Advancing regulations for intentional genomic alterations in animals

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The FDA made some significant moves to improve how it oversees intentional genomic alterations (IGAs) in animals. The changes aim to make the FDA's process for evaluating and supporting innovative animal products more up-to-date and efficient. Additionally, the agency established a memorandum of understanding (MOU) with the US Department of Agriculture (USDA) to clarify roles and responsibilities for regulation of IGAs in animals.¹

According to the FDA, IGAs in animals can be made using modern molecular technologies, which may include random or targeted DNA sequence changes. This can include nucleotide insertions, substitutions, or deletions, or other technologies that introduce specific changes to the genome of the animal.¹ The purpose of IGAs can be beneficial for human health with medications and disease studies; improving the health and well-being of animals and making them resistant to certain diseases; and enhance production and food quality for food animals by adding nutritional benefits.

“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 with the evolution of the science,” Tracey Forfa, director of the FDA’s Center for Veterinary Medicine, said in the release.¹ “These updated guidance documents demonstrate our commitment to facilitating innovation while ensuring product safety. These technologies hold great promise for many uses and public and animal health benefits, such as animal disease resistance, control of zoonotic disease transmission, improved animal husbandry, and increased food production and quality.”

To clarify the existing statutory and regulatory requirements of IGAs, the FDA has released a final version of the Guidance for Industry (GFI) #187A, “Heritable Intentional Genomic Alterations in Animals: Risk-Based Approach,”² document, and a revised draft version of GFI #187B, “Heritable Intentional Genomic Alterations in Animals: The Approval Process.” These documents help explain how the FDA determines when it is appropriate to exercise enforcement discretion over certain products.

GFI #187A focuses on the risk-based regulatory approach to the oversight of heritable IGAs in animals. This document separates the risks into 3 categories being:²

1. Category 1: Products for which developers are not expected to consult with the FDA prior to marketing an animal containing an IGA.
2. Category 2: Products for which developers may not be expected to submit an application for approval of the IGA and, if after looking at data submitted about that product’s risk, the FDA finds that the product’s risks for the specified intended use are understood, any identified risks are appropriately mitigated, and the agency has no further questions that would require additional data to address.
3. Category 3: Products that the FDA will review and, where the data supports it, grant approval using data requirements that are proportionate to the risk associated with the particular product.

GFI #187B provides technical guidance for those IGAs in animals that go through the approval process. This document would be applicable to category 3 products or category 2 in which the FDA needs more data for approval.² Because GFI #187B is still in a draft phase, the FDA is seeking public comments starting on May 2, 2024, until July 31, 2024.

Additionally, the FDA and USDA signed a MOU on April 18, 2024, regarding the FDA's activities related to IGAs, which also fall under USDA jurisdiction. The MOU sets out guidelines for better information sharing, defines each agency's regulatory roles, and encourages coordinated regulatory efforts for a smoother process. It does not introduce new regulations or requirements for developers.^1,3

The FDA encourages developers of IGAs in animals to approach the agency early in their research and development phase to discuss any risks and also recommends participation in the Veterinary Innovation Program to support developers with these processes.

References

1. FDA clarifies approach to genomic alterations in animals. News release. FDA. May 1, 2024. Accessed May 1, 2024. https://www.fda.gov/news-events/press-announcements/fda-clarifies-approach-genomic-alterations-animals
2. CVM GFI #187A Heritable Intentional Genomic Alterations in Animals: Risk-Based Approach. FDA. May 2024. Accessed May 1, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-187a-heritable-intentional-genomic-alterations-animals-risk-based-approach
3. MOU 225-24-010. FDA. April 18, 2024. Accessed May 1, 2024. https://www.fda.gov/about-fda/domestic-mous/mou-225-24-010