Regulatory Comments to Docket Number FDA-2014-N-1497; Toxicological Principles for the Safety Assessment of Food Ingredients; Public Meeting on Updates and Safety and Risk Assessment Considerations; Extension of Comment Period
In the Federal Register of Oct. 30, 2014 (79 FR 64603), the Food and Drug Administration (FDA) published a notification of a public meeting and requested comments on topics related to the Redbook. The Federal Register announcement indicated that the FDA would hold a public meeting on Dec. 9 for expanding the scope of the Redbook to include, among several new discussions, dietary supplements. The Redbook is the abbreviated name given to the FDA guidance document, titled “Guidance for Industry and Other Stakeholders: Toxicological Principles for the Safety Assessment of Food Ingredients.” Redbook 2000, the most recent version and most recently updated in 2007, has undergone several revisions from its original launch in 1982. Redbook I or “Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food,” published in 1982, was issued as a response to the Select Committee on Generally Recognized as Safe (GRAS) Substances (SCOCS), a U.S. Department of Commerce task force assembled to evaluate the safety of over 450 GRAS substances. SCOGS developed out of President Nixon’s special message to Congress on consumer protection on Oct. 30, 1969.
SCOGS’ conclusions were finalized in 1982 in a report “Insights on Food Safety Evaluation,” which provided the FDA with a structure to evaluate the safety of food additives by providing recommendations to enhance the agency’s scientific approach.2 Redbook I was revised again in 1993 and became known as Redbook II or “Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food, 1993 Draft Revision.” While the title has changed, the ingredients the FDA assessed has stayed the same. The term “food ingredients” in the Redbook 2000 guidance document refers to “food additives and color additives used in food, and those substances which are classified as food contact substances (formerly known as indirect food additives), and those substances which are classified as generally recognized as safe (GRAS).” Guidance on toxicity studies in Redbook 2000 is ultimately designed to be used by petitioners and notifiers in the submission of information to the FDA as part of the safety assessment of food ingredients.
In 1991, the FDA’s Dykstra Task Force on Dietary Supplements, chaired by Deputy Associate Commissioner for Regulatory Affairs Gary Dykstra, was appointed by then FDA commissioner David Kessler to address whether dietary supplement ingredients should be regulated as drugs or food additives. The Dykstra report, released June 18, 1993, was issued as background for an advance notice of public rulemaking (ANPR) on dietary supplements. The ANPR suggested drugs and food additives as the model for the regulation of ingredients used in dietary supplements. It concluded that “many amino acid products are … unapproved food additives.”
It asked whether non-vitamin, mineral, or herb dietary supplements were possibly subject to regulation as “food additives.” The Dykstra Report and 1993 ANPR on dietary supplements also considered herbs and botanical extracts as food additives6 and pondered possible potency limits for common everyday vitamins including vitamin B6, selenium, and niacin. In its greatest attack, the ANPR levied that “FDA will consider whether the drug uses of particular amino acids are so well established and wide-spread as to justify rulemaking to establish as a matter of law that these products are drugs”. The released Dykstra report and the ANPR catapulted a series of hearings, debates and proposed bills on Capitol Hill over dietary supplements. The Dietary Supplement Health and Education Act (DSHEA) of 1994, the enacted bill that passed unanimously, resulted in the demise of the Dykstra Report and failure of the ANPR to gain further momentum.
DSHEA retained a significant provision throughout its legislative history in H.R. 1709 and S. 784, which was to exclude from the definition of food additive “dietary ingredients” or “ingredients”10 in or intended for use in a dietary supplement.11 In short, dietary ingredients for use in dietary supplements are exempted from the statute concerning food additive ingredients. Last year commemorated the 20th anniversary of the passing of DSHEA, but your Oct. 30, 2014 Federal Register notice to update and revise your guidance “Toxicological Principles for the Safety Assessment of Food Ingredients,” (the Redbook)12 represents an attack upon that legislation. Specifically, your explicit intent of “possibly expanding the scope of the Redbook to include chemical safety assessments for all products over which the Food and Drug Administration’s (FDA) Center for Food Safety and Applied Nutrition (CFSAN) has statutory authority including regulatory contexts such as food additives, food contact substances, dietary supplement ingredients, food contaminants, and cosmetics” blurs the line Congress created between dietary ingredients and food additives.
The inclusion of toxicological assessment of dietary supplements in a food additive guidance document and created by the Office of Food Additive Safety (OFAS), a science and programmatic office dedicated to food additives, color additives, food additive petitions, GRAS notices, and food contact notifications, is a serious concern to our industry and an assault on DSHEA and its framers. The Federal Register announcement to update Redbook on dietary supplements runs counter to the Federal Food, Drug, and Cosmetic Act (FFDCA). Any toxicological evaluation of dietary supplement ingredients should be discussed in a revision to the New Dietary Ingredients Draft Guidance or a separate guidance originating from the Office of Nutrition, Labeling, and Dietary Supplements (ONLDS), the science and programmatic office dedicated to the regulation of dietary ingredients for use in dietary supplements. Any discussion of dietary supplements in a revision of the Redbook, a guidance document reserved for food additives, color additives, GRAS notices, and food contact notifications, represents significant “scope creep” and a blurring of jurisdictional lines and authorities of the agency. Sens. Tom Harkin, D-Iowa, and Orrin Hatch, R-Utah in their joint letter13 to the agency supported the exclusion of the topic of dietary supplements in any planned Redbook revision. This is a logical approach given the statutory wall between food additives and supplements.
- Food Additive Exemption for Dietary Ingredients: Redbook Update Blurs Current Jurisdictional Lines
- Toxicology Assessment of Dietary Ingredients Should Originate in ONLDS
- FDA’s Approach Ignores Two Separate Safety Standards: Food Additives v. Dietary Ingredients
- FDA’s Approach Violation of the Administrative Procedures Act
The intent of the announced plan to update Redbook, a well-recognized guidance for food additives, is to include dietary supplements. The Federal Register announcement by the FDA to provide an update to the “Toxicological Principles for the Safety Assessment of Food Ingredients” by including dietary supplement ingredients in a guidance document that is intimately associated with § 201(s) of FFDCA and the evaluation of food additives undermines DSHEA in a number of important aspects discussed above. Therefore, we urge the FDA to withdraw its planned update to broaden the scope of Redbook to include dietary supplements and the toxicological assessment of dietary ingredients for use in dietary supplements.