The FDA perspective on the development of stereoisomers

The current regulatory position of the Food and Drug Administration is discussed with regard to the approval of racemates and pure stereoisomers. Circumstances in which stereochemically sensitive analytical methods are necessary to ensure the safety and efficacy of a drug are described. Regulatory guidelines are interpreted for applications for the approval of a pure enantiomer in which the racemate is marketed, for the approval of either a racemate or a pure enantiomer in which neither is marketed, and for clinical investigations to compare the safety and efficacy of a racemate and its enantiomers. Examples of the basis for such regulation are drawn from historical situations (thalidomide, benoxaprofen) as well as currently marketed drugs (arylpropionic acids, disopyramide, indacrinone).