消费者保护与全民健康

Safety Assessment of Food Additives,Anna P. Shanklin, Ph.D.Department of Health and Human ServicesU.S. Food and Drug AdministrationCenter for Food Safety and Applied Nutrition,Food Advisory CommitteeAdditives and Ingredients SubcommitteeLATEX ALLERGYAugust 26-28, 2003,How FDA Regulates Food Additives?,OVERVIEW,IntroductionFood & Drug LawEvaluation of SafetyNatural Rubber Latex (NRL)Latex Allergy and Food SafetyConclusion,CFSANs Mission,To promote and protect the public health by ensuring that:The food supply is safe and wholesome and cosmetics are safeFood and cosmetic products are honestly and accurately labeled,OFAS - Food Ingredients,OFASs “Food Ingredients” Universe,Direct Food IngredientsColor AdditivesGRAS IngredientsFoods/Ingredients produced using modern biotechnology,Processing AidsFood Irradiation EquipmentFood Packaging/Food Contact Substances,Sweeteners; Preservatives; Fat;Nutrients; Texturizers (thickeners,Emulsifiers, etc.); Flavors,To process foodTo inspect food,In food, animal feed, drugs, cosmetics,medical devices(i.e. sutures and contact lenses),Antimicrobials(meat and poultry Processing); Defoamers; Ion exchangeresins,Enzymes; Fiber; Proteins;Lipids; Sugars; MSG; Antimicrobials;Phytosterols/stanols; Flavors; Infant formula ingredients,Plants w/herbicide resistance or insect resistance, delayed ripening, etc.; often use GRAS concept,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”,Food and Drug Law,Federal, Food, Drug, and Cosmetic Act FFDCA,Federal Food, Drug, And Cosmetic Act,FDA Authority,FFDCA,“The LAW”,OFAS & FFDCA,Food Additive ProvisionsSec. 409,Federal Food, Drug,And Cosmetic Act,409,Regulations,LAW,NOT,Food Additive,FFDCA,21 CFR,“PRE-MARKET” APPROVAL,1958 Food Additives Amendment of FFDCASec. 409,What is a Food Additive?,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,Sec. 201(s) FFDCA: Definition,21 CFR 170.3(e)(1),What is a Food Additive?,Sec. 201(s) FFDCA: Definition,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),IN SHORT,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 adulteratedif 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,MOMS Apple Pies,Sweetner Unapproved Food Additive,Adulterated Food,Interstate Commerce,FDA Enforcement,Maryland Virginia,Food and Drug Law,New antioxidant “Unapproved”,Antioxidant migratesAdulterated Food,A,A,Interstate Commerce,FDA Enforcement,Daves Candy,Food and Drug Law,Why are food additives regulated?,FDA has authority to prevent adulteration of Food (FFDCA),Unsafe Food Additive = Adulterated FoodUnapproved Food Additive = Unsafe Food AdditiveUnapproved Food Additive = Adulterated Food,Food Drug & Cosmetic Act (As amended, 1958),Defines “food additive” w/GRAS exemptionRequires premarket approval of new uses of food additivesEstablishes the standard of reviewEstablishes the standard of safetyEstablishes formal rulemaking procedures,Sec. 409 FFDCA,Food Drug & Cosmetic Act (As amended, 1958),Defines “food additive” w/GRAS exemptionRequires premarket approval of new uses of food additivesEstablishes the standard of reviewEstablishes the standard of safetyEstablishes formal rulemaking procedures,Sec. 409 FFDCA,Food Drug & Cosmetic Act (As amended, 1958),Defines “food additive” w/GRAS exemptionRequires premarket approval of new uses of food additivesEstablishes the standard of reviewEstablishes the standard of safetyEstablishes formal rulemaking procedures,Sec. 409 FFDCA,Standard of Review,“Fair evaluation of the data ”,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.”,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 Secretarys 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”,Standard of Safety,“Reasonable certainty of no harm”,Standard of Safety,“Reasonable certainty of no harm”,Standard of Safety,“Reasonable certainty of no harm”,Standard of Safety,“Reasonable certainty of no harm”,Standard of Safety,“Reasonable certainty of no harm”,Standard of Safety,“Reasonable certainty of no harm”,Standard of Safety,“Reasonable certainty of no harm”,21 CFR 170.3(i),SAFE,Standard of Safety,“Reasonable certainty of no Harm”,Standard of Safety,“Reasonable certainty of no Harm”,What is Harm?,- Harm refers to Health,Man or Animal,Standard of Safety,“Reasonable certainty of no Harm”,What is Harm?,- Harm refers to Health,Man or Animal,Standard of Safety,Petitioner burden to demonstrate a “reasonable certainty of no harm”FDA Assessment,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 no harm will result from the proposed use of an additive.It does notand cannotrequire proof beyond any possible doubt that no harm will result under any conceivable circumstance.,H.R. Report, No. 2284, 85th Congress (1958),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 no harm will result from the proposed use of an additive.It does notand cannotrequire proof beyond any possible doubt that no harm will result under any conceivable circumstance.,H.R. Report, No. 2284, 85th Congress (1958),Section 409,Section 409 Requirements,Any person may petition to establish safety,Food Additive Petition Process,Food Additive Petition ReviewThe Safety Decision,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 benefitsIt is NOT intended to enforce or limit consumer choices.,What the evaluation is NOT:,Food Additive Petition ReviewThe Safety Decision,It DOES, in fact, ensure safetyIt 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,Safety Standard,Approvals are Safety Based OnlyReasonable Certainty of No HarmHarm refers to Health of Man or AnimalFair Evaluation of the Entire RecordBenefits not weighed in Safety Decision,Highlights,Key Players,Consumer Safety Officer (CSO)ChemistryToxicologyEnvironmental,E,Data Requirements,IdentityConditions of proposed useIntended technical effectMethod for determining “quantity”Full reports of safety studies (data)Manufacturing methodsEnvironmental information (NEPA),Sec. 409 FFDCA,Safety Evaluation,A “full blown” exhaustive safety evaluation of all appropriate studies, with agency ownership of safety decision.,Standard of Review,Safety Evaluation,Estimation of ExposureProposed Conditions of UseConcentration (safe)Level with no adverse effects observed toxicologically,“ The dose makes the poison”,“Key Determinant”,Technical Review,FDA scientist review data and evaluate petitioners safety argumentFDA communicates with petitioner to resolve any questions and/or additional data needsFDA review, documentationFDA reaches a scientific conclusion and makes a recommendation,Key Players,FDAs Action on the Petition,Complete the reviewEstablish a RegulationDeny the Petition,Section 409 Requirements,Other Legal Requirements,Objections and Public HearingsJudicial ReviewAmendment or Repeal of Regulations,Section 409 Requirements,Amendment or Repeal,INRegulation,OUTRegulation,=,Food Additives,FDA Responsibility,Legal Aspects of Food Additive Approvals,Food Additives unsafe until FDA decisionRegulations stipulate an identity, specifications and conditions of safe useRegulations do not provide specific product approvalsDirect additives or Food-contact substance,Food Additive Regulations21 CFR Parts 170-189,General Provisions170 & 171Direct Food Additive Regulations172 & 173Indirect Food Additive Regulations174-178Irradiation of Foods179Substances permitted on interim basis180Prior Sanctioned Substances181GRAS Ingredients182-186Prohibited Substances189,Title 21 CFR 177.2600 Rubber articles intended for repeat use,Food Drug & Cosmetic Act (As amended, 1958, 1997),Defines “food additive” w/GRAS exemptionRequires premarket approval of new uses of food additivesEstablishes the standard of reviewEstablishes the standard of safetyEstablishes formal rulemaking procedures -As amended 1997(FDAMA)-Defines “food contact substance”(FCS)Establishes a premarket notification program for FCSs,Sec. 409(h) of FFDCA,Food Drug & Cosmetic Act (As amended, 1958, 1997),Defines “food additive” w/GRAS exemptionRequires premarket approval of new uses of food additivesEstablishes the standard of reviewEstablishes the standard of safetyEstablishes formal rulemaking procedures -As amended 1997(FDAMA)-Defines “food contact substance”(FCS)Establishes a premarket notification program for FCSs,Sec. 409(h) of FFDCA,Food Drug & Cosmetic Act (As amended, 1958, 1997),Defines “food additive” w/GRAS exemptionRequires premarket approval of new uses of food additivesEstablishes the standard of reviewEstablishes the standard of safetyEstablishes formal rulemaking procedures -As amended 1997(FDAMA)-Defines “food contact substance”(FCS)Establishes a premarket notification program for FCSs,Sec. 409(h) of FFDCA,What is a Food Contact Substance?,(Section 409(h)(6) of the FFDCA)Any substance intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use is not intended to have any technical effect in food.,FCS,Indirect Food Additives,Food Contact Notifications,Food Additive that is subject of an effective notification Safe food additive,Brief SummaryFood Additive Approvals,Mechanism: FFDCA-Sec. 409-Necessary ToolsProcess: Safety Evaluation-Scientific review teamResult: Regulations, notifications, and exemptions,Brief SummaryFood Additive Approvals,Petitioner is responsible for demonstrating safetyFDA is responsible forConducting a full and fair evaluation of the data and informationIssuing a regulation if FDA scientists conclude the requested use is “SAFE”,FDA,Petitioner,Food Additive Regulations21 CFR Parts 170-189,General Provisions170 & 171Direct Food Additive Regulations172 & 173Indirect Food Additive Regulations174-178Irradiation of Foods179Substances permitted on interim basis180Prior Sanctioned Substances181GRAS Ingredients182-186Prohibited Substances189,Title 21 CFR 177.2600 Rubber articles intended for repeat use,Natural Rubber Latex“NRL”, 172.615Chewing gum base 175.105Adhesives 175.125Pressure-sensitive adhesives 175.300Resinous and polymeric coatings,Regulations,Natural Rubber Latex“NRL”, 177.1010Acrylic and modified acrylic plastics, semirigid and rigid 177.1200Cellophane 177.1210Closures with sealing gaskets for food containers 177.2600Rubber articles intended for repeated use,Regulations,Natural Rubbe