Thalidomide, removal

The second major change enacted under the 1962 amendment was the change in the approval process from premarket notification to a premarket approval system. Under the terms of the 1938 law, an NDA would take elfect automatically if the FDA did not respond. For example, the only reason thalidomide was not approved was because Dr. Kelsey returned the application to the sponsor with a request for more information. In contrast, the 1962 law required affirmative FDA action before a drug could be put on the market. Under the terms of the 1962 amendments, the FDA was also empowered to withdraw NDA approval and remove the drug from the market for a variety of reasons, including new evidence that the product was unsafe or that the sponsor had misrepresented or under-reported data. 

In Chapter 2 the significance of the placental transfer of drugs from the maternal circulation into the fetus was discussed. At that time, the prototypic teratogen thalidomide was discussed along with several contemporary drugs such as alcohol and cocaine. By the time that thalidomide was finally removed from the market and the medicine cabinets, it had caused severe deformities in approximately 10,000 children in 46 countries. 

A terrible tragedy occurred when this happened with a drug called thalidomide, which was used in the 1960s to treat morning sickness in pregnant women. Scientists found out too late that one of thalidomide s two hands caused horrific birth defects. What s more, researchers discovered that removing the bad hand from a dose of thalidomide didn t take care of the prob-... 

The benefits of such a synthesis are numerous. u addition to lowered toxlclly due to the lowered rate of application, one might also obtain lowered toxicity due to removal of the less active (or inactive) stereoisomer. Such a reduction occurred with the removal of the S isomer of thalidomide leaving all of the desired activity in the B isomer. Had this fact been known at the time of the introduction of thalidomide in Britain, a great tragedy could have been avoided. 

The association between thalidomide exposure and phocomelia was alarming enough that the manufacturer withdrew the compound from the European market in 1961. It has been argued that the real proof of the association between thalidomide and phocomelia was established only after the compound was removed from the market, as phocomelia virtually disappeared following its withdrawal. All told, during the four years that thalidomide was widely marketed, over 10,000 children were born with phocomelia. By April 1962,... 

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