U.S. FDA’s Approach to the Safety Assessment of

Bioengineered Plants Used as Food

Mary Ditto, Ph.D.October 21, 2002

Food and Drug AdministrationCenter For Food Safety and Applied Nutrition

U.S. Federal Oversight for Bioengineered Foods

Coordinated Framework for the regulation of foods

Involves three federal agencies

U.S. Regulatory System for the Evaluation of Bioengineered Food

Products

United States Department of Agriculture (USDA)

Environmental Protection Agency (EPA)

Food and Drug Administration (FDA)

U.S. Federal Statutory Authority

USDA/APHIS - Federal Plant Protection Act (FPPA) and Plant Quarantine Act (PQA)– regulation of the introduction (importation,

interstate movement, or release into the environment) of genetically engineered organisms

U.S. Federal Statutory Authority

EPA – Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) and FFDCA - regulation of pesticidal substances including those produced in plants- sets tolerances (or establishes exemptions from tolerance) for pesticides in or on food

U.S. Federal Statutory Authority

FDA - Federal Food, Drug and Cosmetic Act (FFDCA)– regulation of foods, feeds, food additives, and

labeling of foods• Ensuring the safety and proper labeling of foods and

food substances

FDA Food Biotechnology Policy

• Federal Food, Drug, & Cosmetic Act• Science based regulation• Ensure safe and wholesome food

supply• ‘92 policy; scientific guidance

FDA’s 1992 Policy Statement

Published in the Federal Register, May 29, 1992, (57 FR 22984)

Applies to all methods of breeding, including recombinant DNA

New foods must be as safe as foods on the market today

All foods regulated under existing paradigm, FFDCA

Two provisions of FFDCA gives FDA authority to regulate foods:

Post market adulteration provisions --(Section 402(a)(1))

Premarket approval of food additives

--(Section 409)

Objectives of 1992 Policy

Develop guidance for industry on food safety assessment

Establish procedures for consultations with FDA on scientific and regulatory issues

Ensure a safe and wholesome food supply

General Safety Assessment ApproachGeneral Safety Assessment Approach

Today’s food is the standard

New varieties are evaluated relative to traditional counterparts

Multi-disciplinary approach: Agronomic and quality characteristics; genetic, chemical, nutritional analyses

If questions remain — toxicological tests

Food Safety Assessment

Intended Modification New Substance(s) —

– Identity; structure/function– Source (allergenicity)– digestibility– Dietary exposure– Nutrition

Food Safety Assessment

Unintended ModificationsUnintended Modifications• Genetic stability• Composition —

– Nutrients – Toxicants

FDA’s 1992 Policy Statement “Standard of Care”

Policy statement addresses food safety assessment

allergenicity of newly introduced proteinsnutrient composition and anti-nutrientsknown toxins and new toxinsantibiotic resistance markersunintended effects

Has there been an intentional alteration in the identity,

structure, or composition of fats or oils in the new variety?

No concerns

Have the intentional alterations been in a fat or oil that will be a

macroconstituent in the diet?

Are any unusual or toxic fatty acids produced in the new

variety?

Consult

FDA

Consult

FDA

Yes

Yes

Yes

NoNo

No

New or modified fats or oils

Consultation Procedure

FDA established a consultation procedure to ensure that new products are safe and lawful.

– FDA believes that all developers of commercially marketed bioengineered foods sold in the U.S. have consulted with FDA prior to marketing their products.

Consultation procedure

Firms submit a summary of safety and nutritional data of the product.

– When all safety and regulatory issues have been resolved firms receive a letter stating that FDA has no questions at this time.

– Completed consultations are listed on the FDA’s Internet site.

New Bioengineered Varieties

Beet (2) Canola (8) CantaloupeCorn (16) Cotton (5) FlaxPapaya Potato (4) RadicchioRice Soybean (3) Squash (2)Tomato (6)

Introduced Traits

Herbicide Tolerance

Insect Resistance

Insect Resist./Herb. Tolerance

Pollen Modified/Herb. Tolerance

Virus Resistance

Insect & Virus Resistance

Delayed Ripening

Other

International Approach

‘90 FAO/WHO Expert consultation ‘93 OECD report ‘96 FAO/WHO Expert consultation ‘00 OECD report to G-8 ‘02 FAO/WHO Expert consultation ‘02 Codex Task Force Draft Guidelines

Biotech 2000 and Beyond

FDA held three public meetings in 1999

– Communicate policy and solicit opinions on current policy and procedures

Requested comments Received over 50,000 comments

Public Comments

– No new data to question safety of bioengineered foods currently marketed

– Divergent views on labeling – Consultation process is voluntary– Lacked transparency– Concern that current procedures may not be

sufficient to deal with future developments

New Initiatives: Proposed Rule Premarket Notice Concerning Bioengineered Foods

Published in the Federal Register, January 18, 2001 (66 FR4706)

Proposed Requirement for Premarket Notice (PMN)

Requirement for premarket notification for bioengineered plant derived foods

If finalized, would require developers of bioengineered foods to notify FDA 120 d before commercial distribution.

– Would enhance FDA’s ability to assess whether new bioengineered plant varieties comply with FFDCA on an on-going basis.

Proposed Requirement for Premarket Notice (PMN)

Plant-derived bioengineered foods consumed by humans and animals– If a pesticidal substance- EPA evaluates

pesticide; FDA evaluates other issues Timing: 120 days before market Recommend Presubmission Consultation

Safety Standard: “As safe as comparable foods”

Proposed Requirement for Premarket Notice (PMN)

Recommended testing in accordance with the 1992 policy

Proposed codified requires a specific format and content for a submission

Notifier attests that the food is as safe as comparable food and is otherwise lawful

FDA will post notices on the internet when first filed

Current Status FDA received over

- 100,000 comments to the proposed rule for premarket notification

FDA is reviewing comments

Working towards a final regulation

New Initiatives Increased transparency

Issued draft guidance for voluntary labeling

Guidance on allergenicity and antibiotic resistance marker genes

Supplement FACs with scientists with agricultural biotechnology expertise

Enhance research

Draft Guidance for Labeling

Issued January 18, 2001

Agency is considering comments received

On web at – http://www.cfsan.fda.gov/~dms/biolabgu.html

FDA’s Labeling Authority

Federal Food, Drug and Cosmetic Act (FFDCA)-Sections 403(a) and 201(n)

Fair Packaging and Labeling Act (FPLA)

Draft Guidance for Labeling

Restates agency’s policy regarding when special labeling is required for bioengineered foods.– Truthful and not misleading– Misleading if fails to reveal facts that are

material in light of representations made

FDA’s position on labeling of bioengineered foods

Food must be labeled when there is a significant change in the food, i.e.,– nutritional– compositional– change in conditions of use– or when an allergenic component has been introduced in a

food where it does not naturally occur

Status of Initiatives

Finalize the proposed rule for mandatory premarket notification

Finalize guidance on labeling Finalize guidance on the use of antibiotic

resistance marker genes Developing guidance for the assessment of

allergenicity– Recent meeting of Biotech subcommittee of FAC

International Activities

International activities - promote harmonization– Codex– OECD

Interact with foreign governments to provide information and expertise

Information about FDA

FDA Main Web site: www.fda.gov FDA Biotechnology Web site

www.cfsan.fda.gov/~lrd/biotechm.html