The Business of Disease Prevention

Huw Hughes and Paul Wood

Veterinary Medicine Research and Development

Pfizer Animal Health

Introduction

Technologies & Delivery

Manufacturing

Challenges

Endnote

Introduction to Animal Biologicals

Animal Health Biologicals

• Need to answer different customer needs

– Basic classes fall into classification by animal husbandry category

– Pets, sport animals

– Large animal production (cattle)

Complex

Wide Client – Large animal production (cattle)

– Large animal production (swine)

– Poultry

– “minor species” Goats, sheep, exotics

• Huge variation in Price to consumer varying from 0.02 cents per dose to 1000 $ per dose

• Huge variation in technologies and platforms.

Wide Client

Base

Global Animal Health Sales

Global sales in 2009 were 18.6 BN USD

FarEast

N.America

W Europe

E Europe ROW

MFA

Biologicals

Anti-infectives

Parasiticides

Other Pharmas

Biologicals represent 25% of global sales

Veterinary Vaccine Cost

10

100

1000

10000Melanoma

Kennel cough

Lyme WNV

Neospora

per dose

0.001

0.01

0.1

1

10

1 100 10000 1000000

Cattle Respiratory

Feline line

Canine lineBTV

Mareks

Neospora

Relative No of doses sold

US$ Cost

Introduction

Technologies & Delivery

Manufacturing

Challenges

Endnote

Living up to the Promise

Biotechnology applications in Animal Health have yielded over 100 Biotechnology applications in Animal Health have yielded over 100 new products and servicesnew products and services

•• DiagnosticsDiagnostics

•• Gene markers for genetic selectionGene markers for genetic selection

•• VaccinesVaccines•• VaccinesVaccines

•• BiomarkersBiomarkers

•• BiopharmaceuticalsBiopharmaceuticals

TECHNOLOGY APPLICATION HOST SPECIES GEOGRAPHY

Canarypox vector Distemper virus HA and F Dog, Ferret Americas

Canarypox vector Rabies G Cat

Canarypox vector FeLV Env, Gag/pro cat EMEA, N. America

Canarypox vector Equine Flu HA Horse EMEA (Australia)

Canarypox vector WNV prM-E Horse N America

Fowlpox vector H5 avian flu poultry S. America Asia

HVT Vector Newcastle Disease poultry N America

HVT Vector Bursal Disease poultry Global

Virus Deletion/truncation IBR Killed virus Cattle Europe

Virus Deletion/truncation IBR MLV Cattle Europe

Virus Deletion/truncation Aujesky's Pigs N America

Licensed Novel Technologies

Virus Deletion/truncation Aujesky's Pigs N America

DNA Infectious haematopoietic necrosis virus Salmon N. America

DNA WNV Horse N America

DNA Melanoma Dog N America

Peptide/protein Interferon omega Dog/Cat Europe

Peptide/protein GnRH Pigs Global

Peptide/protein Baculo PCV2 Pigs N America

Plant NDV Poulltry N America

Peptide/protein Lyme Disease (OSP A) Dog N America

Fowlpox vector Avian Encephalomyelitis poultry N America

HVT Vector Mareks Disease poultry N America

Fowlpox vector Laryngotracheitis poultry N America

Peptide/protein IFN-Omega cats Europe

Chimeric viruses PCV1/2 Pigs N America

Vaccinia vector Rabies G Wildllife EMEA, N. America

Fowlpox vector Newcastle Disease poultry N America

Peptide/protein GnRH (immunotherapeutic for BPH) canine N America

Subunit technology Neonatal scours - E coli pili Pigs Global

Adjuvant technologies disease prevention, immunotherapeutics All Global

Biopharma / Nomenclature

• For AH:

– Biological = vaccines

– Biopharmaceuticals = protein-based therapeutics

• For HH:

– Biological = large molecule (therapeutic or vaccine)

– 3 main targets: Growth enhancement, cancer and immunomodulation

Biopharmaceuticals

– 3 main targets: Growth enhancement, cancer and immunomodulation

• 3 types of products at this time with several specific characteristics

– Anti-peptide vaccine (hormone RF)

– Bioactive peptides (immunomodulator or antiinfective)

– Monoclonal antibodies (anti-cancer/immunomodulator/anti-infective)

Diverse regulatory environment

• US: FDA for growth enhancement but the antiinfectives/immunomodulators could be linked to a disease and go through USDA

• EU: EMEA registration as vaccine (including growth enhancement) or drug

Substitute for endogenous proteinsSmall molecules often cannot replace naturally occurring proteins

Expand druggable targetsBiologics can interact with targets not amenable to small molecules

• Less toxic (no residues)

• Easier to predict distribution,

metabolism and elimination

• Suitable for EU market that is

reluctant to growth inducing drugs

Upsides vs. Downsides

Provide selective targetingBiologics will always be more selective for their targets reducing side effects

amenable to small molecules resulting in new mechanisms of action (e.g., protein-protein interactions)

• Faster to POC

• Faster development cycles

• Reduces expensive medicinal

chemistry

• Reduces expensive HTS

• No erosion of market by generics to date

Immuno-privileged sites

Extracellular targets

Routes of administration

Supply chain issues

–

Rectal Suppository

Control Release Device

DNA Vaccination

Vaccine Delivery Technologies

Viral/Bacterial Vectors

Biodegradable Implant

Intranasal puffer

Transgenic Plants

Transdermal Patchbait

Introduction

Technologies & Delivery

Manufacturing

Challenges

Endnote

The Animal Health Global Factory

Technologies under the same roof:

• Bacterial fermentation

• Roller bottle

• Cell factory

• Disposables and Hard Pipe reactors

• Egg culture• Egg culture

• Live animals

Inspected by:

• USDA, EMEA/VMD, FDA, JMAFFD..

Over 40 products released

• Final product release

• For further manufacturing

Manufacturing Technologies

ANAPLASMOSISNecrotic hepatitisof rabbits

IBDVCOCCIDIOSIS

NDVIBFLU

Disposable Technology

Hard pipe vs. PlasticHard pipe vs. Plastic

•• Capital cost vs. consumable costCapital cost vs. consumable cost–– Dedicated facility to make plastic worth whileDedicated facility to make plastic worth while

•• Running costsRunning costs–– Lower running costsLower running costs

–– Environmental balance plastic disposal vs. CIP fluidsEnvironmental balance plastic disposal vs. CIP fluids–– Environmental balance plastic disposal vs. CIP fluidsEnvironmental balance plastic disposal vs. CIP fluids

•• Down timeDown time–– TroubleshootingTroubleshooting

–– ReRe--validation/qualificationvalidation/qualification

–– Media runsMedia runs

–– D..D..

•• QualityQuality–– Need consistencyNeed consistency

–– Customers need to be aware of/be integrated into change control Customers need to be aware of/be integrated into change control processes of plastic suppliersprocesses of plastic suppliers

Disposable Technologies

Cells

• Non-adherent

Cell scale-up

• Wave bags

• SUBs (250L)

Virus production

• SUBs (1000L)

Controller

• Finesse• Finesse

Probes

• Finesse Optical

In Addition6

The Challenges of ScaleThe Challenges of Scale Cost constraints are critical

• Scale up should not compromise costs and yields.

• Inactivation often a bottleneck

• DSP is expensive, time consuming and also can be a bottleneck.

Safety, particularly for pets and sport horses is critical

bottleneck.

• Veterinary vaccines typically have little or no DSP

vs.

Animal Health Human Health

Introduction

Technologies & Delivery

Manufacturing

Challenges

Endnote

Case Study: Mission Impossible

Active ingredient X

• For use in pets, production animals and wildlife

• COGs of >0.10 USD per dose

• Live presentation– Stable expression over 10 passages

– Must pass shed/spread criteria

• Formulations– Lyophilized for companion animals

– Bait for wildlife

– RTU for Production animals

• Refrigerator storage OK, RT preferred

• Stable for 12 (24 h preferred) hours at 25 to 30°C in bait, 24 months at 4°C

Multiple Regulatory Pathways

Animal Health Biological Regulation

FDA

• US Biotherapeutics

USDA/CFIA

• N. American Biologicals

JMAFF

• Japan

Autogenous Vaccines

• USDA (9CFR)

Conditional license

• USDA, EMEA

Strain swap

• Provisions in 9CFR and EMEA• Japan

EMEA

• Europe

AQIS

• Australia

Other

• China, Latin America

EMEA

Exceptional MA

• EMEA

• Flu, FMD, BTV

Provisional MA

• EMEA

Biotherapeutics

• USDA, FDA and/or EMEA

MUMS

• Minor use, minor species

Examples of Speed-to-Market

Industry uses a conditional license or provisional market authorization to be First to market

• Provisional Market Authorizations in EU have included vaccines protecting against PMWS in pigs through sow vaccination.

• Allows vaccine to be available to producers in multiple countries without the rigours of a full MAwithout the rigours of a full MA

• Conditional licenses in the US are granted to companies with new disease entities (or new field strains) and are renewable after one year, until a full license is granted

– ‘Reasonable expectation of efficacy’

Industry works with regulators to answer specific and urgent needs in the field

• Vaccine stocks for government use– Q Fever, CSF, FMDD

• Exceptional MA– BTV, FMD & Influenza

• Strain updates– Influenza – swine and equine.

Executed in similar ways by both the USDA and EMEA

Timeline for an Emergency

pH1N1 Influenza vaccine for pigs

Outbreak

USDA Policy established

Strain available to industry Strain available to industry from USDA

MS, WS production

Efficacy serial production

Prelicense serials (field trials waived due to the use of existing technologies and formulations)

Approval November 2009

4

Months

Introduction

Technologies & Delivery

Manufacturing

Challenges

Endnote

Basic Tenets of Animal Health Vaccines

Superior Efficacy

• Stronger claims– Prevention/reduction

– Infection/disease

• Higher proportion of protected animals

• Less severe clinical signs

• Reduced shedding

• Cross-protection

Price

• COGs low

• Production improvements

• Competitive pricing

Convenience

• Combination vaccines

• Single dose• Cross-protection

• Protection in the face of MDA

• Minimum age

• Longer DOI

• Onset of immunity

Superior Safety

• Fewer smaller or no reaction

• Safe in pregnant/lactating animals

• Safe in small breeds

• Vaccination frequency

• Mass vaccination

• Needle free injection

• Longer DOI

• Route(s)

• Husbandry compatible

Other

• State of the art – “High Tech”

ENDNOTE

The Animal Health industry is a complex environment in terms of client base, product mix and technologies.

Biotechnology applications have been successfully integrated into product offerings, with over 100 products registered and launched in the field. These new vaccines have been successfully integrated into combinations with conventional vaccines

Production methods and registration pathways reflect the complexity of the business. The modern Animal Health factory is extremely versatile, with new manufacturing technologies being optimized to ensure maximum flexibility and speed especially when addressing emergency vaccine requests.

Vaccines still need to be safe, efficacious and answer client needs. Technology by itself does not sell products

THANKS

Pfizer Animal Health

Jay Thompson

Tedd Childers

Hans Draayer

Jim FreemanJim Freeman