The Biotechnology Science Coordinating Committee (BSCC), at the behest of the White House Office of Science and Technology Policy (OSTP), held the first of three public meetings to discuss an update to the coordinated framework which serves as the regulatory guidelines for genetically engineered organisms. This meeting provided an opportunity for representatives from the primary agencies involved in GMO regulation, the Food and Drug Administration (FDA), Environmental Protection Agency (EPA), and US Department of Agriculture (USDA) to clarify their roles in the current framework.

Dr. John P. Holdren, Senior Advisor to President Barack Obama and Director of OSTP, opened the meeting, providing the history behind the formation of the coordinated framework and citing rapid advances in the field of gene editing as the impetus to update regulations and speed innovation. The Assistant Director for Biological Innovation at OSTP, Dr. Roberto Barbero delved deeper into the intentions behind the call to update the coordinated framework, highlighting the need to improve transparency in the regulatory process and engage the best scientific evidence as a part of the deliberations. Further, Barbero reiterated the need to support research science that underpins regulatory strategy to maintain evidence-based decision making.

Following OSTP’s introduction, Dr. John Turner, Director of the Biotechnology Risk Analysis Program in the Animal and Plant Health Inspection Service (APHIS) at USDA cited the Plant Protection Act of 2000 as the enabling authority to regulate genetically engineered plants that have a “plant pest component” with the goal of protecting plants and plant products from pests. The animal component of USDA oversight was presented by Dr. Lisa Ferguson, National Director of Policy Permitting and Regulatory Services in APHIS-Veterinary Service. Ferguson demonstrated the USDA authority over genetically engineered animals through the Animal Health Protection Act, specifically refers to the import of animals, the interstate movement of animals infected with certain diseases, and insects which are vectors of animal diseases. To simplify the charge, Ferguson asserted the agency’s goal to regulate anything that might impact the health of US livestock.

“Mais” by Martin CC BY-NC 2.0

The EPA sent two representatives to explain the agency’s role in the coordinated framework to regulation biotechnology. Mike Mendelson, Senior Regulatory Specialist in the Microbial Pesticides Branch of the Office of Pesticides Programs, Biopesticides and Pollution Prevention, began the segment by referencing four key laws that govern the activities his office: Federal Insecticide, Fungicide, and Rodenticide Act; Federal Food, Drug, and Cosmetic Act; Food Quality Protection Act; and the Pesticide Registration Improvement Act. Most relevant to the discussion of genetically engineered organisms are “plant incorporated protectants,” defined as any pesticide substance intended to be produced and used in a living plant and the genetic material necessary for the production of such pesticidal substance. The regulatory reach of EPA also encompasses pesticidal products, such as the Bt Cry1Ab protein and the cry1Ab gene found in Bt corn. Underscoring the need for coordination among federal agencies for pesticides, Mendelson distilled the framework, stating the EPA ensures an organism is safe for use as a pesticide, FDA ensures an organism is safe for use in food and feed, and USDA ensures an organism is safe for agriculture and the environment.

Dr. Mark Segal, Senior Microbiologist in the Office of Pollution Prevention and Toxics at the EPA described the gap-filling function of the Toxic Substances Control Act of 1976. This legislation gave the EPA the authority to regulate the manufacture, use, distribution in commerce, and disposal of chemical substances and mixtures. The oversight includes microorganisms constructed with synthetic genes that are not identical to DNA that would be derived from the same genus as the recipient. Biomass conversion for chemical production, microbial fuel cells, and non-pesticidal agriculture are among the biotechnology products under the purview of the Toxic Substances Control Act. Segal noted that the proposed update to the coordinated framework was timely, as new technologies have byproducts that are excluded from oversight and require “new potential interactions between regulatory agencies that were not anticipated when the framework was published.”

The final presentation was given by Leslie Kux, Associate Commissioner for Policy at the FDA, who referenced the Food and Drug Cosmetic Act‘s provision to ensure the safety of adulterated foods and food additives. Kux noted that transferred genetic material and the intended expression products could be subject to food additives regulations, unless the material and intended products are deemed “generally recognized as safe.” In a 1992 statement, FDA stated “that the regulatory status of a food, irrespective of the method by which it is developed, is dependent upon the objective characteristics of the food.” Stated plainly, the FDA regulates the product of genetic engineering and not the process. In an effort to ensure the safety of genetically engineered foods, the FDA has implemented a pre-market consultation process whereby companies work with the FDA to address all safety and regulatory issues prior to a product coming to market. As a result, over 150 genetically engineered plant varieties that were subject to this consultation process were generally recognized as safe once they were  available to the public, and therefore not regulated by the FDA.

Kux also provided an overview of new animal drug provisions, which prohibit the introduction of unapproved drugs into commerce. This covers all genetically engineered animals bearing heritable rDNA constructs including biopharm animals. Such cases are evaluated by a risk-based approach where applicants must demonstrate that the genetic change is safe to the animal and that food from that animal is safe for human consumption. Genetically engineered animals for research applications are exempt from this regulation to allow for animal drug shipments and labeling, record keeping, and an open path for confidential communication during the development process. To demonstrate successful FDA oversight, Kux highlighted GTC’s Atryn Producing Genetically Engineered Goats, which produce an anti-clotting agent for humans with hereditary clotting disorders in high-risk situations.

Several representatives from various stakeholder organizations were present to provide input to the committee. These ranged from consumer organizations—who asked that the update to the framework mandate all genetically engineered organisms undergo extensive pre- and post-market review—to scientific societies, who requested greater transparency and public engagement to stem public distrust in the biotechnology regulatory process and urged the committee to incorporate the latest scientific evidence into their deliberations.

Dr. Nina Fedoroff

Molecular biologist and long-time GSA member Nina Fedoroff, author of  Mendel in the Kitchen: A Scientist’s View on Genetically Modified Food, also addressed the committee, reminding them of previous scientific studies of genetically modified food which found them to have no negative consequences for human consumption. Her complete remarks are reprinted with her permission here. Those interested in these topics are also encouraged to read Pamela Ronald’s 2011 review on genetically modified crops in GENETICS, which discusses the science behind the testing of genetically engineered food. 

If you feel strongly about the way in which genetically engineered organisms are currently regulated and have suggestions for the committee as they update the framework, you should consider responding to the request for information issued by the Office of Science and Technology Policy. Responses must be received by November 13, 2015, at 5 pm ET and can be submitted through the Federal eRulemaking Portal.

Responses are specifically requested to the following questions:

1. What additional clarification could be provided regarding which biotechnology product areas are within the statutory authority and responsibility of each agency?
2. What additional clarification could be provided regarding the roles that each agency plays for different biotechnology product areas, particularly for those product areas that fall within the responsibility of multiple agencies, and how those roles relate to each other in the course of a regulatory assessment?
3. How can Federal agencies improve their communication to consumers, industry, and other stakeholders regarding the authorities, practices, and bases for decision-making used to ensure the safety of the products of biotechnology?
4. Are there relevant data and information, including case studies, that can inform the update to the CF or the development of the long-term strategy regarding how to improve the transparency, coordination, predictability, and efficiency of the regulatory system for the products of biotechnology?
5. Are there specific issues that should be addressed in the update of the CF or in the long-term strategy in order to increase the transparency, coordination, predictability, and efficiency of the regulatory system for the products of biotechnology?

Related on Genes to Genomes:

• “Biotechnology regulations to be updated,” October 25, 2015
• “Nina Fedoroff comments on GMO regulatory reform,” November 2, 2015.

Also read:

Ronald, P. (2011). Plant genetics, sustainable agriculture and global food security. GENETICS, 188(1), 11-20. doi:10.1534/genetics.111.128553

The comments below were offered by long-time GSA member Nina Fedoroff at a public meeting on updating the Coordinated Framework for the Regulation of Biotechnology held on October 30, 2015. In addition to her academic research career, Dr. Fedoroff served as Science & Technology Adviser to Secretaries of State Condoleeza Rice and Hillary Clinton and U.S. Agency for International Development Administrator Rajiv Shah.

Nina Fedoroff

My name is Dr. Nina Fedoroff. I am a molecular biologist and geneticist, and I was one of the first to apply molecular techniques in plant biology commencing in the 1970s. I have been involved in the regulatory issues around modern genetic modifications (GM) since the early 1980s, when I served on the NIH Recombinant DNA Advisory Committee. I was also one of the authors of the 1987 National Academy of Sciences White Paper titled Introduction of Recombinant DNA-Engineered Organisms into the Environment: Key Issues. Then, as now, there was no evidence that unique hazards attend the use of modern GM techniques or in the movement of genes between unrelated organisms. The paper further states:

The risks associated with the introduction of recombinant DNA-engineered organisms are the same in kind as those associated with the introduction of unmodified organisms and organisms modified by other methods.

And concludes that:

Assessment of the risks of introducing recombinant DNA-engineered organisms into the environment should be based on the nature of the organism and the environment into which it is introduced, not on the method by which it was produced.

The president’s recent directive creates an unprecedented opportunity for the EPA, USDA, and FDA to 1) review the evidence that has accumulated in the intervening 30 years of biosafety research and field experience and 2) to move the regulatory system from de facto process-based to truly risk-based.

Going forward it is critically important to facilitate the use of GM techniques in agriculture. The warming climate, among other factors, is changing pest and disease profiles and distributions. This necessitates far more rapid adaptation responses, particularly for crops, than can be achieved through the older breeding approaches. And because so many different crops and animals are being —and will be—affected, the participation of many more skilled scientists will be necessary to meet these challenges than just those employed by big biotech companies. Tragically, today our public sector agricultural scientists have all but ceased using GM techniques for crop and animal protection and improvement. This is largely because the cost and time involved in obtaining regulatory approval for a GMO release is simply prohibitive.

It is therefore imperative that the present regulatory restructuring yields a framework that is truly risk-based and readily traversed at reasonable cost. The kinds of decision trees that should be developed, albeit based on current knowledge and decades of experience, we already laid out as long ago as the 1989 National Research Council report titled: Field Testing Genetically Modified Organisms: Framework for Decisions. This is especially important in the face of emerging gene modification technologies, such as the CRISPR/Cas system, that provide unprecedented control over what genes are modified and how—something that has never been possible in the entire history of agriculture.

The views expressed in guest posts are those of the author and are not necessarily endorsed by the Genetics Society of America.

The federal regulatory policy in use today for biotechnology products, known as the Coordinated Framework for the Regulation of Biotechnology, was created in 1986 through a joint effort between the U.S. Department of Agriculture (USDA), the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), the National Institutes of Health (NIH), the National Science Foundation (NSF), and the Occupational Safety and Health Administration (OSHA).  At that time, the overarching group, the Biotechnology Science Coordinating Committee (BSCC) sought to ensure the safety of genetically modified crops, manufactured food, medicine, pesticides, and other uses.

The BSCC’s framework summarized the roles of each agency in this joint regulatory effort as follows:

The FDA regulates products of genetically engineered (GE) organisms that fall within FDA’s authority under the Federal Food, Drug, and Cosmetic (FD&C) Act and other statutes. The FDA is responsible for ensuring the safety of all plant-derived human and animal foods, including those that are from genetically engineered sources. FDA also regulates GE animals under the new animal drug provisions of the FD&C Act, and FDA’s regulations for new animal drugs. (The actual regulated article is the recombinant DNA construct inserted into a specific site in the genome of an animal; as a shorthand, the FDA refers to the regulation of GE animals.)

Within USDA, the Animal and Plant Health Inspection Service (APHIS) is responsible for protecting agriculture from pests and diseases. Under the Plant Protection Act (PPA) and the Animal Health Protection Act (AHPA), USDA-APHIS has regulatory oversight over products of modern biotechnology that could pose a risk to plant and animal health. The AHPA provides authority to prohibit or restrict imports or entry into the United States or dissemination of any pest or disease of livestock. GE animals and insects would be subject to import or transport restrictions if there is a risk to animal health. The PPA, as amended, provides authority to regulate the introduction (i.e., importation, interstate movement, or release into the environment) of certain GE organisms and products. A GE organism is considered a regulated article if the donor organism, recipient organism, vector, or vector agent used in engineering the organism belongs to one of the taxa listed in the regulation and is also considered a plant pest. A GE organism is also regulated when APHIS has reason to believe that the GE organism may be a plant pest. A GE organism is no longer subject to the plant pest provisions of the PPA or to regulatory requirements when APHIS determines that it is unlikely to pose a plant pest risk.

The EPA under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the FD&C Act regulates the sale and distribution of all pesticides, including those produced through genetic engineering. This includes microorganisms, biochemicals isolated from organisms, and plant-incorporated protectants (PIPs), a type of pesticide intended to be produced and used in living plants. Under the Toxic Substances Control Act (TSCA), EPA has oversight responsibilities for a wide range of commercial, industrial, and consumer applications of microbial biotechnology. New chemicals produced through those microbial biotechnology applications are subject to premanufacturing review under TSCA.

In July of this year, the Executive Office of the President issued a memorandum directing the primary agencies that regulate the products of biotechnology—EPA, FDA, and USDA—to update the Coordinated Framework, develop a long-term strategy to ensure that the Federal biotechnology regulatory system is prepared for the future products of biotechnology, and commission an expert analysis of the future landscape of biotechnology products to support this effort. This memo comes as gene editing technology advances once again with the advent of the easily adaptable CRISPR, TALEN, and zinc finger nuclease methods.

In response to this memo the White House Office of Science and Technology Policy issued a request for information to “solicit relevant data and information, including case studies, that can assist in the development of the proposed update to the Coordinated Framework for the Regulation of Biotechnology (CF) to clarify the current roles and responsibilities of the EPA, FDA, and USDA” to develop a long-term strategy. Responses must be received by November 13, 2015, at 5 pm ET and can be submitted through the Federal eRulemaking Portal.

Responses are specifically requested to the following questions:

1. What additional clarification could be provided regarding which biotechnology product areas are within the statutory authority and responsibility of each agency?
2. What additional clarification could be provided regarding the roles that each agency plays for different biotechnology product areas, particularly for those product areas that fall within the responsibility of multiple agencies, and how those roles relate to each other in the course of a regulatory assessment?
3. How can Federal agencies improve their communication to consumers, industry, and other stakeholders regarding the authorities, practices, and bases for decision-making used to ensure the safety of the products of biotechnology?
4. Are there relevant data and information, including case studies, that can inform the update to the CF or the development of the long-term strategy regarding how to improve the transparency, coordination, predictability, and efficiency of the regulatory system for the products of biotechnology?
5. Are there specific issues that should be addressed in the update of the CF or in the long-term strategy in order to increase the transparency, coordination, predictability, and efficiency of the regulatory system for the products of biotechnology?

A public meeting where comments from the public are invited will be held on October 30, 2015, at FDA’s White Oak Campus just outside of Washington, DC. The purpose of this meeting is to inform the public of the activities taking place as a result of the July memorandum, invite oral comments from interested parties, and provide information about how to submit written comments, data, or other information to the docket. GSA plans to participate in that meeting, but others who wish to attend are encouraged to register as well.

Additional Information:

• John P. Holdren, Howard Shelanski, Darci Vetter, and Christy Goldfuss. “Improving Transparency and Ensuring Continued Safety in Biotechnology,” White House Blog, July 2, 2015.

A new report from the National Academies of Sciences, Engineering, and Medicine concludes that the continuing growth of federal research regulations and requirements is “diminishing the effectiveness of the nation’s research investment” by forcing investigators to spend more time on administrative and compliance matters, rather than research.

Optimizing the Nation’s Investment in Academic Research: A New Regulatory Framework for the 21st Century: Part 1 identifies specific actions to reduce the regulatory burden, with different recommendations aimed at Congress, the White House Office of Management and Budget (OMB), federal agencies, and academic research institutions.

The report calls for strengthening the partnership between the government and university research and urges the establishment of a government-enabled, private-sector Research Policy Board to support this partnerships and work to streamline research policies.

The Academies point out that different federal agencies have differing—and sometimes conflicting—guidance on compliance in areas such as financial conflict of interest, animal care, grant proposals, and the like.

Some of the specific recommendations in the report include the following:

• Congress should work with OMB to conduct a review of agency research grant proposal documents for the purpose of developing a uniform format to be used by all funding agencies;
• Congress should work with the White House Office and Science and Technology Policy (OSTP) and research institutions to develop a single financial conflict-of-interest policy to be used by all research funding agencies;
• Congress should instruct OSTP to convene representatives from federal agencies that fund animal research and from the research community to assess and report back to Congress on the feasibility and usefulness of a unified federal approach to policies and regulations pertaining to the care and use of research animals;
• OMB should require that research funding agencies use a uniform format for research progress reporting;
• Federal agencies should limit research proposals to the minimum information necessary to permit peer evaluation of the merit of the scientific questions being asked, the feasibility of answering those questions, and the ability of the investigator to carry out that research; and
• Universities should conduct a review of institutional policies developed to comply with federal regulations of research to determine whether the institution itself has created excessive or unnecessary self-imposed burden;

The study was mandated by Congress and supported, in part, by funds from the U.S. Department of Education and the National Institutes of Health. The committee is chaired by University of Texas president emeritus Larry Faulkner, with Rockefeller University vice president and general counsel Harriet Rabb serving as vice-chair.

Additional Information:

• “Inconsistent, Duplicative Regulations Undercut Productivity of U.S. Research Enterprise; Actions Needed to Streamline and Harmonize Regulations, Reinvigorate Government-University Partnership,” September 22, 2015.
• National Academies of Sciences, Engineering, and Medicine. 2015. Optimizing the Nation’s Investment in Academic Research: A New Regulatory Framework for the 21st Century. Washington, DC: The National Academies Press.