Pharmaceutical safety

As mentioned above, significant changes in dmg regulation in Australia, Cypms and the Netherlands, were made as a result of the thalidomide disaster that occurred in Europe in 1961. This is a classic example of a crisis-led change. The disaster increased public concerns about pharmaceutical safety governments responded by imposing more stringent controls on the pharmaceutical sector, and with less resistance from the industry than would normally have been the case. 

A governing principle of pharmaceutical safety assessment is the determination of safety factors the ratio between the therapeutic dose (that which achieves the desired therapeutic effect) and the highest dose which evokes no toxicity. This grows yet more complex (but has less uncertainty) if one bases these ratios on plasma levels rather than administered doses. Traditionally based on beliefs as to differences of species sensitivity, it has been held that a minimum of a five-fold (5X) safety factor should be observed based on toxicity findings in nonrodents and a ten-fold (10X) based on rodents. 

Gad, S.C. (1989b). A tier testing strategy incorporating in vitro testing methods for pharmaceutical safety assessment. Flumane Innovations and Alternatives in Animal Experimentation 3 75-79. 

While they were not quite as sweeping in approach as the aforementioned guidelines, a toxicologist working in pharmaceutical safety assessment should become familiar with the all the other ICH Guidelines in the S series. 

IRRITATION AND LOCAL TISSUE TOLERANCE IN PHARMACEUTICAL SAFETY ASSESSMENT... 

TISSUE TOLERANCE IN PHARMACEUTICAL SAFETY ASSESSMENT TABLE 11.1. Evaluation of Local Tissue Reactions in Tissue Irritation Studies... 

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