Thalidomide toxicity testing

The U.S.-based pharmaceutical company William S. Merrell, Inc., licensed thalidomide from its German manufacturer, Chemie Griinenthal, in 1958. After carrying out laboratory, animal, and initial human tests, the company submitted an application to the FDA for marketing authorization. Frances Kelsey, the medical officer assigned to review the application, found deficiencies in the animal studies and criticized the company s testing methods.20 She then requested additional toxicity tests, putting the application on hold. 

Pharmacopeial compendia establish a couple of tests that should be carried out with raw material batches to determine their level of impurities. Concomitants usually detected are heavy metals, chloride, or sulfated ash. The presence of byproducts varies from raw material to raw material. Examples can be both innocuous substances such as monohydrogen phosphate, which is an impurity in dihydrogen phosphate salts and glycine, which is an impurity in alanine, and toxic substances, such as the classical enantiomer S of thalidomide. 

We often hold up thalidomide as the ultimate example of what may occur when we fail to test drugs rigorously enough. Advocates of natural medicine use the thalidomide saga in their campaign to heap muck on mainstream, scientific medicine, forgetting that numerous natural substances can also have serious toxic effects. Thalidomide has become the villain. Too bad. Recent research indicates that it could be an effective treatment for a variety of conditions. 

Although thalidomide showed no toxicity to laboratory animals when tested by Ciba and Chemie Grunenthal A.G., potentially irreversible peripheral polyneuritis was soon identified in patients following long-term use of thalidomide. Symptoms... 

---