"Lot Release and Laboratory Access" Training Course

The following is an overview of the 4 day training course.

It is designed to provide the trainees with an understanding of the lot release system for bacterial and viral vaccines. It includes the reasons for the lot release of vaccines, procedural requirements and guidelines, the protocol review process, the requirement for testing, the characteristics required for a testing laboratory, and the options available for external testing.

Protocol review and testing requirements as according to WHO summary protocols are discussed for the following specific vaccines: pertussis, tetanus toxoid, combination vaccines, Haemophilus b conjugate vaccines, BCG, measles, oral polio, Hepatitis b and influenza. Information on recent pneumococcal conjugate vaccines and meningococcal conjugate vaccines is also provided.

This course is broken down into 4 sections: Lot Release General, Lot Release of Bacterial Vaccines, Lot Release of Viral Vaccines, and Testing Laboratory/Assessment and Access. Click on the appropriate heading above or return to the home page.

Here are the subjects covered in this section ...

• Lot release of Biologics
• Definition of a Biologic
• Schedule D Drugs - Canada
• Differences between Biologics and Conventional Drugs
• Essential Features of a Regulatory System for Biologics/Vaccines
• Variation of Features According to Source/Supply of Biologic/Vaccine Product
• Model of a Regulatory Organization - Canada
• Functions of the Bureau of Biologics and Radiopharmaceutics - Canada
• Definition of Lot Release
• Factors to be Considered for Review/Sample Testing/ Approval
• Product Indication
• Well-Characterized Products
• Production Lot Failures
• Re-Processed Lots
• Inspection History
• Testing History
• Categorization of Products for Lot Release - Canada
• CBER Biologic Lot Release
• Essentials of a Lot Release System
• Legislation/Statutory
• Model Legislation - Canada
• Establishment of a Responsible Unit
• Preparation of Guidelines for Registration for Lot Release
• Preparation of Procedures for Receipt and Handling of Protocols and Samples
• Tombstone Data List
• Sample Requirements
• Product Profile
• Protocol Review
• Summary Protocol for Vaccines (WHO)
• Review of a National Control Authority Release Certificate
• Laboratory Testing (Optional)
• Targeted Testing
• Approval / Release Certificate
• Trend Analysis of Lot Release Data
• Summary of Lot Release Options for A Procuring Country
• Summary Check List for Lot Release

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Lot Release of Bacterial Vaccines

Here are the subjects covered in this section ...

• Lot Release of Bacterial Vaccines
• Bacterial Products Requiring Release - Canada
  • Category 2, Category 3
• Bacterial Products Released by BBR for WHO
• Pertussis Vaccine - General
• Pertussis Vaccine Specific Considerations
  • opacity, agglutinogen content, potency, toxicity
• WHO Summary Protocol for Pertussis Vaccine Production and Testing
• Final Lot Summary Information
• Production Control
• Control of Source Materials - strain
• Control of Single Harvests
  • general, bacterial purity, opacity, methods and dates of inactivation
• Final Bulk - General Information
  • identification, volume, opacity units (calculated from opacities of single harvests)
• Final Bulk - Release Tests and Specifications
  • agglutinogens 1, 2 and 3, preservative, adjuvant, pH, sterility, specific toxicity test (mouse weight gain test), other specific toxicity tests, potency test
• Sterility Test
• Specific Toxicity Test (Mouse Weight Gain Test)
• Intracerebral Mouse potency Test
• Mouse Potency Test Description
  • mice, immunization, bacterial culture injection (challenge), recording and calculation of results
• Requirements for Test Validity
• Potency Requirements
• Actual Potency Information to be included in Summary Protocol
  • strain, weight and sex of mice, date of immunization, LD50 in challenge dose, cfu in challenge dose, date of challenge, date of end of observation, results of one or more tests
  • reference vaccine - three dilutions, # of survivors / # challenged for each dilution, ED50 ml; - test vaccine - three dilutions, # of survivors / # challenged for each dilution, ED50 ml; - potency of test vaccine IU per single human dose; 95% interval (in %)
• Final Product testing and Specifications
  • identity, sterility, adjuvant, pH, preservative
• Manufacturer’s Certification
• National Control Authority Certification
• Tetanus Toxoid - General
• Tetanus Toxoid Specific Considerations
• Who Summary Protocol for Tetanus Adsorbed Vaccine Production and Testing
• Final Lot Summary Information
• Production Control
  • control of source material, single harvests, final bulk and final container
• Control of Source Materials
• Control of Single Harvests
• Control of Purified Toxoid Bulk
• Antigenic Purity
• Specific Toxicity
• Test of Irreversibility
• Final Bulk - General Information
• Final Bulk Tests and Specifications
  • sterility, residual free detoxifying agent, pH, potency
• Potency Test - Lethal or Paralytic Challenge
• Immunization - Mice or Guinea Pigs
• Challenge of Mice or Guinea Pigs
• Test Validity
• Potency requirements
• Alternate One - Dilution Potency Test
• Actual Potency Information to be included in Summary Protocol
• Final Product Tests and Specifications
  • identity, sterility, adjuvant, pH, preservative
• Manufacturer’s Certification
• National Control Authority Certification
• Bacterial Combination Vaccines
• Haemophilus influenzae Conjugate Polysaccharide Vaccines
• Characteristics of Haemophilus Conjugate Vaccines
• Summary Protocol for Hib conjugate Vaccines
• Control of the Purified Polysaccharide
• Control of Processed Polysaccharide
• Control of Carrier Protein
• Final Bulk Tests
  • residual reagents, unbound polysaccharide, polysaccharide content, polysaccharide/protein ratio, molecular size, absence of blood group substances, sterility stability
• Final Product Tests
• Summary of Release Specifications for Hib Conjugate Vaccines
• Pneumococcal Conjugate vaccines
• Meningococcal Conjugate Vaccines
• BCG Vaccines

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Lot Release of Viral Vaccines

Here are the subjects covered in this section ...

• Lot Release of Viral Vaccines
• Oral Poliomyelitis Vaccine (OPV) - General
• OPV - Specific Considerations
• WHO Summary protocol for Oral Poliomyelitis Vaccine
• Summary information
• Control of source materials
• Cell seed
• Manufacturer’s working cell bank (MWCB)
• Virus strains
• Test for consistency of virus characteristics
• Control of vaccine production
• Control of cell cultures
• Cell cultures for vaccine production
• Control of single harvests
• Control of the bulk suspension
• Final bulk
• Control tests on final product
  • identity test, tests for bacteria and fungi, virus titration, stability
• Measles Vaccine
• Influenza Vaccine
• Hepatitis b Vaccine

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Testing Laboratory/Assessment and Access

Here are the subjects covered in this section ...

• Requirement to Test Vaccines
• Necessary Characteristics of a Vaccine Testing Laboratory
• Functions of a National Control Laboratory
• Legal Basis - National Control Laboratory
• Quality Systems Manual for a Quality Control Laboratory
• Good Laboratory Practice (GLP)
• Organizational Structure
• Personnel
• Premises
• Equipment
• Standard Operating Procedures
• Reagents
• Reference Material
• Receipt and Handling of Samples and Documents
• Test Methods
• Test Validation
• Documentation/Records
• Training Program
• Quality Assurance
• Audit Programme
• Animal Use
• Standardization in Vaccine Potency Testing
• Participation in Proficiency Testing
• Functions requiring Laboratory Access
• Factors complicating establishment of a National Control Laboratory
• Need to Contract Outside Laboratory
• Characteristics of an Acceptable Contract Laboratory
• Development of a List of Qualified Laboratories
• Contract Process
• Audit of a Contract Laboratory by NRA

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