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

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

CFSANs 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

OFASs Food Ingredients Universe

Direct Food Ingredients
Sweeteners; Preservatives; Fat; Nutrients; Texturizers (thickeners, Emulsifiers, etc.); Flavors

Processing Aids
Antimicrobials(meat and poultry Processing); Defoamers; Ion exchange resins

Color Additives
In food, animal feed, drugs, cosmetics,medical devices(i.e. sutures and contact lenses)

Food Irradiation Equipment

To process food To inspect food

GRAS Ingredients
Enzymes; Fiber; Proteins; Lipids; Sugars; MSG; Antimicrobials; Phytosterols/stanols; Flavors; Infant formula ingredients

Food Packaging/Food Contact Substances

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

Foods/Ingredients produced using modern biotechnology

Plants w/herbicide resistance or insect resistance, delayed ripening, etc.; often use GRAS concept

Food and Drug Law

Federal, Food, Drug, and Cosmetic Act

FFDCA

FDA Authority
FFDCA

The LAW

OFAS & FFDCA

Food Additive Provisions Sec. 409

Food Additive Regulations

NOT

LAW

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

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)

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)

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.

MOMS
Apple Pies

Sweetner Unapproved Food Additive Maryland Virginia

Adulterated Food

Interstate Commerce

FDA Enforcement

Food and Drug Law

[A]

Daves Candy

New antioxidant Antioxidant migrates Unapproved Adulterated Food

Interstate Commerce

FDA Enforcement

Food and Drug Law

Why are food additives regulated?

Unsafe Food Additive = Adulterated Food Unapproved Food Additive = Unsafe Food Additive Unapproved 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

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

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

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

Commissioner David Kessler --- November 1995

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
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 HARM

Legislative 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 HARM

Legislative 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 Review

The 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.

Food Additive Petition Review

The 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
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

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

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
Key Determinant
Estimation of Exposure Proposed Conditions of Use Concentration (safe)
Level with no adverse effects observed toxicologically

The dose makes the poison

Key Players

Technical Review
FDA scientist review data and evaluate petitioners 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

Section 409 Requirements

FDAs Action on the Petition
Complete the review Establish a Regulation Deny the Petition

Section 409 Requirements

Other Legal Requirements
Objections and Public Hearings Judicial Review Amendment or Repeal of Regulations

Amendment or Repeal

IN Regulation

OUT Regulation

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 Regulations 21 CFR Parts 170-189

General Provisions Direct Food Additive Regulations 170 & 171 172 & 173

Indirect Food Additive Regulations

Irradiation of Foods Substances permitted on interim basis Prior Sanctioned Substances GRAS Ingredients Prohibited Substances

174-178
179 180 181 182-186 189

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

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

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

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 Summary Food Additive Approvals

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

Process: Safety Evaluation---Scientific review team

Result: Regulations, notifications, and exemptions

Brief Summary Food 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 FDA

Petitioner

Food Additive Regulations 21 CFR Parts 170-189

General Provisions Direct Food Additive Regulations 170 & 171 172 & 173

Indirect Food Additive Regulations

Irradiation of Foods Substances permitted on interim basis Prior Sanctioned Substances GRAS Ingredients Prohibited Substances

174-178
179 180 181 182-186 189

Title 21 CFR 177.2600 Rubber articles intended for repeat use

Natural Rubber Latex NRL

172.615 Chewing gum base

175.105
175.125 175.300

Adhesives
Pressure-sensitive adhesives Resinous and polymeric coatings

Natural Rubber Latex NRL

177.1010 Acrylic and modified acrylic plastics, semirigid and rigid

177.1200
177.1210

Cellophane
Closures with sealing gaskets for food containers Rubber articles intended for repeated use

177.2600

Natural Rubber Latex NRL

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

Natural Rubber Latex NRL

The Issues

Exposure ---- Response Allergic Reactions Latex Proteins

Latex Allergy and 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

Latex Allergy and Food Safety

Standard of Safety
Reasonable certainty of no harm

Latex Allergy and Food Safety

Food Mediated Latex Allergic Reactions How do we address the Problem

Latex Allergy and Food Safety

Addressing 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

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
Food and Drug Law
Evaluation of Safety Latex Allergy and Food Safety