FDA/CFSAN’s Science-based FDA/CFSAN’s Science-based Approach to the Safety of Foods Approach to the Safety of Foods

Derived from Modern Derived from Modern BiotechnologyBiotechnology

Thomas A. Cebula, Ph.D.Thomas A. Cebula, Ph.D.

Director, Office of Applied Research Director, Office of Applied Research

and Safety Assessmentand Safety Assessment

Center for Food Safety and Applied NutritionCenter for Food Safety and Applied Nutrition

The Process

• Requests notification when industry plans to market a product derived by bioengineered plants

• Encourages that industry consult with us and provide necessary documentation to ensure ‘reasonable certainty of no harm’ Opportunity to discuss plans for future

cultivars

The Process

• Specific tests are not specified

Intent: To focus on the characteristics of the food product

Scientific Evaluation

Food Safety

Strengths/Limitations

• Approach is multidisciplinary Agronomic and quality characteristics Characteristics of new substances Chemical and nutritional analysis Genetic analysis

• A bioengineered variety is evaluated relative to its traditional counterpart

Scientific Evaluation

Food Safety

• Identity and source of introduced genetic materials

• Genetic stability

• Intended changes to the composition of the food

Scientific Evaluation

Food Safety

Scientific Evaluation

Food Safety

Allergenicity Toxins Nutrient Levels Antibiotic Resistance

Food Safety Assessment

• Description of rDNA plant

• Description of the host plant & use as food

• Description of the donor organism(s)

• Description of the genetic modification

• Characterization of the genetic modification

Safety Assessment, cont’d

• Expressed substances (non-nucleic acid)

• Compositional analyses (key components)

• Evaluation of metabolites

• Food processing

• Nutritional modification

• Other considerations (e.g. marker genes)

Description of the Genetic Modification

• The transformation process/host plant– Specific method (Agrobacterium-mediated)

– Source, identity, function of DNA

– Intermediate hosts

• The DNA to be introduced• All genetic components (genes, markers,

regulatory sequences, etc.)• Size, identity; location/orientation; function

Characterization of the Genetic Modification/DNA Insertion

• Number of sites & organization; copy number & sequence data of insert & surrounding region, sufficient to identify expressed substances, or analysis of transcripts or expression products that may be present in food.

• Open reading frames & insertions with contiguous plant DNA (fusion proteins)

Characterization of the Genetic Modification/ Expressed

Substances• Gene products, including un-translated

RNA• Function & phenotype• Level & site of expression; level of

metabolites in food• Amount of target gene product, if

function is to alter endogenous mRNA or protein

Genetic Modification Additional Information

• Arrangement of genetic material• Whether modifications to protein

sequence affect post-translation/function• Intended effect & heritable stability• Expression in appropriate tissues & any

evidence that host plant is affected• Identity & expression of any fusion

protein

As only one or a few genes are being incorporated into the plants, there is a limited number of manipulations.

As we move forward, traditional breeding will likely be used to transfer a desired rDNA modification into desired plant varieties.

Strengths/Limitations Scientific

Scientific Evaluation

Evaluating Bioengineered Plants

What tests are necessary?

Are there tests that should be required?

What tests are necessary?

Are there tests that should be required?

RR vs rr: 62 of 636 protein spots on a 2-D gel are qualitatively different. R-locus affects sugar content, lipid content, storage protein composition, and shape and size of starch granules.

Evaluating Bioengineered Plants

What tests are necessary?

Are there tests that should be required?

Afila (af) mutants which replace leaflets with tendrils, and the tendril-less (tl) mutant which replaces tendrils with leaflets. Both tl/tl and af/af lines have the identical 686 protein profiles.--Gottlieb & de Vienne, Genetics, 119:705-710 (1988)

Evaluating Bioengineered Plants

Pleiotropy is virtually universal, i.e., essentially all gene substitutions have multiple phenotypic consequences when the phenotype is examined in sufficient detail.

Evaluating Bioengineered Plants

Can Pattern Recognition Work?