New Livestock Biotechnology Guidance Misses the Mark

Yesterday the FDA released two guidance documents that clarify the agency’s approach to regulating gene-edited animals. FDA claims that their updates show the agency’s commitment to modernize its regulatory approach and make it more flexible, predictable, and efficient. Instead, they change very little, and existing problems and inefficiencies remain.

Regulation of gene-edited animals, like all FDA regulation, should protect the health of humans, animals, and the environment using efficient, risk-based regulation. In order to accomplish this goal, FDA regulation of gene-edited animals should focus on the traits of the animal and the risks they pose, rather than the type of genetic change or whether it could have been created using conventional breeding. Current technologies for genetic modification and gene editing are not new, and many authorities agree that they do not pose any new or unique risks compared to conventional breeding.

Despite this knowledge, FDA’s new guidance is not sufficiently risk-based and focuses too much on the type of genetic change, makes few improvements, and requires developers of gene edited animals that pose a low risk to submit unnecessary data.

Using genetic modification, CRISPR gene editing, and other genetic technologies to develop what FDA calls Intentional Genomic Alterations (IGAs) in livestock could offer significant public benefits. Developing livestock with IGAs could enhance animal health, increase productivity, and reduce resource use and environmental impacts per pound of meat or gallon of milk. For example, altering the genetic makeup of cattle to make them resistant to diseases like bovine respiratory disease (BRD) and bovine viral diarrhea virus (BVDV) would enable farmers to produce more dairy and beef with fewer animals, reducing emissions by up to 4 and 2 million metric tons of CO2 equivalents per year, respectively, according to a Breakthrough Institute analysis.

Yesterday the agency released final guidance 187a and draft guidance 187b, both descended from draft guidance 187 which was initially published in 2017 as an update to the agency’s 2009 regulations of genetically modified animals. This blog post discusses only final guidance 187a, comments on draft guidance 187b will follow in a later post.

Final guidance 187a describes FDA’s approach to enforcement discretion — when the agency decides that a developer of an IGA does not need to submit a full application for pre-market approval. However, final guidance 187a doesn’t substantially modernize FDA’s approach to IGAs, but rather maintains the agency’s (very limited) uses of enforcement discretion so far. These past uses of enforcement discretion include decisions to not require an application for approval for genetically modified lab animals, genetically modified aquarium fish that glow, and gene-edited cattle with a smooth coat. That’s it, from 2003 to 2024.

FDA’s guidance establishes three categories for IGAs. For Category 1 products, developers do not need to consult FDA before marketing these animals. For Category 2, FDA requests that developers submit extensive data on the risks associated with a product, among other information, and determines whether to apply enforcement discretion or to require the developer to submit a full application for approval. For Category 3, FDA requires developers to apply for approval and submit extensive data that FDA considers proportional to its risk level.

The requirements for data submission for “risk review” of Category 2 IGAs listed in guidance 187a are far too extensive, considering the definition of the category is very narrow and the agency considers it low risk. Data requirements for Category 2 risk review include comparison to an unmodified animal of the same species, description of the method used to generate the IGA, characterization of the genomic sequence, and information addressing risks to humans, animals, and the environment. In particular, genomic data can be very costly and time consuming to generate and analyze, making the regulatory burden prohibitive for smaller developers.

Unlike USDA’s routine use of full exemptions for biotech plants that “could have been created using conventional breeding,” FDA still requires substantial data submission for Category 2 IGAs to confirm that they do indeed fit into this category. USDA has made significant changes to eliminate regulatory burden for biotech plants the agency deems low risk, while FDA and EPA only somewhat lower the regulatory burden for some products. Maintaining a high regulatory burden for almost all IGAs in animals — including those that FDA deems low risk and which are similar to types of products that USDA fully exempts — is an inefficient use of resources and detrimental to innovation.

Though FDA claims in final guidance 187a that “We generally do not make these types of decisions about products based on the technology used or the size or type of the genomic alteration made,” the definitions of Category 2 IGAs do just that. Category 2 IGAs currently include only those that 1) mimic existing genes of the same species that are already used for food production, and 2) that could have been made using conventional breeding techniques. For genetic changes that could have been made using conventional breeding, the guidance text explicitly excludes insertion of transgenes, and leaves open the possibility to include “deletions, small insertions in coding regions, and possibly deletions, small insertions, and changes to non-coding regions”. Regulations that define risk based on the type of genetic change do not efficiently focus resources on high-risk products, and are not adaptable to future technological innovations.

The United States needs more efficient and risk-based regulations of biotechnology in order to be a leader in innovation, to be competitive in a global economy, and to benefit from uses of IGA animals in food production and elsewhere.