SHORT SUMMARY The salmon evaluated by the FDA is a genetically modified (“engineered” or also “transgenic”) Atlantic salmon to be produced and grown under specified conditions. This fish, named AquAdvantage Salmon, is a triploid (effectively sterile) female fish containing a rDNA construct designed to exhibit a rapid-growth phenotype that allows it to reach smolt size (or approximately 100 g) faster than non-genetically modified farmed salmon. The objective of the project is to meet increasing demand for fish protein in light of declining stocks and diminishing capture of wild fish.
FDA has made the preliminary determination, based on the evidence collected and evaluated, that it is reasonable to believe that approval of the AquAdvantage Salmon NADA will not have any significant impacts on the quality of the human environment of the United States, and on the populations of endangered Atlantic salmon when produced and grown under the conditions of use for the proposed action.
The US-FDA regulates animals containing rDNA constructs under the new animal drug provisions of the FD&C Act, must meet environmental review requirements under the National Environmental Policy Act (NEPA) and FDA’s regulations.
The FDA’s Center for Veterinary Medicine (CVM) has evaluated both the direct and indirect food safety impacts of AquAdvantage Salmon and any potential impacts of the rDNA insertion on target animal safety. CVM has also thoroughly evaluated the potential environmental impacts of approving an NADA for AquAdvantage Salmon.
The potential hazards and harms to the environment include the hypothesis that the transgenic salmon would escape the conditions of confinement but, as the transgenic salmon would be produced and grown-out in secure facilities that have been verified and validated by FDA, the possibility that transgenic fish could escape from containment, survive and reproduce is extremely remote. In addition, because populations produced will be triploid (effectively sterile), all-female animals, the possibility of their reproducing in the wild is likewise extremely remote. FDA, has also considered that approval of the AquAdvantage Salmon will not jeopardize the continued existence of United States populations of threatened or endangered Atlantic salmon.
The potential effects on the local environments of Canada and Panama have not been considered and evaluated in this draft assessement because the US NEPA does not require an analysis of environmental effects in foreign sovereign countries, except if there would be significant effects on the environment of the United States.
With respect to food safety, FDA has concluded that food from AquAdvantage Salmon is as safe as food from conventional Atlantic salmon, and that there is a reasonable certainty of no harm from consumption of food from triploid AquAdvantage Salmon.
1. What is the genetically modified (“engineered” or also transgenic) salmon which is evaluated by the FDA?
The development of a genetically modified salmon is the end result of advances in genetic engineering within the past 30+ years. Recombinant DNA technology was first used to produce genetically modified (engineered or transgenic) animals in 1973. Although initial interest centered primarily on mammals, by the late-1990s, genetically modified (or engineered – GE) carp, trout, loach, tilapia, catfish, and salmon had been produced.
AquaBounty Technologies, Inc. (ABT or the sponsor) has provided data and information in support of a New Animal Drug Application (NADA) for a genetically modified Atlantic salmon1 to be produced and grown under specified conditions. This fish, named AquAdvantage Salmon, is designed to exhibit a rapid-growth phenotype that allows it to reach smolt size (or approximately 100 g) faster than non-genetically modified farmed salmon.
The AquAdvantage Salmon founder animal was generated in 1989 by micro-injecting a recombinant deoxyribonucleic acid (rDNA) construct, composed of a element from an ocean pout antifreeze protein gene and a protein-coding sequence from a chinook salmon growth hormone gene into the fertilized eggs of wild Atlantic salmon.
This salmon produced by AquaBounty Technologies, Inc. is a triploid (effectively sterile) female fish containing a rDNA construct, called opAFP-GHc2, which imparts a rapid-growth phenotype allowing populations of these animals to reach a common growth measure (smolt size) more quickly than populations of comparator Atlantic salmon.
2. What led to the development of a genetically modified salmon strain?
To meet increasing demand for fish protein in light of declining stocks and diminishing capture of wild fish, the use of commercial aquaculture—colloquially known as fish farming—has expanded significantly in recent years.
The Food and Agricultural Organization (FAO) of the United Nations has estimated in 2008 that by 2030, annual commercial aquaculture production will need to increase by an additional 28.8 MM MT (i.e., 80.5 MM MT total) in order to maintain per capita fish consumption at current levels.
The recently issued (2010) Dietary Guidelines for Americans specifically recommend that Americans increase the amount and variety of seafood consumed by choosing seafood in place of some meat and poultry. These guidelines indicate that consumption of seafood, which provides an average consumption of 250 mg per day of eicosapentaenoic acid and docosahexaenoic acid, is associated with reduced cardiac deaths among individuals with and without pre-existing cardiovascular disease, and thus recommend the consumption of higher levels of seafood to help prevent heart disease. These recommendations are expected to further contribute to increased demands for seafood in the future.
The dominant interest in genetically modified salmon and several other genetically modified fish species has been to increase growth rate and feed conversion efficiency, which are principal drivers of production and the economic viability of commercial farming operations (for all production agriculture). The development of what is now known as AquAdvantage Salmon began in 1989 and is the most commercially advanced of those efforts to date.
3. What is the regulatory context in place in the US to manage the request to produce and put on the market of such a genetically modified salmon?
An rDNA construct that is intended to affect the structure or function of a transgenic animal meets the statutory definition of a new animal drug and must be approved by FDA prior to commercialization. FDA regulates indeed animals containing rDNA constructs under the new animal drug provisions of the FD&C Act, and meets it obligations for environmental analysis under Approvals of this type constitute “major Federal actions” for which FDA must meet environmental review requirements under the National Environmental Policy Act (NEPA) and FDA’s regulations, thus triggering the requirement to perform such environmental assessment.
FDA approvals for articles regulated under the new animal drug provisions of the FD&C Act may be for a specific set of conditions that are proposed in the drug sponsor’s New Animal Drug Application (NADA), or are required by FDA to mitigate potential risks, and are explicitly set forth in the conditions of approval. Sponsors must notify FDA of any modifications to the approved conditions of use, ranging from changes in labels to alterations of the conditions of husbandry. Major and moderate changes require a supplemental application that must be approved by the agency prior to implementation.
4. How does the FDA evaluate the potential risks related to the transgenic salmon?
The FDA’s Center for Veterinary Medicine (CVM) has evaluated both the direct and indirect food safety impacts of AquAdvantage Salmon and any potential impacts of the rDNA insertion on target animal safety. CVM has also thoroughly evaluated the potential environmental impacts of approving an NADA for AquAdvantage Salmon, and has prepared this draft Environmental Assessment (EA).
In the overall process, FDA’S CVM examines (1) safety of the rDNA construct to the animal; (2) safety of the food from the animal; (3) environmental impact; and (4) the extent to which the producers of GE animals (referred to as “sponsors”) have met the claims made for those GE animals (effectiveness). All of these are based on a thorough analysis of the rDNA construct, its integration into the animal’s DNA, and its stability in the animal over multiple generations. GFI 187 describes this in seven steps that we summarize in the following discussion. Each step is dependent on the results of the analysis performed in the preceding steps, so that the review in effect “rolls up” conclusions as it progresses through the entire process.
The performance of such evaluation is a seven steps process:
1.- First, the FDA reviews data and information on how the construct is made, and whether it contains any pieces of DNA from viruses or other organisms that could pose adverse health risks to the animal or people or other animals eating food from the animal. The FDA also looks to see if any pieces of the construct will make new proteins (except for the intended ones) that could possibly cause health concerns.
2.- Second, FDA evaluates studies submitted by the producer to determine what happens when the rDNA construct is incorporated into the animal, and how it behaves over multiple generations. This includes analyzing whether the construct remains in the same place over time, and whether animals continue to express the trait (characteristic) that the construct is supposed to introduce.
3.- Third, FDA determines whether the rDNA construct is safe for the resulting line of the transgenic animal what is called a the Phenotypic Characterization. They do so by reviewing studies that characterize the actual transgenic animals over several generations. Questions that the agency asks include whether the resulting transgenic animals look like their “regular” counterparts by comparing them to both closely related animals and to animals of the species in general. The agency asks whether the transgenic animals are healthy, including disease resistance, and whether they reach the same developmental milestones that comparison animals do. Another safety question that is evaluated is whether there are any abnormalities that would not be found in other relatives of the transgenic animal which might express similar traits, but via conventional breeding.
In addition, we evaluate the results of necropsies (examinations of the bodies and tissues of animals that have been sacrificed for that purpose) to make sure that cells, tissues, and organs look normal. We also assess the results of the kinds of tests that doctors might perform on people when they get a physical, such as blood cells, blood chemistries, etc., to determine whether the animals not only look healthy, but also that their bodies are functioning appropriately.
4.- Fourth, the FDA performs reviews the plan that the sponsor will agree to in order to ensure that the GE animals produced in the future will be equivalent to the GE animals that we evaluate as part of the pre-approval review.
5.- Fifth, FDA assesses whether the transgenic animals are safe to eat. This evaluation relies on information gathered in the parts of the application that look at the rDNA construct and the health of the animal. FDA experts in food safety look carefully at the composition of the edible tissues of the transgenic animal to determine whether its meat or milk or eggs differ in any way that affects safety or nutrition from the non-transgenic counterparts that we eat today.
Further, FDA’s food safety experts evaluate data to determine whether the transgenic animal poses any more allergenicity risks than its non-transgenic counterparts currently on the market.
6.- Sixth, the agency evaluates the potential for the GE animal to cause significant environmental impacts. We do this by evaluating the results of an EA for the specific proposed conditions of use for a particular application.
7.- In the seventh and final step of the process, sponsors submit information and data in support of their claims for the transgenic animal. For an animal that is intended to grow faster, the agency evaluates data to determine if the GE animals do indeed reach some size or weight more rapidly than their conventional counterparts.
5. Where the potential environmental effects of the development of the transgenic salmon evaluated in the countries where it will take place?
Effects on the local environments of Canada and Panama have not been considered and evaluated in this draft assessement because the US NEPA does not require an analysis of environmental effects in foreign sovereign countries, except insofar as it was necessary to do so in order to determine whether there would be significant effects on the environment of the United States due to the origination of exposure pathways from the production and grow-out facilities in Canada and Panama.
The potential hazards and harms addressed in this draft Environmental Assessment center on the likelihood and consequences of AquAdvantage salmon for the production of eyed-eggs and grow-out to market size :
1. The likelihood that the transgenic salmon will escape the conditions of confinement;
2. The likelihood that the transgenic salmon will survive and disperse if they escape the conditions of confinement;
3. The likelihood that the transgenic salmon will reproduce and establish if they escape the conditions of confinement;
4. The likely consequences to, or effects on, the environment of theUnited Statesshould the genetically salmon escape the conditions of confinement.
As the transgenic salmon would be produced and grown-out in secure facilities that have been verified and validated by FDA, the possibility that transgenic fish could escape from containment, enter the local environments of Canada or Panama, and survive to reproduce is extremely remote. In addition, because the production process for AquAdvantage Salmon would ensure that populations produced will be triploid (effectively sterile), all-female animals, the possibility of their reproducing in the wild is likewise extremely remote. Finally, the inhospitable environmental conditions around the egg production and grow-out facilities further reduce the possibility of establishment and spread.
6. What are the preliminary conclusions of the FDA evaluation?
Based on the evidence collected and evaluated, FDA has made the preliminary determination that it is reasonable to believe that approval of the AquAdvantage Salmon NADA will not have any significant impacts on the quality of the human environment of the United States (including populations of endangered Atlantic salmon) when produced and grown under the conditions of use for the proposed action.
FDA preliminarily concludes that the development, production, and grow-out of AquAdvantage Salmon under the conditions proposed in the materials submitted by the sponsor in support of an NADA, and as described in this draft Environmental Assessment, will not result in significant effects on the quality of the human environment in theUnited States.
With respect to food safety, FDA has concluded that food from AquAdvantage Salmon is as safe as food from conventional Atlantic salmon, and that there is a reasonable certainty of no harm from consumption of food from triploid AquAdvantage Salmon. Further, FDA has concluded that no significant food safety hazards or risks have been identified with respect to the phenotype of the AquAdvantage Salmon.
FDA, having reviewed the materials submitted in support of an NADA for AquAdvantage Salmon, has also made a “no effect” determination under the Endangered Species Act (ESA), that approval of the AquAdvantage Salmon NADA will not jeopardize the continued existence of United States populations of threatened or endangered Atlantic salmon, or result in the destruction or adverse modification of their critical habitat, when produced and reared under the conditions described within this draft Environmental Assessment.
The two federal agencies responsible for administering the ESA, the National Marine Fisheries Service (NMFS) of the National Oceanic and Atmospheric Administration (Department of Commerce) and the U.S. Fish and Wildlife Service (FWS) of the Department of Interior, have either concurred with, or indicated no disagreement with, FDA’s “no effect” determination.
7. Where and how would the transgenic salmon be produced and grown and in with which limits ?
The specific proposed limitations on the production and use (grow-out) of AquAdvantage Salmon, including the production of triploid, all-female fish populations, are designed to mitigate potential adverse environmental impacts.
The conditions proposed in the materials submitted by the sponsor in support of an NADA would limit production of eyed-eggs to a single specific facility on Prince Edward Island, Canada, for delivery to a single specific land-based facility in Panama for grow-out (i.e., rearing to market size), in secure facilities that have been verified and validated by FDA, with harvesting and processing (e.g., preparation of fish fillets, steaks, etc.) in Panama prior to retail sale in theUnited States.
In Canada, regulation of fish that are the product of biotechnology takes place under the New Substances Notification Regulations (Organisms) of the Canadian Environmental Protection Act. The Canadian governmental authorities charged with responsibility for the regulatory oversight of the research and development and the commercial deployment of transgenic aquatic organisms are Environment Canada and DFO.
Panama operates a National Biosafety Commission that coordinates activities related to the biosafety of transgenic organisms. In theRepublicofPanama, product approval and commercialization of AquAdvantage Salmon inPanamawill primarily require involvement of the Sectorial Biosafety Committee for the agriculture sector, which is involved with review of applications for research and marketing of transgenic organisms. and includes members from relevant Panamanian institutions (e.g., Agricultural Development Ministry, Food Safety Authority, Authority of Aquatic Resources).
Based on observations made and information gathered during the site visit by the FDA, the descriptions and schematics provided by the sponsor on thePanamagrow-out facility and the river and surrounding environment have been accurately represented. There are a minimum of three or four levels of containment between both the fry tanks and grow-out tanks and the river.
8. What are the limits of the application that would be allowed to produce, grow and market the transgenic salmon?
Approvals by FDA of NADAs related to transgenic animals are limited to a very specific set of conditions. FDA approvals for articles regulated under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act) may be for a specific set of conditions with the transgenic animal remaining under regulatory oversight as long as it is produced and marketed and where such conditions are proposed in the drug sponsor’s NADA, or are required by FDA to mitigate potential risks, and are explicitly set forth in the conditions of approval. FDA has determined that for the proposed action, conditions of use should include appropriate and redundant mitigation measures such as use of physical, biological, and geographical/ geophysical forms of containment.
Major and moderate changes require the filing and review of a supplemental NADA. Approvals of such supplemental applications would constitute agency actions and trigger environmental analyses under NEPA.
Any other uses are not approved, and the sponsor must notify FDA about each proposed change in each condition established in an approved application and obtain FDA approval of a supplemental application for the change where necessary.
FDA has determined that this application for AquAdvantage Salmon should include appropriate and redundant mitigation measures such as use of physical, biological, and geographical/ geophysical forms of containment..
The proposed specific limitations on the production and use (grow-out) of AquAdvantage Salmon, including the production of triploid (effectively sterile), all-female fish populations, are designed to mitigate potential adverse environmental impacts,
9. Did the FDA considered the consequences of not allowing the production of the transgenic AquAdvantage Salmon?
For the scenario where production of AquAdvantage Salmon at locations outside theUnited States, says the FDA draft report, an assessment of potential effects on the environment becomes highly uncertain. Because production of AquAdvantage Salmon would be possible at any number of locations worldwide, under different containment conditions, and potentially within areas where native Atlantic salmon are present, there are too many variables and unknowns to perform a comprehensive assessment and make any predictions with respect to potential environmental impacts on the United States. To the extent that production would occur with less restrictive containment conditions than those proposed (e.g., fish might not be triploid, might not be reared in land-based facilities, or might not be subjected to multiple and redundant forms of physical containment), it is expected that adverse environmental impacts to the United States might be more likely to occur than under the conditions of production and grow-out for the proposed action.
Reference : AquAdvantage® Salmon Draft Environmental Assessment.
In support of a proposed agency action on a New Animal Drug Application for the integrated α-form of the opAFP-GHc2 gene construct at the α-locus in the EO-1α line of triploid, all-female genetically engineered Atlantic salmon (AquAdvantage Salmon) to be produced as eyed-eggs and grown-out only in the physically-contained freshwater culture facilities specified in the sponsor’s application – 4 May 2012 – 145 p
Prepared by the Center forVeterinary Medicine,United StatesFood and Drug Administration, Department of Health and Human Services.
Note : The GreenFacts Highlights are not peer reviewed by its Scientific Board.