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U. S. Food and Drug Administration
Center for Food Safety and Applied Nutrition
FDA Education/Compliance Program: 1995
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FDA'S Policy for Foods Developed by Biotechnology
Emerging Technologies -- Biotechnology
GENETIC ENGINEERING
Biotechnological methods of genetic engineering are
relatively new techniques that plant breeders have
to make direct modifications of DNA, a living
thing's genetic materials. Scientists make copies to
genes for desired traits and introduce the gene copy
into an organism such as a food crop. The new gene
is usually a single gene whose function is well
understood. These new techniques avoid one of the
major problems encountered by plant breeders who use
cross hybridization - no unwanted or undesirable
genes are introduced with the desired gene. In
addition, scientists can make copies of genes from
any organism - plant, animal, or microbe - that may
yield a desired trait and introduce that gene into a
food crop. This greatly expands the pool of
potentially useful traits available to plant
breeders to improve food crops.
Once a desired gene has been introduced into a crop
via genetic engineering, the gene is usually crossed
into other crop lines that have desired commercial
traits. Such crossing also permits the breeder to
evaluate the genetic stability of the new gene.
Overall, genetic engineering allows breeders to
develop new varieties more rapidly, but at this
stage of the technology, the new methods are used in
conjunction with other methods of plant breeding,
such as cross-hybridization.
The time required to evaluate new varieties and the
number of field trials will vary depending on the
need to confirm performance, to evaluate
characteristics of the food, to evaluate
environmental effects, and to produce the required
amount of seed before the new plant variety can be
grown commercially by farmers.
Genetic engineering is used to achieve the same
goals of agronomic and quality characteristics as
traditional techniques and allows the breeder to
make some modifications that would not be possible
through other methods of plant breeding.
Genetically engineered food crops have been
developed to:
-
resist pests and disease and to tolerate chemical
herbicides;
-
exhibit improved food processing traits; exhibit
improved nutritional content;
-
resist adverse soil and weather conditions; and
-
to exhibit improved fruit ripening or softening,
texture, or flavor.
FOODS PRODUCED BY GENETIC ENGINEERING
FDA evaluated the safety data and information
developed by Calgene, Inc. regarding the FLAVR SAVRTM
tomato, the first food derived from a plant modified
via recombinant DNA techniques to be evaluated by
the agency. In May, 1994, FDA and the FDA Food
Advisory Committee agreed with Calgene that the
FLAVR SAVRTM tomato was as safe as other commercial
varieties of tomato.
In response to a petition by Calgene, FDA also
issued a food additive regulation for the use of the
selectable marker gene, kanamycin resistance, to
develop via recombinant DNA techniques new varieties
of tomato, including the FLAVR SAVRTM tomato, cotton,
and oilseed rape (canola) plants.
In November, 1994, FDA reviewed the process for the
FDA Food Advisory Committee (FAC) by which firms are
informing the agency that they have completed their
safety and nutritional assessment of foods derived
from new plant varieties developed through
recombinant DNA techniques. The agency also
presented to the FAC the summary of the safety and
nutritional assessment provided to FDA on seven new
products. These included the following:
- Delayed ripening tomatoes (DNA Plant Technology,
Monsanto, Co., and Zeneca Plant Sciences).
- Pest resistant crops: Virus-resistant squash
(Asgrow); and Colorado potato beetle-resistant
potato (Monsanto, Co.).
- Herbicide-tolerant crops: Bromoxynil-tolerant
cotton (Calgene, Inc.); and Glyphosate-tolerant
soybean (Monsanto Co.).
The FAC agreed with FDA that there are no
outstanding food safety issues associated with these
products.
These examples of foods derived from new plant
varieties modified via recombinant DNA techniques,
including the FLAVR SAVRTM tomato, were evaluated by
the developers using safety and nutritional
assessments consistent with the standard to care
contained in FDA's 1992 policy.
FDA'S 1992 POLICY
In 1992, FDA published a policy statement that
explains how foods- fruits, vegetables, grains, and
their by products such as vegetable oils - are
regulated under the FD&C Act. This policy applies
to foods and food ingredients, including animal
feeds, derived from plants modified through all
methods of plant breeding, including genetic
engineering.
Highlights of some of the important factors included
in FDA's guidance to industry are the following:
- GENETIC MODIFICATION
The introduced genetic materials should be
well-characterized to ensure that any introduced
genes do not encode harmful substances and should be
stably inserted in the plant genome to minimize the
chance for subsequent undesired genetic
rearrangements.
- TOXICANTS
Plants are known to produce toxicants and
antinutritional factors, such as protease
inhibitors, hemolytic agents, and alkaloids which
often protect the plant against pests and disease.
Many of these toxicants are present in today's crops
at levels that do not cause acute toxicity or do not
affect humans or animals when the food is properly
prepared. New plant varieties should not contain
levels of such toxicants that are above the range
that exists in today's crops.
- NUTRIENTS
Another unintended consequence of genetic
modification of the plant may be an alteration
(relative to the total diet) in levels of important
nutrients and bioavailability of a nutrient due to
changes in the form of the nutrient or of other
constituents that effect absorption or metabolism of
nutrients.
- NEW SUBSTANCE
In some cases using genetic engineering, plant
breeders may introduce genes into food crops that
encode substances that differ substantially in
structure and function from substances currently
found in food. Based on current developments, such
substances would be expected to be proteins or
protein enzymes that modify carbohydrates and fatty
acids in the food. In some cases, such substances
will require premarket approval as food additives;
in other cases, the food may require new labeling to
properly inform consumers of the new attributes of
the food. However, in most cases to date, the
substances that occur in food as a result of gene
transfer have been safely consumed as food
previously or are substantially similar to food
substances and would not require premarket review by
FDA.
- ALLERGENICITY
There are thousands of different proteins in our
food supply, and only a few cause food allergy
reactions. However, because genetic engineering can
result in the introduction of genetic material from
essentially any source (plant, animal, or microbe)
into food, there is a possibility that a protein
encoded by the newly introduced genetic material
will be an allergen and produce an allergic response
in some members of the population. FDA has raised
this issue in its guidance to industry, especially
in cases where the transferred genetic material is
derived from a source that is known to be commonly
allergenic. Examples of such foods that affect the
U.S. population include milk, eggs, fish crustacea,
mollusks, tree nuts, wheat, and legumes
(particularly peanuts and soybeans). FDA believes
that proteins derived from commonly allergenic
sources should be presumed to be allergens and
special labeling would be required, unless
scientific evidence demonstrates otherwise.
In cases where a protein is derived from a source
that is not known to be allergenic, it is not
possible to definitively predict allergenic
potential. While it is unlikely that a new protein
that occurs in very low concentrations in food will
be an allergen (as is the case for most proteins
introduced via genetic engineering at this time),
developers have taken steps to minimize the
likelihood that a new protein will be an allergen by
evaluating whether the new proteins exhibit
characteristics typical of allergenic proteins (such
as stability to heat, acid, and enzyme degradation).
FDA encourages developers to discuss questions
regarding allergenicity with agency scientists.
- ANTIBIOTIC RESISTANCE MARKERS
In experiments involving genetic engineering, only a
few plants cells take up the desired new gene.
Developers use selectablemarker genes during gene
transfer experiments to improve their chances of
selecting plants that have successfully incorporated
the desired gene. The most widely used marker is
kanamycin resistance gene that produces the enzyme,
aminoglycoside 3'-phosphotransferase II (also
referred to as APH(3')II and neomycin
phosphotransferase II). Plant cells are normally
killed by antibiotics. APH3'II inactivates the
antibiotics kanamycin and neomycin and permits plant
cells to grow in culture that have incorporated gene
and express the APH(3')II enzyme.
Once the desired plant variety has been selected,
the marker gene serves no useful purpose in the new
plant, but it does continue to produce the gene
product, APH(3')II in the case of kanamycin
resistance. This enzyme is present at very low
concentrations in food.
The use of marker genes that encode resistance to
clinically important antibiotics raises questions
regarding whether the enzyme in the food could
inactivate oral doses of the antibioticor whether
the gene present in the plant DNA could
betransferredto pathogenic microbes in the GI tract
or in soil rendering themresistant to treatment with
the antibiotic. FDA evaluated thesequestions for
the use of kanamycin resistance in tomato, cotton,
canola.
FDA found that kanamycin and neomycin are very toxic
antibiotics and as such have very limited oral
clinical use and are used onlyin situations where
patients are not consuming food. There is also too
little of the essential cofactor, ATP, present in
food for the enzyme to degrade a significant amount
of antibiotic.
There is no known mechanism by which a gene can be
transferred from a plant chromosome to a microbe.
Thus, the possibility of that such transfer would
generate new resistant organisms is very small,
especially when compared to the high rate of spread
ofresistance through known mechanisms of microbe to
microbe transfer to antibiotic resistance. FDA
believes that the use of marker genes that encode
resistance to other clinically useful antibiotics
can be evaluated by similar criteria that were
usedfor kanamycin resistance.
- ANIMAL FEEDS
Feeds developed for animals raised as food sources
must be meet the same safety standards as human food
under the FD&C Act. In contrast to the human diet,
an animal feed derived from a singleplant may make
up over half of the animal's diet. Further,animals
consume plants and plant parts that are not part of
the human diet. Nutrient composition and
availability of nutrients are important
considerations for animal health.
- LABELING
The FD&C Act defines the information that must be
disclosed in labeling (including the food label).
The Act requires that all labeling be truthful and
not misleading. The Act does not require disclosure
in labeling of information solely on the basis of
consumer desire to know. The Act does require that
a food be given a common or usual name, and that the
label disclose information that is material to
representations made or suggested about the product
and consequences that may arise from the use of the
product.
FDA will require special labeling if the composition
of a food developed through genetic engineering
differs significantly from its conventional
counterpart. For example, if a food contained a
major new sweetener as a result of genetic
modification, new common or usual name or other
labeling may be required. Similarly, if a new food
contains an allergen that consumers would not expect
in that food, labeling would be necessary to alert
sensitive consumer. However, if a protein commonly
produces very serious allergic reactions (e.g.
peanut protein) and is transferred to another food,
FDA would need to evaluate whether labeling would
provide sufficient consumer protection.
To date, FDA is not aware of information that would
distinguish genetically engineered foods as a class
from foods developed through other methods of plant
breeding and, thus, require such foods to be
specially labeled to disclose the method of
development. The agency has not required labeling
for other methods of plant breeding such as chemical
- or radiation-induced not required to be labeled
"hybrid sweet corn" because it wasdeveloped through
cross-hybridization.
FDA is reviewing public comments on labeling issues.
One issue that is particularly difficult is the
question of whether special labeling should be
required for a food derived from a plant that has
been modified to express a gene derived from an
animal and whether the presence of such a gene or
its product affects certain ethical or religious
beliefs. Currently, no foods areapproaching the
market that raise this issue. However, the issue
is very complex, and FDA believes that further
discussion is warranted.
SUMMARY
FDA has provided guidance for developers that
establishes a standard to care to ensure that foods
derived from new plant varieties are safe and
wholesome. Irrespective of the method by which a
food is produced, all foods must meet the same
stringent safety standards and be properly labeled
in accordance with the FD&C Act.
REFERENCES
- Statement of Policy: Foods Derived from new
Plant Varieties, Federal Register, May 29, 1992,
Vol. 57, pages 22984-23005.
- Food Labeling; Foods Derived from New Varieties,
Federal Register, April 28, 1993, Vol. 58 pages
25837-25841.
- Memorandum, Summary of Consultation with
Calgene, Inc. Concerning FLAVR SAVRTM Tomatoes, May
17, 1994, HFS-206 to HFS-200.
- Secondary Direct Food Additives Permitted in
Food for Human Consumption; Food Additives Permitted
in Feed and Drinking Water of Animals;
Aminoglycoside 3'-Phosphotransferase II, Federal
Register, May 23, 1994, Vol. 59, pages 26700-26711.
- Procedures of Industry-FDA Interaction Prior to
Commercial Distribution of Foods Derived from New
Plant Varieties Developed Using Recombinant DNA
Techniques and Memoranda of Conference on Seven
Genetically Engineered Crops.
Hypertext updated by dms, 07/03/97