SLR/CLC Meeting Fort Collins, CO, April 2017

Biopesticides in the U.S. Risk Assessment/Risk Management Regulatory Processes & Emerging

Technologies

Russell S. Jones, Ph.D. Senior Scientist Risk Assessment Branch

Biopesticides & Pollution Prevention Division Office of Pesticide Programs

U. S. Environmental Protection Agency

Presentation Outline

• EPA Organization • Pesticide Regulation Summary • Overview of Biopesticides

• Biochemicals

• Microbials

• Plant Incorporated Protectants (PIPs)

• Registration and Data Requirements • Emerging Technologies

Environmental Protection Agency

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Office of the Administrator

Office of the Chief Financial Officer

Office of the Inspector General

Office of Enforcement and

Compliance Assurance

Office of Air and Radiation

Office of International and

Tribal Affairs

Office of Environmental

Information

Office of Chemical Safety and Pollution

Prevention

Office of General Counsel

Office of Administration &

Resources Management

Office of Water Office of Research and Development

Office of Land and Emergency

Management

Ten Regional Offices Region 8/Denver CO, MT, ND, SD,

UT, and WY

Office of Chemical Safety and Pollution Prevention (OCSPP)

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Immediate Office

Office of Pollution Prevention and

Toxics

Office of Science Coordination and

Policy

Office of Pesticide Programs

Office of Pesticide Programs (OPP)

Immediate Office

Environmental Fate and Effects

Division

Pesticide Re-evaluation

Division

Field and External Affairs

Division

Biological and Economic Analysis

Division

Registration Division

Health Effects Division

Antimicrobial Division

Biopesticides and Pollution Prevention

Division

IT & Resources Managment

Division

Biopesticides & Pollution Prevention Division (BPPD)

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Emerging Technologies

Branch

Microbial Pesticides

Branch

Biochemical Pesticides

Branch

Immediate

Office

Risk Assessment

Branch

Environmental Stewardship

Branch

Biopesticides And Pollution Prevention Division (BPPD)

• Established in 1994 to streamline registrations

• Reduced Regulatory Burden

• Bring safer pesticide products to market place

• Encourage uses in IPM strategic IPM programs

Pesticide Regulation Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

Federal Food, Drug, and Cosmetic Act (FFDCA)

Food Quality Protection Act (FQPA)

Pesticide Registration Improvement Act (PRIA)

Other Statutes: • Endangered Species Act • Migratory Bird Treaty Act • Clean Water Act

Pesticide Registration Improvement Act (PRIA)

• Result of support from a coalition of industry, growers, environmental groups, and farm worker advocates.

• PRIA 1 (2004) established a registration fee-for-service system with specific fees and decision times by type of action

• PRIA 2 (2007) revised fee payment process and increased registration categories from 90 to 140

• PRIA 3 (2012)

• Registration categories expanded from 140 to 189 • Changes in Maintenance Fees • Includes fee reductions and waivers • IT set-aside: Improve tracking and databases • 45/90 Day Technical Screen

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Pesticide Registration Improvement Act (PRIA) • PRIA 4 (proposed 2017?): Highlights*

• Seven-year extension (FY 2017 through FY 2023)

• Increases fee categories from 189 to 212 - New pest categories requiring efficacy data - New EUP categories and PIP categories

• Eliminates IT set-aside; creates GLP inspection set-aside

• Creates a set-aside to support efficacy guideline development and rule-making for public health pests.

• Incentives for new reduced-risk actives by higher fees on new conventional actives

* May not reflect final language of Bill

Pesticide Registration Improvement Act (PRIA 4)

• House Agriculture Committee passed PRIA 4 (HR 1029) in February 2017

• House Re-authorization passed on March 20, 2017

• Full text of HR 1029 at: https://www.congress.gov/115/bills/hr1029/BILLS-115hr1029ih.pdf

Overview of

Biopesticides

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Characteristics of Biopesticides

• Substances, Organisms Found in Nature • Or Structurally-similar synthetic substances

• “Unique” Modes Of Action

• Typically Low Use Rates

• Typically “Reduced Risk”

Characteristics of Biopesticides • Inherently less toxic, or non-toxic, when compared to

conventional pesticides.

• Many biopesticides affect only the target pest and closely related organisms

• Some are broad spectrum.

• Typically have low use rates and rapidly degrade in the environment

• Lower exposures to non-target organisms.

Benefits of Biopesticides • Useful tools in IPM programs to decrease the use of

conventional pesticides and reduce likelihood of pesticide resistance

• Often: • Exempt from requirement for tolerances • Have no PHI • Have substantially shorter REIs

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Biopesticide Categories

• Biochemicals • Microbials • Plant-incorporated Protectants

(PIPS)

• OTHER BIOTECHNOLOGY PRODUCTS

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Biochemical Pesticides

• Naturally-Occurring Substances

• Non-Toxic Mode of Action to Target Pest(s)

• History of Exposure to Humans and Environment with Minimal Toxicity

US CRITERIA 40 CFR 158.2000 (a)(1)(i), (ii), & (iii)

Examples of Non-Toxic Modes of Action

• Growth and developmental changes • e.g. Plant regulators, insect growth regulators

• Attractants, Repellents, Anti-feedants • e.g. Pheromones

• Suffocation

• Desiccation

• Coatings (Irritants & Barriers)

Semiochemicals – Pheromones

Mating Disruptants Pheromone Traps

Non-Toxic Desiccants - Herbicides

Acetic Acid (Vinegar)

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Non-Toxic Coatings

Kaolin clay - barrier & irritant

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“Naturally-occurring” does not presume a non-toxic mode of action

Non-toxic substances can be lethal Physical Action Dissolving Action Suffocation

Biochemical Pesticides

Other Uses May Include:

• Herbicides

• Insecticides

• Fungicides

• Nematicides

• Molluscicides

Microbial Pesticides

• Naturally Occurring and Genetically-modified Microorganisms used as Pesticides:

• bacteria, fungi, viruses, and bacteriophages

• Uses may include:

• Herbicides, fungicides, insecticides, nematicides’ molluscicides

US CRITERIA 40 CFR 158.2100 (b)(1)(2) & (3)

Microbial Pesticides Characteristics

• (May) Survive, reproduce in the environment

• Modes of action can include

• Competition

• Inhibition

• Use of pest as a growth substrate

• Toxicity

• Typically

• Low mammalian toxicity

• Target specificity

• Low use rates

Microbial Pesticides – Mycoinsecticides Pathogenicity Mycotoxins

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Microbial Pesticides – Mycoherbicides

Hemp sesbania control with Colletotrichum truncatum

Plant Incorporated Protectants (PIPs)

• Overview • Key Features of PIPs

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Plant-Incorporated Protectants (PIPs)

• Pesticidal substance (e.g., a protein) produced by a genetically altered plant and the genetic material needed to produce the substance

• To date, primarily Bacillus thuringiensis (Bt) transgenic crops to control insects

• Also, plant virus-resistant crops

• PIP Overview https://www.epa.gov/regulation-biotechnology-under-tsca-and-

fifra/overview-plant-incorporated-protectants

Plant-Incorporated Protectants (PIPs)

• Products Derived from Biotechnology are Regulated in accordance with the Coordinated Framework for Biotechnology

• PIPs are regulated in coordination with USDA and FDA

2017 Update: https://www.epa.gov/sites/production/files/2017-

01/documents/2017_coordinated_framework_update.pdf

U.S. Oversight of Genetically-Engineered Plants

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To be registered as a Biopesticide . . .

• Must contain a Biochemical, Microbial, or PIP active ingredient (or other biotech product)

• Must contain only approved inerts • CANNOT contain a Conventional Chemical a.i.

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General information on inerts

https://www.epa.gov/pesticide-registration/inert-ingredients-overview-and-guidance

Inerts that can be used in 25b products https://www.epa.gov/minimum-risk-pesticides/inert-

ingredients-approved-use-minimum-risk-pesticide-products

Ingredients of Biopesticides

New Biopesticide Registration Process

• Pre-Submission Meeting

• Submission of Application under PRIA

• Scientific Review of Data

• Label Review

• Decision Document (BRAD) for public comment (30 days)

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Data Requirements Overview

• OCSPP Series Guideline study protocols

• Grouped according to intended uses and type of biopesticide

• Major disciplines of product characterization, mammalian toxicity, and ecological effects are tiered

• Information used in support of risk assessments

• Significantly reduced compared to conventional pesticides

DATA REQUIREMENTS

• Biochemical pesticides:

• Tables under 40 CFR 158.2030 - 158.2060

• Microbial pesticides:

• Tables under 40 CFR 158.2120 - 158.2150

• Plant Incorporated Protectants:

• 40 CFR 174 http://www.ecfr.gov/

Product Chemistry, Product Analysis, Product Characterization

Mammalian Tests Tier I

Acute & subchronic toxicity, mutagenicity, developmental; pathogenicity (M only)

Mammalian Tests Tier II Mutagenicity, developmental,

immunotoxicity, applicator exposure; pathogenicity (M only)

Mammalian Tests Tier III Chronic, longer term toxicity,

carcinogenicity; infectivity analysis (M only)

Non-Target Organisms Tier I Acute toxicity; pathogenicity (M only)

Non-Target Organisms Tier II Environmental fate/expression

Non-Target Organisms Tier III Chronic, Life Cycle, & Field Testing;

Mesocosm Studies (M only)

Non-Target Organisms: Tier IV

Simulated or Actual Field tests (M only)

Biopesticide Data Requirements

Product Chemistry, Product Analysis, Product Characterization

Mammalian Tests Tier I

Acute & subchronic toxicity, mutagenicity, developmental; pathogenicity (M only)

Non-Target Organisms Tier I Acute toxicity; pathogenicity (M only)

Product Performance (Efficacy):

Public Health Pests Only

Biopesticide Data Requirements Initial Submission

Exemptions from FIFRA

• Pheromones used in pheromone traps

• “Foods” used to attract pests

• “Natural cedar” chips, panels, etc

• Devices

• “Minimum Risk Pesticides”*(aka “25b list) https://www.epa.gov/sites/production/files/2015-12/documents/minrisk-

active-ingredients-tolerances-2015-12-15.pdf

*Not necessarily exempt FFDCA

Emerging Technologies

Plant Biostimulants

RNAi

CRISPR

Plant Biostimulants

Mixtures of naturally-occurring substances and/or microbes intended to:

• In small quantities, enhance plant growth/development/vigor

• Improve resistance to abiotic stress

• Increase nutrient and water use efficiency

• Improve soil characteristics

• Support growth/activity of beneficial microbes

Plant Biostimulants May consist of one or more of the following:

• Beneficial fungi or bacteria

• Seaweed extracts/other plant extracts

• Humates, organic acids, amino acids, oligosaccharides

• Hydrolyzed proteins, polypeptides

• Other similar inorganic/organic substances

• Plant hormones and other naturally-occurring plant growth substances

Plant Biostimulants

Do not provide nutritionally-relevant fertilizer benefit to plants.

Are not intended for use in the control of pests.

Are they pesticides?

Plant Biostimulants FIFRA Section 2(u) includes Plant Regulators as

substances considered to be Pesticides

Are Plant Biostimulants = Plant Regulators?

• Plant Regulator = Pesticide

• Plant Regulator Claim = Pesticidal Claim

• No Federal statutory or regulatory definition for a Plant Biostimulant

Plant Biostimulants

FIFRA Section 2(v) defines a Plant Regulators as:

Through physiological action, does the substance or mixture of substances:

• Accelerate or retarding the rate of growth?

• Accelerate or retard the rate of maturation?

• Alter the behavior of plants or the produce • thereof?

Regulatory Exclusions from the Plant Regulator Definition

• Plant nutrients & trace elements (e.g. fertilizers)

• Nutritional chemicals (not defined in FIFRA)

• Plant inoculants

• Soil amendments

• Vitamin-hormone horticultural products

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Plant Biostimulant Guidance

• EPA has developed guidance for Plant Biostimulant (PBS) products and associated label claims that may be included in, or excluded from regulation under FIFRA

• Exclusions based on Substances Excluded from Regulation by

FIFRA under 40 CFR 152.6 (f)(1) & (2) and (g)(1), (2) & (3) and FIFRA Section 2(u):

• Includes guidance on Generic Product Label Claims for

Products Not Covered by the Exclusions from the FIFRA Section 2(u) Definition of a Plant Regulator.

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Ribonucleic Acid Interference (RNAi)

• Natural biological process

• Process identified in nematodes in 1998

• Fire and Mellow win Nobel Prize in 2006

• dsRNA molecules used to inhibit gene expression

• Typically suppress production of protein necessary for a biological process

RNAi (Ribonucleic Acid Interference) Possible Pesticidal Applications

• Direct pest control

• Increase plant resistance to pests

• Decrease plant (weed) resistance to pests

• Suppress resistance to chemical pesticides

• May be PIPs

• May be spray-applied microbials/biochemicals

Clustered Regularly-interspersed Short Palindromic Repeats (CRISPR)

• A gene editing technique (CRISPR-Cas9)

• Natural process in bacteria – virus resistance

• May be used to develop pathogen resistant crops

-Rice resistant to bacterial blight and rice blast (Iowa State) -Blight-resistant potatoes (Penn State) -Wheat resistant to powdery mildew (China Academy of Sciences)

Is it pesticidal?

Overall EPA recognizes: • The value and benefits of biopesticides

• Continual advances in the science of biopesticide technology

• The ever-changing nature of the business.

EPA is committed to: • Approval of safer pesticides in accordance with

PRIA timeframes; and

• Transparent, predictable processes.

For More Information

To search for information on biopesticide active ingredients . . .

www.epa.gov/pesticides/chemicalsearch

To search for product labels using the Pesticide Product Label System (PPLS) . . . http://iaspub.epa.gov/apex/pesticides/f?p=PPLS:1

For More Information • Contact

– Cara Finn, BPPD Ombudsman • BPPDQuestions@epa.gov

• Visit Us on the Web https://www.epa.gov/pesticides/biopesticides

https://www.epa.gov/pesticide-contacts/contacts-office-

pesticide-programs-biopesticides-and-pollution-prevention

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