Safety Assessment of Food Additives

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Safety Assessment of Food Additives
How FDA Regulates 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
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OVERVIEW

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

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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

OFAS --- Food Ingredients
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OFASs 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
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
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Food and Drug Law

• Federal, Food, Drug, and Cosmetic Act
• FFDCA

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FDA Authority

• FFDCA

The LAW
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OFAS FFDCA

• Food Additive Provisions
• Sec. 409

Federal Food, Drug, And Cosmetic Act
409
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Regulations
21 CFR
Food Additive
?
NOT

• LAW

FFDCA
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PRE-MARKET APPROVAL

• 1958 Food Additives Amendment
• of FFDCA
• Sec. 409

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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)
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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)

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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
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MOMS Apple Pies
Sweetner Unapproved Food Additive
Maryland ? Virginia
Interstate Commerce
FDA Enforcement
Adulterated Food
Food and Drug Law
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A
A
FDA Enforcement
New antioxidant Unapproved
Antioxidant migrates Adulterated Food
Interstate Commerce
Food and Drug Law
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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
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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
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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
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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
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Standard of Review

• Fair evaluation of the data

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From the Senate Report on theFood 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.

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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

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Standard of Safety

• Reasonable certainty of no harm

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Standard of Safety

• Reasonable certainty of no harm

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Standard of Safety

• Reasonable certainty of no harm

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Standard of Safety

• Reasonable certainty of no harm

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Standard of Safety

• Reasonable certainty of no harm

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Standard of Safety

• Reasonable certainty of no harm

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Standard of Safety

• Reasonable certainty of no harm

"SAFE"
21 CFR 170.3(i)
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Standard of Safety

• Reasonable certainty of no Harm

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Standard of Safety

• Reasonable certainty of no Harm

What is Harm?
- Harm refers to Health
Man or Animal
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Standard of Safety

• Reasonable certainty of no Harm

What is Harm?
- Harm refers to Health
Man or Animal
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Standard of Safety

• Petitioner burden to demonstrate a reasonable
  certainty of no harm
• FDA Assessment

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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)
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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)
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Section 409
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Section 409 Requirements

• Any person may petition to establish safety

"Food Additive Petition Process"
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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.

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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

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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

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Key Players

• Consumer Safety Officer (CSO)
• Chemistry
• Toxicology
• Environmental

E
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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
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Safety Evaluation

• A full blown exhaustive
• safety evaluation of all
• appropriate studies, with agency ownership of
  safety decision.

Standard of Review
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Safety Evaluation

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

The dose makes the poison
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Technical Review
Key Players

• 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

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FDAs Action on the Petition
Section 409 Requirements

• Complete the review
• Establish a Regulation
• Deny the Petition

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Other Legal Requirements
Section 409 Requirements

• Objections and Public Hearings
• Judicial Review
• Amendment or Repeal of Regulations

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Amendment or Repeal
Food Additives

• IN
• Regulation

• OUT
• Regulation

FDA Responsibility
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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

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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
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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

Sec. 409(h) of FFDCA
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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

Sec. 409(h) of FFDCA
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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

Sec. 409(h) of FFDCA
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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
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Food Contact Notifications
Food Additive that is subject of an effective
notification ? Safe food additive
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Brief SummaryFood Additive Approvals

• Mechanism FFDCA---Sec. 409---Necessary Tools
• Process Safety Evaluation---Scientific review
  team
• Result Regulations, notifications, and exemptions

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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

FDA
Petitioner
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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
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Natural Rubber LatexNRL
Regulations

• 172.615 Chewing gum base
• 175.105 Adhesives
• 175.125 Pressure-sensitive adhesives
• 175.300 Resinous and polymeric coatings

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Natural Rubber LatexNRL
Regulations

• 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

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Natural Rubber LatexNRL

• 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

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Natural Rubber LatexNRL
The Issues

• Exposure ---- Response
• Allergic Reactions
• Latex Proteins

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Latex Allergyand Food Safety
Problem Food Mediated Latex Allergic Reactions
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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
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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
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Standard of Safety

• Reasonable certainty of no harm

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Latex Allergyand Food Safety
Food Mediated Latex Allergic Reactions How do we
address the Problem
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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

Use of additive Unsafe food?
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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

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