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13.3 Requirements in the United States 327

applies. Data on stereoisomers not previously approved should be provided together
with justification for the fixed combination.

13.2.4.5 Abridged Applications

Generic applications for chiral medicinal products should be supported by bioequiv-
alence studies using enantiospecific bioanalytical methods unless both products con-
tain the same, stable, single enantiomer or both products contain a racemate where
both enantiomers show linear pharmacokinetics.
The guideline concludes with a note that there is no intention to require further
data on established medicinal products which contain a racemic drug unless new evi-
dence emerges concerning the safety or efficacy of one enantiomer. If new claims
related to the chiral nature of the active substance are made, then supporting studies
on the individual enantiomers will be required.

13.3 Requirements in the United States

13.3.1 Introduction

The Food and Drug Administration (FDA) is responsible for authorizing human
medicinal products in the USA through its Center for Drug Evaluation and Research
(CDER). Policy and guidance relating to drug registration for chemical substances
is published in the Federal Register and is available on the FDA Internet web-site at
http://www.fda.gov/cder/guidance/index.htm. The relevant guidance for chiral drugs
is the policy statement for the development of new stereoisomeric drugs which is
described below.

13.3.2 Policy Statement for the Development of New Stereoisomeric
Drugs

The FDA has taken essentially the same view as the EU with respect to the devel-
opment of chiral drugs but emphasizes different aspects in its guidance. The FDA’s
Policy statement for the development of new stereoisomeric drugs was first published
in January 1992, with corrections made in January 1997. The statement was pro-
duced in response to the technological advances which permitted production of
many single enantiomers on a commercial scale. The policy relates only to enan-
tiomers and not to geometric isomers or to diastereoisomers which have chemically
and pharmacologically distinct actions. Except in rare cases where biotransforma-
tion occurs, such compounds are treated as separate drugs, and mixtures are not
developed unless fortuitously as a fixed-dose combination. The guideline acknowl-