Vaccine production toxicity testing

The quality control of both diphtheria and tetanus vaccines requires that the products are tested for the presence of free toxin, that is for specific toxicity due to inadequate detoxification with formalin, at the final-product stage. By this stage, however, the toxoid concentrates used in the preparation of the vaccines have been much diluted and, as the volume ofvaccine that can be inoculated into the test animals (guinea-pigs)... 

Clinical trials, also known as clinical studies, test potential treatments in human volunteers to see whether they should be approved for wider use in the general population. A treatment could be a drug, medical device, or biologic, such as a vaccine, blood product, or gene therapy. Potential treatments, however, must be studied in laboratory animals first to determine potential toxicity before they can be tried in people. Treatments having acceptable safety profiles and showing the most promise are then moved into clinical trials. 

If, for example, reproductive toxicity studies are required for vaccines, the trial duration and details of clinical and pathological investigations of standard trial procedures may be adopted, whereas the dosing must be chosen individually for each product to be tested and should be justified in the study protocol. Most likely it will be similar to the clinical use of the vaccine. 

Vaccine excipients (adjuvants and other substances used in the formulation) are treated in the same way as chemical substances. If new substances are introduced, a full safety assessment is required. It may be necessary to assess their toxic potential separately from the vaccine, since the vaccine formulation may interfere with a proper testing. In addition the normal pharmacological and safety tests for vaccines must be performed with the final, formulated product. 

The development of veterinary products for cattle, pigs, sheep, poultry and other food producing animals also includes residue testing of all new pharmaceutical products, including adjuvants or other excipients in vaccines. Residue safety studies address the potential risk to humans due to the consumption of food from treated animals. Accordingly, the test substances in these toxicity studies are applied orally. Residue depletion studies (pharmacokinetic studies) in the target species must be carried out to define the occurence, concentration and elimination of the substance and its metabolites in edible tissues, milk and eggs. 

Figure 10.2-1 Maximizing the benefit-to-risk in vaccine development. No vaccine can be administered to humans without solid data showing safety. Product development and safety testing for these products relies very heavily on animal studies which are relied upon to predict both efficacy and safety. Toxicity assessments for vaccines are challenging because, in general, vaccines trigger complex immune reactions.There must be a balance between desired immunogenicity and unwanted adverse side effects.

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