Considerations and Regulatory Approaches in the USA and in the EU for dsRNA-Based Externally Applied Pesticides for Plant Protection

Abstract

Increasing pest and pathogen challenges as well as having fewer conventional pesticides to employ require innovative and sustainable solutions for plant protection. One group of pesticides that is in the pipeline and is expected to be subject to regulation and risk assessment procedures in the near future, is based on the natural gene silencing mechanism RNA interference (RNAi). These dsRNA-based products can be highly specific for a target organism due to the sequence-specific interaction between effective small interfering RNAs (siRNAs) and a complementary target RNA. General regulatory frameworks for pesticide authorization in the U.S. and in the EU are presented. In addition, production and application procedures and specific characteristics of dsRNA-based pesticides relevant for risk assessment and regulation are considered.

Advances and Challenges in RNA Interference Technology for Citrus Huanglongbing Vector Control

“…It can help control this insect pest through two modes of application: non-transformative (bioproduct) and transformative (transgenic plants) delivery. The non-transformative delivery presents some advantages for use in pest management because of the rapid product development, low cost, low resistance risk, and high viability for all crops [87], although there are no stringent regulations in different countries [88].…”

RNAi-Based Biocontrol Products: Market Status, Regulatory Aspects, and Risk Assessment

“…In the USA, SIGS-based RNAi products for plant protection are considered biochemical pesticides (Figure 1). In contrast to conventional pesticides, which are generally synthetic compounds that directly kill or inactivate the pest, biochemical pesticides are naturally occurring compounds which are usually inherently less toxic (16). However, these biochemical pesticides still require a US Environmental Protection Agency (EPA) registration before manufacture, transport, and sale (17).…”

“…Therefore, no unreasonable adverse effect(s) to man or the environment should result from the use of the pesticide in order to support its registration under FIFRA. In addition, FFDCA allows to set maximum residue levels for pesticides used in or on food or feed (16). During this investigation, technical grade material of the pesticide is tested along with product formulation.…”

“…Important to take into consideration for the risk assessment is that, in contrast to conventional pesticides, RNAi-based products might take a longer time to display efficacy. This lag-effect should be considered when assessing RNAi-based products by extending the observation period and to take into account nonlethal phenotypes and life cycle analysis in addition to mortality (7,16).…”

Lab-to-Field Transition of RNA Spray Applications – How Far Are We?

“…However, lab-to-field transitions require further precision and accuracy in off-target predictions and their controllability for adequate risk assessment. Currently, data requirements specific for RNA spray-based plant protection products are not yet in place under the regulatory frameworks for pesticides and plant protection products in the United States and EU (Dietz-Pfeilstetter et al, 2021). The OECD (Organization for Economic Cooperation and Development) organized a meeting on this question, which represented a major step forward in terms of testing regulation and research direction for future external dsRNA products (OECD, 2020).…”