1. Overview of Risk Assessment and Risk Management of PIPs in the U.S.
BRAG PD Meeting
Chris Wozniak, Ph.D.
U.S. EPA, Office of Pesticide Programs
Biopesticides and Pollution Prevention Division
June 14, 2013

3. Background
The EPA Office of Pesticides regulates the sale, distribution, and use of all pesticides in the U.S. in order to protect human health and the environment.
Including: GMOs such as GE Plant-Incorporated protectants (PIPs) and Microbial Pest Control Agents within the Biopesticides and Pollution Prevention Division (BPPD) and GEMs.

4. EPA’s Regulatory Role
Federal Insecticide, Fungicide and Rodenticide Act – (FIFRA) pesticides
Federal Food Drug and Cosmetic Act – (FFDCA) food and feed safety
Food Quality Protection Act - (FQPA) amends FIFRA and FFDCA; sensitive groups
Endangered Species Act - (ESA) any impact on threatened or endangered species

5. Microbial Biopesticides
Bacteriophage
Viruses (baculoviruses)
Bacteria
Fungi
Algae
Protozoa
Not entomopathogenic nematodes*, mites or other biocontrol organisms
We do regulate paratransgenic insect symbionts such as Wolbachia in mosquitoes
* if symbiont is engineered, then it is regulated

6. Experimental Use Permits - Microbials
If GE, need a Notification Permit at any size field release
If non-GE, need an EUP at > 10A
Need a FFDCA tolerance any time pesticide may enter food / feed supply
We do regulate GE paratransgenic pesticidal products

7. What is a Plant-Incorporated Protectant (PIP)?
“ a pesticidal substance that is intended to be produced and used in a living plant, or in the produce thereof, and the genetic material necessary for production of such a pesticidal substance. “
It also includes any inert ingredient contained in the plant, or produce thereof.” (40 CFR Sec )
e.g., antibiotic or herbicide tolerance marker used in the selection of a PIP product.

8. Experimental Use Permits - PIPs
Cumulative acreage > 10 A (4 HA) per year per pest requires EPA approval
Food / feed tolerance required (at any size)
EUPs are all time limited and require reporting of results as well as any adverse events – [6(a)2 of FIFRA]
Products of EUPs are not eligible for advertising or promotion
EUPs may only be used to collect data required for FIFRA Section 3 registration

9. FIFRA Registration Typically follows an EUP
FIFRA is a licensing statute – pesticides require periodic review and annual maintenance fee for sale and distribution
Adverse events require reporting to EPA for the life of the product

10. RISK Ecological Human Health (acute & chronic) (acute & chronic)
Aquatic
Terrestrial
Populations & Subpopulations
Special protection
for children

11. How EPA Characterizes PIPs
Characterization
Product
Molecular
Expression
Levels
Protein
Methods
Analytical

12. How EPA Assesses Human Health Effects for PIPs
Assessment
Human Health
Acute Oral
Toxicity
Biochemical
Properties
Amino Acid
Homology
Sequence

13. How EPA Assesses Environmental Effects for PIPs
Assessment
Environmental
Non-target
Effects
Fate
Gene Flow

14. Gene Flow Considerations
An assessment of the impacts of gene flow is needed for EPA registration of PIPs
Potential for Invasiveness / Adverse effects
Sexual compatibility to wild relatives for the crop
Any NTO effects due to gene flow
For EUPs: Any compatible sympatric species will require containment or mitigation measures or data for the field test

15. Food / Feed Tolerance Federal Food Drug and Cosmetic Act
Residue of pesticide on food or feed requires a tolerance or exemption
Toxicity profiles are used to determine safety of pesticide residues
FDA enforces tolerance violations

16. FFDCA - Tolerances
Tolerance actions include inert ingredients (markers)
Tolerances can be for all crops / commodities or more restricted
Trade with unapproved PIPs in commerce can be problematic

17. RNAi Regulatory Considerations
Lack of novel protein production eliminates allergenicity assessment requirements
Nucleic acids have an existing exemption from the requirement of a food tolerance (FFDCA)
DNA / RNA part of human / animal diet
RNAi (siRNA, miRNA) already exists in cells
High sequence specificity required for activity?
We do not have extensive genomics information on all the NTOs we would like to assess (i.e., how much similarity exists?)
Can be delivered as plant, microbial or biochemical

18. PRIA Fees Regulatory actions are fee-based
Fees depend on the type of action and the requesting organization
PRIA provides for date of response
Food use vs non-food use, first use, EUP vs registration all affect fees

20. U.S. Government Biotechnology – Principal Regulatory Websites
US EPA PIP Website
US Department of Agriculture Biotech
US Food and Drug Administration Biotech
Assistance for national database creation

21. Useful Links
Regulation of Biotechnology for Use in Pest Management – U.S. EPA
Introduction to Biotechnology Regulation for Pesticides – U.S. EPA
Regulating Biopesticides – U.S. EPA
Bt-maize and scorpion toxin NPV case studies

22. Useful websites

23. Questions ?