European food approval still elusive for Enogen corn

In a decision last month that seems to have gone a bit under-reported in the trade press, the European Food Safety Authority (EFSA) announced that it could not reach a conclusion on an application from Syngenta Crop Protection AG for the approval of the use of Syngenta’s Enogen® corn in food and feed. While fully in line with the reluctance of the EU and its member states to allow commercial growth and food uses of transgenic plants and their products, this represents another setback in the long saga of Syngenta’s development of this modified corn variety.

I’ve described Enogen corn in earlier blog entries, including a post on February 14, 2011 when the corn variety was approved by the U.S. Department of Agriculture for commercial cultivation in the U.S. As described in my earlier posts, Enogen, originally known as “Corn [Maize] event 3272”, is a variety of corn expressing two heterologous genes: the amy797E gene and the pmi gene. The amy797E gene is derived from three naturally-occurring genes and encodes a thermostable alpha-amylase which catalyses the hydrolysis of starch by cleaving the internal alpha-1,4-glucosidic bonds into dextrins, maltose and glucose. The pmi gene from Escherichia coli encodes the phosphomannose isomerase (PMI) enzyme, which allows the plant to utilize mannose as a carbon source. The expression of thermostable alpha-amylase directly in plant tissue can potentially lead to significant yield increases in production of corn-based ethanol.

To my knowledge, Enogen is the only genetically modified plant variety that has achieved commercial approval in any industrialized country for use as a biofuel feedstock, and it has been approved for use in the U.S. and in a number of other countries. It appears to be doing well in the market – although sales figures are not readily available, Syngenta announced in June 2013 that Enogen is now grown by 300 growers covering more than 64,000 acres in the U.S., and is being used as a feedstock at eleven U.S. ethanol facilities. In addition to its USDA regulatory approval in February 2011, the company says that the U.S. Food and Drug Administration concluded its review of the food safety of the corn in 2007, which would clear U.S. use in animal feed (e.g., distillers grains) of corn residues remaining after ethanol fermentation.

The ultimate (although time-consuming) success of the U.S. regulatory process is in contrast to the situation in the European Union, a region that has long been suspicious, if not downright hostile, towards proposals to use transgenic plants in agriculture and food. Enogen has not been approved for cultivation in the EU, and the recent regulatory action arises from an application first filed by Syngenta in 2006 to obtain approval to import Enogen corn grown elsewhere and allow it to be processed and used in human food or animal feed in the EU. Syngenta’s application was made to the European Food Safety Authority (EFSA) pursuant to EC Regulation Number 1829/2003, which governs the placing on the market of genetically modified organisms (GMOs) and foodstuffs containing GMOs, both for human and animal food purposes (click here for a summary of this regulation). EFSA is the agency that is responsible for evaluating the food safety of GMO plants proposed for use in Europe.

On June 20, 2013, EFSA announced that it could not reach a conclusion on the safety of Enogen (variety 3272) corn, because Syngenta had not provided “key information to allow a full risk assessment to take place”.  The primary data deficiency appeared to be that the company’s choice of a conventional corn species as the “comparator” was inadequate due to lack of data and because that species did not have a history of safe use. The scientific report of EFSA’s Panel on Genetically Modified Organisms can be found here. Among its findings and other comments, as summarized in the published abstract, are the following:

In delivering its scientific opinion, the EFSA GMO Panel considered the application EFSA-GMO-UK-2006-34, additional information provided by the applicant (Syngenta Crop Protection AG) and the scientific comments submitted by the Member States. The scope of application EFSA-GMO-UK-2006-34 is for food and feed uses and import and processing of maize 3272 and all derived products, but excludes cultivation in the European Union (EU).

The EFSA GMO Panel could not conclude on the comparative assessment of the compositional, agronomic and phenotypic characteristics of maize 3272, on the basis of the data provided. In the absence of an appropriately performed comparative assessment, the safety assessment could not be completed and has focused mainly on the newly expressed proteins AMY797E and PMI.

The AMY797E and PMI proteins did not show significant similarity to known toxins in bioinformatic analyses. The EFSA GMO Panel concluded that administration of the AMY797E protein to rats for 28 days did not induce adverse effects up to the highest dose tested. Based on all the available information, the EFSA GMO Panel considers that there are no indications that the newly expressed PMI protein in maize 3272 may be allergenic. In relation to the AMY797E protein, the EFSA GMO Panel could not conclude on the de novo sensitisation potential of the protein.

[T]here is no requirement for scientific information on possible environmental effects associated with the cultivation of maize 3272. …  However, … the EFSA GMO Panel concluded that there is very little likelihood of any adverse environmental impacts as a result of the accidental release into the environment of viable grains from maize 3272. In the case of accidental release into the environment of viable grains of maize 3272, there are no indications of an increased likelihood of spread and establishment of feral maize 3272 plants.

In the absence of an appropriately performed comparative assessment by the applicant, the EFSA GMO Panel was not in the position to complete its risk assessment on maize 3272 and therefore does not conclude on the safety of maize 3272 compared with its conventional counterpart with respect to potential effects on human and animal health. However, the EFSA GMO Panel concluded that maize event 3272 is unlikely to have any adverse effect on the environment in the context of its intended uses.

So, the panel reached favorable conclusions on the lack of toxicity of the introduced gene products, and for one of the gene products was able to conclude that there were no allergenicity concerns. And while not within the panel’s formal remit, it found no evidence that use of Enogen corn would have any adverse environmental effects. In spite of these favorable rulings, the panel could not reach an ultimate conclusion on food safety and has apparently asked Syngenta for additional data. This is apparently not an unusual outcome: EFSA’s own press release says that it has requested more data for 98% of the GMO applications it has received to date.

In its public statement, Syngenta has said that it was “disappointed with the EFSA response,” but that it “remains committed to working with EFSA, including providing information based on sound science to allow EFSA to conclude the risk assessment.” Syngenta also noted that EFSA’s opinion was not related to the safety of the product.

This decision, while no doubt disconcerting for the company, is in the abstract not surprising, given the extreme skepticism that European governments and the public have expressed towards any use of GMO plants on the continent. It comes on the heels of the recent disclosure by agbiotech giant Monsanto that it will no longer seek regulatory approvals for any genetically modified crop plants in Europe (with the apparent exception of one pending application), a decision which itself arises from many years of frustration with the EU regulatory system for transgenic plants and the many obstacles the system has placed in the pathway for commercial approvals.

The impact of this decision on Syngenta’s business and on the overall ethanol industry is far from clear. As noted above, Enogen seems to be selling well and making significant inroads into ethanol markets in the U.S. And while there is certainly a substantial market for ethanol in Europe, especially as mandated under the EU Renewable Energy Directive (RED), long-term prospects do not look good for the use of cornstarch-derived ethanol on the continent. There is significant public and governmental sentiment developing against the use of food crops for the production of fuels, as evidenced by the recent proposals to place limits on the volume of food crop derived fuels that could count towards the mandated targets under the RED (these proposed amendments were described in a January post on Biofuel Policy Watch,  and the most recent developments were described in a post earlier this week).  By the time Enogen is approved for use in Europe (if that decision ever comes), regulatory pressures against corn-derived ethanol may severely limit the product’s market potential.

With regard to the bigger picture, I’m not aware of any other GMO plant variety that is close to commercialization, for which the current European regulatory situation would pose an imminent problem. However, this won’t always be the case, and as transgenic plants, particularly non-food energy crops, become available in the U.S. and elsewhere for fuel production, the European Union risks shutting itself off from such technological innovations. On the other hand, GMO plants of nonfood species would by definition not require EFSA approval for use in Europe and may therefore face an easier regulatory path, although approvals under the biotechnology directives would be needed for growth or importation of such plants in Europe, which might also prove controversial.

D. Glass Associates, Inc. is a consulting company specializing in government and regulatory affairs support for renewable fuels and industrial biotechnology. David Glass, Ph.D. is a veteran of over thirty years in the biotechnology industry, with expertise in industrial biotechnology regulatory affairs, U.S. and international renewable fuels regulation, patents, technology licensing, and market and technology assessments. Dr. Glass also serves as director of regulatory affairs for Joule Unlimited Technologies, Inc. More information on D. Glass Associates’ regulatory affairs consulting capabilities, and copies of some of Dr. Glass’s prior presentations on biofuels and biotechnology regulation, are available at www.slideshare.net/djglass99 and at www.dglassassociates.com. The views expressed in this blog are those of Dr. Glass and D. Glass Associates and do not represent the views of Joule Unlimited Technologies, Inc. or any other organization with which Dr. Glass is affiliated. Please visit our other blog, Biofuel Policy Watch.

Advertisements

One thought on “European food approval still elusive for Enogen corn

  1. The application EFSA-GMO-UK-2006-34 concerns food and feed uses, import and processing. Therefore, there is no requirement for scientific information on possible environmental effects associated with the cultivation of maize 3272. The EFSA GMO Panel has identified a gap in the data on the agronomic and phenotypic characterisation of GM maize 3272 and considers that uncertainty over these characteristics remains. However, considering the scope of this application, a weight of evidence approach from different sources of available data and the poor ability of maize to survive outside cultivated land, the EFSA GMO Panel concluded that there is very little likelihood of any adverse environmental impacts as a result of the accidental release into the environment of viable grains from maize 3272. In the case of accidental release into the environment of viable grains of maize 3272, there are no indications of an increased likelihood of spread and establishment of feral maize 3272 plants. Considering its intended uses as food and feed, interactions with the biotic and abiotic environment were not considered to be an issue. Risks associated with a theoretically possible horizontal gene transfer from maize 3272 to prokaryotes (i.e. bacteria, Archaea) have been analysed and did not raise safety concerns. The post-market environmental monitoring plan and reporting intervals were in line with the intended uses of maize 3272.

Comments are closed.