Toxicity testing, vaccines

Unlike the regulatory reproductive toxicity testing of conventional medicines, the developmental toxicity testing of vaccines may be performed in a single species, provided that the chosen species is relevant for the vaccine in question. 

Differences in preclinical requirements for developmental toxicity testing between vaccines and medicinal agents... 

The ICH S5 guidelines (13) are now applied worldwide for the reproductive toxicity testing of new medicines, but are not applicable to vaccines. The differences between the testing requirements of vaccines and other pharmaceuticals are outlined in Table 1. 

Verdier F, Barrow PC, Bruge J (2003) Reproductive toxicity testing of vaccines. Toxicology 185 213-219... 

Barrow P (2011) Developmental and reproductive toxicity testing of vaccines. J Pharmacol Toxicol Methods 65(2) 58-63. doi 10.1016/j. vascn.2011.12.001... 

Newmann MJ, Wu JY, Coughlin RT, Murphy CL, Seals JR, Wyand, MS, Kensil CR (1992) Immunogenicity and toxicity testing of an experimental HIV-1 vaccine in non human primates. AIDS Res Human Retroviruses 8 1413-1418... 

Whooping-cough (Pertussis) (aceiiuiar)t Cultures of Bord. pertussis 1 Harvest 2 Extraction and blending of cell components As for whole-cell whooping-cough vaccine Weight gain test in mice to exclude excess toxicity... 

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)... 

The effect of alum as adjuvant was also tested in the liposphere-vaccine formulation. In the presence of lipid A, enhanced immune response is obtained even in the absence of alum. This observation is very important because there is increasing concern about the toxic side effects of alum in the long term. Research has suggested a link between aluminum and diseases of the brain, including Alzheimer s disease. 

Biotechnology-derived vaccines that do not induce an immune response in lower species may have to be tested in a primate species, such as the cynomolgus monkey. A study design in the monkey has been suggested for this purpose (6), based on a proposed developmental toxicity study design for monoclonal antibodies (7). 

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