The FEMA GRAS Program for Flavors

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The FEMA GRAS Program for Flavors
John Hallagan DMF Workshop 25 March 2002
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The Flavor and Extract Manufacturers Association

• Founded in 1909
• Based in Washington, D.C.
• National association of the flavor industry
• 130 members

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Primary FEMA Activities

• Safety Evaluation of Flavor Ingredients
• GRAS List of Flavor Ingredients
• Government Relations
• - U.S.
• - International

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FEMA GRAS

• Expert Panel - 1960
• 8 Members Expert in Flavor Safety Evaluation
• So Far, Over 2000 Materials are FEMA GRAS

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FEMA Expert Panel Members
ROBERT L. SMITH, Ph.D., Chairman PHILIP S.
PORTOGHESE, Ph.D. Imperial College School of
Medicine University of Minnesota London
SAMUEL M. Cohen, M.D., Ph.D. WILLIAM J. WADDELL,
M.D. University of Nebraska University of
Louisville Kentucky VICTOR J. FERON,
Ph.D. BERNARD M. WAGNER, M.D. TNO Nutrition
Food Research Bernard Wagner Associates The
Netherlands Millburn, NJ JAY I. GOODMAN,
Ph.D. JOHN DOULL, M.D., Ph.D. Michigan State
University University of Kansas
(Consultant) LAWRENCE J. MARNETT, Ph.D. IAN C.
MUNRO, Ph.D. Vanderbilt University CanTox Inc,
Canada (Consultant)

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FEMA GRAS

• Cooperation with FDA CFSAN
• Extensive databases
• GRAS List
• Publications
• Regular GRAS Publications
• Supporting Publications

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The Flavor Industry

• Global Sales 5 Billion
• U.S. Sales 2 Billion
• Companies
• Top 15 account for 75 of Sales

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Intellectual Property

• Flavor Formulas
• Protected as trade secrets
• Industry is very competitive
• Industry consolidation increasing

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Characteristics of Flavors

• Complex mixtures of flavoring substances
• Each flavoring substance used at low levels
  Self- limiting
• Most occur in food
• gt 2,000 Flavoring substances used in U.S.

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Flavoring Substances

• 1. Single chemically defined substances
• May be natural or artificial
• Usually compounded to form flavors
• 2. Natural Flavoring Complexes
• Extracts, essential oils
• Compounded or used as is

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Flavoring Substances

• Numerous gt2000 substances
• Types
• natural flavor complexes (300)
• Single chemically defined substances
• nature identical (1400)
• Xenobiotics (300)

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Flavoring Substances
Use levels generally self-limiting Exposure
generally low (lt1.5mg/person/day) 34
Structurally related groups Many belong to the
same well-defined structural class (e.g. 400
simple esters)
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Criteria For Safety Evaluation of Flavoring
Substances

• Chemical identity, purity and Method of
  preparation
• Natural occurrence
• Consumption ratio(food intake/flavor intake)
• Exposure from intended use
• Metabolic and pharmacokinetic characteristics
• Toxicology data

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Safety Evaluation of A Flavor Substance
Natural Chemical Occurrence
Structure Exposure Metabolism Consumption
Toxicology Ratio
Database for homologous series and structural
congeners
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Safety Evaluation of A Flavor Ingredient Example
Occurs in gt200 Foods
Database for 400 Aliphatic Esters Studies Acute
Toxicity (250) Subchronic/Chronic (50) Metabolism
(gt400)
Ethyl butyrate
Hydrolysis and Metabolism to CO2H2O
Intake, 30mg/kg/d
Acute Subchronic Feeding studies
Food Predominant
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Safety Assessment of Naturals
Expert judgment is key factor History of safe
use Exposure weighted safety assessment focused
on constituents
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Safety Assessment of Naturals

• Constituents are evaluated
• Principles same as chemically defined
• substances
• Assigned to structural class
• Unknown constituents
• Quantified
• Compared to threshold for class 3
• More analytical data if necessary

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FDA Office of Pharmaceutical Science

• 10 August 2001 Presentation
• Videotape
• Notebook

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FEMA is Available to Help

• Call us with your questions
• Assistance
• Safety data
• Use information
• Regulatory assistance