The field of bioengineering is rapidly evolving with new tools that allow for simple, efficient, and highly-specific DNA and RNA editing. For instance, CRISPR gene editing, which borrows from the natural defense system of bacteria to cut and alter DNA, has immense potential for use in a variety of agricultural and therapeutic contexts.
The application of these techniques to food and agriculture poses a unique challenge to both governmental agencies and the private actors subject to their oversight. Determining where modified plants and animals fit within the coordinated regulatory framework established between the various agencies is an ongoing task. In a regulatory landscape that is often overlapping and frequently subject to change, this article is designed to help navigate the complicated terrain.
Bioengineering in Agriculture
Economic growth, population dynamics, land availability, and volatile weather are all variables in an increasingly complex and interdependent global agriculture industry. The world’s population is expected to grow to almost 10 billion by 2050,[1] leading to an increase in agricultural demand by roughly fifty percent compared to 2013 levels.[2] As consumption continues on an upward trajectory in the coming decades, bioengineering has become a major factor in the growth and sustainability of global food supplies.[3]
There is ample activity in a number of arenas of bioengineering in agriculture, but CRISPR is leading the way and generating the most headlines. It has been used in a host of applications such as boosting crop resistance and protecting against disease in livestock.[4] This is not to say that CRISPR is the only mechanism for bioengineering in agriculture; some companies are focusing on alternative techniques,[5] such as recombinant DNA (rDNA), zinc finger nucleases (ZFN), and transcription activator-like effector nucleases (TALENs).
The market for genetically engineered products was worth almost $2 billion in 2014 and is expected to double by 2019.[6] Despite continued calls for improved and updated oversight, regulation, and ethical accountability, some have declared it “open season” in gene editing of plants and animals.[7],[8]
Regulatory Background and Overview
Spurred by developments in recombinant DNA in the 1980s, the White House Office of Science and Technology Policy (OSTP) issued the “Coordinated Framework for the Regulation of Biotechnology” (hereinafter “Coordinated Framework”) on June 26, 1986.[9] The Coordinated Framework was designed to outline a Federal regulatory policy for ensuring the safety of biotechnology products.[10] Under the Framework, Congress charged three Federal agencies with spearheading the implementation of an array of laws[11]: the Environmental Protection Agency (EPA), the U.S. Department of Agriculture (USDA), and the Food and Drug Administration (FDA).
EPA’s primary mission is to protect human health and the environment. In pursuing that goal, EPA’s statutory authority in the biotechnology space stems largely from the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), the Federal, Food, Drug, and Cosmetics Act (FDCA) and the Toxic Substances Control Act (TSCA). Under FIFRA, EPA regulates pesticides, under the FDCA EPA established the amount of pesticide chemical residues that may be present in food, and under the TSCA EPA regulates biotechnology products that are new organisms not specifically excluded by the statute.[12]
EPA regulation of bioengineered products is largely focused on plant products which incorporate pesticide substances and toxic materials. To the extent that newly bioengineered products incorporate such pesticides and toxic materials, EPA may assess the safety of dietary exposures to residues of these substances in human or animal feed. For instance, if a genetically engineered (GE) CRISPR crop is altered to create its own pesticide, that would trigger EPA oversight.[13]
USDA focuses on agriculture and, for biotechnology purposes, this mostly relates to plant health and safety. The Animal and Plant Health Inspection Service (APHIS), an agency within USDA, has the general authority to regulate the importation, interstate movement, and environmental release of plants that pose a plant pest risk and animals used in feed that pose a health risk to livestock. A bioengineered organism is deemed a “regulated article” by APHIS if it is engineered using a donor organism, recipient organism, or a vector or vector agent.
FDA is largely tasked with keeping genetically engineered foods safe. Human and animal foods (including dietary supplements), cosmetics, human and veterinary drugs, human biological products and medical devices are just some of the categories of goods that fall under the ambit of FDA’s regulations. FDA draws much of its authority from the Federal Food, Drug, and Cosmetic Act (FDCA) to ensure that foods offered to consumers, including those developed using genome editing techniques, are in compliance with legal requirements.
Recent Developments
OSTP updated the 1986 Coordinated Framework in 1992, making relatively minor adjustments that remained mostly unchanged until July 2015. In the intervening years, many large biotechnology breakthroughs occurred that have left the Coordinated Framework outdated and found the OSTP and the three designated agencies playing catch up.[14]
Due to the substantial advancements in the gene editing field, the Obama administration’s Executive Office of the President (EOP) issued a memorandum,[15] on July 2, 2015, to the three government agencies to update the Coordinated Framework. Their task was to clarify current roles and responsibilities, with the stated goal of preventing unnecessary barriers to future innovation. In response to EOP’s request, the National Academies of Science produced an “Update to the Coordinated Framework,”[16] released in January 2017. While the Update is comprehensive in its discussion of the statutory basis for regulating biotechnology, it does little to modernize the framework or discuss how to regulate emerging technologies, such as CRISPR.[17]
In the absence of needed adjustments to the Coordinated Framework, FDA, USDA and EPA have each taken a different tack on how to proceed in response to the gaps in regulation. In January 2017, FDA published draft guidance[18] on regulating intentionally altered genomic DNA in animals, as well as guidance on gene-edited foods and mosquitoes.
FDA regulates bioengineered animals as “new animal drugs” since the modifications are intended for use in diagnosis, cure, mitigation, or treatment of animal diseases and/or affect the structure or function of the animals.[19] The draft guidance indicated that the safety and efficacy of genetically edited animals would need to be demonstrated in a new animal drug application (NADA) submission. The guidance raised some eyebrows in the bioengineering field because it discussed making the trigger for regulation whether the GE animal was intended to be made, rather than the specific attributes of the GE animal or its manufacturing process.[20]
The period for comment on the draft guidance ended, however, and the results of the final guidance did not issue. As of April 2018, according to an FDA spokesperson, the agency is considering new public comments on whether gene-edited plants and foods pose added risks, but they have not provided any timeline for new policies.[21]
On July 29, 2016, Congress amended the Agricultural Marketing Act of 1947 to establish a National Bioengineered Food Disclosure Standard.[22] The amendment gave USDA’s Agricultural Marketing Service (AMS) two years to establish the standard and procedures for its implementation.
With the two year deadline fast approaching, AMS recently issued a proposed rule which was open to public comment until July 3, 2018.[23] The proposed rule includes[24]:
- Suggested uses of the term “bioengineering” (BE) or “BE foods” instead of GMO
- Request for comments on two alternate definitions of BE food, the first requiring that any food derived from BE material is subject to disclosure requirements, and the second narrowing the meaning to only those foods containing “genetic material”
- Lists of bioengineered commodities (both highly adopted and non-highly adopted)
- Different options as to the parameters of a BE disclosure statement, including a one-sentence label, a standardized icon, a QR code or digital marker, and separate options for small food manufacturers
- Three suggested thresholds for bioengineered food content that could necessitate disclosure
- Record keeping procedures
- A discussion of AMS’s enforcement power
- Compliance deadlines, currently set at January 1, 2020, for large companies and a year later for small companies (those with less than $10 million in annual receipts)
Since this proposed rule is not yet finalized, the list above is still subject to change.
In tandem with the proposed rule, USDA has been steadily approving more CRISPR edited crops. In April 2016, USDA announced that it would forego regulation of a CRISPR edited mushroom altered to resist browning.[25] Not long after, it made a similar announcement regarding CRISPR edited corn created by DuPont.[26] In September 2017, USDA greenlit an oilseed crop altered with CRISPR to produce enhanced omega-3 oil. The unifying logic in the recent spate of approvals is that, although these crops are certainly gene-edited, they are not genetically “modified,” since they do not include foreign DNA.[27]
In a formal statement in March 2018, Secretary of Agriculture, Sonny Perdue, confirmed and clarified USDA’s trend of allowing plant gene editing, saying that USDA “does not regulate or have any plans to regulate plants that could otherwise have been developed through traditional breeding techniques, as long as they are not plant pests or developed using plant pests.”[28] This implies that as long as a genetic alteration could have been bred in a plant – for example, a deletion, a base pair swap, or insertion – the plant will not be regulated, including CRISPR edited crops.[29] His statement has led to speculation that a number of recently approved crops could reach supermarket shelves much quicker than originally anticipated.[30], [31]
There are important developments and rulings occurring outside the United States as well. As of this writing, the European Court of Justice is set to issue a preliminary opinion on whether New Plant Breeding Techniques (NPBT), like CRISPR, should fall under the European Union’s laws on genetically modified organisms.[32] Europe generally has fairly stringent laws on the regulation of GMO foods. But the European Court of Justice’s opinion may soon more closely resemble rulings in the United States, where foods whose genomes have been edited without introducing foreign DNA from an another organism are given more leeway as compared to other recombinant products and foods.[33]
The Path Ahead
The multi-pronged approach to regulation of bioengineered products established by EPA, FDA, and USDA’s Coordinated Regulatory Framework is still evolving and in flux. Efforts to develop and commercialize bioengineered foods will require careful scrutiny and attention to the changing regulations surrounding these products. With aforementioned FDA and USDA guidance in the works, but not yet finalized, and proposed rule changes frequently withdrawn, the regulatory landscape for genetically engineered foods and animals is rapidly recalibrating.
As circumstances fluctuate and technologies evolve, it is necessary to have counsel dedicated to monitoring regulatory changes and approval standards. After all, “open season” in agricultural bioengineering can shift quickly.
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[1] Food and Agriculture Organization, United Nations, The Future of Food and Agriculture (2017).
[2] Id. at x.
[3] Jennifer Kahn, The Crispr Quandary, N.Y. Times, Nov. 9, 2015, at MM63 (Sunday Magazine, headline in print as “Life Edited”).
[4] Id.
[5] Brooke Borel, CRISPR, Microbes and More Are Joining the War Against Crop Killers, Nature, 543, 302-304, March 16, 2017.
[6] Kahn, supra note 3.
[7] Amy Harmon, Open Season is Seen in Gene Editing of Animals, N.Y. Times, Nov. 26, 2015, at A1..
[8] Kahn, supra note 3.
[9] Proposal for a Coordinated Framework for Regulation of Biotechnology, 49 Fed. Reg. 50856 (December 31, 1984). See also, Modernizing the Regulatory System for Biotechnology Products: Final Version of the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology, at 4, fn. 8. (“The Federal Government recognized that a number of agencies, in addition to the EPA, FDA, and USDA, might have laws, regulations or guidelines that might be applicable to biotechnology products at some point in research, development, marketing, shipment, use, or disposal. The 1984 Proposal provided a matrix describing all the laws, regulations or guidelines that could potentially play a role. In addition to those agencies generally recognized as part of the Coordinated Framework, the matrix referenced Federal entities such as the Council on Environmental Quality, the U.S. Department of the Interior and the National Marine Fisheries Service. The Proposal noted that the matrix would be updated as appropriate, indicating that the Coordinated Framework was to be flexible in terms of which agencies might play a role in the regulation of biotechnology.”)
[10] Modernizing the Regulatory System for Biotechnology Products: Final Version of the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology, Executive Office of the President, at 2 (January 2017), available at https://www.fda.gov/downloads/Food/IngredientsPackagingLabeling/GEPlants/UCM537311.pdf
[11] Id. at 3.
[12] Id. at 10.
[13] Brooke Borel, The U.S. Regulations for Biotechnology are Woefully Out of Date, Slate, April 21, 2017, available at http://www.slate.com/articles/technology/future_tense/2017/04/u_s_biotechnology_regulations_are_woefully_out_of_date.html.
[14] Brooke Borel, The U.S. Regulations for Biotechnology are Woefully Out of Date, Slate, April 21, 2017, available at http://www.slate.com/articles/technology/future_tense/2017/04/u_s_biotechnology_regulations_are_woefully_out_of_date.html.
[15] John P. Holdren, et al. Memorandum for Heads of Food and Drug Administration, Environmental Protection Agency, and Department of Agriculture, Off. of Sci. and Tech. Pol’y, July 2, 2015.
[16] Modernizing the Regulatory System for Biotechnology Products, supra note 26.
[17] Ryan Cross, White House Attempts to Clarify, But Not Change, Genetic Engineering Regulations, Chemical & Engineering Mag.,, American Chemical Society, Jan. 9, 2017, available at https://cen.acs.org/articles/95/web/2017/01/White-House-attempts-clarify-change.html?type=paidArticleContent.
[18] Guidance for Industry: Regulation of Intentionally Altered Genomic DNA in Animals, Draft Guidance #187, Food and Drug Admin., Jan. 2017, available at https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM113903.pdf.
[19] See, e.g., FDA’s approval for AquAdvantage Salmon, available at https://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/GeneticEngineering/GeneticallyEngineeredAnimals/ucm280853.htm.
[20] Amy Maxmen, Gene-edited Animals Face US Regulatory Crackdown: Last-minute Proposal from Obama Administration Addresses CRISPR and Other Cutting-edge Technologies, Nature, Jan. 19, 2017, available at https://www.nature.com/news/gene-edited-animals-face-us-regulatory-crackdown-1.21331.
[21] Megan Molteni, CRISPR’D Food, Coming Soon to a Supermarket Near You, WIRED, March 30, 2018, available at https://www.wired.com/story/crisprd-food-coming-soon-to-a-supermarket-near-you/.
[22] Riette Van Laack, AMS’s Proposal for BE (Bioengineered) Labeling; A Number of Questions Remain, Hyman, Phelps, & McNamara PC: FDA Law Blog, May 25, 2018, available at http://www.fdalawblog.net/2018/05/amss-proposal-for-be-bioengineered-labeling-a-number-of-questions-remain/.
[23] Id.
[24] Id.
[25] Maxmen, supra note 20.
[26] Erin Brodwin, The Next Generation of GMO Food is Here, and It’s Technically Not a GMO, Bus. Insider (April 18, 2016), http://www.businessinsider.com/dupont-crispr-corn-in-stores-in-5-years#pq=nfDL8l.
[27] Kristen V. Brown, Why CRISPR-Edited Food May Be in Supermarkets Sooner than you Think, Gizmodo, Jan. 16, 2018.
[28] Secretary Perdue Issues USDA Statement on Plant Breeding Innovation, USDA, Press Release, March 28, 2018, available at https://www.usda.gov/media/press-releases/2018/03/28/secretary-perdue-issues-usda-statement-plant-breeding-innovation.
[29] Megan Molteni, CRISPR’D Food, Coming Soon to a Supermarket Near You, WIRED, March 30, 2018, available at https://www.wired.com/story/crisprd-food-coming-soon-to-a-supermarket-near-you/.
[30] Kristen V. Brown, Why CRISPR-Edited Food May Be in Supermarkets Sooner than you Think, Gizmodo, Jan. 16, 2018.
[31] Katherine Ellen Foley, The USDA Says Crispr-Edited Foods Are Just As Safe As Ones Bred The Old-Fashioned Way, QUARTZ, April 2, 2018, available at https://qz.com/1242882/the-usda-drops-all-regulation-for-crispr-edited-crops/.
[32] Simon Marks, EU Braces for Landmark Decision on Whether CRISPR, Other New Plant Breeding Techniques Will be Regulated as GMOs, Politico, January 18, 2018.
[33] Id.
