GUIDELINES FOR THE REGULATION OF GENETICALLY ENGINEERED ANIMALS

The FDA has been regulating genetically engineered (GE) animals under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act or the Act) since producers of these animals first approached the agency in the mid-1990s, although it did not issue a final Guidance for Industry clarifying its statutory authority until 2009 (Regulation of Genetically Engineered Animals Containing Heritable rDNA Constructs: http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM113903.pdf). The regulatory trigger that enables the regulation of these animals under the new animal drug provisions of the Act is the definition of a drug as “an article (other than food) that is intended to affect the structure or any function of the body of man or other animals.” The products of modern biotechnology (such as spliced recombinant DNA) are technically the “articles” that must be approved, but for shorthand, we often refer to the regulation of “genetically engineered” animals. For the purpose of the guidance, FDA defined “genetically engineered (GE) animals” as those animals modified by rDNA techniques, including all progeny that contain the modification. The term GE animal can refer both to an animal with a heritable rDNA construct or its residues and to an animal with a nonheritable rDNA construct (e.g. a construct intended as therapy for a disease in that animal). If the agency engages in an “action,” such as an approval, obligations under the National Environmental Policy Act (NEPA) are triggered, such that the agency must perform an environmental assessment to determine whether a significant impact is likely to occur on the environment of the United States. If not, the agency issues a Finding of No Significant Impact (FONSI). If a significant impact is likely to occur as the result of an agency action, the agency must engage in a more complex process to characterise that impact in an Environmental Impact Statement (EIS). This regulation is consistent with the Coordinated Framework for the Regulation of Biotechnology, a policy that was first issued by issued by the Office of Science and Technology Policy [51 Fed Reg 23,302 (1986)] of the United States Government. It describes the interagency mechanism for “sharing scientific information related to biotechnology,” and states that, to the extent possible, jurisdiction of the products of biotechnology lies with a single agency. Where more than one agency will review a particular product, “the policy establishes a lead agency and consolidated or coordinated reviews.” Consistent with this policy, FDA has leveraged, and intends to continue to leverage, the expertise of other agencies in the review of GE animal-related applications. Under certain conditions, based on risk, the agency may not enforce the premarket approval requirement for some GE animals. In general, these include GE animals of non-food species that are regulated by other government agencies or entities, such as GE animals of non-food species that are raised and used in contained and controlled conditions such as GE laboratory animals (e.g. mice, rats, some model fish) used in research institutions. In addition, on a case-by-case basis, the agency may consider exercising enforcement discretion for GE animals of very low risk, non-food species GE animals, such as the Zebra danio aquarium fish genetically engineered to fluoresce in the dark (GloFish). An exemption from the prohibition on introducing an unapproved new animal drug in interstate commerce is provided for in the regulations covering “investigations,” which allow for lawful research to occur, including the shipping of GE animals or their gametes from the sponsor of an investigation to other qualified investigators. These and other responsibilities are outlined in GFI 187, as are recommendations for the submission of data to be reviewed by CVM’s hierarchical risk-based review, and will be the subject of this talk.