FDA

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 CommitteeAdditives and Ingredients Subcommittee

LATEX ALLERGYAugust 26-28, 2003

OVERVIEW

• Introduction

• Food & Drug Law

• Evaluation of Safety

• Natural Rubber Latex (NRL)

• Latex Allergy and Food Safety

• Conclusion

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’s “Food Ingredients” Universe• Direct Food Ingredients

• Color Additives

• GRAS Ingredients

• Foods/Ingredients produced using modern biotechnology

• Processing Aids

• Food Irradiation Equipment

• Food 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 & FFDCAFood Additive Provisions

Sec. 409

Federal Food,

Drug,

And Cosmetic Act

409

Regulations

LAW

NOT

Food Additive

“PRE-MARKET” APPROVAL

1958 Food Additives Amendment

of FFDCA

Sec. 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 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.

MOM’S 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 CommerceFDA Enforcement

Dave’s Candy

Food and Drug Law

Why are food additives regulated?

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 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







Sec. 409 FFDCA







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 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…”

Standard of Safety

“Reasonable certainty of no harm”

Standard of Safety


Standard of Safety


Standard of Safety


Standard of Safety


Standard of Safety


Commissioner David Kessler --- November 1995

Standard of Safety


Standard of Safety

“Reasonable certainty of no Harm”

- Harm refers to Health

Man or Animal

What is Harm?

Standard of Safety


What is Harm?


Man or Animal

Standard of Safety


What is Harm?


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 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)

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 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)

Section 409

Federal Food, Drug,

And Cosmetic Act

409

Section 409 Requirements

• Any person may petition to establish safety

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 benefits

• It 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 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

Safety Standard

• 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

Highlights

Key Players

• Consumer Safety Officer (CSO)

• Chemistry

• Toxicology

• Environmental

CSO

C

T

E

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

Safety Evaluation

A “full blown” exhaustive

safety evaluation of all

appropriate studies, with agency ownership of safety decision.

Safety Evaluation

• Estimation of Exposure• Proposed Conditions of Use• Concentration (safe)

• Level with no adverse effects observed toxicologically

“ The dose makes the poison”

“Key Determinant”

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

Key Players

FDA’s Action on the Petition

• Complete the review

• Establish a Regulation

• Deny the Petition


Other Legal Requirements

• Objections and Public Hearings

• Judicial Review

• Amendment or Repeal of Regulations


Amendment or Repeal

INRegulation

OUTRegulation

=

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

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

Food Drug & Cosmetic Act (As amended, 1958, 1997)

• 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

-----As amended 1997(FDAMA)-----• Defines “food contact substance”(FCS)• Establishes a premarket notification

program for FCSs





program for FCSs





program for FCSs

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.

Food Contact Notifications

Food Additive that is subject of an effective notification

Safe food additive

Brief SummaryFood Additive Approvals

• Mechanism: FFDCA---Sec. 409---Necessary Tools

• Process: Safety Evaluation---Scientific review team

• Result: Regulations, notifications, and exemptions

Brief SummaryFood Additive Approvals

• Petitioner is responsible for demonstrating safety• FDA is responsible for

– Conducting a full and fair evaluation of the data and information– Issuing a regulation if FDA scientists conclude the requested use

is “SAFE”

FDAPetitioner

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

Natural Rubber Latex“NRL”

• § 172.615 Chewing gum base

• § 175.105 Adhesives

• § 175.125 Pressure-sensitive adhesives

• § 175.300 Resinous and polymeric coatings


• § 177.1010 Acrylic and modified acrylic plastics, semirigid and rigid

• § 177.1200 Cellophane

• § 177.1210 Closures with sealing gaskets for food containers

• § 177.2600 Rubber articles intended for repeated use


• 21 CFR 177.2600 (Feb. 1, 1963)

• Manufacture of Latex Food Service Gloves• Acceptable “indirect” food additive---FCS

• FDA Position• NRL currently “safe” food additive


• Exposure ---- Response

• Allergic Reactions

• Latex Proteins

The Issues

Latex Allergyand

Food Safety

Problem: Food Mediated Latex Allergic Reactions

The Glove

• Barrier to Infectious Agents

• Food Contact Material

• Subject to the Law (FFDCA)

• Approval

Intended Use

Fair Evaluation

Reasonable Certainty of No Harm

Latex Allergy and Food Safety

Latex Allergenic Proteins

• Indicated in Food Mediated Allergic reactions

• Constituents of an Indirect Food Additive

• FFDCA (Sec. 409)---Food & Drug Law

• Evaluation---General Safety Standard


Standard of Safety


Latex Allergyand

Food Safety

Food Mediated Latex Allergic Reactions How do we address the Problem


• Safety First

• FDA must operate under the Law (FFDCA)

• Approval --- Issuance of a Regulation

• Approvals are “safety” based only

• No explicit balancing of risks/benefits

• Amendment or Repeal --- Issuance of a Regulation

Addressing the Problem

SUMMARY• Sec. 409 FFDCA---Food Additive Provisions

• Review Process

• Fair Evaluation of the Data --- “Review”

• Reasonable Certainty of No Harm --- “Safety”

• NRL---21 CFR 177.2600

CONCLUSIONS

Evaluation of Safety

Food and Drug Law


FDA

Documents

notand cannotrequire

foods substances

premarket

safety requires

defines food

food drug

food additives

food additives