donald w. edgecomb, phd director, international business development agraquest, inc. usa challenges...

Donald W. Edgecomb, PhDDirector, International Business Development

AgraQuest, Inc. USA

Challenges to Bio-Pesticide Global Registration Challenges to Bio-Pesticide Global Registration and Adoption – and Adoption –

a Manufacturer's Perspectivea Manufacturer's Perspective

'Bio-Pesticides: The Way Ahead' October 18, 2006

Challenges to Bio-Pesticide Global Registration Challenges to Bio-Pesticide Global Registration and Adoption – and Adoption –

a Manufacturer's Perspectivea Manufacturer's Perspective

'Bio-Pesticides: The Way Ahead' October 18, 2006

Innovative natural product solutions for pest management.

AgraQuest MissionAgraQuest Mission

AgraQuestAgraQuest discovers, discovers, develops,manufactures and develops,manufactures and markets effective, safe, and markets effective, safe, and environmentally friendly naturalenvironmentally friendly naturalproducts for farm, home and products for farm, home and public health pest managementpublic health pest management


AgraQuest - Overview Founded in 1995; Headquartered in Davis, CA

Manufacturing in Tlaxcala, Mexico

70 full-time employees, 14 in sales & mkting, 19 R&D, regulatory and tech support to sales; 30 in mfg

5 products on the market; 2 pending at the EPA; 20 more candidates identified

29 U.S. patents and 2 U.S. patent applications; 15 foreign patents and 60+ foreign patent applications

>$60 million of invested equity capital

Presidential Green Chemistry Award - 2003

World Technology Award for the Environment- 2004


AgraQuest Founded on Natural Opportunities

• 50% of pharmaceuticals vs. 7% of pesticides derived from plants/microbes

• Commercialization advantages exist for natural products; ratio of products per microbes screened:

Synthetic chemicals 1:150K, AQ Screen 4:7K

• Less time from discovery to commercialization

3 yrs natural vs. 7-10 yrs synthetic

• Lower cost to develop

$10-15 MM vs. $150-200 MM

• “Short” timeline: EPA – BPPD registration pathway

1.5 yrs vs. 3-5 yrs


Biological / Natural Product Control Technologies

Increased Demand for Alternatives to Pesticides• Rising consumer concerns regarding safety of pesticide residues on fruits,

vegetables and salads

• Government initiatives to reduce pesticide use

- EU Common Agriculture Policy: Pesticide reduction schemes in MS

• Grower organization / Retail initiatives

- New Zealand wine producers: Zero-pesticide residue in wine

- China “Green Food” government directive

- Supermarket programs: Organic and zero-detectable pesticide residues on food products

• Maximum Residue Levels (MRL) –Global disharmony for permissible levels

- non-tariff trade barriers for food exports

• Fewer conventional pest control products, especially “minor” crops

- industry consolidation

- high cost, time to market and resistance potential


Internal Pipeline•AQ Platform: Serenade, Sonata, 6047, 4800• 20+ leads

External Pipeline•Muscodor, bioherbicides, bioinsecticides, nematicides, and fertilizers

InternalCandidates

External Candidates

Product Filter

Criteria:• Efficacy• Natural Product Chemistry• BPPD Registration• Intellectual Property• Cost to Commercialization• Time to Market• Price Competitive• Fills Customer Need• Fits strategy

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Internal Pipeline•AQ Platform: Serenade, Sonata, 6047, 4800• 20+ leads

External Pipeline•Muscodor, bioherbicides, bioinsecticides,nematicide, and fertilizers

Conventional Agriculture

Post-harvest Agriculture

OrganicTurf &

OrnamentalRetail

Commercialization Matrix

NEW PRODUCTS

Product Development Product Management & LogisticsField Trials and Demos

Registration – EPA, State, Int’l

Marketing, Branding, Packaging

Product Support & Product Improvement

Manufacturing

Sales & Positioning


Natural Pest Management Products From Microorganisms

Natural Pest Management Products From Microorganisms

Collectionand Isolation

Fermentation

Primary Screening

Preliminary Toxicology

Natural Product

Chemistry

Pre-Development

Testing

Process & Formulation

Advanced Toxicology

Field Testing

Registration& Commercial Development

Development / Registration / Development / Registration / CommercializationCommercialization

Development / Registration / Development / Registration / CommercializationCommercialization

DiscoveryDiscoveryDiscoveryDiscovery


DiscoverySourcing and Isolation of Microorganisms

Collect from targetedsources and habitats based

on experience and database of 20,000+

microbes

Isolate bacteria, fungi, actinomycetes

on proprietary media


Ferment samples in miniature using a suite of proprietary media recipes

Media mimics large-scale recipes for faster scale-up

Fermentation of Microorganisms for Testing


Automated, Miniaturized, In-vivo Screening

Insects, Mites, Nematodes

Plant Pathogens

Robotic station for dispensing sample, eggs,

nematodes and spores


Natural Product Chemistry

Eliminate strains with harmful toxins

Using proprietary library, identify metabolites produced by microorganism

Develop analytical methods for fermentation optimization and production quality control


Fermentation and Formulation

Develop / improve processDevelop / improve processScale-up for field trialsScale-up for field trials

Develop Develop farmer-farmer-friendly friendly formulationsformulations

Pilot Plant


Product Development – A Process

Characterization under Field Conditions

• Pest Spectrum• Application Rates• Formulation • Adjuvants• Crop Safety• Commercial Programs• Demonstration Plots

• Commercial Label• Registration Support• Product Positioning• Commercial Exposure


Product DevelopmentMicroorganism / Natural Product -

Challenges

• Less time from discovery to commercialization vs. conventional pesticide (US – 3 years vs. 7-10 years)

- Aggressive timeline to develop efficacy, formulation and registration packages and commercialization strategy

• Conventional pesticide experience – Does not always apply• Formulation technology – Unique challenges

- Live organism shelf life- Physical and biological compatibility with other products- Organic compliance for ingredients- Compatible with conventional application equipment


Product Registration Process - Global

Microorganism / Natural Product Technologies• Designed for conventional pesticide registration, few if any

pathways specific to microbial pest control technologies• Regulatory agencies have little to no microbial expertise • Lack of flexibility with regard to data requirements

Provisions for data waivers / provisional registrations• Strict efficacy requirements, protocols designed for

conventional pesticides, GEP requirement• No guidance docs / pre-submission / arbitration process• No priority for bio-control agents• EU - all of above + lack of member state harmonization


Product Registration Process (US-EPA)

Microorganism / Natural Product Technologies• Separate pathway vs. conventional pesticides

BPPD (Bio-pesticide Pollution / Prevention Division)• Microbial / bio-pesticide technical expertise• Registrant not competing with conventional chemistry for

review timeline = quicker review / market access• Requirements less than conventional pesticides however,

address product composition, risk and exposure information, not concerned with environmental fate

• Tiered data requirements – if trigger, then next tier, ensures that only minimum data sufficient to make sound regulatory decision will be required

Faster Timeline from Submission to Approval



EU REBECA Project

Regulation of Biological Control Agents (BCAs)Background:• EU Common Agricultural Policy (CAP) – demands for

pesticide use reduction schemes in Member States• BCAs are vital to meet commitment to sustainable use of

plant protection products, reduce conventional pesticide use• Current system (Directive 91/414/EEC) has been ineffective

in providing BCA alternatives to EU growers

>25 BCAs registered as PPP in US, only 6 in EU



EU REBECA Project

Regulation of Biological Control Agents (BCAs)Overall Objectives:• European funded Specific Support Action• Aim to accelerate BCA registration process; improve cost

effectiveness without compromising safety / health concerns• Engage key stakeholders for assessment and input

Industry, science, reg. authorities, policy and environment• Review current EU system; compare to countries which

have successfully registered BCAs • Development proposals for changes to EU system


Product Registration Process - GlobalEU REBECA Project

Regulation of Biological Control Agents (BCAs)Interim Assessments / Recommendations

• Long term (2-5 yrs): New EU system specific to BCAs- Tiered evaluation format- More balanced view of risk / benefit- BCA positive list; minimal requirements based on profile- Reduce / eliminate / harmonize fees

• Short term (0-2 yrs): Modify current system- > Acceptance in granting wavier requests / provisional reg.- Develop non-binding guidance documents- Set up EU bio-control panel of experts; guidance / education- Promote exchange between registrant / regulators

e.g., pre-submission meetings, help desks


Microorganism / Natural Product Technologies

Challenges to Grower Adoption• Growers - reluctant to change unless compelling reasons exist

Generally – adoption period exist for new technologies• Bio-control companies vs. multinational pesticide companies

Small; lack recognition, history with growers and consultants• Historically a negative perception of BCAs

Initial products lacked consistency, quality control, broad claimsUnregistered “plant strengtheners” / “bio-fertilizers lacked pest claims

• BCAs – “relatively” short registration timeline (US)Minimal performance data / exposure to researchers & growers

• Conventional testing protocols do not demonstrate full potentialStand alone treatments often under high, inoculated pest pressureFocus on pest control alone rather than quality and yield



Challenges to Grower AdoptionSteps to Improve Perception / Acceptance

Product testing phase• Participation in strategic research evaluation programs

Clearly defined objectives and expectations

Joint protocol development

Periodic trial visits during in-life phase

Pre-commercial phase• Large plot-demonstration programs

Selected growers – progressive “early adopters”

Closely monitored – application through harvest• Product training – grower workshops / seminars

Create awareness, proper positioning and use



Challenges to Grower AdoptionSteps to Improve Perception / Acceptance

Industry Alliances

Commitment to BCA Standards

Bio-Pesticide Industry Alliance (BPIA) - US

International Bio-control Manufacturing Assn (IBMA)


• Bacillus subtilis Strain QST 713• Discovered in an Organic Peach Orchard – California

Isolated from Soil• Unique – Patented Bacillus Strain

Distinguished by Previously Unknown Metabolites• US - EPA Registration – July 2000

Presidential Green Chemistry Award – 2003• World Technology Award for Environment - 2004• Now Registered Globally

Asia / Pacific Rim, Europe / Mideast, Latin America

First “Effective” Broad Spectrum Biological Fungicide


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1999 2000 2001 2002 2003 2004 2005 2006

Chile U.S. Mexico

N.Z.

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Israel

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Switz.

Turkey

Argen.

France

Italy

Korea

Ecuador

Columbia

Germany

UK

Spain

Greece

Australia

Peru

Thailand

Global Registration

Bold = Sales

Bacillus subtilis (Strain QST 713)


EU Annex 1 Inclusion

Bacillus subtilis strain QST 713, the active ingredient of biofungicide product Serenade® was voted for inclusion into Annex 1 of Directive 91/414/EEC at the EU Standing Committee on the Food Chain and Animal Health meeting on July 14, 2006.

Bacillus subtilis, Strain QST 713

Registration Milestone


Grapes Gray Mold (Botrytis cinerea)

Bananas Black Sigatoka (Mycosphaeraella fijiensis)

Tomato / Pepper Bacterial Leaf Spot (Xanthomonas spp.)

Early Blight (Alternaria solani)

P.Mildew (Leveillula taurica)

Cucurbits P.Mildew (Erysiphe / Sphaerotheca spp.)

Lettuce Leaf Drop (Sclerotinia spp.)

Pome Fruit Fire Blight (Erwinia amylovora)

Scab (Venturia spp.)

Mango Anthracnose

Beans White Mold (Sclerotinia sclerotiorum)

Onions/Garlic Neck Rot (Botrytis spp.)

Purple Blotch (Alternaria porri)

Major Global Crops / Diseases


• Formulations: (AS) Aqueous Suspension

(WP) Wettable Powder• Active Ingredients Spec. = Minimum 1 X 109 cfu / g• Organic Formulations (OMRI, IMO, BCS, JAS)• > Two Year Storage Stability • Excellent Suspensibility• Physical / Biological Tank Mix Compatibility with

standard fungicides



• B.s. spores – Colonize and Out-compete Pathogen• Fungicidal Metabolites – Lipopeptides

Present in Formulation / Produced by Colonizing B.s.

Destroy Pathogen Spore & Mycelium Membranes

Provide Barrier to Infection by Pathogen• Inducer of Systemic Acquired Resistance (SAR)• Optimal Use = Preventative Control Program• New / Unique Resistance Management Tool

Novel / Multiple Modes of ActionBacillus subtilis, Strain QST 713


Use in Integrated Programs with Conventional

Fungicides



　 0 Day 7 Day 13 Day 20 Day % Control

Untreated Water Water Water Water 0

Chemical Repeating

Fungicide Fungicide Fungicide Fungicide 98.8

Biological Repeating

Serenade Serenade Serenade Serenade 86.9

Chemical + Biological

Fungicide Serenade Fungicide Serenade 98.6

Chemical + Biological

Serenade Fungicide Serenade Fungicide 98.4

“Less-Chem” Program for Cucurbit Powdery Mildew (Sphaerotheca fuliginea)

****50% Reduction in Chemical Fungicide****

Chemical standard fungicide = Quinomethionate

Serenade (Bacillus subtilis, Strain QST 713

Use in Integrated Disease Control Program

Bacillus subtilis Strain QST 713 - Bananas

Black Sigatoka (Mycosphaerella fijiensisMycosphaerella fijiensis)

Requirement = 6 Functional Leaves at HarvestRequirement = 6 Functional Leaves at Harvest


Mycosphaerella fijiensisMycosphaerella fijiensis ControlControl

Mycosphaerella fijiensisMycosphaerella fijiensis ~100% inhibition~100% inhibition

Serenade 100 ppmSerenade 100 ppm


Black sigatoka - Bananas


Treatment

(rate / hectare)

Visible Streaks

On Leaves

Functional Leaves

At Harvest

B.subtilis 2 liters 3.9 a 7.8 a

B.subtilis + mancozeb

2 + 0.9 liters

3.9 a 7.4 a

Standard Program

Mancozeb – 1.8 liters

4.1 a 8.5 a

Untreated 3.4 b 4.9 b

Serenade (Bacillus subtilis, Strain QST 713) “Sustainable” Black Sigatoka (Mycosphaerella

fijiensis) Control Program in Bananas

Mindanao – The Philippines (March to August 2003)Mindanao – The Philippines (March to August 2003)


Product Positioning – Features• Effective “Non-Chemical” Option for Disease Control Programs• Broad Spectrum Disease Control – Fungal and Bacterial Pathogens• Tank mix and Rotation with Protectants / Systemics in Programs• MRL Management / Sustainable / Organic Production Tool • Resistance Management

Single Site Compounds – e.g., Strobilurin and Triazole Fungicides• Exempt From Tolerance / 0-Day PHI / No CODEX

- Late Season, Pre-Harvest Option / No Residues• Integrated Pest Management

Not toxic to Non-target Organisms -

Honeybees, Lady Beetles, Lacewings, Parasitic Wasps, and Earthworms• Safe to Workers / Environment


© AgraQuest, Inc. 2006Serenade, Sonata, Serenade MAX, Rhapsody, & Ballad Plus are registered trademarks of AgraQuest, Inc. Serenade MAX - EPA Reg. No. 69592-11; Serenade ASO - EPA Reg. No. 69592-12; Sonata - EPA Reg. No. 69592-13

donald w. edgecomb, phd director, international business development agraquest, inc. usa challenges...

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