The Environmental Protection Agency (EPA) is exempting a class of plant-incorporated protectants (PIPs) that have been created using genetic engineering from certain registration requirements under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and from the requirements to establish a tolerance or tolerance exemption for residues of these substances on food or feed under the Federal Food, Drug, and Cosmetic Act (FFDCA). Specifically, EPA is finalizing its exemptions as described in its October 2020 proposal for PIPs now termed "PIPs created through genetic engineering from a sexually compatible plant" and "loss-of-function PIPs," finalizing the process through which the Agency determines their eligibility for exemption, and finalizing the associated recordkeeping requirements. This set of exemptions reflects the biotechnological advances made since 2001, when EPA first exempted PIPs derived through conventional breeding and excluded from the exemptions those PIPs that are created through biotechnology. EPA anticipates that today's exemptions will benefit the public by ensuring that human health and the environment are adequately protected, while also reducing the regulatory burden for the regulated community. These exemptions may also result in increased research and development activities, commercialization of new pest control options for farmers, particularly in minor crops, and increase the diversity of options for pest and disease management, which could provide environmental benefits.