FDA Clarifies Approach to Genomic Alterations in Animals

May 2, 2024

The Food and Drug Administration will continue to take the lead in regulating intentional genomic alterations in animals, with assistance from the Agriculture Department on specific products, FDA said Wednesday.

The two agencies released a memorandum of understanding signed last month outlining how they plan to communicate and collaborate on oversight of genetically altered animals, settling a years-long debate.

"The MOU establishes policies and procedures to enhance the exchange of information between the agencies, describes the regulatory roles of the agencies, and promotes coordination of regulatory responsibilities in a manner that will enable an efficient, seamless regulatory process," FDA said in a news release. "It does not change or add regulatory requirements for developers." 

“We recognize that innovations in animal biotechnology offer tremendous opportunities for advancing human and animal health, and that we as an agency need to keep our regulatory approach current and flexible with the evolution of the science,” said Tracey Forfa, director of FDA’s Center for Veterinary Medicine.

The key change from current practice is that FDA will now be allowed to share information with USDA as some products go through the review process. 

“To me that’s a step in the right direction, but it’s not to the right endpoint yet,” said Jon Oatley, an associate dean in the college of Veterinary Medicine at Washington State University, who favors more USDA involvement in biotech regulations. 

FDA has been criticized in the past, especially by the livestock industry, for its lack of approvals of biotech animal traits and a cumbersome regulatory process. In the final days of the Trump administration, then-Ag Secretary Sonny Perdue tried unsuccessfully to have some of FDA’s authority over biotech animals moved to USDA.

On the consumer side, Peter Lurie, president of the Center for Science in the Public Interest, welcomed the decision. He said at least at the time the debate over regulatory authority started, USDA did not have sufficient in-house scientific expertise, and the agency only has regulatory authority over certain animals, like cattle, swine, goats, horses and poultry.

If regulatory oversight had shifted to USDA, the result could have been a “bifurcated” approach to genomically altered animals, Lurie said. 

In addition to the MOU, FDA released updated, final guidance for heritable IGAs in animals, to help the industry better understand existing statutory and regulatory requirements. (It also asked for comments on draft revised guidance, “Heritable Intentional Genomic Alterations in Animals: The Approval Process.”) 

The final guidance clarifies a path for developers to obtain enforcement discretion for IGAs, and establishes a risk-based approach for products.

“It seems to take a thoughtful, risk-based approach to these products in which the ones of greatest risk are subject to the greatest scrutiny, those with lesser risk are waived through the enforcement discretion,” Lurie said. “I think that's appropriate because it clearly is a spectrum of risk that is presented by these products.”

Developers have struggled with the ambiguity in the approval process and understanding what is needed for approval, said Oatley. While the draft guidance will hopefully fix this, Oatley said the risk-based approach document remains primarily the same and doesn’t address concerns among developers. 

The guidance makes clear that FDA would consider using enforcement discretion, which means the agency does not expect the submission of an approval application for some food producing animals, said Laura Epstein, associate director for regulatory affairs at CVM. The previous guidelines did not create a pathway for food-producing animals to get enforcement discretion, but will now allow it when there’s an alteration equivalent to one that already exists in animals of the same species with a history of safe use.

This is a policy decision that could apply to alterations like cattle modified to have a short-hair “slick” coat, Epstein said. 

“The animal biotech industry has needed this guidance to ensure an efficient and risk-based system for review, so that needed breakthroughs in IGA’s in animals can come to market,” the Biotechnology Innovation Organization said in a statement. “We applaud the work of FDA-CVM in listening to their stakeholders to issue this guidance. We appreciate their hard work and regular engagement with our members.”

For academic researchers, the updated guidance has little to no effect and doubles down on the approach of classifying IGAs as animal drugs, said Alison Van Eenennaam, professor of animal genomics and biotechnology at the University of California-Davis. 

“For companies, it's probably fine,” said Van Eenennaam. “But for academia and research animals, it still creates this barrier to doing the research because those animals will have to go through this expensive, regulatory evaluation that basically means it's just less expensive to just incinerate them.” 

Ahead of the guidance release, Van Eenennaam said she was hoping “category one” animals, or those that can obtain enforcement discretion with no application for approval expected or prior review, would apply to food animals with “simple edits” and no plasma DNA insertion. Under this categorization, researchers would not have to go through the FDA’s regulatory process, which saves academics time and money, she said.

Instead, food animals fall under category two, which still requires much of the data gathering that disadvantages small research labs, Van Eenennaam said. For these researchers, it will continue to be more cost-effective to incinerate or compost food-producing research animals, which means they miss out the opportunity cost of the animal. 

“What you've done is just raised the cost of doing large animal research in America,” Van Eenennaam said. 

The guidance does not hamstring innovation on the ground level, Oatley said. Instead, the regulatory process creates barriers when researchers want to translate findings into something “meaningful” for the marketplace, he explained. 

For example, he said the process still includes the “almost impossible” request of assessing if IGAs change the composition of an animal product. Simply feeding an animal a different diet can change its composition, and it’s difficult to see how a developer will ever be able to meet that requirement. 

“It seems like you're still gonna have these bottlenecks and walls that are very difficult to overcome in translating something from a research and development standpoint to a producer-applied tool,” Oatley said. 

In response to some of these concerns, Forfa said there are some flexibilities and resources like waiver provisions for user fees to still support innovation. However, these need to be balanced with the FDA’s core mission of providing safe and reliable products to consumers. 

“We work very closely with developers and sponsors on a case by case basis to make sure that we're not the impediments,” Forfa said. “But we do a careful risk-based scientific review.”