1. © 2009 Hogan & Hartson LLP. All rights reserved. Toward Closer Cooperation in the New Decade? FDA Issues Martin J. Hahn Hogan & Hartson, L.L.P. NABCA 17 th Annual Symposium March 10, 2010

2. 2 © 2009 Hogan & Hartson LLP. All rights reserved. Outline What is GRAS? What is safety? Can it be marketed in foods if it is marketed in dietary supplements?

3. 3 © 2009 Hogan & Hartson LLP. All rights reserved. Food Additive Defined “The term ‘food additive’ means any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food (including any substance intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food; and including any source of radiation intended for any such use)…” FDCA Section 201(s)

4. 4 © 2009 Hogan & Hartson LLP. All rights reserved. GRAS Exemption The term ‘food additive’ excludes…. a substance “generally recognized, among experts, qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use.”

5. 5 © 2009 Hogan & Hartson LLP. All rights reserved. What is GRAS? Generally recognized as safe (GRAS) An ingredient is GRAS and exempt from the food additive definition and the premarket approval requirements if – Common use in Foods: The food ingredient has been used in the food supply for the same use prior to 1958; or – Scientific Procedures: There are published data, of the same type required to approve a food additive, serving as the foundation for general recognition of safety

6. 6 © 2009 Hogan & Hartson LLP. All rights reserved. Dietary Ingredients Dietary ingredients in dietary supplements are exempt from the food additive definition Dietary ingredients in dietary supplements are deemed lawful if marketed in dietary supplements or food prior to October 15, 1994— FDA bears the burden in proving such dietary ingredients are unsafe “New dietary ingredients,” which are those marketed for the first time after October 15, 1994, are subject to a premarket notification program if they have no history of use in foods or dietary supplements

7. 7 © 2009 Hogan & Hartson LLP. All rights reserved. Why should you care about dietary ingredients? There are many dietary ingredients that lawfully may be marketed in dietary supplements that cannot lawfully be marketed in foods because they are not approved food additives and there are insufficient data to support GRAS status The first question you should ask is NOT, whether you see the substance marketed in supplements or energy drinks but whether there are sufficient data to support the GRAS status of the ingredient

8. 8 © 2009 Hogan & Hartson LLP. All rights reserved. Quick Review Food Additives: Must be approved by FDA (which will issue a regulation); burden is on petitioner to demonstrate safety GRAS Ingredients: Exempt from food additive definition and FDA approval; burden is on user to demonstrate safety Dietary Ingredients: Exempt from food additive definition and FDA approval; burden is on FDA to demonstrate they are unsafe

9. 9 © 2009 Hogan & Hartson LLP. All rights reserved. “Reasonable Certainty of No Harm” Safety Standard “Safe” or “safety” means that there is a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use. It is impossible in the present state of scientific knowledge to establish with complete certainty the absolute harmlessness of the use of any substance. Safety may be determined by scientific procedures or by general recognition of safety. 21 C.F.R. 170.3(i)

10. 10 © 2009 Hogan & Hartson LLP. All rights reserved. What type of safety studies? Always/Usually Required Genetic toxicity studies Short-term toxicity tests with rodents Subchronic toxicity studies with rodents Subchronic toxicity studies with non-rodents Reproduction Studies Developmental toxicity studies Metabolism and Pharmacokinetic studies Sometimes/Rarely Required One-year toxicity studies with non-rodents Chronic toxicity studies Carcinogenicity studies with rodents Human Studies

11. 11 © 2009 Hogan & Hartson LLP. All rights reserved. Safety Analyses FDA focuses its safety review on traditional animal toxicity studies Many foods can be safe for the general population or at typical consumption levels but present concerns for subsets of the population or at abuse levels – Water (hyper hydration for marathon runners) – Peanuts (anaphylaxis for peanut allergic) – Sulfites (trigger potentially severe reactions in sensitized people) In unique situations, FDA historically has required disclosures rather than challenge the safety

12. 12 © 2009 Hogan & Hartson LLP. All rights reserved. Aspartame Aspartame is a combination of two amino acids— phenylalanine and aspartic acid A small subset of the population has phenylketonuria, a metabolic disorder that does not allow for the metabolism of phenylalanine As part of the approval, all products containing aspartame must bear the statement, “PHENYLKETONURICS: CONTAIN PHENYLALANINE”

13. 13 © 2009 Hogan & Hartson LLP. All rights reserved. Polydextrose Is a bulking agent that is used in a wide variety of foods, but it is only partially digestible If a serving of a food contains more than 15 gram of polydextrose, the label must state: “Sensitive individuals may experience a laxative effect from excessive consumption of this product”

14. 14 © 2009 Hogan & Hartson LLP. All rights reserved.

15. 15 © 2009 Hogan & Hartson LLP. All rights reserved. Olestra  When approved by FDA in 1996, the agency required a warning.  2005/6, FDA amended the regulation and removed the need for the warning statement after re-evaluating the data

16. 16 © 2009 Hogan & Hartson LLP. All rights reserved. Safety Quick Review GRAS ingredients and food additives must meet reasonable certainty of no harm under intended conditions of use If there are conditions of use or abuse that could present potential safety issues, the FDA precedent would support labeling rather than a conclusion that an ingredient is not GRAS

17. 17 © 2009 Hogan & Hartson LLP. All rights reserved. Functional Ingredients Decision Tree Is it an approved food additive for the intended use? If not, has it been reviewed by FDA as a GRAS ingredient for the intended use? If not, are there sufficient data to support the GRAS status for the intended use? If not, find another ingredient; if so, are there warnings (or state laws) that should be considered to ensure the safe use of the ingredient?

18. 18 © 2009 Hogan & Hartson LLP. All rights reserved. Caffeine There are no food additive regulations or GRAS authorizations for the use of caffeine in alcoholic beverages There are multiple published studies supporting the safety of caffeine at relatively high levels that show great promise in supporting the GRAS status To the extent the science demonstrates that caffeine can be safely consumed with alcohol in moderation, in my view, FDA would be honoring earlier precedent if it dealt with concerns involving abuses through the use of a warning rather than a finding that it is not GRAS

19. 19 © 2009 Hogan & Hartson LLP. All rights reserved. Other Functional Ingredients The decision tree will work for other functional ingredients – Guarana – Melatonin – Taurine – Ginseng (Siberian vs. Panax) – Valerian Root

20. 20 © 2009 Hogan & Hartson LLP. All rights reserved. Conclusions Remember the decision tree—the functional ingredient must be an approved food additive or GRAS or it cannot be used Safety evaluations and GRAS assessment should focus on traditional toxicological data Issues concerning abuse or misuse should be handled through labeling rather than conclusions that the ingredient is not GRAS

21. 21 © 2009 Hogan & Hartson LLP. All rights reserved. Contact Information Martin J. Hahn Hogan & Hartson LLP 555 13 th Street NW Washington, DC 20004 MJHahn@HHLaw.com 202/637-5926 (direct) 202/637-5910 (fax)