Laboratory animals in vaccine production and control

1: Introduction..- 2: Animal Experimentation and the Development of Vaccines: A Brief Historical Outline.- 1. The Ancient World.- 2. The 19Th Century.- 2.1. Claude Bernard.- 2.2. Louis Pasteur and Robert Koch.- 2.3. The beginnings of vaccine development.- 2.4. The rabies vaccine.- 3. The 20th Century.- 4. References.- 3: The Historical Role of Animal Experiments in the Development of Diphtheria Prophylaxis.- 1. Introduction.- 2. Clinico-Pathological Research.- 3. Diphtheria Prophylaxis.- 3.1. Development of the diphtheria antiserum.- 3.2. Toxin-antitoxin mixtures.- 3.3. Diphtheria toxoid.- 4. Quality Control.- 4.1. Historical development.- 4.2. The French and German methods.- 4.3. The influence of statistics.- 4.4. The “Kollektivversuch” or “group test”.- 5. Recent Developments.- 6. References.- 4: Vaccine Development and Production.- 1. Development.- 2. Production.- 2.1. Bacterial vaccines.- 2.2. Virus vaccines.- 3. Vaccine Production in the Netherlands.- 4. Quality Control.- 4.1. Safety evaluation.- 4.2. Potency testing.- 5. Guidelines.- 6. Good Manufacturing Practice (GMP).- 7. References.- 5: Experimental Animals and Animal Experiments..- 1. Extent of the Research.- 2. Purpose of the Research.- 2.1. production.- 2.2. Quality control.- 2.2.1. Safety evaluation.- 2.2.2. Potency testing.- 3. Relevance of the Tests.- 4. Distress.- 5. References.- 6: Animal Experimentation and its Shortcomings.- 1. Introduction.- 2. Limitations of Animal Experimentation.- 2.1. Moral aspects.- 2.2. Economic aspects.- 2.3. Zootechnical aspects.- 2.4. Safety aspects.- 2.5. Practical aspects.- 3. References.- 7: Alternatives to and in Animal Experimentation.- 1. Definition.- 2. History.- 3. Possibilities.- 4. Approach.- 5. References.- 8: Opportunities for Replacement, Reduction or Refinement: Human Bacterial Vaccines.- 1. Introduction.- 2. Bcg Vaccine.- 2.1. Test for absence of virulent mycobacteria.- 2.2. Jensen test (skin reactivity test).- 2.3. Test for abnormal toxicity.- 3. Cholera Vaccine.- 3.1. Identity test.- 3.2. Test for specific toxicity.- 3.4. Potency test.- 3.5. Test for abnormal toxicity.- 4. Diphtheria Vaccine.- 4.1. Identity test.- 4.2. Test for specific toxicity.- 4.3. Potency test.- 4.3.1. Alternative methods.- 4.3.2. Reduction of group size.- 4.3.3. Summary of the opportunities for reducing the number of animals required for the potency testing of the diphtheria component in vaccines.- 4.4. Abnormal toxicity test.- 5. Pertussis Vaccine.- 5.1. Specific-toxicity test.- 5.2. Potency test.- 5.3. Test for endotoxins.- 5.4. Test for abnormal toxicity.- 5.5. Future.- 6. Tetanus Vaccine.- 6.1. Identity test.- 6.2. Test for specific toxicity.- 6.3. Potency test.- 6.3.1. Reduction of group size.- 6.4. Test for abnormal toxicity.- 7. Typhoid Vaccine.- 7.1. Test for endotoxins.- 7.2. Potency test.- 7.3. Test for abnormal/specific toxicity.- 8. Summary.- 9. References.- 9: Opportunities for Replacement, Reduction and Refinement: Human Viral Vaccines.- 1. Introduction.- 2. Tests for Extraneous Microorganisms.- 3. Mumps Vaccine.- 4. Hepatitis B Vaccine.- 4.1. Test for freedom from live hepatitis virus.- 4.2. Potency test.- 5. Influenza Vaccine.- 5.1. Potency test.- 5.2. Abnormal-toxicity test.- 6. Measles Vaccine.- 6.1. Tests for extraneous agents.- 6.1.1. Test for Mycobacterium tuberculosis.- 6.1.2. Test for extraneous viruses.- 6.2. Abnormal-toxicity test.- 7. Poliomyelitis Vaccine.- 7.A. Inactivated poliomyelitis vaccine.- 7.A.1. Production.- 7.A.2. Test for residual live virus.- 7.A.3. Tests for extraneous agents.- 7.A.3.1. Test for Mycobacterium tuberculosis.- 7.A.3.2. Test for extraneous viruses.- 7.A.4. Tumourigenicity test.- 7.A.5. Potency test.- 7.A.6. Test for abnormal toxicity.- 7.B. Live, oral poliomyelitis vaccine.- 7.B.1. Test for extraneous agents.- 7.B.2. Test for neurovirulence.- 7.B.3. Test for abnormal toxicity.- 8. Rabies Vaccine.- 8.1. Production.- 8.2. Test for residual live virus.- 8.3. Tests for extraneous microorganisms.- 8.3.1. Test for Mycobacterium tuberculosis.- 8.3.2. Tests for extraneous viruses.- 8.3.2.1. In dogs.- 8.3.2.2. In mice.- 8.4. Potency test.- 8.5. Test for abnormal toxicity.- 9. Rubella Vaccine.- 9.1. Production.- 9.2. Tests for extraneous agents.- 9.3. Abnormal-toxicity test.- 10. Summary.- 11. References.- 10: Opportunities for Replacement, Reduction or Refinement: Poultry Vaccines.- 1. Introduction.- 2. Live, Attenuated Poultry Vaccines.- 2.1. Tests for contamination with extraneous agents.- 2.1.1. Test for extraneous agents in chicks.- 2.1.2. Test for contamination with avian encephalomyelitis virus in chick embryos or day-old chicks.- 2.2. Safety evaluation.- 2.3. Titration of the attenuated avian encephalomyelitis vaccine virus.- 2.4. Titration of the attenuated fowlpox vaccine virus.- 2.5. General.- 3. Inactivated Poultry Vaccines.- 3.1. Testing the potency of two or more vaccines in a single experiment.- 3.2. Combining the potency test and the safety test.- 3.3. Sequential testing.- 4. Summary.- 5. References.- 11: Opportunities for Replacement, Reduction or Refinement: Veterinary Vaccines For Mammals..- 1. Introduction.- 2. Safety Evaluation (general).- 3. Vaccines for Dogs.- 3.1. Potency test on inactivated vaccines.- 3.1.1. Leptospirosis vaccine.- 3.1.2. Canine parvovirus, hepatitis (HCC) and distemper vaccines.- 3.1.3. Rabies vaccine.- 3.2. Potency tests on live, attenuated vaccines.- 3.3. Test for freedom from contaminating rabies virus.- 4. Vaccines for Horses.- 4.1. Potency test on influenza vaccine.- 4.2. Potency test on tetanus vaccine.- 5. Vaccines for Cattle.- 5.1. Potency test on Brucella abortus vaccine.- 5.2. Potency test on footh-and-mouth disease vaccine.- 5.3. Safety test on foot-and-mouth disease vaccine.- 5.4. Potency test on E. coli vaccine.- 6. Vaccines for Pigs.- 6.1. Potency test on clostridial vaccines.- 6.2. Potency test on swine influenza vaccine.- 6.3. Potency test on vaccines against atrophic rhinitis, E. coli infection and swine erysipelas.- 7. Summary.- 7.1. Dogs.- 7.2. Cat.- 7.3. Horse.- 7.4. Cattle.- 7.5. Pig.- 8. References.- 12: Replacement, Reduction or Refinement: An Indirect Approach.- 1. Introduction.- 2. Harmonizing the Guidelines.- 3. Reviewing the Need for Re-Testing by the National Control Authorities.- 4. Combining Several Tests.- 5. Using Inbred Animal Strains.- 6. Increasing the Size of Vaccine Batches.- 7. Relaxing The Body Weight Specifications.- 8. Re-Using Animals.- 9. Using Specific Pathogen-Free (Spf) Animals.- 10. Reducing or Suppressing Pain.- 11. References.- 13: Future Prospects.- 1. Introduction.- 2. Vaccine Production.- 2.1. Subunit vaccines.- 2.2. Synthetic peptide vaccines.- 2.3. Idiotype vaccines.- 3. Vaccine Control.- 3.1. Safety evaluation.- 3.2. Potency testing.- 4. References.- 14: Final Comments and Recommendations.