Food Safety Assessment

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Food Safety Assessment

• Kevin Greenlees, PhD, DABT
• Kathleen Jones, PhD

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Food/Feed Safety

• What hazards/risks have been identified in the
  hierarchical review?

3
If GE Animal Not for Food
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Established Food Safety Standard

• The food safety standard is reasonable certainty
  of no harm NOT absolute safety

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Whole Foods

• Toxicological testing of whole foods in animal
  models is challenging
• Complex mixtures
• Wide variation in composition
• Impact on dietary balance
• High dose testing not possible

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Outcome Characterization
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Approach

• Identify and characterize hazards
• Direct effects
• Indirect effects
• Analytical methods

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Direct v IndirectIntended v Unintended

• Direct Adverse Effect (Food Safety)? adverse
  outcome resulting from human consumption of
  edible products from the rDNA animal coming into
  contact with the construct or its gene product(s)
• Indirect Adverse Effect (Food Safety) ? adverse
  outcome resulting from human consumption of
  edible products from the rDNA animal that contain
  hazards due to the construct or gene product
  perturbing the food animals physiology
• Intended effects ? changes in the rDNA animal
  brought about deliberately by introduction of the
  rDNA construct and its predicted gene product(s).
  These may or may not pose direct or indirect
  effects on food safety.
• Unintended effects ? changes in the rDNA animal
  resulting from the interaction of the rDNA
  construct or its gene product(s) with the
  physiology of the animal such that its metabolism
  is altered. These may or may not pose direct or
  indirect effects on food safety.

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Direct Effects

• Result from the expression product(s) of the
  inserted construct directly producing harm
• Toxicological testing on case-by-case basis
• Allergic assessment of proteins new to food

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Indirect Effects

• Effects other than direct impact of the
  expression product in food.
• Nutritional deficiency identified in
  compositional analysis

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Conceptual Overview of Food Safety Evaluation
Construct
Gene Product
Indirect Effects
Direct Effects
Direct Effects
Indirect Effects
Metabolic ? such that consumption of edible
tissue may pose risk (altered levels of expected
nutrients, inherent metabolites or sequestered
xenobiotics)
Consumption of edible product containing GP
causes toxicity (allergenicity, GI disturbance,
other tox)
Insertional Mutagenesis in structural or
regulatory region
None (DNA is GRAS)
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Conceptual Overview of Food Safety Evaluation

• The previous slide is a graphical summary of how
  one may approach the evaluation of food safety of
  edible products from GE animals. It indicates a
  GE animal, the construct that goes into it, and
  the resulting gene expression products. It
  subsequently indicates direct and indirect
  effects that may occur as the result of the
  construct or the expression products. The
  construct is not expected to cause direct effects
  as the agency has previously determined that DNA
  is generally recognized as safe (GRAS). Indirect
  effects caused by the construct could result from
  insertional mutagenesis in either structural or
  regulatory regions of the genome.
• The gene product can cause direct effects via the
  consumption of edible products, products
  containing gene products that cause toxicity
  (allergenicity, gastrointestinal disturbance, or
  other toxicity). Indirect toxicity can result
  from metabolic changes such that consumption of
  edible tissue that may pose risk, for example,
  altered levels of expected nutrients, inherent
  metabolites or sequestered xenobiotics).

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Analytical Methods for GE Animal

• For a tolerance
• For identity

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Analytical Method for a Tolerance

• Only in food producing animals
• Only if a tolerance is needed
• Demonstrates marker analyte present at or below
  tolerance in target tissue

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Analytical Method for Identity Characteristics

• Identifies approved GE animal in mixed population
• Determines edible tissue is from approved GE
  animal
• Discriminates approved product from knock-off
• Practical in a regulatory laboratory
• May provide useful information if durability
  failure

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Food/Feed Safety of

• No food/feed from this lineage of GE animals will
  enter food/feed supply

• Information Reviewed
• Sponsor affirmation
• Animal identification facilities containment
  procedures
• Animal and product disposition methods and
  records
• Regulatory Method ?procedures for transgene
  identification for animals and edible tissues
• Conclusions
• Plan likely to ensure that GE animals will not
  enter the food or feed supply
• Regulatory method adequate to identify
  animals/meat