 Fed. Reg. 49,859, 49,860 (Sept. 23, 1997) (codified at 21 C.F.R. 101).

84 Interagency Committee on Human Nutrition Research, Definition of Human Research, available at http://hnrim.nih.gov/pdf/codesdefins.pdf (emphasis added).

85 AMERICAN DIETETIC ASS’N, Institute of Medicine, Proposed Framework for the Evaluation of Dietary Supplements, available at http://www.eatright.org/Public/GovernmentAffairs/98_lg092602.cfm (Sept. 26, 2002) [hereinafter IOM Proposal].

86 Id. at 14. Indeed, two of the six ingredients selected for the IOM prototype reviews include products which would not meet FDA's proposed definition of a dietary supplement. Glucosamine (one of the top 25 dietary supplements sold in 2001), which was on the market in 1994, is made from the shells of shellfish.

87 FDA, Dietary Supplements Public Meeting Pre-Market Notification Program for New Dietary Ingredients, available at http://www.fda.gov/ohrms/dockets/dockets/04n0454/04n-0454-tr00001-vol2.pdf (Nov. 15, 2004).

88 FDA, Regulatory Strategy for the Further Implementation and Enforcement of the Dietary Supplement Health and Education Act of 1994, available at http://www.cfsan.fda.gov/∼dms/ds3strat.html.

89 FDA has never specified the quantity and type of information required in an NDI submission. This is one of the issues raised by industry at FDA's November 15, 2004, public meeting and will likely be one of the inquiries submitted to FDA as a part of the public comment period.

90 DSHEA § 8.

91 See 21 U.S.C. § 321(ff)(1). FDA's application of the dietary supplement definition is inconsistent. Moreover, FDA is inconsistent in applying the § 321(ff)(1) definition to the NDI section. The definition of dietary supplement added by DSHEA contains not only the list of potential dietary ingredients in § 321(ff)(1), but also the form and labeling requirements of § 321(ff)(2) and the specifications that a dietary supplement may not be an article approved as a new drug (“NDA”) or authorized as an investigational new drug (“IND”), biological or antibiotic in 21 U.S.C. § 321(ff)(3)(B).

92 Letter from Felicia B. Satchell, Director, Division of Standards and Labeling Regulations, Office of Nutritional Products, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, Food and Drug Administration to Jason Crush, Attorney, Christopher & Weisberg, P.A. (Aug. 29, 2002), available at http://www.fda.gov/OHRMS/DOCKETS/dockets/95s0316/95s-0316-rpt0162-02-vol116.pdf.

93 Id.

94 See id.

95 Letter from Christopher & Weisberg, P.A. to Division of Standards and Labeling Regulations, Office of Nutritional Products, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, Food and Drug Administration (June 10, 2002), available at http://www.fda.gov/OHRMS/DOCKETS/dockets/95s0316/95s-0316-rpt0162-03-vol116.pdf.

96 Id.

97 Letter from Felicia B. Satchell, supra note 92.

98 Id.

99 Id.

100 Id.

101 Id.

102 Id. (“[B]ecause [FDA] has concluded that the subject of your notification cannot be marketed as a dietary supplement, FDA did not review the evidence of safety information you submitted on CLA.”).

103 See Letter from Susan J. Walker, M.D., Acting Director, Division of Dietary Supplements Programs, Office of Nutritional Products, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, FDA (Mar. 12, 2003) (on file with authors) [hereinafter March 12, 2003 Letter from FDA; Response to March 12, 2003 Letter, to Felicia B. Satchell, Director, Division of Standards and Labeling Regulations, Office of Nutritional Products, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, FDA (Sept. 13, 2002), available at http://www.fda.gov/ohrms/dockets/dailys/04/jan04/012304/95s-0316-sup00014-vol119.pdf [hereinafter Response Letter].

104 Response Letter, supra note 103.

105 March 12, 2003 Letter from FDA, supra note 103.

106 Letter from Felicia B. Satchell, Director, Division of Standards and Labeling Regulations, Office of Nutritional Products, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, FDA, to Shirming Han, Vice President, Wealth Express Industrial, Ltd. (May 24, 2002), available at http://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-rpt0120-01-vol83.pdf.

107 Id.

108 Id.

109 Id.

110 FDA Dietary Supplements Public Meeting, Pre-Market Notification Program for New Dietary Ingredients (Nov. 15, 2004), available at http://www.fda.gov/ohrms/dockets/dockets/04n0454/04n-0454-tr00001.htm.

111 Id.

112 Id.

113 See Dietary Supplements; Premarket Notification for New Dietary Ingredient Notifications; Public Meeting, 69 Fed. Reg. 61,680, 61,682 (Oct. 20, 2004).

114 Id.

115 69 Fed. Reg. 61,683 (Oct. 20, 2004).

116 21 C.F.R. § 190.6 (2005).

117 See supra note 88 and accompanying text.

118 See 21 U.S.C. § 321(ff)(1).

119 See id.

120 § 321(ff)(2).

121 Id.

122 § 321(ff)(3)(B).

123 Importantly, in the drug context, FDA does not assess whether a substance falls within the definition of “drug” when granting an IND to explore safety. § 321(g)(1).

124 See, e.g., HHS Launches Crackdown, supra note 71 (describing FDA's delayed reaction to the non-submittal of an NDI).

125 See DSHEA § 3.

126 See supra notes 59-61 and accompanying text.

127 See 21 U.S.C. § 321(f)(f)(1)(E) (essentially allowing non-food substances to become dietary supplements).

128 See FDA Dietary Supplements Public Meeting, supra note 110.

129 Letter from Edward W. Thomas, Acting District Director, New York District, FDA to Chao Zhang, President, Blue Light Inc. (Dec. 18, 2000), available at http://www.fda.gov/foi/warning_letters/m4975n.pdf.

130 Id.

131 Id.

132 Id.

133 Letter from Michael A. Chappell, District Director, Dallas District Office, FDA to Tony Stires, Global Internet Alliance (Feb. 18, 2004), available at http://www.fda.gov/foi/warning_letters/g4543d.htm; see also Letter from W. Charles Becoat, Director, Minneapolis District, FDA to Yvone Ashen & Linda Longrie, Can-x Products (Dec. 14, 2004), available at http://www.fda.gov/foi/warning_letters/g5120d.htm (stating that a topic treatment cannot be a dietary supplement because it is not intended for ingestion, but rather to bypass the alimentary canal by direct absorption through the skin).

134 See HHS Launches Crackdown, supra note 71.

135 Id.

136 Id.

137 See, e.g., Letter to The Sanapac Co., Inc., supra note 70 (stating that androstenedione is adulterated under 21 U.S.C. § 342(f)(1)(b) and § 350b(a) because it was marketed without a notification for a new dietary ingredient).

138 See S. REP. NO. 103-410 (1994).

139 See supra Section II.B.