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
Innovative natural product solutions for 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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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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Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
Automated, Miniaturized, In-vivo Screening
Insects, Mites, Nematodes
Plant Pathogens
Robotic station for dispensing sample, eggs,
nematodes and spores
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
Product Registration Process - Global
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
Innovative natural product solutions for pest management.
Product Registration Process - Global
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
Microorganism / Natural Product Technologies
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
Innovative natural product solutions for pest management.
Microorganism / Natural Product Technologies
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)
Innovative natural product solutions for pest management.
• 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
Innovative natural product solutions for pest management.
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Chile U.S. Mexico
N.Z.
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Israel
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France
Italy
Korea
Ecuador
Columbia
Germany
UK
Spain
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Australia
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Global Registration
Bold = Sales
Bacillus subtilis (Strain QST 713)
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
• 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
Bacillus subtilis, Strain QST 713
Innovative natural product solutions for pest management.
• 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
Innovative natural product solutions for pest management.
Use in Integrated Programs with Conventional
Fungicides
Bacillus subtilis, Strain QST 713
Innovative natural product solutions for pest management.
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
Innovative natural product solutions for pest management.
Mycosphaerella fijiensisMycosphaerella fijiensis ControlControl
Mycosphaerella fijiensisMycosphaerella fijiensis ~100% inhibition~100% inhibition
Serenade 100 ppmSerenade 100 ppm
Bacillus subtilis, Strain QST 713
Black sigatoka - Bananas
Innovative natural product solutions for pest management.
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)
Innovative natural product solutions for pest management.
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
Bacillus subtilis, Strain QST 713