fda regulation of food from ge...

FDA Regulation of Food from GE Crops

Patrick Cournoyer, Ph.D. U.S. Food and Drug Administration (FDA)

Center for Food Safety and Applied Nutrition Office of Food Additive Safety

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Overview

• Historical perspective: – FDA’s involvement in plant breeding and plant biotechnology

• FDA’s regulatory approach:

– Legal authority related to food from GE plants

• How to consult with us: – The types of data and information FDA evaluates

• Past consultations

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• 1938: The Federal Food Drug & Cosmetic Act – 1958: Food Additive Amendment – Food additives require approval – Exempted: Substances whose uses

are “Generally Recognized as Safe” (GRAS)

• 1970: Regulation on plant breeding

and GRAS – Emerging concerns cited:

• Glycoalkaloids in potatoes • Endogenous defensive compounds • Key vitamins and nutrients

Regulating plant breeding: A historical perspective

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• 1986 Coordinated Framework – USDA – EPA – FDA – Existing legal authorities sufficient

Endogenous Substances

Must not contain substances at levels that are harmful

Added Substances Ingredients must meet safety criteria, may

require FDA review and approval

Including substances added through biotechnology (1984)

Including sufficient levels of key nutrients (1970)


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• FDA’s 1992 Statement of Policy: Foods Derived from New Plant Varieties

• FDA views on plant breeding in general • Discussed new methods of biotechnology

• Recommended consultation • Flow charts to help developers determine if important safety

and regulatory concerns exist

Endogenous Substances Must not contain substances at levels that

are harmful



Labeling Labeling must be truthful and not misleading (misbranding)


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Overview




• How to consult with us: – Data and information FDA evaluates


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Federal Food Drug & Cosmetic Act (FD&C Act) Core Provisions

FD&C Act Labeling

Labeling must be truthful and not misleading (misbranding)

Safety Food must be safe

(adulteration)


are harmful



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Federal Food Drug & Cosmetic Act (FD&C Act) Core Provisions

FD&C Act Labeling



(adulteration)


are harmful



Legal without premarket approval If safety info is publically available

and widely accepted by experts (GRAS)

Premarket review required If safety info is NOT publically available or

NOT widely accepted by experts

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What does GRAS mean?

• GRAS: generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use. (FD&C Act, Section 201(s))

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What does “safe” mean?

With respect to added substances: • Safe or safety means that there is a reasonable

certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use. (Code of Federal Regulations 170.3(i))

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The FD&C Act applies to food from GE crops

FD&C Act Labeling



(adulteration)


are harmful







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are harmful

Above 200 milligrams total glycoalkaloid per kilogram of potato

Below 200 milligrams total glycoalkaloid per kilogram of potato

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FD&C Act Labeling



(adulteration)


are harmful







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Glyphosate tolerant corn with added CP4 EPSPS

protein

CP4 EPSPS

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FD&C Act Labeling



(adulteration)


are harmful







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Must disclose “material” facts

Common or Usual Name


25%

75% 72%

0%

20%

40%

60%

80%

GE Soybean with increased levels of

oleic acid Oleic acid content in

oil

New name: “High oleic soybean

oil”

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Overview






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Consulting with FDA

FD&C Act Labeling



(adulteration)


are harmful







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Consulting with FDA



are harmful



Consultation with FDA to resolve safety and regulatory questions before

marketing

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Consulting with FDA

Developer submits

safety and regulatory

assessment

FDA team of experts

evaluates the data and information

FDA requests additional

information as needed

Repeat until safety and regulatory questions

are resolved

FDA summarizes

evaluation in a memo

FDA ends the

consultation by sending a letter to the developer

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Consulting with FDA

Developer submits

safety and regulatory

assessment

FDA team of experts

evaluates the data and information

FDA requests additional

information as needed

Repeat until safety and regulatory questions

are resolved

FDA summarizes

evaluation in a memo

FDA ends the

consultation by sending a letter to the developer

Before sending us a submission for a “final consultation”

Consult with us early! Consult with us often!

Meet with us in person or by teleconference No cost

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Elements of a Submission

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are harmful



Basic Information

• Trait description • Crop uses • Molecular characterization • Trait stability


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Basic Information

Characterize insertion(s), copy

number Vector Backbone?

New proteins from alternative

open reading frames?

Stability?

• Trait description • Crop uses • Molecular characterization • Trait stability

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are harmful



Basic Information


Compositional assessment:

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Compositional Analysis

Key Nutrients

proximates

fatty acids

amino acids

minerals

vitamins

?

Anti-Nutrients

lectins

raffinose stachyose

phytic acid

protease inhibitors

cyanogenic glycosides

?

Endogenous Toxicants

glycoalkaloids

gossypol

glucosinolates

benzyl isothiocyanate

isoflavones*

?

Endogenous Allergens

soybean

wheat

rice

?

“Good stuff” “Bad stuff”

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Appropriate comparator (Grown concurrently)

To characterize changes

Reference varieties (Grown concurrently)

To characterize existing variation

Published data To characterize existing

variation

New GE variety

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• Field trial design

– Number of locations, years? • Need to represent range of conditions

– Number of replicates?

• Need to control for variables • Need statistical power

• Field trials should be designed to answer

necessary regulatory questions – Case by case

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are harmful



Basic Information


Proteins: Toxicity, allergenicity Metabolites

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Evaluating new substances for safety

• What is it? – Prior knowledge – What happens after consumption? (ADME) – What do we know about potential toxicity?

• How much is safe to consume?

– Are feeding studies needed? – NOAEL

• How much is consumed?

– Calculating exposure

• Are expected exposure levels safe? – Margin of exposure

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are harmful



Basic Information


Common or usual name “Material” differences?

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New Protein Consultations

• Potential unintended presence in food • FDA issued guidance in 2006 to establish

mechanism for FDA to evaluate new proteins before field testing

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Overview






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Completed New Protein Consultations

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Completed Consultations

www.fda.gov/bioconinventory

http://www.fda.gov/bioconinventory

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Completed Consultations Crops (# of events)

Herbicide tolerance

(52)

Corn (45)

Potato (35)

Cotton (25)

Soybean (19)

Canola (18)

Tomato (7) Sugar beet (3)

Alfalfa (3) Radicchio (3)

Other* (14)

* Squash (2), cantaloupe (2), apple (2), rice (2), papaya (2), plum (1), flax (1), wheat (1), creeping bentgrass (1)

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Completed Consultations Traits (# of events)

Insect resistance (Bt)* (71)

Herbicide tolerance (52)

Male sterility (13)

Reduced browning (9)

Insect resistance (RNAi)* (1)

Increased yield (2) Drought tolerance (1)

Processing enzymes (5) Lower acrylamide potential (7)

Altered composition (8) Delayed ripening (8)

Virus resistance (RNAi)* (19)

Disease resistance (R protein)* (1)

Insect resistance (Bt)* (71)

Herbicide tolerance (52)

* Plant-incorporated protectants regulated by EPA

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Thank You • FDA Home Page

– www.fda.gov

• FDA’s Plant Biotechnology Consultation Program – www.fda.gov/GEPlantFoods – Food from GE Plants – How FDA regulates Food from GE Plants – Q&As – Links to guidance and policy documents

• Listing of all completed consultations

– www.fda.gov/bioconinventory – Documents from completed consultations

• Contact

– [email protected] – [email protected] (Biotech program lead) – [email protected] (New Protein Consultation Program lead)

http://www.fda.gov/

http://www.fda.gov/GEPlantFoods

http://www.fda.gov/bioconinventory

mailto:[email protected]

