Transcript Document 7172181

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
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
•
Sweeteners; Preservatives; Fat;
Nutrients; Texturizers (thickeners,
Emulsifiers, etc.); Flavors
•
Color Additives
In food, animal feed, drugs,
cosmetics,medical devices(i.e. sutures
and contact lenses)
•
GRAS Ingredients
Enzymes; Fiber; Proteins;
Lipids; Sugars; MSG; Antimicrobials;
Phytosterols/stanols; Flavors;
Infant formula ingredients
•
Foods/Ingredients produced using
modern biotechnology
Plants w/herbicide resistance or insect
resistance, delayed ripening, etc.;
often use GRAS concept
Processing Aids
Antimicrobials(meat and poultry
Processing); Defoamers; Ion exchange
resins
•
Food Irradiation Equipment
To process food
To inspect food
• 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”
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 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
Maryland  Virginia
Adulterated Food
Interstate Commerce
FDA
Enforcement
Food and Drug Law
[A]
New antioxidant Antioxidant migrates
“Unapproved”
Adulterated Food
Dave’s Candy
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 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
“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 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 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 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
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 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
Section 409 Requirements
FDA’s 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
174-178
•
•
•
•
•
179
180
181
182-186
189
Irradiation of Foods
Substances permitted on interim basis
Prior Sanctioned Substances
GRAS Ingredients
Prohibited Substances
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
174-178
•
•
•
•
•
179
180
181
182-186
189
Irradiation of Foods
Substances permitted on interim basis
Prior Sanctioned Substances
GRAS Ingredients
Prohibited Substances
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
Natural Rubber Latex
“NRL”
• § 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
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