Toxicity studies costs

The establishment of TTC is based on the analysis of the toxicological and stmctural data of a broad range of different substances. It might be used as a substitute for substance-specific information in situations where there are limited or no information on the toxicity of a given substance to which the human exposure is so low that undertaking toxicity studies is considered not warranted, because of the costs incurred in the use of animals, manpower, and laboratory resources as well as for animal welfare reasons. 

Toxicity studies are costly in terms of both animals and resources, as indicated in Table 3.7. For a product developed for chronic oral therapy, approximately 4000 rats, 1300 mice, 100 rabbits, 50 guinea pigs and 160 dogs, a total of over 5000 animals, is used. If the foetuses and offspring from the reproductive toxicity studies are... 

Table 3.7 Toxicity studies - approximate cost, test material requirement and reporting times...

Latif, M. and Zach, A. (2000) Toxicity studies of treated residual wastes in Austria using different types of conventional assays and cost-effective microbiotests, in G. Persoone, C. Janssen and W.M. De Coen (eds.), New Microbiotests for Routine Toxicity Screening and Biomonitoring, Kluwer Academic/Plenum Publishers, New York, pp. 367-383. 

Toxicity studies are undoubtedly expensive in both financial and resource terms. Part of the cost is related to the number of animals and the extent of clinical, necropsy, and histopathologic investigations required. Considering the inherent variability of biological systems, there must always be a balance between the number of animals theoretically required to detect all effects (from the weakest upward) and the number required to detect significant toxic effects. In a well-conducted study that goes according to plan, it is possible to use fewer animals. 

This permit usually contains the volumetric flow allowed and the allowable concentration or poundage of listed materials that may be discharged. If your project increases anything in the permit, the plant must obtain a permit modification. Recently, agencies have begun to require Toxicity Studies to asses any impact on aquatic life. Such studies are lengthy and costly. 

In a randomized, prospective, cost-effectiveness study both teicoplanin and vancomycin were assessed as second-line therapy in 66 neutropenic patients after the failure of empirical treatment with a combination of piperacillin -I- tazobactam and amikacin (10). The primary success of second-line therapy was equivalent, and the direct total costs were similar. Acquisition costs per dose were in favor of vancomycin, but costs derived from administering vancomycin and serum concentration monitoring led to similar costs for both regimens. With the exception of the red man syndrome, which occurred in 10% of vancomycin-treated patients but none of the tei-coplanin-treated patients, toxicity (renal, liver, and ear toxicity, diarrhea, phlebitis) was also similar. 

The use of in vitro systems such as cell cultures, tissue slices, and cell lines has become of major importance for several reasons. First of all, the common practice of the use of experimental animal models for studying toxicity of chemicals meets serious and growing criticism for ethical and economic reasons. Toxicity studies aiming at performing a hazard or a risk assessment inevitably will include adverse effects and thus discomfort for the animals involved. Moreover, the cost of running an animal facility and performing toxicity studies is an increasingly important limitation. 

Because of their size and duration and the corresponding costs involved, oncogenicity studies are usually conducted towards the end of the development of a pharmaceutical when clinical efficacy has been established and the majority of the toxicity studies have been completed. The requirements in USA, Japan and Europe for clinical trials and marketing are compared in Table 3.4. 

An exhaustive search for new propellants was made at the time of the switch away from CFCs, and it is unlikely that new ones will be found with the necessary physicochemical properties combined with an excellent safety profile. New surfactants are possible, but there is the major cost hurdle of drug toxicity studies to NCE standards. Particle engineering may provide benefits, e.g., production by supercritical fluid technology. 

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