QUALITY CONTROL OF VACCINE PRODUCTION

In vaccine production animals are used most extensively for quality control. Vaccine formulations include constituents such as living tissues, viruses and bacteria. Thus, since all vaccine batches are not the same, their content and effects must be tested regularly at selected stages of production to monitor safety, as required by federal regulations.  

Quality control is the most essential aspect of vaccine production. Human lives have been lost when quality control has not been sufficient. For example, thirteen children died in 1901 from tetanus, after receiving doses of diphtheria antitoxin which had been prepared from horse serum contaminated with the tetanus bacilli. In 1955,  79 cases of poliomyelitis occurred due to inadequate safety test procedures on polio vaccine; seven of the seventeen batches were later found to contain the living virus. The experimental animal is still the main indicator of desirably and undesirable activities of newly produced vaccine batches.

SAFETY TESTING

1         Test For  Specific Toxicity

Used to detect any incomplete inactivation of the vaccine product. Mice are injected with concentrated crude or purified product and observed for clinical symptoms.

2         Test For Freedom From Extraneous Micro- organisms

Used to detect inappropriate micro organisms such as viruses in the animal tissues used for production. Many can be detected by in vitro testing, but some still require animal testing. For human viral vaccines, intrapritoneal and intracerebral administration of vaccine to adult or newborn mice is used, with examination for clinical symptoms and/or specific antibodies in the blood serum. 

3         Test For Residual Live Virus  

Used to detect live viruses. Cell culture is used in many cases. Rabies virus causes clinical symptoms or death in mice when administered intracerebrally. 

4         Tumorigenicity Test   

Used to detect oncogenic properties in cells used for production of virus vaccines. Two groups of animals are used; the controls are injected subcutaneously  with specific tumour cells, and the others are injected with cells from the production culture. The two groups are then compared for the development of tumours. 

Safety test : Used to detect harmfulness. Multiple does of the product are administered to two animals of the intended species, with observation for development of symptoms during a specified period. 

5         Identity Test   

Used to verify that the product stimulates specific antibodies in an animal after immunization. Usually it is possible to use in vitro techniques. When it is necessary to use in vivo techniques, the specific antibodies must be demonstrated in the animal after immunization, either by challenging the animal with the virulent micro organism or by a serum - antibody assay. 

6         Test For Abnormal Toxicity   

Used to detect any unknown contamination of the vaccine from added chemicals. Either each of two guinea pigs gets five human doses, or each of 2 -5 mice gets one human dose, and animal is monitored for health and weight maintenance. 

7         Potency Testing  

Qualitative and quantitative assays are required to verify that the batch of vaccine induces protective immunity. In live, attenuated vaccine material, the numbers of live particles are determined by counting or by titration (an in vitro process). When a new seed strain is being used, a potency test is also conducted on animals.  

For inactivated vaccine, each batch is tested in vivo, and the animals are monitored to assure that the vaccine has the efficacy expected in relation to its contents and, for example, that it is not weakening over time.  

Vaccination to prevent disease is routine today for cattle, poultry, companion animals, and people. The knowledge gained from vaccination of animals helps improve human health, and vice versa. The typical human vaccine for tuberculosis, BCG, was derived from a related disease organism in cows. A new, experimental, genetically engineered TB vaccine uses isolated proteins from the BCG bacteria. Lacking live bacteria, this vaccine, if effective, would avoid risks and other shortcomings of the BCG vaccine. New developments are also underway in vaccines for malaria, chicken pox, whooping cough, and cancer.