On May 7, 2014, the Environmental Protection Agency (EPA) posted the Meeting Minutes of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Science Advisory Panel’s January 28, 2014, meeting on “RNAi Technology as a Pesticide: Problem Formulation for Human Health and Ecological Risk Assessment.” This report by the FIFRA Science Advice Panel (SAP or the Panel) is a long-awaited analysis of critical science issues central to effective and efficient risk assessment of a promising new pest control technology.
In sum, the Panel opined that, while additional study must be done, pest control products that are developed that utilize RNA interference (RNAi) technology are not likely to result in adverse effects to humans through ingestion exposures. The Panel recommended further study of the possibility of inhalation and dermal exposures, and of possible effects to individuals with certain medical conditions. Regarding possible ecological effects, the Panel noted significant uncertainties based on the currently available data and information. The Panel concluded that a substantial amount of new data should be generated to better understand environmental fate, likelihood of exposure, and modes of action and potential effects. Moreover, the Panel recommended that EPA develop a new ecological risk assessment paradigm for RNAi products. If EPA follows the Panel’s recommendations, there may be significant delays in the actual RNAi regulatory process as new data and information are generated and as EPA develops an ecological risk assessment model specific to these products.
The phenomenon of RNAi was first elucidated by Andrew Fire and Craig Mello in 1998. In essence, RNAi is a means of controlling protein expression in cells. For this work, the pair was awarded the Nobel Prize in Physiology or Medicine in 2006. A number of agricultural and pharmaceutical products are now in development that attempt to utilize RNAi, either as genetically transformed constructs, or as exogenously applied products. EPA anticipates receipt of applications for registration of pest control RNAi products.
Recognizing that RNAi technology will raise novel science questions that will be crucial to appropriate regulatory treatment of these products, EPA began preparing in about 2012 to convene a meeting of the FIFRA SAP to advise the Agency on these complex science issues.
At the January 28, 2014 SAP meeting, the Panel was asked seven broad questions related specifically to problem formulation for RNAi risk assessment. Three of these broad questions related to human health considerations, and four addressed ecological risks. Regarding human health considerations, the Panel opined that current information on the genetic composition of the human genome can be used to assess whether RNAi sequences could possibly bind to human genes; the Panel also concluded that there is no evidence supporting a concern that ingested RNAi sequences could survive mammalian digestive processes and lead to adverse health effects. The Panel recommended additional study to confirm that physiologically active sequences do not survive the digestive process, that RNAi constructs be evaluated for potential for exposure through inhalation and dermal routes, and that the possibility of adverse effects in individuals with certain health conditions be examined.
Regarding potential ecological impacts of RNAi constructs, the Panel raised significant concerns as to whether EPA’s current ecological testing framework is adequate to address the unique risks that may be posed by RNAi products. The Panel identified concerns with how these products may affect non-target species, including developmental and long-term effects; the appropriate test species to enable the Agency to draw conclusions regarding non-target effects; and lack of understanding of how long these constructs may survive in the environment. The Panel made numerous recommendations to the Agency to assist it in developing a scientifically valid ecological risk assessment scheme for these products.
Given the Panel’s large number of recommendations to EPA, it is clear that companies developing these products may face significant regulatory hurdles in obtaining product approvals. While EPA’s regulatory processes for the current set of genetically engineered plant-incorporated-protectants (PIPs) is well established and the risk assessment process for these products is now routine, it is clear that, at least with respect to ecological risk assessment, the SAP is recommending that EPA develop a new RNAi risk assessment paradigm, based on RNAi-specific data and information that may yet have to be generated. If much of the new data identified by the SAP has not been generated, this could mean that regulatory approvals for RNAi products could be significantly delayed. Thus, if adopted, the SAP’s recommendations will have significant impacts on the time it takes to obtain a registration, the total cost of required data development, and could impact product development decisions. We believe that EPA should move quickly to identify for technology producers exactly what new data will be required, so that this extraordinarily promising technology is not unduly delayed.
To obtain a copy of the FIFRA SAP’s report on RNAi risk assessment product formulationclick here.