Veterinary Biological Regulatory Requirements in a Global Market

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Lecture No. 16 - April 8th, 2004 Veterinary
Biological Regulatory Requirements in a Global
Market Robby Robinson
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Veterinary Biological Regulatory Requirements in
a Global Market

• Dr. Robby Robinson
• Pfizer Global Manufacturing
• Lincoln Operations

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US Regulatory Framework

• Virus-Serum-Toxin (VST) Act 1913 Prevented the
  importation and interstate shipment of biological
  products that were worthless, contaminated,
  dangerous or harmful
• VST Amendment, Food Security Act 1985
• Expanded to include all products shipped
  into, within and from the United States

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US Regulatory Framework

• USDA United States
  Department of Agriculture
• APHIS Animal and Plant Health
  Inspection Service
• Center for Veterinary Biologics Ames, IO
• Title 9 Code of Federal Regulation
• Sections 101 to
  118 (Primarily 113)

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CVB Mission

• Ensure biologics are free of disease producing
  agents, especially foreign animal diseases.
• Develop appropriate standards and procedures for
  product release.
• Issue licenses and permits
• Monitor and inspect products and facilities.
• Control field tests and release of veterinary
  biologics.

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Regulatory Requirements

• Pure Free of contaminating agents
• Safe In the target species and other
  species
• Potent Formulated and tested to ensure
  potency
• 
  exceeds minimum Outline requirements
• 
  Through assigned expiry dating
• Effective When used in accordance with label
  
• 
  directions

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US Veterinary Biologicals

• Licensing
• Inspection
• Check Testing
• Countries do not always have all three

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USDA Regulatory Framework
USDA Veterinary Services Administrator
Center for Veterinary Biologics Directors Dr.
Rick Hill and Dr. Steve Karli
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CVBPolicy, Evaluation Licensing

• Policy / rule making
• Issues establishment, product licenses
• Issues permits Importation,
  exportation, etc
• Reviews protocols/data/labeling/
• disputed marketing claims/production methods
• Interfaces on Agent BioSecurity Reference
  Management

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CVBPolicy, Evaluation Licensing

• Confirmatory testing Master Seeds
• 
  Pre-Licensing serials
• 
  Final product
• Test evaluation and approval
• Vaccinovigilance testing
• US International references
• Reagent / standard supply
• Standard Assay Methods (SAMs)

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CVBPolicy, Evaluation Licensing

• Facility inspections
• Serial release
• Enforcement
• Vaccinovigilance Quality Assurance
• Assists PEL with BioSecurity Issues

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Efficacy

• Host animal immunogenicity
• Controlled vaccination/challenge study
• Statistical significance required
• Prevention vs. aid in prevention claim
• Interference
• Maternal antibody override
• When minimum vaccination age indicates
• Required overages
• 0.7 log for MLV 2X for KV
• Duration of immunity
• Significant diseases
• Added marketing claim

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Safety

• 2x-10X host animal safety (GLP)
• Lab animal (mice, guinea pig) safety
• Lack of reversion to virulence
• Shed and spread
• Reproductive safety or contraindication
• Safety under field usage conditions

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References

• Espeseth, D., Part 4. Procedures and Norms in
  the United States, Veterinary Vaccinology, 1997,
  Elsevier, Chapter 19, pp. 680-686
• Center for Veterinary Biologics
• http//www.aphis.usda.gov/vs/cvb
• USDA/APHIS
• http//www.aphis.usda.gov

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Europe

• Formation of the European Union
• Harmonization of Veterinary Medical Products
  1965
• Extended to Immunological Veterinary Medical
  Products (IVMP) 1990
• Directives, Guidelines, European Pharmacopoeia

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Directives

• Form the regulatory framework
• Difficult to revise or appeal
• General in nature
• Major Directives
• 81/851 Basic Veterinary Medicinal
  Products
• 90/677 Extending 81/851 to IVMPs
• 92/19 Clinical Standards/testing IMVPs
• 91/412 Principles of GMP

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Guidelines

• Facilitate registration
• Method to communicate ideas
• Set standards for QC, reviews, etc.
• interpretation shall be flexible, pragmatic,
  realistic
• Major Guidelines
• 111/3181/91 Production and control of
  inactivated mammalian vaccines
• 111/3182/91 Production and control of
  inactivated mammalian vaccines
• Various species specific guidelines

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European Pharmacopoeia

• Legally binding standards, including minimum
  requirements for registration and testing
• Apply only to products for which there are
  monographs

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USDA vs. EU Requirements

• EU GMP vs. US testing and inspection
• Good Laboratory Practice (GLP)
• Good Clinical Practice (GCP)
• Efficacy
• Safety
• Product testing methods

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Regulatory Control Systems

• 
  ________Inspection________
• Quality
  Check
• Concern Registration
  ___GMP___ ___Testing____
• Design
  -
• Man -
  
• Method
  
• Machine/Facility -
  
• Material
  
• Measure -
  
  
• Mother Nature -
  
• Performance
  -

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Harmonization Efforts

• GATT Uruguay Round
• No non-technical barriers to trade
• International appeal process
• Mutual Recognition Agreements (MRAs)
  Manufacturing (GMP vs USDA) Facility Inspection
• VICH

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Risk Assessment

• Originally US and others had
• zero-risk policy
• Most important concerns Exotic agents,
  protection of livestock
• Not possible with GATT
• Risk assessment now used instead
• Based on Nuclear/Chemical industry
  Probability Analysis Summary Information
  Format (SIF)

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VICH Harmonization

• International Cooperation on Harmonization of
  Technical Requirements for Registration of
  Veterinary Medicinal Products
• A trilateral (EU-Japan-USA) program to harmonize
  technical requirements for veterinary product
  registration
• Launched in April, 1996
• Observers Australia, New Zealand, Canada (S.
  America)

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VICH Steering Committee

• Government EU (EC, EMEA, US (FDA, USDA),
• 
  Japan (JMAFF)
• Trade Groups FEDESA, AHI, JVBP
• Observers Australia, NZ, Canada
• 
  South America (Requested)
• Chair OIE Office international des
  Epizooties
• Secretariat IFAH International Federation of
• 
  Animal Health

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VICH Objectives

• Provide a forum for a constructive dialogue
  between authorities and industry to catalyze
  harmonization
• Identify areas where modification could lead to
  more economical use of human, animal and material
  resources
• Maintain transparency to public
• Progress is
  painstakingly slow, but real

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Industry Needs

• Free movement of products
• Philosophical compatibility in approaches
• A common understanding of Quality Assurance while
  still permitting national flexibility
• Agreement on basic standards that will accelerate
  mutual recognition and eventual harmonization

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GMP Purity Assurance Standards
Final Product Extran Test
Probability of Contamination
Bacterial Global Standard?
Viral Global Standard?