Page 276 - Chiral Separation Techniques

10.1 Introduction 255

cal effect. The pharmacologically different properties, which may occur due to in
vivo interconversion during drug absorption, gave rise to the FDA policy [20].
The FDA’s policy regarding fixed-combination dosage where the racemic drug is
used with a combination of different stereoisomeric forms defines that two or more
drugs may be combined into a single dosage form only when each component con-
tributes. The claimed effects of the combined drug and the dosage of each should be
deemed as a safe combination and effective. An interpretation of the FDA’s policy
forewarns pharmaceutical companies that develop or manufactures enantiopure
drugs. Unless the “component or components” represent a fixed dose combination,
parallel studies for the racemate and the resulting enantiopure drug should be imple-
mented to ensure compliance.
Although in many cases an enantiopure drug can be safer than the racemate, the
advantages are clear. The final formulation of the drug product could be reduced in-
half, potential side effects could be minimized, and the resulting pharmokinetic and
pharmacodynamic studies could clearly determine the efficacy of the active phar-
maceutical ingredient (API) [21].
Due to FDA policies, this was a pivotal point for the pharmaceutical industry and
established the onslaught of mergers for the development of enantiopure drugs.

10.1.1.3 Pharmaceutical Industry: Mergers

Pharmaceutical manufacturers began to develop technologies either to resolve or
selectively synthesize enantiopure drugs. The justification was that the active enan-
tiopure drug would prove to be more efficacious, and this would allow drug compa-
nies to extend expiring originator patents.
Merger and acquisition activity is heating up in the fine chemicals and pharma-
ceutical intermediates arena as many companies seek to acquire cGMP facilities.
They are targeting this high-margin business, a result of increasing outsourcing of
the production of intermediates by large pharmaceutical companies. The emergence
of “virtual” pharmaceutical companies is also driving demand for fine chemicals.
These small companies have no other option but to outsource production, since they
have no manufacturing facilities of their own.
With the combined lure of high-margin business and attractive growth prospects,
chemical companies of all types and sizes are actively seeking acquisitions. Major
firms have been very aggressively acquiring or setting up alliances.
As markets for enantiopure drugs continue to develop, the pharmaceutical indus-
try, fine chemical companies, and academic chemists are prospecting for new enan-
tioselective technologies to produce them.