Racemates or enantiomers: regulatory approaches

1. Racemic drugs contain enantiomers which can differ substantially in pharmacological and dispositional properties. The development of chemical methods to separate and analyse drug enantiomers has led to a growing understanding of their biological properties and a regulatory dilemma as to whether only enantiomerically pure drugs should be marketed. 2. Advantages of enantiomerically pure drugs include more selective pharmacological profiles leading to better therapeutic indices, less complex pharmacokinetics and interactions, and simpler interpretation of plasma concentration response relationships. 3. As racemic drugs that are currently marketed and reaching marketing were developed when knowledge of drug enantiomers was less sophisticated, a flexible regulatory approach is required. At present, it is probably reasonable to require substantial information on the properties of enantiomers of racemic drugs but the balance is on the side of regulatory agencies needing to justify, provided adequate information is submitted, requirements for enantiomerically pure drugs. 4. This balance will gradually change to a situation where enantiomerically pure drugs will be the standard, and a strong case will need to be put by sponsors wishing to market racemic drugs.