Safety Assessment of Food Additives

2. How FDA Regulates Food Additives? Safety Assessment of Food Additives Anna P. Shanklin, Ph.D. Department of Health and Human Services U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition Food Advisory Committee Additives and Ingredients Subcommittee LATEX ALLERGY August 26-28, 2003

3. OVERVIEW • Introduction • Food & Drug Law • Evaluation of Safety • Natural Rubber Latex (NRL) • Latex Allergy and Food Safety • Conclusion

4. CFSAN’s Mission • To promote and protect the public health by ensuring that: • The food supply is safe and wholesome and cosmetics are safe • Food and cosmetic products are honestly and accurately labeled OFAS --- Food Ingredients

5. Direct Food Ingredients Color Additives GRAS Ingredients Foods/Ingredients produced using modern biotechnology Processing Aids Food Irradiation Equipment Food Packaging/Food Contact Substances OFAS’s “Food Ingredients” Universe Sweeteners; Preservatives; Fat; Nutrients; Texturizers (thickeners, Emulsifiers, etc.); Flavors Antimicrobials(meat and poultry Processing); Defoamers; Ion exchange resins In food, animal feed, drugs, cosmetics,medical devices(i.e. sutures and contact lenses) To process food To inspect food Enzymes; Fiber; Proteins; Lipids; Sugars; MSG; Antimicrobials; Phytosterols/stanols; Flavors; Infant formula ingredients Coatings (paper, metal, etc); New/recycled plastics including both polymers and monomers; Paper; Adhesives; Ingredients in Pkgs.(i.e. colorants, antimicrobials, antixoxidants, etc.);Packaging material for use during food irradiation,; Food packaging “formulations” Plants w/herbicide resistance or insect resistance, delayed ripening, etc.; often use GRAS concept

6. Federal Food, Drug, And Cosmetic Act Food and Drug Law • Federal, Food, Drug, and Cosmetic Act FFDCA

7. FDA Authority FFDCA “The LAW”

8. OFAS & FFDCA Food Additive Provisions Sec. 409 Federal Food, Drug, And Cosmetic Act 409

9. 21 CFR Food Additive Regulations  NOT LAW FFDCA

10. “PRE-MARKET” APPROVAL 1958 Food Additives Amendment of FFDCA Sec. 409

11. What is a Food Additive? Sec. 201(s) FFDCA: Definition 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;…. if such substance is not Generally Recognized As Safe, 21 CFR 170.3(e)(1)

12. What is a Food Additive? Sec. 201(s) FFDCA: Definition IN SHORT • Any substance, that is reasonably expected to become a component of food as a result of its intended use, • If such use in not Generally Recognized As Safe (GRAS)

13. Food and Drug Law • Sec. 409 Unsafe Food Additives:the use of a food additive is unsafe, unless that use conforms to a regulation, notification, or exemption issued by FDA under Sec. 409. • Sec. 402 Adulterated Food: a food is adulterated…if it is, or if it contains any food additive that is unsafe. • Sec. 301 Prohibited Acts: the introduction or delivery into interstate commerce of any food that is adulterated or misbranded. FFDCA

14. MOM’S Apple Pies Sweetner Unapproved Food Additive Maryland  Virginia Interstate Commerce FDA Enforcement Adulterated Food Food and Drug Law

15. Dave’s Candy [A] [A] FDA Enforcement New antioxidant “Unapproved” Antioxidant migrates Adulterated Food Interstate Commerce Food and Drug Law

16. Why are food additives regulated? FDA has authority to prevent adulteration of Food (FFDCA) Unsafe Food Additive = Adulterated Food Unapproved Food Additive = Unsafe Food Additive Unapproved Food Additive = Adulterated Food

17. Food Drug & Cosmetic Act (As amended, 1958) • Defines “food additive” w/GRAS exemption • Requires premarket approval of new uses of food additives • Establishes the standard of review • Establishes the standard of safety • Establishes formal rulemaking procedures Sec. 409 FFDCA

18. Food Drug & Cosmetic Act (As amended, 1958) • Defines “food additive” w/GRAS exemption • Requires premarket approval of new uses of food additives • Establishes the standard of review • Establishes the standard of safety • Establishes formal rulemaking procedures Sec. 409 FFDCA

19. Food Drug & Cosmetic Act (As amended, 1958) • Defines “food additive” w/GRAS exemption • Requires premarket approval of new uses of food additives • Establishes the standard of review • Establishes the standard of safety • Establishes formal rulemaking procedures Sec. 409 FFDCA

20. Standard of Review “Fair evaluation of the data …”

21. From the Senate Report on the“Food Additives Amendment of 1958” “The committee has endeavored to prescribe a new statutory criterion requiring that a high standard of fairness be observed in administrative rule-making under this bill. Personal attitudes or preferences of administrative officials could not prevail on the basis of being supported by substantial evidence picked from the record without regard to other evidence of probative value in the record.”

22. House of Representatives, Report No. 2284,“Food Additives Amendment of 1958” • Committee on Interstate & Foreign Commerce, 85th Congress, 2nd Session, July 28, 1958 • “The committee feels that the Secretary’s findings of fact and orders should not be based on isolated evidence in the record, which evidence in and of itself may be considered substantial without taking account of the contradictory evidence of equal or even greater substance…”

23. Standard of Safety “Reasonable certainty of no harm”

24. Standard of Safety “Reasonable certainty of no harm”

25. Standard of Safety “Reasonable certainty of no harm”

26. Standard of Safety “Reasonable certainty of no harm”

27. Standard of Safety “Reasonable certainty of no harm”

28. Equal Emphasis on Each Word Commissioner David Kessler --- November 1995 Standard of Safety “Reasonable certainty of no harm”

29. Standard of Safety "SAFE" “Reasonable certainty of no harm” 21 CFR 170.3(i)

30. “Reasonable certainty of no Harm” What is Harm? - Harm refers to Health Man or Animal Standard of Safety

31. “Reasonable certainty of no Harm” Standard of Safety What is Harm? - Harm refers to Health Man or Animal

32. “Reasonable certainty of no Harm” Standard of Safety What is Harm? - Harm refers to Health Man or Animal

33. Standard of Safety • Petitioner burden to demonstrate a “reasonable certainty of no harm” • FDA Assessment

34. REASONABLE CERTAINTY OF NO HARMLegislative History of the FFDCA The concept of safety used in this legislation involves the question of whether a substance is hazardous to the health of man or animal. Safety requires proof of a reasonable certainty that noharm will result from the proposed use of an additive. It does not—and cannot—require proof beyond any possible doubt that no harm will result under any conceivable circumstance. H.R. Report, No. 2284, 85th Congress (1958)

35. REASONABLE CERTAINTY OF NO HARMLegislative History of the FFDCA The concept of safety used in this legislation involves the question of whether a substance is hazardous to the health of man or animal. Safety requires proof of a reasonable certainty that noharm will result from the proposed use of an additive. It does not—and cannot—require proof beyond any possible doubt that no harm will result under any conceivable circumstance. H.R. Report, No. 2284, 85th Congress (1958)

36. Federal Food, Drug, And Cosmetic Act 409 Section 409

37. Section 409 Requirements • Any person may petition to establish safety "Food Additive Petition Process"

38. Food Additive Petition ReviewThe Safety Decision What the evaluation is NOT: • It is NOT intended to ensure, nor is it possible to ensure, safety with absolute certainty: (“Reasonable Certainty of No Harm rather than “Certainty of No Theoretical Possibility of Harm”) • Does NOT weigh risks and benefits • It is NOT intended to enforce or limit consumer choices.

39. Food Additive Petition ReviewThe Safety Decision • It DOES, in fact, ensure safety • It IS a consensus decision made under uncertainty that provides a fair evaluation of all the data of record… -That must protect the public health -That will withstand scientific, procedural, and legal challenge from all sides

40. Safety Standard Highlights • Approvals are Safety Based Only • Reasonable Certainty of No Harm • Harm refers to Health of Man or Animal • Fair Evaluation of the Entire Record • Benefits not weighed in Safety Decision

41. CSO C T Key Players • Consumer Safety Officer (CSO) • Chemistry • Toxicology • Environmental E

42. Data Requirements • Identity • Conditions of proposed use • Intended technical effect • Method for determining “quantity” • Full reports of safety studies (data) • Manufacturing methods • Environmental information (NEPA) Sec. 409 FFDCA

43. Safety Evaluation A “full blown” exhaustive safety evaluation of all appropriate studies, with agency ownership of safety decision. Standard of Review

44. “Key Determinant” Safety Evaluation • Estimation of Exposure • Proposed Conditions of Use • Concentration (safe) • Level with no adverse effects observed toxicologically “ The dose makes the poison”

45. Key Players Technical Review • FDA scientist review data and evaluate petitioner’s safety argument • FDA communicates with petitioner to resolve any questions and/or additional data needs • FDA review, documentation • FDA reaches a scientific conclusion and makes a recommendation

46. Section 409 Requirements FDA’s Action on the Petition • Complete the review • Establish a Regulation • Deny the Petition

47. Section 409 Requirements Other Legal Requirements • Objections and Public Hearings • Judicial Review • Amendment or Repeal of Regulations

48. IN Regulation OUT Regulation Amendment or Repeal Food Additives = FDA Responsibility

49. Legal Aspects of Food Additive Approvals • Food Additives unsafe until FDA decision • Regulations stipulate an identity, specifications and conditions of safe use • Regulations do not provide specific product approvals • Direct additives or Food-contact substance

50. Food Additive Regulations21 CFR Parts 170-189 • General Provisions 170 & 171 • Direct Food Additive Regulations 172 & 173 • Indirect Food Additive Regulations 174-178 • Irradiation of Foods 179 • Substances permitted on interim basis 180 • Prior Sanctioned Substances 181 • GRAS Ingredients 182-186 • Prohibited Substances 189 Title 21 CFR 177.2600 Rubber articles intended for repeat use